Annual Report 2024-2025 - The Consortium for Medical Marijuana Clinical Outcomes Research

ANNUAL REPORT | 2024-2025

February 2025

Prepared by the Consortium for Medical Marijuana Clinical Outcomes Research For more information about the Consortium visit: mmjoutcomes.org For questions or comments, contact: Almut G. Winterstein, RPh, PhD, FISPE Director, Consortium for Medical Marijuana Clinical Outcomes Research Email: mmj.outcomes@cop.ufl.edu Phone: 352-273-6984

TABLE OF CONTENTS EXECUTIVE SUMMARY................................................................................................... 3 CONSORTIUM RESEARCH PROGRAM..........................................................................3 Grants Program ....................................................................................................... 4 Medical Marijuana Clinical Outcomes Repository (MEMORY) ............................ 4 Clinical Research Core............................................................................................. 4 Evidence Core ...........................................................................................................5 Outreach.....................................................................................................................5 CONSORTIUM OUTPUTS 2024-25............................................................................... 6 CONSORTIUM RESEARCH PLAN 2025-26.................................................................. 6 INTRODUCTION............................................................................................................... 7 CONSORTIUM LEADERSHIP AND ADMINISTRATIVE STRUCTURE..............................9 BOARD MEETINGS....................................................................................................... 10 SUMMARY OF CONSORTIUM ACTIVITIES 2024-25.................................................... 11 GRANTS PROGRAM......................................................................................................12 List of Completed Research Studies from the 2019-20 Grant Cycles................13 Summary of Findings of Completed Research Studies of the 2021-23 Grant Cycles............................................................................................................ 14 New Studies from the 2024 Grant Cycle ............................................................. 20 Highlights of Research Conducted by Consortium Grant Awardees ................21 MEMORY....................................................................................................................... 28 MEMORY Development.......................................................................................... 28 Highlights of MEMORY Analyses.......................................................................... 29 CLINICAL CORE............................................................................................................ 34 Medical Marijuana Patient Contact Registry....................................................... 34 Medical Marijuana & Me (M3)................................................................................ 35 CARMMA................................................................................................................. 38 EVIDENCE CORE.......................................................................................................... 39 Evidence in Context Series.................................................................................... 39 Evidence Synthesis for Food and Drug Administration (FDA)........................... 41 Consumer/Patient and Clinician Info Sheets....................................................... 43 OUTREACH .................................................................................................................. 47 Cannabis Clinical Outcomes Research Conference (CCORC) ............................ 47 Website....................................................................................................................48 Newsletter...............................................................................................................48 Researcher Spotlight Series..................................................................................48

SUMMARY OF CONSORTIUM RESEARCH PRODUCTIVITY.........................................49 BIBLIOGRAPHY – PEER-REVIEWED PUBLICATIONS............................................... 50 EXTRAMURAL GRANTS SUBMITTED BY CONSORTIUM FACULTY AND GRANT AWARDEES............................................................................................ 55 MEDIA COVERAGE AND INVITED TALKS...................................................................57 PATENTS AND INDs .....................................................................................................57 CLINICAL TRIALS REGISTERED AT CLINICALTRIALS.GOV.......................................57 CONSORTIUM RESEARCH PLAN 2025-2026..............................................................58 GRANTS PROGRAM..................................................................................................... 59 MEMORY.......................................................................................................................60 CLINICAL CORE............................................................................................................ 61 EVIDENCE CORE.......................................................................................................... 61 OUTREACH................................................................................................................... 61 APPENDICES.................................................................................................................62 APPENDIX A: THE CONSORTIUM FOR MMJ CLINICAL OUTCOMES RESEARCH BOARD...................................................................................................... 62 APPENDIX B: CORE FACULTY, STAFF, AND TRAINEES OF THE CONSORTIUM FOR MMJ CLINICAL OUTCOMES RESEARCH........................................................... 66 APPENDIX C: REVIEWERS OF THE 2024 RESEARCH GRANTS PROGRAM............71 APPENDIX D: A SUMMARY BROCHURE FOR CANNABIS CLINICAL OUTCOMES RESEARCH CONFERENCE (CCORC) 2024................................................... 72

EXECUTIVE SUMMARY Since the passing of the Compassionate Use Act in 2014, Florida citizens have access to marijuana and marijuana products for the treatment of certain debilitating conditions.

While medical marijuana (MMJ) may improve health outcomes, evidence to support its effectiveness for the treatment of most conditions is still lacking and there exist safety concerns related to cognitive effects, risk of accidents, interactions with other medications, psychosis, or addiction. Moreover, cannabis products vary in terms of components and modes of administration, but there is limited research to elude which plant components, doses and delivery methods provide the optimal benefit-risk. This need for research and lack of evidence is in stark contrast to the rapid uptake of MMJ. As of January 3, 2025, the number of licensed MMJ users in Florida was 895,469 as compared to 54,251 on January 5, 2018. The number of physicians licensed to treat their patients with MMJ has grown from 883 to 2,462 over the same period. By the end of 2024, Florida dispensaries supplied more than 409 kg Tetrahydrocannabinol (THC) in non-smokable MMJ products weekly, and 735 kg THC in smokable MMJ, assuming an average content of 20% THC in smokable MMJ products.

The following report details activities of the Consortium for Medical Marijuana Clinical Outcomes Research (Consortium), which was established by Florida statute to conduct, disseminate and support rigorous scientific research on the clinical outcomes of MMJ use. This report is completed during the Consortium’s sixth year (2024-2025), with the previous five reports available at mmjoutcomes.org/our-consortium/annualreport/. An overview of recent Consortium activities was also provided to the Health Professions and Programs Subcommittee of the Florida House of Representatives on February 4, 2025, and can be viewed on the Florida channel: flhouse.gov/VideoPlayer.aspx?eventID=9829 (Dr. Winterstein’s presentation begins at 40:48).

CONSORTIUM RESEARCH PROGRAM The Consortium research program rests on five pillars aimed at supporting the Consortium mission to foster MMJ clinical outcomes research including: A Grants Program, a unique research data repository known as the MEdical Marijuana Clinical Outcomes RepositorY (MEMORY), a Clinical Research Core, an Evidence Core and an Outreach Program.

Following is a brief overview of the purpose and accomplishments of each pillar.

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Grants Program Launched in September 2019, the Consortium grants program has since completed six award cycles and initiated its seventh cycle by releasing a Request for Proposals (RFP).

During the first six grant cycles, 146 research proposals were received, peer-reviewed, and approximately $600,000 per year distributed to a total of 54 researchers from 7 Consortium member institutions. Research outcomes and health conditions addressed in these proposals include outcomes of use of different forms of marijuana in, treating pain of various origins; cancer and chemotherapy related symptom relief; anxiety and post-traumatic stress disorder (PTSD); cardiovascular health; drug interactions with MMJ; MMJ adverse events; patterns, motives and risks of MMJ use; MMJ access in Florida; safety in pregnancy; psychiatric outcomes in older adults; effect of cannabis smoke on human lung enzymes and effect of smoking vs vaping on the human brain, amongst others. Several of these research studies have now been published and been pivotal in securing extramural funding.

Medical Marijuana Clinical Outcomes Repository (MEMORY) The growing use of MMJ in Florida offers a unique opportunity for real-world evaluations of MMJ clinical outcomes that can help overcome the lack of randomized clinical trials and accelerate the availability of evidence on clinical outcomes. MEMORY has been conceived to establish the infrastructure for real-world evidence generation similar to that employed by the United States Food and Drug Administration (U.S. FDA) to evaluate and monitor the benefit-risk of approved prescription medications. To facilitate longitudinal follow-up on clinical conditions, the Consortium has now linked the Office of Medical Marijuana Use (OMMU) Medical Marijuana Use Registry (MMUR) with other clinical databases commonly used for outcomes research. The Consortium has established an application process to provide a de-identified version of this unique repository accessible to interested Consortium researchers, thus providing a state-wide infrastructure to assess the benefit-risk of MMJ. As of the publication of this report, data from MMUR have been provided to the Consortium from July 2016 through June 2024 and have been incorporated into the MEMORY data architecture. New evidence generated from MEMORY and an overview of ongoing studies are provided in this report.

Clinical Research Core As companion to MEMORY, the Consortium Clinical Research Core was established to provide infrastructure support for prospective studies such as randomized controlled trials.

To facilitate such studies, a MMJ patient contact registry to support recruitment was rolled out statewide, with a registry portal on the consortium website (mmjoutcomes.org/ get-involved/registry/). As of January 2025, over 1,700 individuals who are using or are planning to use MMJ have registered. In addition, clinical and industry partners interested in collaborations are registered in the online Connect and Advance Research for Medical Marijuana Analysis (CARMMA) database (mmjoutcomes.org/collaborate/carmma).

In May 2022, the Consortium launched Medical Marijuana and Me (M3), its first large prospective MMJ patient cohort in Florida, and one of the first in the United States. M3 design was guided by a scientific planning committee, including six researchers from consortium member universities, four MMJ physicians, and one MMJ patient representative.

Enrollees completed a sequence of surveys about their general health, use, and experiences with MMJ and related health outcomes. Recruitment efforts for M3 ended in May 2023 and follow-ups were completed in early spring 2024. Data curation has been completed and de-identified survey data of the 1,234 M3 participants are now available to Consortium members. Several findings of M3-based studies are presented in this report.

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Evidence Core The evidence core focuses on the synthesis and dissemination of scientific evidence regarding MMJ clinical outcomes. Evidence core activities include publication of its Evidence in Context series, provision of scientific expertise, and evidence reviews tailored to scientific, clinical and patient communities. The Evidence in Context series addresses a need for rapid distillation and appraisal of emerging evidence on MMJ clinical outcomes and is available as open access in the scientific journal Medical Cannabis and Cannabinoids and on the Consortium website at mmjoutcomes.org/evidence/evidencein-context.

Several Consortium members, led by Principal Investigator Amie Goodin, PhD, MPP, contracted with the U.S. FDA in 2023 to support their review of evidence informing the classification status of cannabis as a Schedule I substance in the United States.

Consortium researchers examined the effectiveness and safety of cannabis when used as therapeutic intervention for several indications, in addition to examining a series of specific safety outcomes described in studies that examined cannabis use for medical, nonmedical, and unknown purposes.

The Evidence Core has also developed info sheets for consumer-patients and clinicians that focus on the safety and effectiveness of MMJ for specific conditions, available in print and on the Consortium website at mmjoutcomes.org/factsheets.

Outreach The Consortium continues to enhance its outreach activities via its websites (mmjoutcomes.org and ccorc.mmjoutcomes.org), quarterly newsletter, and its researcher spotlight video series.

The first Cannabis Clinical Outcomes Research Conference (CCORC) was hosted virtually on April 8 and 9, 2021 and drew participants from 31 U.S. states and five countries. Since then, the Consortium has organized CCORC in a hybrid format (with both in person and virtual options) to promote inclusivity and broad outreach, in May of ’22, ’23, and ’24, at the UF Research and Academic Center at Lake Nona, Orlando, FL. CCORC, which has become the largest cannabis research conference in Florida, offers keynote addresses by national-level experts in cannabis research, panel discussions, workshops, and oral presentations and poster sessions for scientific abstracts selected following peer review.

The fifth annual CCORC is planned for May 29–30, 2025, in Orlando, FL.

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CONSORTIUM OUTPUTS 2024-25 Since its inception, the Consortium has supported the generation of important evidence, resulting in 74 peer-reviewed publications, 1 book chapter, 2 filed patents, 3 approved investigational new drug (IND) applications for research, and 49 new extramural grant applications, 14 of which were awarded. Noteworthy, 117 trainees have been involved in funded research grants, and two new courses have been developed, supporting the development of research capacity in the state. In addition, University of Florida (UF) Consortium Core Faculty developed a comprehensive evidence synthesis on cannabis benefit-risk for the FDA that informed controlled substance schedule change recommendations. Publications on these findings will be forthcoming.

CONSORTIUM RESEARCH PLAN 2025-26 In the coming year, the Consortium will continue its efforts towards facilitating and conducting research that informs clinical care and policy within the five original Consortium research program pillars: the Grants program, MEMORY, the Clinical Core, the Evidence Core, and Outreach activities.

The Grants program will continue with Consortium Board approved updated research priorities including a focus on critical populations, the impact of emerging synthetic and high concentration products, studies on public health impact of cannabis laws, and mitigation strategies for risks of MMJ use. MEMORY development will continue with quarterly data refreshers, new linkages, and development of analytical cohorts to support studies on MMJ effectiveness and safety, utilization and access. The Clinical Core will complete several analyses of M3 data to understand aspects of MMJ use that patients find effective or associated with harms such as cannabis use disorder. It will continue to support prospective studies via its patient contact registry and CARMMA database and provide support for investigators on regulatory issues involving such research. The Evidence Core will publish findings of its evidence review for FDA and evaluate emerging evidence to inform Consortium research priorities. It will also provide required continuing medical education (CME) for physicians authorized to certify MMJ, in collaboration with Florida Department of Health (FL DoH)/OMMU and the Florida Medical Association (FMA). Additional info sheets for clinicians on nausea, and anorexia within HIV/AIDS are planned. In addition to holding its fifth annual conference CCORC, the Outreach Core will disseminate emerging evidence via the Consortium website, its quarterly newsletter, the Researcher Spotlight Series, and participation in scientific conferences.

The Consortium board, core faculty and staff look forward to continuing this critical work to support the Florida MMJ program’s primary goal to improve the health of Florida citizens and provide evidence on the safe and effective use of MMJ.

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INTRODUCTION Beginning with the Compassionate Use Act passed in 2014 and followed by several amendments, Florida law allows the use of marijuana for the treatment of certain debilitating conditions. While there are some promises that MMJ may improve certain health outcomes, evidence in support of its effectiveness for treatment of most conditions is incomplete and there remain safety concerns related to cognitive effects, risk of accidents, interactions with other medications, psychosis, or addiction. Moreover, marijuana products vary in terms of specific components and modes of administration, but little is known about what components, doses, and delivery methods provide the optimal health benefit. There is a substantial and urgent need to understand how MMJ impacts health, to guide both policy and clinical decision-making. However, due to the complex legal restrictions, the research infrastructure to support MMJ evaluations is lagging far behind the rapid uptake of MMJ in the state.

The number of Floridians licensed to use MMJ has continued to increase, with a total of 892,705 licensed users, as of December 2024.

Number of certified MMJ patients in Florida, 2018 - 2024

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To address the need for rigorous evidence on the safety and effectiveness of MMJ for the various patient populations who are seeking certification for use, the state legislature introduced Section 1004.4351, Florida Statutes, to establish the Consortium of Medical Marijuana Clinical Outcomes Research. The statutory-defined mission of the Consortium is to conduct, disseminate, and support rigorous scientific research on the clinical outcomes of MMJ use. In July 2019, the Florida State University System Board of Governors, following a competitive request for proposals, designated the University of Florida as the lead university of the Consortium. Nine additional universities have joined the Consortium to date, the latest being Nova Southeastern University. This signifies retention, build up and expansion of the Consortium, which remains steadfast in executing the assigned statute mission.

Consortium member universities

Consortium responsibilities as defined in its charter and consistent with statute include: • Conduct rigorous scientific research • Disseminate research • Guide statewide policy on ordering and dosing practices for the medical use of marijuana.

The Consortium of MMJ Clinical Outcomes Research presents its sixth Annual Report on its accomplishments in research and outreach and its Research Plan for 2025-2026.

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CONSORTIUM LEADERSHIP AND ADMINISTRATIVE STRUCTURE The Consortium of Medical Marijuana Clinical Outcomes Research is open to all public and private universities in Florida. The Consortium is directed by the MMJ Research Board, which is composed of representatives nominated by the President of each participating university.

Board members represent a variety of scientific and medical fields as required per statute.

Profiles of the Consortium Board members are available in Appendix A. CONSORTIUM FOR MEDICAL MARIJUANA CLINICAL OUTCOMES RESEARCH BOARD BOARD MEMBER

INSTITUTION

Max. C. E. Orezzoli, PhD (Chair)

Florida Memorial University

Dinender Singla, PhD (Vice Chair)

University of Central Florida

William Anderson, PhD

Florida International University

Ken Dawson-Scully, PhD

Nova Southeastern University

Peter Holland, MD

Florida Atlantic University

Eric H. Holmes, PhD

Florida State University

Christopher McCurdy, PhD

University of Florida

Martha S. Rosenthal, PhD

Florida Gulf Coast University

Jacqueline Sagen, PhD

University of Miami

Charles Weatherford, PhD

Florida A&M University

Pursuant to statute, the board appointed Almut G. Winterstein, RPh, PhD, FISPE, Distinguished Professor in Pharmaceutical Outcomes and Policy and Epidemiology, and Director of the Center for Drug Evaluations and Safety (CoDES) at UF, as its director. She is supported by Dr. Robert Cook, MD, MPH, Professor of Epidemiology and Internal Medicine, and director of the Southern HIV and Alcohol Research Consortium (SHARC) Center for Translational HIV Research. They are supported by Assistant Directors for MEMORY, the Clinical Research Core, the Evidence Core, and an Assistant Director for Research Administration. Taking advantage of its academic base, Consortium leadership involves several trainees in Consortium activities. Profiles of the Consortium Core Faculty, staff, and trainees are available in Appendix B.

Consortium Administrative Structure

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BOARD MEETINGS Since its inception, the board has met 20 times between August 2019 and Feb 1, 2025. Key accomplishments and decisions at the board meetings in the past year are summarized below and complete meeting minutes are available on the Consortium website at mmjoutcomes.org/our-consortium/board-meetings/.

MAY 31, 2024 • Dr. Amie Goodin provided a post-hoc overview of CCORC 2024, and the board offered their congratulations on its success and agreed on continuation of this outreach activity.

• Dr. Winterstein presented a Consortium activities update.

• Dr. William Anderson and Dr. Martha Rosenthal were recognized for their service as chair and vice-chair of the Consortium board.

JUNE 20, 2024 • The board finalized the selection of research proposals to be awarded for the 2024 grants funding cycle.

• Dr. Max Orezzoli was elected in as the new chair and Dr. Dinender Singla was elected as the new vice chair of the board.

OCTOBER 15, 2024 • Dr. Winterstein shared the Consortium outputs from 2023-24 and presented the Consortium research plan for 2024-25.

• The board approved the FY25 budget including support for MEMORY driven safety and efficacy studies, MMJ and Me (M3) phase II planning, and approved the plans for the fifth conference of the consortium to be held in May 2025 in Orlando.

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SUMMARY OF CONSORTIUM ACTIVITIES 2024-25 Central to the Consortium is its mission to foster clinical outcomes research on MMJ across the state. Five pillars constitute the Consortium Research Program: A Grants Program, the MEdical Marijuana clinical Outcomes RepositorY (MEMORY), a Clinical Research Core, an Evidence Core and Outreach core. Consistent with its charter, the Consortium has engaged scientists with relevant research programs to participate in the Consortium and foster research collaborations to accelerate the development of evidence on MMJ clinical outcomes. The following sections provide a description of each of the Consortium functions and a detailed progress report.

Consortium Structure and Functions

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GRANTS PROGRAM Each year, the Consortium offers a research grants program, open to all members of the Consortium and teaching nursing homes as stipulated by statute. The research focus of the grants program is prioritized based on statutory guidance and the annual Consortium research plan. Applications are peer-reviewed by external reviewers, recruited from out-ofstate, using National Institute of Health (NIH) review criteria. Final grant awards are made by the MMJ Research Board based on study quality, impact, and relevance to the Consortium research priorities. Calls for proposals are disseminated by each board member within their university and through the Consortium website, newsletter, and listservs. We have completed the 2019-2023 grants program cycles, are mid-way through the 2024 grants program cycle and have launched the 2025 grants cycle.

Consortium Grant Program Timeline

Between 2019 and 2024, the Consortium Grants Program received 146 research proposals and after review, awarded 54 of these to researchers of 7 of its member institutions. These awards, totaling more than $3.6 million, cover a broad range of focus areas consistent with Consortium research priorities.

Overview of Consortium-awarded Research Study Topics

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List of Completed Research Studies from the 2019-20 Grant Cycles (findings summarized in 2023-24 report) 2019 GRANT AWARDEES PRINCIPAL INVESTIGATOR

STUDY TITLE

Paul Borsa, PhD University of Florida

Efficacy of a Controlled Short-Term Trial of CBD Ingestion on Reducing Symptomatic Response and Facilitating Recovery After Induced Muscle Injury

Helen Bramlett, PhD University of Miami

Therapeutic Dosing of a Cannabinoid (CBD) After Mild and Moderate Brain Injury for Translation to the Clinic

Joshua Brown, PharmD, MS, PhD University of Florida

Characterizing Community and Physician-Level Factors Associated with Medical Marijuana Prescriber Registration and Patient Access

Andrea Cippitelli, PhD Florida Atlantic University

Cannabidiol: A Potential Treatment for Migraine-Like Pain, Negative Emotion and Photophobia

Gregory McManus, PhD Florida Golf Coast University

Rapid Identification and Quantification of Heavy Metals and Microplastics in CBD Oil

Mandip Singh Sachdeva, PhD Florida Agricultural & Mechanical University

Hyaluronic Acid Functionalized, Cannabidiol-Loaded Mesenchymal Stem Cells (MSC)-Derived Exosomes for Drug Resistant Cancers

Jacqueline Sagen, MBA, PhD University of Miami

Evaluation of Medical Marijuana for the Treatment of Chronic Spinal Cord Injury Pain Using a Rat Central Neuropathic Pain Model

Krishna Vaddiparti, MSW, MPE, PhD University of Florida

A Feasibility Study of Real-Time Monitoring of Posttraumatic Stress Disorder Related Sleep Disturbances and Other Symptoms Among Patients on Medical Marijuana

Jenny L Wilkerson, PhD University of Florida

Marijuana-Derived Terpenes for the Treatment of Chemotherapy-Induced Pain

Ali M Yurasek, PhD University of Florida

The Relationship Between State Medical Marijuana Laws, Substance Use and Mental Health Disorder Diagnoses, and Associated Health Care Costs 2020 GRANT AWARDEES

Hassan Azari, PhD University of Florida

Hemp Derived Extracellular Vesicles (EVS) for the Treatment of Glioblastoma

Lisa Eckel, PhD Florida State University

Cannabinoid Medication for Treatment of a Pre-Clinical Model of Anorexia Nervosa (AN)

Debra Fadool, PhD Florida State University

Mechanisms of Action for Cannabidiol in a Mouse Model of Anxiety

Jason Ford, PhD University of Central Florida

Patterns, Motives, and Risks Associated with Marijuana Use: A Comparison of Medical Marijuana Patients and Non-Patient Marijuana Users in Florida

John Markowitz, PhD University of Florida

An Assessment of the Drug Interaction Potential Between Oral Cannabidiol (Epidiolex®) and the CES1 Substrate Methylphenidate in Healthy Volunteers

David Newman, PhD Florida Atlantic University

Assessing and Supporting Effective and Safe Use of Medical Marijuana for Older Adults with Chronic Pain

Mandip Sachdeva, PhD Florida Agricultural & Mechanical University

Preclinical Evaluation of Exosomal Cannabinoid Formulations in Chemotherapy Induced Peripheral Neuropathy

Douglas Storace, PhD Florida State University

The Influence of Cannabinoid Receptors on Olfactory Function

Roberto Vincis, PhD Florida State University

Endocannabinoid Mechanism in the Neural Processing of FoodPredicting Sensory Cues

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Summary of Findings of Completed Research Studies of the 2021-23 Grant Cycles 2021 GRANT AWARDEES PRINCIPAL INVESTIGATOR

STUDY TITLE

SUMMARY OF RESEARCH OUTCOMES PROVIDED BY GRANTEES*

Jennifer Attonito, PhD Florida Atlantic University

Acceptance of and Access to Medical Marijuana and CBD as a Palliative Care and Hospice Treatments for Nursing Home Patients*

Published results report on a survey of 126 clinicians and interviews of 25 patients in nursing homes and assisted living facilities. Respondents expressed major barriers to utilization existed, including lack of education/training and clinical guidelines. Some participants considered MMJ and recreational MJ use to be similar. Patients interviewed reported that they have not been offered MMJ by their providers and are unfamiliar with the procedures for obtaining a MMJ card.

Joshua Brown, PharmD, PhD, MS University of Florida

Characterizing Adverse Drug Events Reports Involving Cannabis and Cannabinoids

Upon evaluation of over 15,000 adverse event reports from the FDA Adverse Event Reporting System including cannabis or cannabinoids used medically/ recreationally, over 500 types of adverse events were represented among 200 different product names. Prevalent reactions were neuropsychiatric (19%), cardiovascular (14%), infections (12%), and sedation (5%). The most common medications that were concomitantly used by patients with reactions included gabapentin (19%), pantoprazole (19%), lorazepam (18%), amitriptyline (13%), and duloxetine (13%). Opioids were also commonly included as comedications (e.g., fentanyl (6%), morphine (7%), and tramadol (12%).

Jenny Wilkerson, PhD and Joshua Brown, PharmD, MS, PhD University of Florida

Translational Examination of the Pharmacological Interactions of Medical Marijuana with Neuropathic Pain Analgesics in Both Young and Older Adults

Results show that in both young and aged female mice, when compared to their age matched male cohort, THC, morphine, and gabapentin have small but significant increased potency to attenuate chemotherapy induced peripheral neuropathy (CIPN)related behaviors. Likewise, in younger mice of both sexes, compared to aged cohorts of both sexes, THC, morphine, and gabapentin have increased potency to attenuate CIPN-related behaviors. Thus, confirming the original hypothesis that age and sex both play roles in the effect of MMJ and other analgesics for pain.

Andrea Cippitelli, PhD Florida Atlantic University

Investigating Cannabidiol AntiHeadache Actions Through PPAR Signaling

The effects of the pharmacological blockade of PPAR-γ with GW9662 (PPAR antagonist), in reversing the anti-allodynic effects of CBD were tested in male and female mice. Both activation and inhibition of PPARγ lead to anti-allodynic effects, just as CBD does.

However, the anti-allodynic effect of CBD was not blocked by pretreatment with a PPARγ antagonist, suggesting that the antiallodynic effect of CBD was not mediated by PPARγ. This demonstrates a new role for PPARγ on migraine and other headache disorders.

These findings need further exploration and represent critical pilot data to attract extramural funding.

*Cited in Consortium bibliography and outputs on pages 50-57

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Lisa Eckel, PhD Florida State University

Cannabinoid Modulation of Neuroinflammation in a Pre-Clinical Animal Model of Anorexia Nervosa

Research revealed that THC treatment slowed the weight loss associated with activity-based anorexia, in a pre-clinical animal model of anorexia, and this was mediated primarily by a decrease in exercise, rather than an improvement in appetite. Further it was confirmed that rats with activity-based anorexia display neuroinflammation (quantified by increases in microglia) in the arcuate nucleus of the hypothalamus, and that this inflammatory response is attenuated

by THC treatment. This pre-clinical study offers a translational model for the development of new cannabinoid-based pharmacotherapies, including the use of MMJ.

Mariola Edelmann, PhD University of Florida

The Role of Endocannabinoids and Cannabinoids in the Clearance of Bacterial Infections and Macrophage Polarization

Murine bone marrow-derived RAW264.7 macrophages were infected with S. typhimurium, followed by exposure to several concentrations of THC-mimicking WIN55,212-2, and this cannabinoid (CB) completely blocked proinflammatory tumor necrosis factor (TNF)alpha responses. Effect of CBs on bacterial clearance was evaluated, where WIN55,212-2 increased bacterial clearance. However, there was no direct suppression of Salmonella’s growth by WIN 55,212-2. These results suggest that CBs decrease inflammation and promote pro-phagocytic functions during Salmonella infection.

Debra Fadool, PhD Florida State University

Early Developmental Mechanisms of Action for Cannabidiol (CBD) in a Mouse Model of Anxiety

Using a new mouse model having trait anxiety and attention deficits (Kv1.3-/- mice) these researchers observed that when the offspring were raised to adults, CBD exposure in utero turned out to be anxiolytic in females but not in males. However, both sexes in mice exhibited increased obsessive compulsive-like (OCD) behaviors, and this behavior was not lessoned by cross-fostering in the males. While ADHD behaviors were not affected by in utero CBD exposure, female mice had a reduction in long-term object memory.

Developmental changes in the brain were also observed in response to CBD exposure. Of note, fetal exposure to CBD significantly decreased survival of the pups.

Simone Marini, PhD, University of Florida

CBD-Induced Biomarkers Of Inflammation Reduction in People Living With HIV (PLWH)at the Single Cell Level*

Findings suggest that a group of genes is underexpressed after CBD treatment in myeloid cells, including monocytes and granulocytes. Both monocytes and granulocytes play a pivotal role in the inflammatory process, and the great majority of genes emerging from the analysis play a well-known pro-inflammatory role. As chronic inflammation is a condition common to a plethora of different diseases, this study is a first step towards the understanding of how CBD may be used for anti-inflammatory therapeutic strategies for PLWH. Study findings have supported a successful application for NIH funding.

*Cited in Consortium bibliography and outputs on pages 50-57

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Mandip Sachdeva, PhD, Florida Agricultural & Mechanical University

Evaluation of Minor Cannabinoids loaded Exosomes in Chronic Diabetic Neuropathy*

This study demonstrated the role of phytocannabinoids, CBD, Tetrahydrocannabivarin (THCV), and cannabigerol (CBG) in alleviating diabetic induced neuropathic pain via various antiinflammatory and mitochondrial pathways. Results have supported a successful application for FL DoH funding.

Jacqueline Sagen, Alleviation of PhD, MBA Phantom Limb Pain University of Miami in a Rat Model by Treatment with Components of Cannabis

Research reveals that a low dose of THC together with a synergistic combination of CBD, and terpene β-caryophyllene (BCP), can significantly block the onset of phantom limb pain symptoms. This combination can also significantly attenuate further progression of phantom limb pain severity once it has begun.

Ellen Zimmermann, MD University of Florida

Using a well-established animal model of inflammatory bowel disease (IBD) to test the effectiveness of THCtreatment, it was observed that THC treatment had mixed efficacy with little to no effect on hematocrit and colon length but altered gene expression consistent with previous data in human cells.

Surprisingly, THC had a suppressive effect on normal weight gain in healthy mice, and exacerbated colitisassociated weight loss in treated mice. This surprising result raises new questions and potentially new research paths.

The Effect of Delta-9-Tetrahydrocannabinol (THC) on Intestinal Inflammation and Fibrosis in Experimental Crohn’s Disease

2022 GRANT AWARDEES PRINCIPAL INVESTIGATOR

STUDY TITLE

SUMMARY OF RESEARCH OUTCOMES PROVIDED BY GRANTEES*

Naueen Chaudhry, MD University of Florida

Cannabinoid Use in Young Adults with Crohn’s Disease

Using surveys and focus groups, researchers found distinct differences in patterns of MJ use of collegeaged students with Crohn’s disease, varying by age, gender, and duration of disease diagnosis.

Rodrigo Cristofoletti, PhD University of Florida

Quantitative Assessment of Complex Drug-Drug Interaction (DDI) Networks Involving Medical Cannabis Products in Special Populations

A model-based approach was used to assess the magnitude of cytochrome P-450 (CYP)-mediated drug interactions precipitated by CBD and Δ9-THC. The basic model showed an interaction potential of CBD with all major CYP enzymes, whereas, for Δ9-THC, risk was detected with CYPs 1A1, 1A2, and 2C9. Metabolic pathways sensitive to interactions with cannabinoids were further investigated using the static mechanistic model, which showed that CBD has a high potential to precipitate severe to moderate interactions on major CYP-mediated metabolic pathways, including CYP3A and CYP2C19. Δ9-THC showed a moderate risk for interactions. These CBD-mediated interactions will be translated from in vitro to in vivo scenarios using physiological-based pharmacokinetic (PBPK) modeling.

Robert Dvorak, PhD University of Central Florida

Event-Level Changes in Psychiatric and Physical Symptoms Following Medicinal Cannabis Use in Older Adults*

A national sample of older adults (n = 106) with MMJ qualifying conditions provided 5,156 momentary assessments across 1,106 use days. Symptom trajectories were examined across the day. The data suggest that MMJ may be effective in reducing common symptom clusters. However, the negative reinforcing effect may complicate it’s therapeutic nature.

*Cited in Consortium bibliography and outputs on pages 50-57

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Debra Fadool, PhD Florida State University

Long-Term Molecular, Metabolic and Behavioral Consequences of Perinatal Exposure to Cannabidiol (CBD) – A Safety and Efficacy Study

Researchers observed that administration of CBD in utero results in reduced pup survival, accelerated growth rate, decreased anxiety, increased obsessive compulsive behavior especially in males, and decreased object memory as adults. Additional experiments are measuring if there are long-term changes in gene expression that could moderate the observed changes in behavior and brain development detected in adults that were exposed to CBD in utero.

Varan Govind, PhD Evaluation of University of Miami Immunomodulatory Effects of Chronic Medicinal Marijuana Use and Its Routes of Administration on the Cerebral Metabolism, Morphology, Dopamine, and Neural Circuits of the Whole-Brain, and Pain in Young Adults Living With and Without HIV

This study evaluates effects of chronic MJ use and its routes of administration on the brain, systemic inflammation, immune-cell phenotypes associated with activation, exhaustion and homing, and neuropathic pain, and behavioral measures in HIV+/ HIV- subjects. The 93 enrolled individuals include 47 males, 46 females, 43 HIV-positive, 50 HIV-negative, 63 marijuana users, and 30 marijuana non-users. Blood samples for assessing inflammation, immune activation and gut leakage have been collected and magnetic resonance imaging (MRI) based data recorded for analyses.

Lori Knackstedt, PhD University of Florida

A Translational Animal Model to Study Neurobehavioral Consequences of THC and Oxycodone Polysubstance Use

Experiments using a rodent model of sequential oxycodone and cannabis intake suggest that THC reduces motivation to seek oxycodone when the effort exerted to obtain the drug is high, and offers a protective ‘anti-relapse’ effect after a period abstinence. These effects are specific for oxycodone and don’t alter sucrose seeking, nor do they seem to be related to withdrawal symptoms at the time of oxycodone self-administration. These are significant findings as they suggest that offering supervised/ managed access to MMJ to active opioid users has the potential to reduce opioid craving.

Walter Steigleman, MD University of Florida

Randomized, Controlled CrossOver Comparison of Cannabidiol to Oral Opioid for Postoperative Photorefractive Keratectomy (PRK) Pain Control*

A substantial fraction of patients who develop addiction to opioid medications start with a legitimate prescription for postoperative pain. IND approval was obtained for a CBD-based gummy with less than 0.3% THC, with potential applications for ocular or other medical purposes. The IND is used in this study evaluating if an oral CBD product for acute postoperative ocular pain can offer similar pain relief to current standard therapy with an opioid medication, marking a pioneering step in the field. Initial findings indicate that the oral CBD product had similar outcomes in terms of pain control and quality of life for post-PRK pain, as compared to opioid medication.

*Cited in Consortium bibliography and outputs on pages 50-57

2025 ANNUAL REPORT | 17

Eva WiderstromEffects of Noga, PhD Cannabidiol on University of Miami Resting State EEG and Neuropathic Pain Severity in People with Spinal Cord Injury*

Among a survey of 227 participants, 87.9% noted that cannabis reduced their neuropathic pain intensity by more than 30%, and 92.3% reported that cannabis helped them to better deal with their neuropathic pain. Most participants (83.3%) reported substituting their pain medications with cannabis, with the most substituted medication categories being opioids (47.0%), gabapentinoids (42.8%) and over-the-counter pain medications (42.2%). These preliminary results suggest that cannabis and cannabinoids may be effective in reducing neuropathic pain intensity among those with spinal cord injury and may help to reduce the need for certain pain medications. The study team has secured a new CBD source and are resubmitting an updated IND to the FDA.

2023 GRANT AWARDEES PRINCIPAL INVESTIGATOR Lisa Eckel, PhD Florida State University

STUDY TITLE

SUMMARY OF RESEARCH OUTCOMES PROVIDED BY GRANTEES*

Cannabinoid Treatment for Reducing ChemotherapyInduced Cachexia and Neuropathic Pain in a Pre-Clinical Rodent Model

The current project was designed to examine whether cannabinoids, including Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), may attenuate symptoms of cachexia by alleviating inflammation-induced loss of appetite, and lean/adipose muscle mass. Study findings revealed that CBD is more efficacious than THC in alleviating symptoms of cachexia. Ongoing research is examining whether the therapeutic effect of CBD is mediated by its anti-inflammatory effects.

Jennifer Hu, PhD Impacts of Medical University of Miami Marijuana Use on Inflammasome Activation and Breast Cancer Clinical Outcomes*

This pilot study of 63 breast cancer patients demonstrated that elevated inflammasome activation plays a role in exacerbating treatment related side effects and decreasing overall survival rates in breast cancer patients. This study tests a new paradigm that MMJ targets inflammasome in improving breast cancer clinical outcomes, to pave ways for future clinical research to evaluate the effectiveness of MMJ in breast cancer patients, particularly in minority populations with worse treatment outcomes and survival rates.

Pilot data from this study have supported a successful application for extramural funding.

Habibeh Khoshbouei, PhD, PharmD University of Florida

By increasing basal dopamine levels, compounds such as THC could help stabilize the brain’s reward system, reduce cravings, and alleviate withdrawal symptoms.

Using a mouse model of methamphetamine addiction, it was observed that daily administration of THC (2 mg/ kg), but not saline, during the 10-day drug abstinence period, significantly reduced methamphetamine reinstatement. This effect was evidenced by the complete abolishment of methamphetamineinduced stimulation of dopamine release in the striatum and the absence of behavioral responses to methamphetamine.

Development of Cannabinoid Treatments to Ameliorate Methamphetamine Use Disorder

*Cited in Consortium bibliography and outputs on pages 50-57

18 | CONSORTIUM FOR MEDICAL MARIJUANA CLINICAL OUTCOMES RESEARCH

Catalina LopezQuintero, MD, PhD University of Florida

A Pilot Double-Blind Placebo-Controlled, Randomized, Safety, Efficacy, and Acceptability Trial of a Hemp-Derived Cannabidiol Extract for the Treatment of Anxiety*

Regulatory approvals for the study including an IND are in place and the trial has been registered at ClinicalTrials.gov (NCT06672666). The Data and Safety Monitoring Board, comprising two psychiatrists and one hepatologist, has been assembled. Pre-screening processes including laboratory tests for participants have been initiated to conduct a 1:1 randomized, double-blind, 4-week pilot clinical trial.

John S. Markowitz, PharmD University of Florida

The Influence of Cannabis Smoke Condensate on Drug Metabolizing Enzymes in the Human Lung

In this study a novel in vitro approach is used involving a cannabis smoke condensate (CSC) as a representative mixture to assess the influence of MMJ smoking on drug metabolizing enzymes utilizing human lung microsomes. CSC has been produced and collected and LC-MS/MS assay developed and validated to quantify the major cannabinoids (CBs) present in the CSC. Five major CBs were found including cannabidiol (CBD), cannabinol (CBN), delta9-tetrahydrocannabinol (THC), cannabigerol (CBG), and 11-OH-THC. With human lung fractions, it was determined that the model showed no activity for the following enzymes: CYP2C8, CYP2C19, CYP2E1, or CYP2D6, but did show activity for CYP3A4/5, CYP1A2, and carboxylesterase 1 (CES1). Completed assessments showed that CSC produced a moderate inhibitory effect on CYP3A and a potent effect on CES1.

Niall Murphy, PhD University of Florida

Comparative Evaluation of Cannabinoids and Opioids for Treating Chronic Pain in Aged Subjects

Preliminary findings suggest that aged animals exhibit heightened pain sensitivity, with age- and pain-statespecific effects of CBD and THC becoming evident.

These cannabinoids appear to have differing analgesic or hyperalgesic effects depending on the age and pain state of the animal. The inclusion of pharmacokinetic analyses will offer deeper insights into the mechanisms driving these age-related differences. Final data from this ongoing study will provide important information on the safety and efficacy of cannabinoids as analgesic options for the elderly.

*Cited in Consortium bibliography and outputs on pages 50-57

2025 ANNUAL REPORT | 19

New Studies from the 2024 Grant Cycle In June 2024, the Consortium awarded six new grants (up to $75,000 for one year) to researchers as part of their sixth research grants cycle. Additionally, two grant awards ($130,00 over two years) from the 2023 grants cycle were approved for their second year of funding. The new 2024 awardees, their affiliations, along with the project narratives and anticipated impact of their proposed research, are presented below.

PI: ERICA DALE, PHD University of Florida

Anticipated Impact: The results of this study have the potential to inform patient care, policy making, Study Title: Effects of acute cannabis and foster a deeper understanding of MMJ’s public smoke exposure on respiration after health implications. cervical spinal cord injury in rats PI: EARL MORRIS, PHARMD, MPH, Project Narrative: More than half of traumatic PHD spinal cord injuries (SCI) occur at the cervical University of Florida level, leading to respiratory compromise or failure.

Study Title: Medical Cannabis Use Cannabis has been shown to enhance motor and Cardiovascular Health in a output in neural systems for locomotion, however Vulnerable Population of Medicaid Patients the effects of cannabis on the motor neuron networks responsible for breathing have not been Project Narrative: This project aims to fill a critical gap in understanding the cardiovascular explored. We have previously shown multiple effects of MMJ by leveraging linked data from the known cellular pathways that lead to synaptic strengthening of the motor neurons responsible for Florida MMUR and Medicaid claims. By examining trends in cannabis use among patients with controlling breathing, including the serotonergic system. Cannabis may also be neuroprotective and cardiovascular conditions and assessing associated can facilitate synaptic transmission via modulation risks, this study will provide crucial insights into the safety of MMJ in a vulnerable population. of the mammalian serotonin system. We propose to measure respiratory output during cannabis Anticipated Impact: Output from this project smoke exposure in rats with cervical spinal cord will help set priorities for future research into the injury. cardiovascular risk profile of MMJ, will provide novel evidence to healthcare providers for making Anticipated Impact: With cannabis activating more informed treatment decisions, and will guide the prime receptors for neuroplasticity in the policy makers in crafting regulations that ensure respiratory control network, we propose that safer MMJ use. respiratory motor output will facilitate enhanced breathing capacity and thus, dramatically improve PI: MANDIP SACHDEVA, PHD quality of life for those living with SCI. Florida A&M University PI: PANAGIOTA KITSANTA, PHD Study Title: Role of CBD and Full Florida Atlantic University Spectrum CBD in Diabetes Induced Peripheral Neuropathy Study Title: Medical Cannabis Use among Pregnant and non-Pregnant Project Narrative: Diabetic peripheral neuropathy Women of Reproductive Age (DPN) is a prevalent and debilitating complication of diabetes mellitus, marked by the progressive Project Narrative: In the United States, medical loss of sensory function in the lower extremities. marijuana (MMJ) use among pregnant and Existing treatments for DPN provide only partial non-pregnant women of reproductive age symptomatic relief and do not prevent disease (WRA) is increasing. However, there is scarce progression. This project hypothesizes that research detailing the specific uses of MMJ in CBD, either as a standalone treatment or within this population. The objectives for this study a full-spectrum CBD formulation, can alleviate include: (1) identifying the medical conditions for DPN symptoms—such as pain, numbness, and which MMJ is utilized as well as quantifying MMJ dosage, product types, and administration routes; tingling—thereby improving sleep quality, mood, and overall quality of life in diabetic patients.

(2) investigating MMJ’s impact on the use of The study aims to evaluate the effectiveness of controlled substances, including opioids used for these treatments, monitor patient responses to pain management; and (3) assess the occurrence cannabinoid supplements versus placebo. of adverse events associated with MMJ use.

20 | CONSORTIUM FOR MEDICAL MARIJUANA CLINICAL OUTCOMES RESEARCH

Anticipated Impact: By assessing CBD as a single agent versus full-spectrum CBD, this study will provide a crucial baseline for future research on combination therapies or cannabis derivatives as a treatment option for DPN. PI: BARRY SETLOW, PHD University of Florida Study Title: Effects of inhaled THC/ CBD combinations on age-related cognitive impairment

EVA WIDERSTRÖM-NOGA, DDS, PHD, FASIA University of Miami Study Title: Effects of a hempderived cannabidiol and cannabidiolic-acid (CBD-A) oral extract on resting-state electroencephalography (EEG) and neuropathic pain in people with spinal cord injury

Project Narrative: No studies to date have examined the acute effects of oral CBD/CBD-A on neuropathic pain intensity and unpleasantness, Project Narrative: THC may hold potential for and EEG resting state power in people with spinal remediating cognitive deficits in older adults, cord injuries. The proposed research will determine however, it is not clear how other cannabinoids if a single CBD/CBD-A dose produces analgesic found in cannabis (particularly CBD) interact with effects and if these changes can be verified by THC to affect cognition in this age group. Using neuroelectric correlates. We will gain improved well-validated rodent models of cognitive function, understanding of the effects and underlying in combination with a translationally relevant route mechanisms of cannabis and cannabinoids on SCIof administration (vaping), this study will determine related neuropathic pain. how CBD influences the ability of THC to remediate Anticipated Impact: If successful, the outcomes of age-related deficits in several forms of memory. this study will facilitate the development of larger, Anticipated Impact: It is important to determine high-quality clinical trials to evaluate the long-term how cannabinoid mixtures influence the cognitive effects of cannabinoid treatments on neuropathic outcomes of THC use. This project will enable pain and quality of life in people with spinal cord rapid experimental assessment of the impact injuries. of CBD on THC’s effects on cognition in aged subjects, which could inform the clinical use of cannabinoid mixtures.

Highlights of Research Conducted by Consortium Grant Awardees As part of our annual report each year we feature some of the impactful studies concluded in the previous year. Several extensive clinical studies are ongoing and expected to yield additional significant outputs in the coming years.

Knowledge, Attitudes, and Beliefs Regarding Medical Cannabis Among Patients and Providers in Florida’s Long-Term Care Facilities This study employed surveys to assess the knowledge of, attitudes toward, and barriers to MMJ among 126 providers in Florida long-term care (LTC) facilities and in-depth interviews with 25 LTC patients. The age of the providers ranged from 21 to 74 years; 74% were female, 18% were Black/African American, and 17% reported Hispanic ethnicity. Less than half of the providers felt they received adequate training on MMJ (37%), had experience discussing the indications and contraindications of MMJ with patients and/or caregivers (29%), and were confident they could answer patients’ and/or caregivers’ questions about MMJ (35%). Most (68%) stated they understood the difference between THC and CBD, and 70% were aware of the different routes of administration. Nearly all felt that MMJ is a viable treatment option (94%) and that MMJ should be federally legal (81%). They also reported concerns: patients might self-treat with street cannabis (71%), MMJ can interact with other medications (55%), and use can lead to addiction (23%). About a third agreed that there is not enough MMJ research (37%).

2025 ANNUAL REPORT | 21

SELF-PERCEIVED KNOWLEDGE AND BELIEFS ABOUT MMJ AMONG FLORIDA LONG-TERM CARE PROVIDERS (N=126).

N

% STRONGLY OR SOMEWHAT AGREE

I have received adequate training on MMJ.

86

37

I understand the difference between THC and CBD components of MMJ products.

85

68

I am aware of the different routes of administration for MMJ.

77

70

I have experience in discussing the indications and contraindications of MMJ with patients and/or their caregivers.

84

29

I am confident I can answer patients’ and/or caregivers’ questions about MMJ.

84

35

I know how to obtain a MMJ card in the state of Florida.

84

48

MMJ is safe

87

70

MMJ is a viable treatment option

86

94

All clinicians should be trained

85

94

MMJ should be recommended to patients

86

78

MMJ should be federally legal

85

81

Patients might self-treat with street cannabis

84

71

MMJ can interact with other meds

84

55

Not enough MMJ research

85

37

Use of MMJ can lead to addiction

84

23

The MMJ certification process is difficult for patients

84

33

STATEMENT SELF-PERCEIVED KNOWLEDGE

BELIEFS

MMJ: medical marijuana, THC: tetrahydrocannabinol, CBD: cannabidiol.

Regarding patients (n=25), 16% reported using MMJ ever, and less than half (32%) had knowledge of MMJ or how to obtain products (data not shown). Many believed it could help with symptoms and would consider its use, if recommended by a doctor. However, they reported that MMJ was rarely recommended by providers and that they knew little about its use. Positive attitudes toward MMJ as a viable therapy for some patients and an interest in learning more about MMJ appeared to be an important finding in this study.

The top barriers to MMJ recommendation by providers were not having enough training to help patients (31%), lack of clinical guidelines (39%), lack of patient education tools (21%), lack of support from medical association/licensing bodies (14%), risk of losing reimbursement from Medicare/Medicaid (14%), and lack of support from other direct care staff (10%).

22 | CONSORTIUM FOR MEDICAL MARIJUANA CLINICAL OUTCOMES RESEARCH

BARRIERS TO RECOMMENDING MMJ FOR PATIENTS AMONG PROVIDERS IN FLORIDA LONGTERM CARE FACILITIES (N= 126).

BARRIERS Not enough training

N (N = 126)

% WHO ANSWERED YES

39

31

Lack of patient educational tools

26

21

Lack of clinical guidelines

36

29

Lack of support from medical assoc./Licensing bodies

18

14

Availability of Rx cannabinoids

12

10

Poor or diminished patient comprehension of Florida certification process

6

5

Lack of patient interest

2

2

Patient self-dosing

12

10

Concern patients may use recreationally

6

5

Patient challenges to MMJ certification

8

7

Patient challenges to accessing MMJ products

10

8

Potential liability concerns

12

10

Risk of losing reimbursement from Medicare/Medicaid

18

14

Time constraints

1

0.8

Lack of support from other direct care staff

13

10

Facility location or other structural limitations

7

6

Other

10

8

MMJ: medical marijuana.

Copyright 2024, Attonito et al.

Cureus. 2024 Aug 4;16(8):e66115. doi: 10.7759/cureus.66115

Although most providers felt MMJ is a viable treatment option, the main barriers to recommending it to patients were a lack of proper training, clinical guidelines and patient education tools. This study underscores access challenges among seniors in LTC who might benefit most from MMJ’s therapeutic properties.

This work was completed and published by 2021 grant awardee Jennifer Attonito, Florida Atlantic University. Attonito J, Freeman K, Bone MK, Howard H, Blum C, Luck G. Knowledge, Attitudes, and Beliefs Regarding Medical Cannabis Among Patients and Providers in Florida’s Long-Term Care Facilities. Cureus. 2024 Aug 4;16(8):e66115. doi: 10.7759/ cureus.66115. PMID: 39229412; PMCID: PMC11369963. https://pmc.ncbi.nlm.nih.gov/ articles/PMC11369963/

2025 ANNUAL REPORT | 23

THC as a Potential Candidate for Methamphetamine Addiction Methamphetamine (METH) addiction severely disrupts the normal functioning of the dopamine system. By increasing basal dopamine levels, compounds such as THC could help stabilize the brain’s reward system, reduce cravings, and alleviate withdrawal symptoms.

This stabilization may improve recovery outcomes and decrease the likelihood of relapse, positioning THC as a potential candidate for METH addiction treatment programs.

Using a mouse model of METH addiction, Consortium researchers found that daily administration of THC (2 mg/kg), but not saline, during the 10 day drug abstinence period, significantly reduced METH reinstatement. This effect was evidenced by the complete abolishment of METH-induced stimulation of dopamine release in the striatum and the absence of behavioral responses to METH. METH administration induced robust conditioned place preference (CPP), as evidenced by significantly higher CPP scores compared to saline-treated controls. During the abstinence period, THC-treated animals exhibited a significant reduction in reinstatement behavior compared to vehicle-treated controls. On Day 22, animals receiving daily THC (2 mg/ kg) during abstinence displayed no preference for the drug-paired chamber, suggesting complete cessation of METH preference. In contrast, vehicle-treated animals retained a mild preference for the drug-paired chamber. During the reinstatement test on Day 23, THC-treated animals demonstrated a striking absence of METH-induced CPP reinstatement.

This was paralleled by the complete abolishment of METH-induced dopamine release in the striatum, as observed in the dLight1.3 fluorescence recordings. Conversely, vehicle-treated animals exhibited reinstatement of METH preference, accompanied by significant dopamine release upon METH challenge.

THC TREATMENT MITIGATES METH-INDUCED REINSTATEMENT AND SUPPRESSES DOPAMINE ACTIVITY ON THE DRUG-PAIRED SIDE.

During the reinstatement phase, mice were administered 2 mg/kg METH or 0.9% saline via intraperitoneal (i.p.) injection. METH-exposed animals that received THC treatment did not exhibit METH-induced reinstatement behavior (p = 0.08, one-way ANOVA). Interestingly, THC-treated animals displayed a noticeably reduced dopamine peak frequency compared to METH-treated animals following a single METH dose. Representative raster plots of dopamine peaks on the drugpaired side during reinstatement illustrate these findings.

These findings indicate that THC, administered during the abstinence phase, effectively mitigates both behavioral and neurochemical signatures of METH addiction. THC reduced METH reinstatement behavior and suppressed dopamine release associated with drug exposure, suggesting its potential as a therapeutic agent in addiction treatment programs.

These transformative results highlight THC’s capacity to stabilize the brain’s reward system, reduce cravings, and support recovery.

This research was conducted by 2023 grant awardee Habibeh Khoshbuei, University of Florida.

24 | CONSORTIUM FOR MEDICAL MARIJUANA CLINICAL OUTCOMES RESEARCH

Marijuana Use as an Adjunct to Advanced Irritable Bowel Disease (IBD) Care: Perceptions and Patterns of Use and Mental Health Needs in a Single Tertiary Care Setting This study surveyed 108 participants who reported recent MJ use and were recruited from the University of Florida IBD clinic. Participants were 47% male, with median age range of 26-45 years. Patients had disease severity typical of a tertiary care setting with prior hospitalizations (77%), history of fistula or abscess (32-37%), and bowel surgery (43%).

PATIENT CHARACTERISTICS CHARACTERISTICS AGE 17-25 years 26-45 years 46-65 years >65 years GENDER Male Female Non-Binary Prefer not to answer WORKING STATUS College student Employed Self-employed Not working or studying at this time (includes those on disability) Retired CURRENT TREATMENT FOR IBD None Steroids 5-ASA Azathioprine/6-MP Methotrexate Biologics and Small Molecules TYPE OF MARIJUANA USE Recreational Medical Combination MENTAL HEALTH COMORBIDITIES Depression/Anxiety ADD/ADHD Eating disorder Bipolar disorder PTSD Other mental diagnosis IBD-RELATED COMPLICATIONS Hospitalization Bowel Surgery Fistula (excluding peri-anal fistulae) Abscess Bowel cancer None of the Above

NUMBER OF PATIENTS 15 (14%) 54 (50%) 29 (27%) 10 (9%) 51 (47%) 56 (52%) 0 (0%) 1 (1%) 18 (17%) 41 (38%) 10 (9%) 36 (33%) 13 (12%) 19 (18%) 10 (9%) 15 (14%) 23 (21%) 7 (7%) 61 (57%) 15 (14%) 65 (62%) 25 (24%) 66 (61%) 21 (19%) 5 (5%) 7 (7%) 21 (19%) 5 (5%) 83 (7%) 46 (43%) 40 (37%) 35 (32%) 0 (0%) 0 (0%)

2025 ANNUAL REPORT | 25

DURATION OF MARIJUANA USE <1 month 1 to 6 months 3 to 12 months 12 months to 5 years > 5 years FREQUENCY OF MARIJUANA USE Every day or almost every day One or more times per week One or more times a month Less than once a month

2 (2%) 3 (3%) 9 (9%) 45 (43%) 45 (43%) 71 (68%) 17 (16%) 5 (5%) 11 (11%)

A significant number of participants reported being diagnosed by a physician with Depression/Anxiety (61%), ADD/ADHD (19%) and PTSD (19%). Around 43% had used marijuana for >5 years. A majority (68%) of respondents reported daily or almost daily use.

REASONS FOR USE AND IMPACT OF MARIJUANA USE RESPONSES NUMBER OF PATIENTS SYMPTOMS TREATED WITH MARIJUANA Diarrhea 31 (29%) Nausea/vomiting 58 (54%) Bloody stool 5 (5%) Fatigue 32 (30%) Fever/chills 5 (5%) Joint pain (arthritis, arthralgia) 59 (54%) Insomnia 51 (47%) Anxiety 65 (60%) Poor appetite 47 (44%) Weight loss 15 (14%) Other 18 (17%) OVERALL EFFECT ON SYMPTOMS Complete Resolution 5 (5%) Significant Improvement 59 (56%) Mild Improvement 36 (34%) Unchanged 5 (5%) Worsened 0 (0%) EFFECT ON QUALITY OF LIFE Improved 92 (88%) Worsened 0 (0%) Unchanged 13 (12%) EFFECT ON ABILITY TO LIVE INDEPENDENTLY Improved 65 (61%) Worsened 1 (1%) Unchanged 40 (38%) EFFECT ON ABILITY TO FOCUS/CONCENTRATE AT WORK OR SCHOOL Improved 28 (26%) Worsened 4 (4%) Unchanged 43 (40%) Not applicable 32 (30%) EFFECT ON RELATIONSHIPS AT WORK Improved 14 (13%) Worsened 1 (1%) Unchanged 39 (36%) Not applicable 53 (50%)

26 | CONSORTIUM FOR MEDICAL MARIJUANA CLINICAL OUTCOMES RESEARCH

EFFECT ON RELATIONSHIPS OUTSIDE OF WORK Improved Worsened Unchanged Not applicable MONTHLY COST OF MEDICAL MARIJUANA < $100 $101 to $300 >$300 Don't know PRESENCE OF ADVERSE SIDE EFFECTS Yes NEED FOR HOSPITALIZATION DUE TO MARIJUANA SIDE EFFECTS Yes Not sure

38 (36%) 1 (1%) 50 (47%) 18 (17%) 38 (44%) 25 (29%) 6 (7%) 18 (21%) 8 (9%) 2 (2%) 3 (3%)

Patients with IBD cared for in a tertiary IBD center perceive that marijuana helped improve symptoms and improved their ability to live independently. Most (91%) did not observe any adverse side effects.

Notably, 64% believed marijuana use reduced their opioid consumption, regardless of disease severity. Participants reported less need for using immunosuppressive medications and reported improved gut inflammation and symptom reduction. Overall, 88% of respondents reported improvement in their QOL with marijuana use.

Patient Perceptions of Marijuana Use

Survey respondents used marijuana as an adjunct to standard therapies with overall positive perceptions about its benefit-risk.

This research was conducted by 2023 grant awardee Naueen Chaudhry, University of Florida.

2025 ANNUAL REPORT | 27

The growing uptake of MMJ in Florida offers a unique opportunity for real-world evaluations of MMJ outcomes that can help overcome the slow availability of randomized clinical trials and provide timely evidence on MMJ benefit-risk.

MEMORY has been conceived to establish the infrastructure for real-world MMJ clinical outcomes evaluations similar to those employed by the FDA to evaluate and monitor the benefit-risk of prescription medications after marketing.

MEMORY supports: • controlled studies on MMJ effectiveness and safety • active surveillance to capture emerging safety issues involving individual products or generalized effects among MMJ users • MMJ utilization studies on MMJ access and utilization pattern across Floridians In late January 2023, the Consortium received approval by the Florida Department of Health (FL DoH) to access the MMUR and the FL DoH Institutional Review Board (IRB) approved MEMORY in August 2023.

MEMORY Development To facilitate longitudinal follow-up to capture relevant health outcomes and availability of control groups, the MEMORY data science team has linked the Medical Marijuana Use Registry (MMUR) data from the Office of Medical Marijuana Use (OMMU) with other clinical databases commonly used for outcomes research and de-identified the linked database following HIPPA rules to create a robust research-ready repository. This includes administrative insurance claims data for enrollees in Florida Medicaid and Medicare programs, providing detail on diagnoses and procedures on medical encounters and medications dispensed in outpatient pharmacies. Among records of more than 8 million Medicaid enrollees, 295,000 have been linked to the MMUR. About 125,000 Medicare enrollees have been linked to the MMUR among more than 2 million Medicare enrollees in Florida. Cohorts of MMJ users and matching non-users (with similar conditions) created within Medicaid data will allow assessments of vulnerable populations and will also capture a large proportion of children and pregnancies in the state, both priorities for MMJ assessments. Medicare data will facilitate assessments particularly in older citizens.

Linkages included are Florida Vital Statistics Birth and Fetal Death records for the assessment of pregnancy outcome, and death records for assessment of mortality for specific causes such as cardiovascular deaths or opioid overdoses.

28 | CONSORTIUM FOR MEDICAL MARIJUANA CLINICAL OUTCOMES RESEARCH

Total number of individuals by data source and linked

The Consortium has established an ongoing process for data updates, curation and linkages and can currently offer access to data with approximately a 6-months delay. There is now also an established application process for Consortium researchers to request a de-identified version of MEMORY data for specific research questions, thus providing infrastructure for real-world clinical outcomes research. To date, the Consortium has shared de-identified data with two Consortium research groups from the University of Florida and will soon share with a third group from Florida Atlantic University (two of these studies are funded by the Consortium grant program). De-identified data are accessed only within UF’s secure computing environment.

Ongoing analyses of MMJ utilization patterns using MEMORY are summarized below.

Highlights of MEMORY Analyses Physician-Reported Adverse Events in MMUR We conducted a cross-sectional study of MMUR data from July 1, 2017, through August 31, 2023, analyzing reports of adverse events entered by certifying physicians. Emulating spontaneous adverse drug reaction reporting programs implemented by regulatory agencies, such as the FDA’s Adverse Event Reporting System (FAERS), Florida’s MMJ program requires physicians to report adverse outcomes encountered during the course of care, including a description of the event, its severity and seriousness, and whether and how it was resolved.

Participants included those with at least one completed certification and dispensing of MMJ during the study period. Dispensed products could include low-THC cannabis, MMJ, and marijuana flower for smoking. Adverse events and their characteristics were extracted from reports and evaluated by two independent investigators who individually mapped each adverse event to a Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term, an approach used by FAERS. We reported counts and proportions of reports by patient-, physician-, and adverse event-level characteristics.

2025 ANNUAL REPORT | 29

Example of MEDRA preferred term mapping to an adverse event report

We identified 1,170 unique adverse event reports, representing 1,795 adverse events (AE) belonging to 880 patients (0.08% of 1,136,381 patients with MMJ dispensings). AEs were mapped to a total of 142 unique MedDRA preferred terms. The most commonly reported AEs included dry mouth (n=178, 9.9%), increased appetite (n=148, 8.2%), anxiety (n=139, 7.7%), cough (n=129, 7.2%), and dry throat (n=100, 5.5%).

SERIOUSNESS OF AE (N,%)

SEVERITY OF AE (N, %)

No: 1124 (96)

Mild: 659 (56)

No action: 427 (37)

ACTION TAKEN (N, %)

Yes: 46 (4)

Moderate: 332 (28)

Reduced dose: 262 (22)

Severe: 179 (15)

Interrupted treatment/ delayed dose: 278 (24) Discontinued: 203 (17)

Physician-reported adverse events in MMUR from July 1,2017 through August 31, 2023

Most AE reports were rated as medically non-serious (96%) and mild in severity (56%).

Reports for 37% of reports noted no action was needed to manage the AE, and 17% note MMJ was discontinued permanently. AEs listed as medically serious included: death, palpitations, psychosis, syncope, hyperemesis syndrome.

A total of 2,456 unique physicians issued at least one certification within the study period; of these, 46 (1.9%) submitted at least one AE report, with five submitting 1,107 (94.6%) reports. The percent of patients these 5 physicians had certified and for who they issued reports ranged from 0.4% to 12%.

In summary, AE reports were issued for only a small fraction of patients, but analysis of reporting patterns suggests under-reporting by a majority of MMJ certifying physicians.

Reported events were mostly mild, but the reporting of several serious events emphasizes the critical role these data can play in MMJ surveillance and in guiding future safety studies.

30 | CONSORTIUM FOR MEDICAL MARIJUANA CLINICAL OUTCOMES RESEARCH

Persistence of MMJ Use We evaluated the persistence of MMJ use among certified patients by leveraging MMUR data. Persistence was measured as the proportion of patients with an active recertification at 2 years after first certification, allowing a gap of 30 days between certifications. Of 796,676 initiators of MMJ between 2018-2022, 21.50% had retained an active certification at 2 years of follow-up.

Persistence varied by qualifying condition with lowest proportion of patients with active certifications at the 2-year mark using MMJ for ALS, Parkinson’s disease, and cancer.

Two-year persistence of certified MMJ users

Multivariable regression analysis revealed that 2-year persistence was lower for patients aged 0-12 years (OR 0.51, 95% confidence interval 0.42-0.62), and >65 years (OR 0.84, 0.830.85) compared to patients aged 18-64 years, and for female patients (OR 0.93, 0.92-0.94) compared to males. Qualifying conditions, routes of administration, and type of medical cannabis were also associated with persistence.

In summary, we noted lower persistence in MMJ use among the age extremes, female patients and across certain conditions. Further research needs to address whether reasons for MMJ discontinuation are related to lack of effectiveness, safety concerns or other issues.

Children, Adolescents, and Young Adults MMJ Utilization Patterns We used MMUR data to conduct a cross-sectional study of patients aged 0 to 25 years certified to purchase MMJ, between 2018 and 2023. Subgroups were identified based on specific age ranges, with those aged 0 to 11 years defined as children, those aged 12 to 17 as adolescents, and those between 18 to 25 years as young adults. We used the date of birth recorded in the registry to ascertain age at the time of first certification and only considered valid certifications defined as those in effect for at least one day and with at least one purchase of MMJ during the certification period.

2025 ANNUAL REPORT | 31

We estimated the number of unique individuals per month who purchased MMJ by dosage across age groups. Figures indicate the time of introduction of Senate Bill 182, which permitted MMJ flower for smoking and Emergency Rule 64ER20-33, which permitted edible products. Secular trends in those aged 12 to 17 years showed increases in the number of unique persons with purchases of any dosage form except for smokable marijuana flower and suppositories until the end of 2021. Since then, utilization has dropped in this age group, with vaporized and orally administered products remaining the preferred dosage form in this age group.

Number of unique persons aged 12 to 17 years with purchases of MMJ between January 1, 2018, and December 1, 2023, by dosage form

Amongst those aged 18 to 25 at time of purchase, a steady and consistent increase in the number of distinct persons with purchases of MMJ was observed across nearly all dosage forms, with those administered via inhalation (smoking or vaping) experiencing the greatest growth in userbase over time. By 2024, 4.0% of the overall population of Florida had purchased MMJ, while 6.7% of Florida young adults aged 18 to 25 had purchased MMJ, compared to 5.8% of working adults aged 18 to 64.

Number of unique persons aged 18 to 25 years with purchases of MMJ between January 1, 2018, and December 1, 2023, by dosage form

32 | CONSORTIUM FOR MEDICAL MARIJUANA CLINICAL OUTCOMES RESEARCH

Examining medical conditions associated with MMJ certifications among pediatric and young adults, epilepsy and PTSD/anxiety were the predominant conditions among young children and adolescents. Although the representation of epilepsy increased in total counts in young adults, epilepsy played a minor role as qualifying condition with almost 80% of certification attributable to PTSD/anxiety. Pain had increased to 18% compared to 11% across qualifying conditions for adolescents and 7% for children.

THE MOST COMMON QUALIFYING MEDICAL CONDITIONS FOR PATIENTS VARIED BY AGE.

Children, 0-11 yrs N= 1,108 N (%)

Adolescents, 12-17 yrs N = 2,286 N (%)

Young Adults, 18-25 yrs N = 149,852 N (%)

N= 1,108

1,437,013

1,809,840

346 (31.2)

891 (39.0)

63,380 (42.3)

Florida Population in age range* Female

Qualifying Medical Condition (can have ≥1) Post-Traumatic Stress Disorder

90 (8.1)

702 (30.7)

68,970 (46.0)

PTSD — similar in kind

296 (26.7)

698 (30.5)

50,791 (33.9)

Pain

76 (6.9)

242 (10.6)

26,757 (17.9)

Epilepsy

257 (23.2)

228 (10.0)

2,403 (1.6)

Epilepsy — similar in kind

52 (4.7)

45 (2.0)

867 (0.6)

Cancer

60 (5.4)

48 (2.1)

929 (0.6)

Terminal condition

12 (1.1)

17 (0.7)

252 (0.2)

Multiple Sclerosis — similar in kind

20 (1.8)

68 (3.0)

9,776 (6.5)

HIV — similar in kind

25 (2.3)

32 (1.4)

267 (0.2)

Similar condition

255 (23.0)

306 (13.4)

7,951 (5.3)

*Census 2020 for Florida by age group.

Considering concerns about psychiatric and cognitive adverse effects in young adults, and specifically the impact of THC on the developing brain, this rise in MMJ users as well as the shift in qualifying conditions emphasizes the need for further research into the benefit-risk of MMJ in this age group.

This work was completed by Consortium core faculty and the Consortium MEMORY data science team.

2025 ANNUAL REPORT | 33

CLINICAL CORE The Clinical Core establishes infrastructure for prospective studies including randomized controlled trials. With expert guidance from Ms. Sheila Austin, Regulatory Specialist, at the Clinical and Translational Science Institute at UF, the Consortium has assisted researchers in submitting and obtaining three investigational new drug (IND) approvals.

IND designations are required for study of new drugs by the FDA. Collaborators for the Clinical Core span across the state from University of Miami, Florida International University, Florida Atlantic University, Florida A&M University, and Florida State University, and help with patient recruitment, data collection or analysis, clinical research study design, support with regulatory issues (with FDA or Drug Enforcement Agency (DEA)), and access to laboratory experts for product analysis. In addition to research study consultation and support, the Clinical Core also provides three specific resources to support clinical outcomes research: a Patient Contact Registry, the MMJ & Me (M3) survey, and a database of research collaborators (CARMMA).

Medical Marijuana Patient Contact Registry The MMJ contact registry facilitates patient recruitment for future research on MMJ clinical outcomes. The registry was approved by the University of Florida IRB in November 2020. As of January 2025, over 1700 MMJ users across the state are enrolled in the contact registry.

Clinics participating in recruitment and the geographic location of enrolled patients are similar to the current geographic distribution of MMJ clinics and dispensaries.

Medical Marijuana Patient Contract Registry Recruitment: (A) Clinics assisting in patient recruitment (B) Geographic representation of MMJ registry participants

34 | CONSORTIUM FOR MEDICAL MARIJUANA CLINICAL OUTCOMES RESEARCH

Medical Marijuana & Me (M3) In May 2022, the Consortium launched Medical Marijuana & Me (M3). (mmjoutcomes.org/m3study), the first large MMJ patient research cohort in Florida, and one of the first in the United States. M3 provides detailed patient-reported data on MMJ utilization and outcomes to enhance our understanding of patient experiences with MMJ. The strategic goals for M3 were to: • Collect patient-centered data, focusing on the most common health conditions, to characterize the experiences and clinical outcomes among a diverse and representative group of MMJ users in Florida.

M3 data domains

• Provide access to data and recruitment infrastructure for consortium researchers to support pilot studies, papers, and grant proposals.

• Support high-quality, impactful research that can inform state policy, clinician practice and patients.

M3 has recruited a total of 1,234 patients: 602 newly certified MMJ users who were followed over 9 months via consecutive survey waves, and 632 current users who were assessed in one cross-sectional survey.

All data collection from the M3 study was completed in early 2024. Data from both the crosssectional (current users) and the longitudinal study (MMJ initiators followed over 9 months) are now available for sharing. Information about the specific data that were collected from the surveys and the process to request data for analyses is available at mmjoutcomes.org/ m3study Some results from the cross-sectional study of M3 current MMJ user participants were presented in the 2024 annual report. Here, we present results from studies on the longitudinal cohort.

The longitudinal component of M3 enrolled people at the time of their first MMJ certification and new access to the Florida MMJ program. The study participants represent a broad range of ages, racial/ethnic groups, and socioeconomic status.

2025 ANNUAL REPORT | 35

DEMOGRAPHICS AND BASELINE CHARACTERISTICS OF M 3 PARTICIPANTS IN THE LONGITUDINAL STUDY OF PERSONS ENROLLING IN THE FLORIDA MMJ PROGRAM (N=602), IN THE M 3 SURVEY. Race White Black/African American Multiple/Other races Hispanic = Yes Male sex Education attained Less than high school High school or GED Some college or college graduate Graduate degree (e.g., MS, PhD) o Veteran (Yes) Insurance Medicaid Medicare Private health insurance I do not have health insurance Multiple/Other insurances Income Less than $20,000 $20,000 to 39,999 $40,000 to 59,999 $60,000 to 79,999 $80,000 to 99,999 100,000 or more How experienced are you with using marijuana?

Not at all experienced Slightly experienced Somewhat experienced Moderately experienced Very experienced Self-reported main reason for use Anxiety Depression Insomnia/Sleep disturbances Chronic pain Post-Traumatic Stress Disorder Migraine Attention Deficit/Hyperactivity Disorder Bipolar Disorder Fibromyalgia

N (%) 471 (78.6) 67 (11.2) 61 (10.2) 75 (12.5) 232 (38.5) 6 (1.0) 158 (26.2) 355 (59.0) 83 (13.8) 47 (7.8) 65 (10.8) 53 (8.8) 280 (46.5) 92 (15.3) 112 (18.6) 115 (20.4) 142 (25.2) 104 (18.5) 68 (12.1) 42 (7.5) 92 (16.3) 96 (15.9) 110 (18.3) 103 (17.1) 130 (21.6) 163 (27.1) 376 (62.5) 267 (44.4) 222 (36.9) 205 (34.0) 184 (30.6) 131 (21.8) 78 (12.9) 70 (11.6) 30 (4.9)

It was notable that most individuals who were enrolling in the Florida MMJ program had previous experience using marijuana outside of the state system. Anxiety was the most common self-reported reason for MMJ use among participants.

36 | CONSORTIUM FOR MEDICAL MARIJUANA CLINICAL OUTCOMES RESEARCH

In this longitudinal study, we evaluated changes among participants who completed an additional assessment at 3 or 9 months and, at baseline, reported: 1) mild to severe anxiety (GAD-7 score > 4) (n=359); 2) mild to severe bodily pain (n=361); or 3) poor sleep (based on a sleep quality item from the Pittsburgh Sleep Quality Index) (n=361). Improvements in anxiety, pain, or sleep between baseline and the final follow-up assessment were determined based on clinically significant changes established in the literature, specifically improvements in GAD-7 scores of 4 or more, or changes in raw scores reflecting improvements of one standard deviation or more for pain and sleep. No changes were defined as having the same score between baseline and follow-up assessments or not having achieved a clinically meaningful change in the GAD-7 score (i.e., change of 4) for anxiety, or the same score or scores within one standard deviation for pain and sleep. Worsening of symptoms was defined as significant increases in the GAD-7 score for anxiety and changes in the score beyond one standard deviation that indicated exacerbation of symptoms for pain and sleep.

The analyses revealed that among participants with anxiety symptoms, 54% reported clinically meaningful improvement, 32.3% experienced no change, and 13.7% reported exacerbation of symptoms. Among those with mild to very severe pain at baseline, 28% reported improvements, 54% remained unchanged, and 17.7% reported worsening pain during the follow-up period. Finally, among participants with poor sleep, 57.7% reported improvements in sleep quality, 26.6% reported no change, and 15.5% reported deterioration in sleep quality. These findings should be interpreted with caution due to several limitations, including attrition rates varying by condition (32 to 50%), which may have introduced bias, as those who completed the assessments might be more likely to perceive cannabis as effective in alleviating their symptoms.

Changes in Anxiety, Pain or Sleep Symptoms between Baseline and Last Follow-Up Assessment (at 3 or 9 months) among Individuals with Anxiety symptoms, Pain, and Sleep disturbances at Baseline.

The Clinical Core appreciates the input of the M3 scientific planning committee, which consisted of 11 members, including six researchers from consortium member universities, four MMJ physicians, and one MMJ patient representative.

2025 ANNUAL REPORT | 37

SCIENTIFIC PLANNING COMMITTEE MEMBERS — M3 (MMJ PATIENT COHORT) PARTICIPANT

INSTITUTION

ROLE ON PLANNING GROUP

Anonymous patient

University of Florida

MMJ Patient Liaison

John Crump, MD

Releafe Now

Certified MMJ Provider

Justin Davis, MD

Florida Marijuana Doctors

Certified MMJ Provider

Jason Ford, PhD

University of Central Florida

MMJ Researcher

Raul Gonzalez, PhD

Florida International University

MMJ Researcher

Patricia Green-Powell, PhD

Florida A&M University

MMJ Researcher

Dushyantha Jayaweera, MD

University of Miami

MMJ Researcher

Jonathon Quinonez, DO

CannaMD

Certified MMJ Provider

Martha Rosenthal, PhD

Florida Gulf Coast University

MMJ Researcher

Denise Vidot, PhD

University of Miami

MMJ Researcher

Michelle Weiner, DO, MPH

Spine Wellness America

Certified MMJ Provider

The Clinical Core also appreciates the following clinics and practitioners that served as participant recruitment sites for M3: Dr. Bob’s Compassion Clinic, Dr. Justin Davis, MD, Dr. Melanie Bone, MD, CannaMD, DocMJ, Green Health & Wellness, Releafe Now, ReliefMD, and Spine & Wellness Centers of South Florida.

CARMMA The Consortium launched the Connect and Advance Research for Medical Marijuana Analysis (CARMMA) Database to connect researchers, physicians, and industry collaborators with the goal to increase and accelerate MMJ research (mmjoutcomes.org/collaborate/carmma).

Researchers, physicians, and industry collaborators can add their contact information and connect with other collaborators.

38 | CONSORTIUM FOR MEDICAL MARIJUANA CLINICAL OUTCOMES RESEARCH

EVIDENCE CORE The evidence core focuses on the synthesis and dissemination of scientific evidence for researchers, providers and patients.

Activities include publication of its Evidence in Context series and development of evidence reviews to inform the Consortium research priorities. A prominent activity of the Evidence Core recently included the development of an evidence synthesis on cannabis benefit-risk to the FDA to support the agency’s recommendation regarding cannabis Schedule I classification.

Evidence in Context Series The evidence base for medical cannabis and cannabinoids continues to evolve rapidly while researchers, healthcare providers, and patient communities remain in need of clear translation of study findings, to future or current implications for clinical practice. The “Evidence in Context” series addresses these needs for rapid distillation and appraisal in the form of brief, plain-language commentaries.

These articles are available in the scientific journal Medical Cannabis and Cannabinoids and on the Consortium website. Both of these platforms are fully accessible to all members of the public, as the journal uses an open-access publishing format. To date, the journal has published nine articles within this series accessible at mmjoutcomes.org/evidence/evidencein-context and linked to in the Bibliography section. No such resource was previously available specifically for MMJ. The latest piece in the Evidence in Context series is on Cannabis Hyperemesis Syndrome.

2025 ANNUAL REPORT | 39

Medical Cannabis and Cannabinoids

Evidence in Context Med Cannabis Cannabinoids 2024;7:86–90 DOI: 10.1159/000539182

Received: April 22, 2024 Accepted: April 28, 2024 Published online: May 3, 2024

Dionna Shine a Amie Goodin b a

College of Pharmacy, University of Florida, Gainesville, FL, USA; bDepartment of Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, FL, USA

Keywords Cannabis hyperemesis syndrome · Cannabis safety · Cannabis adverse events · Cyclical vomiting

Defining Cannabis Hyperemesis Syndrome

A form of hyperemesis known as cannabis hyperemesis syndrome (CHS) has gained attention as a potential cannabis safety concern. CHS was first described as cyclical vomiting that occurred in individuals with prolonged cannabis use [1], but there is no official definition or criteria to diagnose patients with CHS at the time of this writing. CHS is considered a diagnosis of exclusion, and the American College of Gastroenterology describes common characteristics, which include the following [1–3]: • Age <50 at the onset of symptoms • Prolonged, regular cannabis use (>1 year for at least weekly) • Abdominal pain • Resolution of symptoms upon discontinuation of cannabis • Compulsive hot showers/baths or symptom resolution with hot showers/baths • Severe nausea and vomiting with episodes reoccurring over months

karger@karger.com www.karger.com/mca

© 2024 The Author(s).

Published by S. Karger AG, Basel

• Failure of symptom relief from traditional antiemetics • Weight loss

The US surgeon general released a statement in 2021 warning of potential risk of CHS in chronic cannabis users that further advised caution when ingesting edibles, which have delayed effects that can result in overconsumption and thereby result in increased delta-9-tetrahydrocannabinol (THC) exposures [4]. Despite increasing awareness of CHS by clinicians, the mechanism explaining CHS development remains elusive. One proposed mechanism hypothesizes that THC potentially causes emesis by binding to cannabinoid type 1 receptors on the neurons that are in the vomiting center of the brain [5]. It is not clear how this would prompt cyclical vomiting, but THC (which is highly lipophilic) can cross the blood-brain barrier, resulting in potential accumulation of THC in the brain and overstimulation of receptors [5]. Another proposed mechanism suggests that genetic mutations interfering with cannabinoid metabolism lead to over-accumulation and adverse events like CHS [5].

In this piece, we identify studies and case reports that examine characteristics of patients with CHS and describe the trialed pharmacological and behavioral interventions, along with their successes and failures. We synthesize the developing CHS literature for clinicians to promote prompt CHS recognition and inform patients on risk. See the online supplemental material (for all online suppl. material, see https://doi.org/10.1159/000539182) for in-depth literature search and identification procedures, along with the full results of data extraction from reviewed studies.

Correspondence to: Amie Goodin, amie.goodin @ ufl.edu

This article is licensed under the Creative Commons AttributionNonCommercial 4.0 International License (CC BY-NC) (http://www. karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.

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Downloaded from http://karger.com/mca/article-pdf/7/1/86/4237853/000539182.pdf by University of Florida, Gainesville and Jacksonville user on 03 February 2025

Cannabis Hyperemesis Syndrome: What Do We Know?

The journal tracks when its publications are accessed, suggesting significant interest in the Evidence in Context publications.

SUMMARY OF THE EVIDENCE IN CONTEXT PUBLICATIONS AND THEIR USAGE. TITLE

YEAR

USAGE*

Cannabis Hyperemesis Syndrome: What Do We Know?

2024

1,526

Climbing the Evidence Pyramid: Dosing Considerations for Medical Cannabis in the Management of Chronic Pain

2023

678

Cannabis Effects on Driving Performance: Clinical Considerations

2023

2,486

Clinical Considerations for Cannabis Use and Cardiovascular Health

2022

1,411

Will Cannabis or Cannabinoids Protect You from SARS-CoV-2 Infection or Treat COVID-19?

2022

12,585

Much Ado about Dosing: The Needs and Challenges of Defining a Standardized Cannabis Unit

2021

5,654

Perinatal Cannabis Exposures and Autism Spectrum Disorders

2021

3,561

Evidence in Context: High Risk of Bias in Medical Cannabis and Cannabinoid Clinical Trials Dictates the Need for Cautious Interpretation

2021

3,574

Introducing Commentary Series

2021

1,382

*Article views or downloads.

Evidence Synthesis for Food and Drug Administration (FDA) In January 2023, members of Consortium leadership received funding from the FDA for a project titled, “Medical Literature and Data on Cannabis Use.” The purpose of this project was to synthesize the literature to support a comprehensive assessment of the clinical benefit-risk of cannabis. The results from the project were used by the FDA as supporting evidence as they drafted their recommendations.

The Consortium research team accomplished the assessment of clinical benefit-risk through the conduct of large-scale systematic literature reviews and meta-analyses. Project 1 examined a series of harms outcomes, also known as adverse events, as described in studies that examined cannabis use for medical, nonmedical, and unknown purposes.

Harms outcomes examined included: mortality, mental health, cognitive outcomes, cancer, cardiometabolic risks, respiratory diseases, immunity, injury, substance use disorders, and hyperemesis. Project 2 examined the effectiveness of cannabis for the following therapeutic indications: Pain, PTSD, Anxiety Disorders, Epilepsy, Nausea, Anorexia, and Crohn’s Disease.

Both the selection of harms outcomes and conditions for effectiveness assessments were specified by FDA. In the evidence search, Crohn’s disease was expanded to irritable bowel syndrome (IBD), because several studies did not distinguish between Crohn’s disease and ulcerative colitis, which together are categorized as IBD. Visual inspection of the number, quality and findings of published controlled studies examining the effectiveness of MMJ for the investigated conditions illustrates several key findings. First, most studies have limited scientific rigor, placing them in the low-quality evidence category. The only high-quality evidence identified investigated IBD-specific quality of life among patients with IBD and found no difference between patients treated with MMJ or placebo. Second, the most widely studied conditions are IBD and pain, with limited or no controlled studies available for the other investigated conditions. Third, most studies found no difference or were inconclusive. Considering studies of moderate quality, positive results attributable to MMJ included PTSD symptom severity, severity/frequency of chemotherapy-induced nausea and vomiting, quality of life for patients with anorexia, pain disability, and mood states and quality of life for patients with anxiety. A summary of our findings regarding each condition follows.

2025 ANNUAL REPORT | 41

Summary of findings on effectiveness of cannabis for select conditions (controlled studies)

Nausea. The evidence supporting a positive effect of cannabis on chemotherapy-induced nausea and vomiting was rated as moderate quality. The evidence supporting quality of life, nausea-specific quality of life, and post-operative nausea and vomiting were all rated as low-quality evidence. Evidence supporting a positive effect of cannabis in the treatment of nausea on each of these outcomes was inconclusive or marginal.

Anorexia. There was no significant effect of cannabis in improving appetite or quality of life, while cannabis significantly increased caloric intake and body weight. All reviewed studies assessing this outcome were conducted in participants with HIV. The quality of evidence was rated as moderate or low for these outcomes, respectively.

42 | CONSORTIUM FOR MEDICAL MARIJUANA CLINICAL OUTCOMES RESEARCH

Inflammatory Bowel Disease (IBD). Two outcomes, bloating and appetite, demonstrated improvements following treatment but evidence quality was low. There was no difference in outcomes or inconclusive findings related to clinical disease activity, quality of life, pain, remission, IBD-specific quality of life, and endoscopic evaluations; the quality of these null and inclusive findings was variable, ranging from low to high quality.

Anxiety. There were improvements in two anxiety outcomes following treatment with cannabis relative to placebo (profile of mood states and quality of life) and evidence quality was rated as moderate. For two other outcomes, anxiety symptom severity and fibromyalgia anxiety impact, there was no difference or inconclusive findings, and evidence quality was moderate for each.

Post-Traumatic Stress Disorder (PTSD). The evidence was rated as moderate quality supporting an improvement in PTSD symptom severity from cannabis treatment relative to placebo.

Pain. The evidence for improvement of pain disability was rated as moderate quality. The evidence for pain scores and opioid composite scores were also rated as moderate quality, but findings were mixed (meaning they reported either improvement or inconclusive findings) or inconclusive across studies. The evidence for pain scores assessing pain in specific conditions (e.g., fibromyalgia), sleep quality, and other quality of life outcomes was rated as low, and findings were mixed across studies, with some reporting improvements and many reporting inconclusive findings, but none reporting worsening.

In summary, evidence supporting the effectiveness of MMJ for the selected conditions is still limited and requires higher-quality controlled studies that can make causal inferences. The FDA’s recommendation, to revise the classification status of cannabis to Schedule III, was published as a letter from the Department of Health and Human Services in January 2024 and this recommendation was accepted by the Department of Justice in the fall of 2024.

Consumer/Patient and Clinician Info Sheets The Consortium has developed info sheets on the safety and effectiveness of MMJ for specific conditions that are available to consumers and clinicians via the Consortium’s website or in print.

2025 ANNUAL REPORT | 43

44 | CONSORTIUM FOR MEDICAL MARIJUANA CLINICAL OUTCOMES RESEARCH

2025 ANNUAL REPORT | 45

46 | CONSORTIUM FOR MEDICAL MARIJUANA CLINICAL OUTCOMES RESEARCH

OUTREACH The Consortium’s outreach activities are directed towards community members, providers, researchers, and industry, to maximize participation in research and keep these stakeholders abreast of the latest research findings. The Consortium’s outreach platform includes a website, a quarterly newsletter, the Researcher Spotlight video series, the annual Cannabis Clinical Outcomes Research Conference (CCORC), and Consortium participation in other conferences.

Cannabis Clinical Outcomes Research Conference (CCORC) The Consortium launched its annual Cannabis Clinical Outcomes Research Conference (CCORC) in 2021. This research-centric meeting, open to patients and MMJ providers, offers a venue for sharing research findings, disseminating the latest evidence on the health impacts of marijuana, and catalyzing research collaborations both state-wide and nationally. Specific objectives of CCORC are: • Dissemination of research findings on MMJ use, efficacy, and safety • Provide a venue for clinical and research educational opportunities related to MMJ • Foster research collaboration, and stakeholder engagement, between Consortium member institutions and beyond Adapting to conditions created by COVID-19, the Consortium held its inaugural CCORC conference virtually on April 8th and 9th, 2021. CCORC ’22, ’23, and ’24 were held using a hybrid attendance model; the conference venue was at UF’s satellite campus in Lake Nona, FL with select presentations available to stream online. A summary of CCORC 2024 capturing the highlights of the conference is available in Appendix D. The Consortium is planning its fifth Cannabis Clinical Outcomes Research Conference (CCORC) to be held on May 29th and 30th, 2025 in Orlando, Florida.

A scientific program committee with participation from Consortium member institutions advises the organizing committee on conference themes and scientific content. The CCORC save-the-date announcements and call for abstracts have been widely disseminated.

2025 ANNUAL REPORT | 47

Website The Consortium continues to expand its website (mmjoutcomes.org) to disseminate information to researchers, member institutions, physicians/ providers, patients, and the public.

The website provides a comprehensive and interactive hub for the grants program, research updates, and Consortium news. The Consortium has optimized the website to be fully mobile-responsive.

Further improvements continue to increase website performance across all devices.

Newsletter As part of the communication and outreach plan, the Consortium distributes a quarterly newsletter via email to researchers, physicians/providers, and individuals interested in MMJ research. The newsletter includes updates on Consortium activities and ongoing research. For recognition, the Consortium branded the newsletter as MEDICAMENT, which stands for MEDICAl Marijuana rEsearch NewsleTter. The Consortium has published 21 issues of MEDICAMENT, one every quarter, available at mmjoutcomes.org/newsletter.

Researcher Spotlight Series The Consortium initiated the Researcher Spotlight Series, a video series showcasing Consortium researchers. The spotlight series intends to disseminate Consortium research and raise awareness about Consortium work and the importance of the scientific process in evaluating MMJ outcomes.

Each video includes an overview of the researcher’s study, methodological approaches, clinical relevance, and current/expected results. The first two spotlight videos featuring Dr. John Markowitz and Dr. Paul Borsa, two Consortium funded researchers, are available online at (mmjoutcomes.org/researcher-spotlight) and two new spotlight videos will be available in the coming year.

48 | CONSORTIUM FOR MEDICAL MARIJUANA CLINICAL OUTCOMES RESEARCH

SUMMARY OF CONSORTIUM RESEARCH PRODUCTIVITY Over the 5.5 years of its existence, Consortium core faculty and Consortium grant awardees have generated 74 published manuscripts in peer-reviewed journals and one book chapter.

New data generated through Consortium funding has served as the basis for 2 patents, and 3 INDs. Three clinical trials registered at clinicaltrials.gov and 49 new extramural grant applications were submitted, 14 of which were awarded. Noteworthy, more than 117 trainees have been involved in the funded research grants and two new courses have been developed, supporting the development of MMJ research capacity in the state.

2

patents filed

71

117

conference abstracts

trainees

49

29

extramural grants submitted; 14 funded

invited talks and media interviews

74

3

peer reviewed publications

1

book chapter

INDs obtained

2

new college courses developed

3

registered clinical trials

Outputs of the Consortium Research Program

2025 ANNUAL REPORT | 49

BIBLIOGRAPHY – PEER-REVIEWED PUBLICATIONS 1. Algarin AB, Plazarte GN, Sovich KR, Seeger SD, Li Y, Cohen RA, Striley CW, Goldberger BA, Wang Y, Somboonwit C, Ibañez GE, Spencer EC, Cook RL. Marijuana Use and Health Outcomes in Persons Living With HIV: Protocol for the Marijuana Associated Planning and Long-term Effects (MAPLE) Longitudinal Cohort Study. JMIR Res Protoc. 2022 Aug 30;11(8):e37153. doi: 10.2196/37153 . PMID: 36040775; PMCID: PMC9472048.

2. Alipour Haris G, Sarayani A, Winterstein AG. Letter by Alipour Haris et al Regarding Article, “Marijuana Use Among Young Adults (18-44 Years of Age) and Risk of Stroke: A Behavioral Risk Factor Surveillance System Survey Analysis.” Stroke. 2020 May;51(5): e91. doi: 10.1161/ STROKEAHA.120.029273 . Epub 2020 Apr 7. PMID: 32252600.

3. Attonito J, Freeman K, Bone MK, Howard H, Blum C, Luck G. Knowledge, Attitudes, and Beliefs Regarding Medical Cannabis Among Patients and Providers in Florida’s Long-Term Care Facilities.

Cureus. 2024 Aug 4;16(8):e66115. doi: 10.7759/cureus.66115. PMID: 39229412; PMCID: PMC11369963.

4. Barker H, Ferraro MJ. Exploring the versatile roles of the endocannabinoid system and phytocannabinoids in modulating bacterial infections. Infect Immun. 2024 Jun 11;92(6):e0002024. doi: 10.1128/iai.00020-24 . Epub 2024 May 22. PMID: 38775488; PMCID: PMC11237442.

5. Bilbrey JA, Ortiz YT, Felix JS, McMahon LR, Wilkerson JL. Evaluation of the terpenes β-caryophyllene, α-terpineol, and γ-terpinene in the mouse chronic constriction injury model of neuropathic pain: possible cannabinoid receptor involvement. Psychopharmacology (Berl). 2022 May;239(5):1475-1486. doi: 10.1007/s00213-021-06031-2 . Epub 2021 Nov 30. PMID: 34846548.

6. Blanton HL, Barnes RC, McHann MC, Bilbrey JA, Wilkerson JL, Guindon J. Sex differences and the endocannabinoid system in pain. Pharmacol Biochem Behav. 2021 Mar; 202:173107. doi: 10.1016/j. pbb.2021.173107 . Epub 2021 Jan 12. PMID: 33444598; PMCID: PMC8216879.

7. Boullosa CC, Vaddiparti K, Lopez-Quintero C, Varma DS, Cook RL. Clinical Decision Making

by Medical Marijuana Physicians in Florida: A Qualitative Assessment. Subst Use Misuse.

2022;57(14):2042-2052. doi: 0.1080/10826084.2022.2129995 . Epub 2022 Oct 28. PMID: 36305815.

8. Britton MK, DeFelice J, Porges EC, Cohen R, Li Y, Wang Y, Ibañez GE, Somboonwit C, Cook RL. Association between cannabis use disorder and greater apathy in adults with HIV. Drug Alcohol Depend. 2024 Aug 1;261:111354. doi: 10.1016/j.drugalcdep.2024.111354 Epub 2024 Jun 3. PMID: 38870567; PMCID: PMC11549954.

9. Brown JD, Costales B, van Boemmel-Wegmann S, Goodin AJ, Segal R, Winterstein AG. Characteristics of Older Adults Who Were Early Adopters of Medical Cannabis in the Florida MMJ Use Registry. J Clin Med. 2020 Apr 18;9(4):1166. doi: 10.3390/jcm9041166 PMID: 32325769; PMCID: PMC7230351 10. Brown JD, Goodin AJ. High risk of bias in medical cannabis and cannabinoid clinical trials dictates the need for cautious interpretation. Med Cannabis Cannabinoids. 2021; 4:63-66. PMID: 34676351 PMCID: PMC8525149 doi: 10.1159/000514732 11. Brown JD, Goodin AJ. The prevalence of drivers under the influence of medical cannabis must be considered within proper context. Res Social Adm Pharm. 2019 Nov;15(11):1372-1373. doi: 10.1016/j.sapharm.2019.01.015 Epub 2019 Jan 28. PMID: 30709730.

12. Brown JD, Goodin AJ. Will cannabis or cannabinoids protect from SARS-CoV-2 infection or treat COVID-19? Med Cannabis Cannabinoids 2022;5(1):1-4. https://doi.org/10.1159/000522472 PMID: 35702401 PMCID: PMC9149510 .

13. Brown JD, Rivera KJ, Crespo-Hernandez LY, Doenges MR, Auchey I, Pharm T and AJ Goodin.

Natural and Synthetic Cannabinoids: Pharmacology, Uses, and Adverse Drug Events. J Clin Pharmacol. 2021; Aug; 61 Suppl 2:S37-S52. https://doi.org/10.1002/jcph.1871 . PMID: 34396558.

14. Brown JD, Winterstein AG. Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. J Clin Med. 2019 Jul 8;8(7):989. doi: 10.3390/jcm8070989 PMID: 31288397; PMCID: PMC6678684 15. Brown JD. Potential Adverse Drug Events with Tetrahydrocannabinol (THC) Due to Drug-Drug Interactions. J Clin Med. 2020 Mar 27; 9(4):919. doi: 10.3390/jcm9040919 . PMID: 32230864; PMCID: PMC7231229.

16. Cho H, Kalina E, Wu J, Cook R, Salloum R, Liu Y, Bian J, Guo J, Starkweather A. A scoping review of observational research on cannabis use for symptom management in HIV and cancer: Implications for cannabis nursing. Journal of Clinical Nursing. 2024. In press, https://onlinelibrary.wiley.com/ doi/full/10.1111/jocn.17565

50 | CONSORTIUM FOR MEDICAL MARIJUANA CLINICAL OUTCOMES RESEARCH

17. Costales B, Babalonis S, Brown JD, Goodin, AJ. Cannabis effects on driving performance: clinical considerations. Med Cannabis Cannabinoids. 2023; 6:8-14. doi: https://doi. org/10.1159/000528714 18. Costales B, van Boemmel-Wegmann S, Winterstein A, Segal R. Clinical Conditions and Prescription Drug Utilization among Early Medical Marijuana Registrants in Florida. J Psychoactive Drugs. 2021 Jul-Aug;53(3):185-194. doi: 10.1080/02791072.2020.1864069 Epub 2021 Jan 4. PMID: 33393877.

19. Dvorak RD, Paulson D, Dunn ME, Burr EK, Peterson R, Maynard M, De Leon AN, Klaver SJ, Leary AV, Hayden ER, Allen Q, Toth E. Effects of medical cannabis use on physical and psychiatric symptoms across the day among older adults. Psychiatry Res. 2024 Sep;339:116055. doi: 10.1016/j. psychres.2024.116055. Epub 2024 Jun 23. PMID: 38924900.

20. Eeswara A, Pacheco-Spiewak A, Jergova S, Sagen J. Combined non-psychoactive Cannabis components cannabidiol and β-caryophyllene reduce chronic pain via CB1 interaction in a rat spinal cord injury model. PLoS One. 2023 Mar 13;18(3):e0282920. doi: 10.1371/journal.pone.0282920 .

PMID: 36913400; PMCID: PMC10010563.

21. Goodin A, Guo S, Wang Y, Winterstein A, et al. Medical Literature and Data on Marijuana Use: Report on Harms of Non-Medical Marijuana Use and Marijuana Use of Uncertain Intent. Pages 1 to 183. Consortium for Medical Marijuana Clinical Outcomes Research in partnership with The Sentinel Initiative, for the United States Food and Drug Administration. Technical Report: Project 1A 1C (TO #75F40123F19008). Approval Date: September 20, 2023.

22. Goodin A, Guo S, Wang Y, Winterstein A, et al. Medical Literature and Data on Marijuana Use: Report on Medical Use Effectiveness and Safety. Pages 1 to 205. Consortium for Medical Marijuana Clinical Outcomes Research in partnership with The Sentinel Initiative, for the United States Food and Drug Administration. Technical Report: Project 2 and 1B (TO #75F40123F19008). Approval Date: August 21, 2023.

23. Goodin AJ, Crum J, Fadool DA, Konin JG, Paikoff S, Sachdeva MS, Singla D, Stiffin R, Vidot DC, Villalba K, Jyot J, Winterstein AG. Abstracts for the 2023 Cannabis Clinical Outcomes Research Conference (CCORC), on behalf of the Scientific Program Committee. Med Cannabis Cannabinoids 20 December 2023; 6 (1): 102–124. https://doi.org/10.1159/000534044 24. Goodin AJ, Jyot J, Cook RL, Wang Y, Hasan MM, Winterstein AG. Proceedings of the 2024 Cannabis Clinical Outcomes Research Conference. Med Cannabis Cannabinoids. 2024 Oct 23;7(1):213-217. doi: 10.1159/000541327 . PMID: 39444709; PMCID: PMC11498913.

25. Goodin AJ, Tran PT, McKee S, Sajdeya R, Jyot J, Cook RL, Wang Y, Winterstein AG. Proceedings of the 2023 Cannabis Clinical Outcomes Research Conference. Med Cannabis Cannabinoids. 2023 Sep 29;6(1):97-101. doi: 10.1159/000533943 . PMID: 37900895; PMCID: PMC10601943.

26. Goodin AJ, Wilson DL, Cook RL, Wang Y, Brown J, Winterstein AG: Proceedings of the 2021 Cannabis Clinical Outcomes Research Conference. Med Cannabis Cannabinoids 2021. Sep 10;4(2):143-146 https://doi.org/10.1159/000519037 PMID: 35224433; PMCID: PMC8832197.

27. Goodin AJ, Winterstein AG, Cook R, Wang Y, Brown, JD. Introducing Commentary Series: “Evidence in Context.” Med Cannabis Cannabinoids 2021 Feb 23;4(1):61-62 doi: 10.1159/000512684 PMID: 34676350; PMCID: PMC8525212.

28. Huffstetler CM, Cochran B, May CA, Maykut N, Silver CR, Cedeno C, Franck E, Cox A, Fadool DA. Single cannabidiol administration affects anxiety-, obsessive compulsive-, object memory-, and attention-like behaviors in mice in a sex and concentration dependent manner. Pharmacol Biochem Behav. 2023 Jan; 222:173498. doi: 10.1016/j.pbb.2022.173498 . Epub 2022 Nov 29. PMID: 36455670.

29. Jean-Jacques J, Cook R, Winterstein AG, Goodin A, Brown JD, Jugl S, Wang Y. Priorities for Medical Marijuana Research from the Perspective of Physicians, Dispensary Owners/Staff, and Patients: A Survey Study. Med Cannabis Cannabinoids. 2021 Aug 2;4(2):107-113. doi: 10.1159/000518105 . PMID: 35224430; PMCID: PMC8832249.

30. Jugl S, Goodin AJ, Brown JD. Climbing the Evidence Pyramid: Dosing Considerations for Medical Cannabis in the Management of Chronic Pain. Med Cannabis Cannabinoids. 2023 Apr 26;6(1):4145. doi: 10.1159/000530251. PMCID: PMC10134049 31. Jugl S, Okpeku A, Costales B, Morris E, J, Alipour-Haris G, Hincapie-Castillo J, M, Stetten NE, Sajdeya R, Keshwani S, Joseph V, Zhang Y, Shen Y, Adkins L, Winterstein AG, Goodin A. A Mapping Literature Review of Medical Cannabis Clinical Outcomes and Quality of Evidence in Approved Conditions in the USA from 2016 to 2019. Med Cannabis Cannabinoids 2021; 4:21-42. doi: 10.1159/000515069 PMID: 34676348; PMCID: PMC8525213.

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32. Jugl S, Sajdeya R, Buhlmann M, Cook RL, Brown JD, Winterstein AG, Goodin AJ. Legalization of Smokable Medical Cannabis and Changes in the Dispensed Amount of Δ-9 Tetrahydrocannabinol Per Patient. Cannabis Cannabinoid Res. 2024 Oct 7. doi: 10.1089/can.2024.0073. Epub ahead of print. PMID: 39375043.

33. Jugl S, Sajdeya R, Morris EJ, Goodin AJ, Brown JD. Much Ado about Dosing: The Needs and Challenges of Defining a Standardized Cannabis Unit. Med Cannabis Cannabinoids 2021 Jun 17;4(2):121-124. doi: 10.1159/000517154 PMID: 35224432; PMCID: PMC8832202.

34. Kalvala AK, Bagde A, Arthur P, Kulkarni T, Bhattacharya S, Surapaneni S, Patel NK, Nimma R, Gebeyehu A, Kommineni N, Meckes DG Jr, Sun L, Banjara B, Mosley-Kellum K, Dinh TC, Singh M. Cannabidiol-Loaded Extracellular Vesicles from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Paclitaxel-Induced Peripheral Neuropathy. Pharmaceutics. 2023 Feb 7;15(2):554. doi: 10.3390/pharmaceutics15020554 Erratum in: Pharmaceutics. 2023 Aug 25;15(9): PMID: 36839877; PMCID: PMC9964872.

35. Kalvala AK, Nimma R, Bagde A, Surapaneni SK, Patel N, Arthur P, Sun L, Singh R, Kommineni N, Nathani A, Li Y, Singh M. The role of Cannabidiol and tetrahydrocannabivarin to overcome doxorubicin resistance in MDA-MB-231 xenografts in athymic nude mice. Biochimie. 2022 Dec 17;208:19-30. doi: 10.1016/j.biochi.2022.12.008 Epub ahead of print. PMID: 36535544.

36. Kaur S, Nathani A, Singh M. Exosomal delivery of cannabinoids against cancer. Cancer Lett. 2023 Jul 10;566:216243. doi: 10.1016/j.canlet.2023.216243 Epub 2023 May 29. PMID: 37257632; PMCID: PMC10426019.

37. Khan I, Kaur S, Rishi AK, Boire B, Aare M, Singh M. Cannabidiol and Beta-Caryophyllene Combination Attenuates Diabetic Neuropathy by Inhibiting NLRP3 Inflammasome/NFκB through the AMPK/sirT3/Nrf2 Axis. Biomedicines. 2024 Jun 28;12(7):1442. doi: 10.3390/ biomedicines12071442 . PMID: 39062016; PMCID: PMC11274582.

38. Kinnunen K, Robayo LE, Cherup NP, Frank SI, Widerström-Noga E. A preliminary study evaluating self-reported effects of cannabis and cannabinoids on neuropathic pain and pain medication use in people with spinal cord injury. Front Pain Res (Lausanne). 2023 Dec 21;4:1297223. doi: 10.3389/ fpain.2023.1297223. PMID: 38188193; PMCID: PMC10767995.

39. Kumar Kalvala A, Bagde A, Arthur P, Kumar Surapaneni S, Ramesh N, Nathani A, Singh M. Role of Cannabidiol and Tetrahydrocannabivarin on Paclitaxel-induced neuropathic pain in rodents. Int Immunopharmacol. 2022 Jun; 107:108693. doi: 10.1016/j.intimp.2022.108693 . Epub 2022 Mar 15.

PMID: 35303507.

40. Lorenzo, E, McClean, C, Ford, JA. Young Adult Medical Cannabis Patients in Florida: Gender Differences in Characteristics of use, Experiences at Dispensaries, and Association With HealthRelated Problems. J Drug Issues, 2023. 0(0). https://doi.org/10.1177/00220426231189486 41. Lorenzo, E, McClean, C, Ford, JA. Young Adult Medical Cannabis Patients in Florida: Gender Differences in Characteristics of use, Experiences at Dispensaries, and Association With Health-Related Problems. Journal of Drug Issues, 2025, 55(1), 17-32. https://doi. org/10.1177/00220426231189486 42. Marini S, Huber A, Cash MN, Salemi M, Cook RL, Borsa P, Mavian CN. Oral Cannabidiol Treatment Is Associated with an Anti-Inflammatory Gene Expression Signature in Myeloid Cells of People Living with HIV. Cannabis Cannabinoid Res. 2024 Jan 22. doi: 10.1089/can.2023.0139 . Epub ahead of print. PMID: 38252549.

43. Markowitz JS, De Faria L, Zhang Q, Melchert PW, Frye RF, Klee BO, Qian Y. The Influence of Cannabidiol on the Pharmacokinetics of Methylphenidate in Healthy Subjects. Med Cannabis Cannabinoids. 2022 Nov 4;5(1):199-206. doi: 10.1159/000527189 . PMID: 36467779; PMCID: PMC9710314.

44. McMahon AN, Varma DS, Fechtel H, Sibille K, Li Z, Cook RL, Wang Y. Perceived effectiveness of medical cannabis among adults with chronic pain: Findings from interview data in a three-month pilot study. Cannabis. 2023 Jul 5;6(2):62-75. doi: 10.26828/cannabis/2023/000149 . PMID: 37484052.

45. Mueller J, Sapp J, Attonito J, Villalba K. Cannabis Substitution for Anxiety and Depression Medications in Adult Women J Cannabis Res. 2025 Jan. Accepted, in press.

46. Ortiz, YT, McMahon, LR, & Wilkerson, JL. Medicinal Cannabis and Central Nervous System Disorders. Front Pharmacol. 2022 Apr 21;13:881810. https://doi.org/10.3389/fphar.2022.881810 PMID: 35529444; PMCID: PMC9070567.

52 | CONSORTIUM FOR MEDICAL MARIJUANA CLINICAL OUTCOMES RESEARCH

47. Parisi CE, Wang Y, Varma DS, Vaddiparti K, Ibañez GE, Cruz Carrillo L, Cook RL. Changes in frequency of cannabis use among people with HIV during the COVID-19 pandemic: a multimethods study to explore the underlying reasons for change. Am J Drug Alcohol Abuse. 2023 Jul 4;49(4):470-480. doi: 10.1080/00952990.2023.2176234 . Epub 2023 Mar 10. PMID: 36898081.

48. Patel N, Kommineni N, Surapaneni SK, Kalvala A, Yaun X, Gebeyehu A, Arthur P, Duke LC, York SB, Bagde A, Meckes DG Jr, Singh M. Cannabidiol loaded extracellular vesicles sensitize triplenegative breast cancer to doxorubicin in both in-vitro and in vivo models. Int J Pharm. 2021 Sep 25; 607:120943. doi: 10.1016/j.ijpharm.2021.120943 . Epub 2021 Jul 27. PMID: 34324983; PMCID: PMC8528640.

49. Rosenthal M., Pipitone N. Demographics, Perceptions, and Use of MMJ among Patients in Florida.

Med Cannabis Cannabinoids 2021;.4:13-20. doi: 10.1159/000512342 PMID: 34676347; PMCID: PMC8525215.

50. Roussos-Ross K, Dukharan V, Goodin A. Is In-Utero Marijuana Exposure Associated with Childhood Developmental Delay? [20K], Obstetrics & Gynecology: 135(5):p 118S-119S, May 2020. doi: 10.1097/01.AOG.0000664476.72398.7c 51. Sagen J, Konin J, Paikoff S, Ford J, Newman D, Jyot J, Goodin AJ. Abstracts of the 2022 Cannabis Clinical Outcomes Research Conference (CCORC), on behalf of the Scientific Program Committee.

Med Cannabis Cannabinoids 2022; 5:142-158. https://doi.org/10.1159/000527081 52. Sajdeya R, Brown JD, Goodin AJ: Perinatal Cannabis Exposures and Autism Spectrum Disorders.

Med Cannabis Cannabinoids 2021, 4:67-71. doi: 10.1159/000515871 PMID: 34676352; PMCID: PMC8525188.

53. Sajdeya R, Cook RL. Need to Improve Dose Measurements in Studies of Marijuana Use for Pain. J Acquir Immune Defic Syndr. 2020 Mar 1; 83(3):e23. doi: 10.1097/QAI.0000000000002238 PMID: 32032280.

54. Sajdeya R, Fechtel HJ, Spandau G, Goodin AJ, Brown JD, Jugl S, Smolinski NE, Winterstein AG, Cook RL, Wang Y. Protocol of a Combined Cohort and Cross-Sectional Study of Persons Receiving Medical Cannabis in Florida, USA: The Medical Marijuana and Me (M3) Study. Med Cannabis Cannabinoids. 2023 May 9;6(1):46-57. doi: 10.1159/000530052 . PMID: 37261066; PMCID: PMC10228286.

55. Sajdeya R, Goodin AJ, Tighe PJ. Cannabis use assessment and documentation in healthcare: Priorities for closing the gap. Prev Med. Dec; 153:106798. doi: 10.1016/j.ypmed.2021.106798 Epub 2021 Sep 8 PMID: 34506820.

56. Sajdeya R, Joseph V, Stetten N, Ibañez G, Wang Y, Powell L, Somboonwit C, Corsi K, Cook R. Reasons for Marijuana Use and Its Perceived Effectiveness in Therapeutic and Recreational Marijuana Users Among People Living with HIV in Florida. Cannabis. 2021, Volume 4 (1). doi: 10.26828/cannabis/2021.01.002 57. Sajdeya R, Jugl S, Cook RL, Brown JD, Goodin AJ. Clinical considerations for cannabis use and cardiovascular health. Med Cannabis Cannabinoids 2022; Sept 28;5(1):120-127. https://doi. org/10.1159/000526731 PMID: 36467784; PMCID: PMC9710318.

58. Sajdeya R, Jugl S, Wang Y, Perez JG, Maloney S, Lopez-Quintero C, Goodin AJ, Winterstein AG, Cook RL; Reasons for Use and Perceived Effects of Medical Cannabis: A Cross-Sectional Statewide Survey. Med Cannabis Cannabinoids 26 June 2024; 7 (1): 138–148. https://doi. org/10.1159/000540593 PMID: 39474237; PMCID: PMC11521456.

59. Sajdeya R, Mardini MT, Tighe PJ, Ison RL, Bai C, Jugl S. Hanzhi G, Zandbiglari K, Adiba FI, Winterstein AG, Pearson TA. Cook RL, Rouhizadeh M. Developing and validating a natural language processing algorithm to extract preoperative cannabis use status documentation from unstructured narrative clinical notes. J Am Med Inform Assoc 2023 Jul 19;30(8):1418-1428. doi: 10.1093/jamia/ocad080 . PMID: 37178155; PMCID: PMC10354766.

60. Sajdeya R, Rouhizadeh M, Cook RL, Ison RL, Bai C, Jugl S, Gao H, Mardini MT, Zandbiglari K, Adiba FI, Dasa O, Winterstein AG, Price CC, Pearson TA, Seubert CN, Tighe PJ. Cannabis Use and Inhalational Anesthesia Administration in Older Adults: A Propensity Matched Retrospective Cohort Study. Anesthesiology. 2024 Nov 1;141(5):870-880. doi: 10.1097/ALN.0000000000005146 . Epub ahead of print. PMID: 38980341. PMID: 38980341; PMCID: PMC11461122.

61. Sajdeya R, Rouhizadeh M, Cook RL, Ison RL, Bai C, Jugl S, Gao H, Mardini MT, Dasa O, Zandbiglari K, Adiba FI, Winterstein AG, Price CC, Pearson TA, Seubert CN, Tighe PJ. Cannabis use and acute postoperative pain outcomes in older adults: a propensity matched retrospective cohort study. Reg Anesth Pain Med. 2024 Jun 30:rapm-2024-105633. doi: 10.1136/rapm-2024-105633 . Epub ahead of print. PMID: 38950932.

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62. Sajdeya R, Shavers A, Jean-Jacques J, Costales B, Jugl S, Crump C, Wang Y, Manfio L, Pipitone RN, Rosenthal MS, Winterstein AG, Cook RL. Practice Patterns and Training Needs Among Physicians Certifying Patients for MMJ in Florida. J Prim Care Community Health. 2021 Jan-Dec; 12: 21501327211042790. doi: 10.1177/21501327211042790. PMID: 34452585; PMCID: PMC8404623.

63. Shine D, Goodin A. Cannabis Hyperemesis Syndrome: What Do We Know? Med Cannabis Cannabinoids. 2024 May 3;7(1):86-90. doi: 10.1159/000539182 . PMID: 39015607; PMCID: PMC11250556.

64. Smolinksi N, Sajdeya R, Cook RL, Wang Y, Winterstein AG and AJ Goodin. Proceedings of the 2022 Cannabis Clinical Outcomes Research Conference. Med Cannabis Cannabinoids 2022; 5:138141. https://doi.org/10.1159/000527080 PMID: 36467782; PMCID: PMC9710315.

65. Spandau G, Loizzo J, Jury H, Bunch JC, Stedman N, Pearson B, Goodin, AJ. Patient’s perceptions of cannabis contamination in Florida’s medical program. Medical Cannabis & Cannabinoids. ePub ahead of print: December 9, 2024. https://doi.org/10.1159/000542929 66. Sturaro C, Fakhoury B, Targowska-Duda KM, Zribi G, Schoch J, Ruzza C, Calò G, Toll L, Cippitelli A. Preclinical effects of cannabidiol in an experimental model of migraine. Pain. 2023 Nov 1;164(11):2540-2552. doi: 10.1097/j.pain.0000000000002960 . Epub 2023 Jun 9. PMID: 37310430.

67. Surapaneni SK, Patel N, Sun L, Kommineni N, Kalvala AK, Gebeyehu A, Arthur P, Duke LC, Nimma R, G Meckes D Jr, Singh M. Anticancer and chemosensitization effects of cannabidiol in 2D and 3D cultures of TNBC: involvement of GADD45α, integrin-α5, -β5, -β1, and autophagy. Drug Deliv Transl Res. 2022 Nov;12(11):2762-2777. doi: 10.1007/s13346-022-01137-2 . Epub 2022 Feb 25. PMID: 35217991; PMCID: PMC9811521.

68. Vaddiparti K, Liu Y, Bottari S, Boullosa CC, Zhou Z, Wang Y, Williamson J, Cook RL. Improved PostTraumatic Stress Disorder Symptoms and Related Sleep Disturbances after Initiation of Medical Marijuana Use: Evidence from a Prospective Single Arm Pilot Study. Med Cannabis Cannabinoids.

2023 Nov 13;6(1):160-169. doi: 10.1159/000534710 . PMID: 37965569; PMCID: PMC10642978.

69. Wang Y, Jean Jacques J, Li Z, Sibille KT, Cook RL. Health Outcomes among Adults Initiating Medical Cannabis for Chronic Pain: A 3-month Prospective Study Incorporating Ecological Momentary Assessment (EMA). Cannabis. 2021 Oct;4(2):69-83. doi: 10.26828/cannabis/2021.02.006 PMID: 34671723; PMCID: PMC8525881.

70. Wang Y, Robinson KR, Fechtel HJ, Hartog A. Medical cannabis use and its impact on health among older adults: Recent research findings and future directions. Current Addiction Reports. 2023. https://link.springer.com/article/10.1007/s40429-023-00519-x 71. Wilkerson JL, Alberti LB, Thakur GA, Makriyannis A, Milligan ED. Peripherally administered cannabinoid receptor 2 (CB2R) agonists lose anti-allodynic effects in TRPV1 knockout mice, while intrathecal administration leads to anti-allodynia and reduced GFAP, CCL2 and TRPV1 expression in the dorsal spinal cord and DRG. Brain Res. 2022 Jan 1; 1774:147721. doi: 10.1016/j. brainres.2021.147721 . Epub 2021 Nov 10. PMID: 34774500.

72. Wilkerson JL, Bilbrey JA, Felix JS, Makriyannis A, McMahon LR. Untapped endocannabinoid pharmacological targets: Pipe dream or pipeline? Pharmacol Biochem Behav. 2021 Jul; 206:173192. doi: 10.1016/j.pbb.2021.173192 . Epub 2021 Apr 29. PMID: 33932409.

73. Wilkerson, JL, Alberti, LB, Thakur, GA, Makriyannis, A, Milligan, ED. Peripherally administered cannabinoid receptor 2 (CB2R) agonists lose anti-allodynic effects in TRPV1 knockout mice, while intrathecal administration leads to anti-allodynia and reduced GFAP, CCL2 and TRPV1 expression in the dorsal spinal cord and DRG. Brain Res. 2022 Jan 1; 1774:147721. doi: 0.1016/j. brainres.2021.147721 Epub 2021 Nov 10. PMID: 34774500.

74. Zhang, Q, Melchert, PW, Markowitz, JS. Pharmacokinetic Variability of Oral Cannabidiol and Its Major Metabolites after Short-Term High-Dose Exposure in Healthy Subjects. Med Cannabis Cannabinoids 2024, 7 (1): 1–9. https://doi.org/10.1159/000535726

54 | CONSORTIUM FOR MEDICAL MARIJUANA CLINICAL OUTCOMES RESEARCH

EXTRAMURAL GRANTS SUBMITTED BY CONSORTIUM FACULTY AND GRANT AWARDEES Lead principal investigator, funding agency, title 1. Amie Goodin (co-Is: A Winterstein, Y Wang, S Guo), United States Food and Drug Administration via Sentinel Initiative. Medical Literature and Data on Cannabis Use. Funded from January 2023-May 2023 for $328,281.

2. Amie Goodin (MPIs: D Roussos-Ross, D Varma, B Goldberger), University of Florida Research Opportunity Seed Fund. Assessing Prevalence, Maternal Perceptions, and Fetal Development Outcomes of Perinatal Marijuana Use. Funded from June 2022-May 2024 for $90,000.

3. Amie Goodin (sub-PI; Chris Delcher -PI; S Jugl, Co-I), Center for Disease Control (CDC). Beyond Opioids: Policy Evaluation for the Polysubstance Crisis.

4. Amie Goodin, NIDA. Medication use trajectories for opioid use disorders among pregnant women and resulting neonatal outcomes.

5. Andrea Cippitelli (Co-I; PI-Lawrence Toll), Department of Defense (DOD). Investigation into NOP Receptor Agonists for the Treatment of Chronic Migraine. Funded from 06/01/2021-05/31/2024 for $335,000/year.

6. Andrea Cippitelli, (NIH/NINDS). The involvement of GPR37L1 on a chronic migraine-like state.

Funded from 4/1/2024-3/31/2026 for $419,375.

7. Debra Fadool and Mandip Sachdeva, James and Esther King Foundation. Role of Exosomal Formulations of CBD for Treatment of Cancer-related Peripheral Neuropathy.

8. Debra Fadool, Council on Research and Creativity (CRC). Does cannabidiol (CBD) really lessen anxiety behavior and is it safe to use during pregnancy, Funded June 2022- June 2023 for $25,000.

9. Debra Fadool, HEERF III (Federal Government). Higher Education Emergency Relief Fund, Funded from Sept 2021-Sept 2022 for $42,091.

10. Douglas Storace (Co-I: Adam Dewan), NSF. Defining the role of orexin input to the mouse olfactory bulb.

11. Douglas Storace, NIDCD. Defining the role(s) of the olfactory bulb in adaptation.

12. Douglas Storace, NIDCD. Defining the role(s) of the olfactory bulb in adaptation.

13. Ellen Zimmerman (Co-I- Ana Maria Porres) Crohn’s & Colitis Foundation; Fibrosis in IBD Research Initiative. The Extracellular Matrix in IBD: Effect of Delta-9-tetrahydrocannabinol (THC) on Intestinal Fibrosis.

14. Ellen Zimmerman (Co-I; PI- Mariola J. Ferraro), Crohn’s and Colitis Foundation. Investigating Delta-8 tetrahydrocannabinol (delta-8-THC) Mediated Modulation of the Microbiome and Inflammation in Inflammatory Bowel Disease.

15. Ellen Zimmerman (Co-I; PI- Mariola J. Ferraro), DOD. Investigating Delta-8 tetrahydrocannabinol (delta-8-THC) Mediated Modulation of the Microbiome and Inflammation in Inflammatory Bowel Disease.

16. Hasan Azari (Co-I Brent Reynolds), Florida Dept of Health, Live Like Bella Foundation. Intranasal delivery of BMP-4 using plant-derived extracellular vesicles for treatment of pediatric glioma.

Funded from April 1, 2023 to March 31, 2025 for $250,000.

17. Hasan Azari (Co-I; PI and Co-I-Brent Reynolds, John Neubert, Nasser Koopaei), NIH. Developing novel hemp-derived cannabinoid exosomes as a non-opioid alternative for pain relief.

18. Hasan Azari (Co-I; PI and Co-I-Brent Reynolds, Nasser Koopaei), DOD. Plant-Derived Extracellular Vesicles As A Therapeutic Delivery Platform To The Brain: A Novel Approach With The Potential To Improve Brain Cancer Treatment Outcomes.

19. Hasan Azari (Co-I; PI and Co-I-Brent Reynolds, Nasser Koopaei), DOD. Novel intranasal delivery system for HPbCD to treat Alzheimer’s disease.

20. Hasan Azari (Co-I; PI and Co-I-Brent Reynolds, Nasser Koopaei), NIH. Evaluation of the OpioidSparing Potential of CBDa-Enriched Plant-Derived Extracellular Vesicles (PEVs) in a Preclinical Pain Model.

21. Hasan Azari (Co-I; PI and Co-I-Brent Reynolds, Nasser Koopaei), NIH. Intranasal delivery of psychedelics using plant-derived extracellular vesicles.

22. Hasan Azari (Co-Is: Brent Reynolds & Vinata Vedam-Mai), NIH. Extracellular Vesical Delivery of HPβCD for Targeted Treatment of Parkinson’s Disease and Dementia with Lewy Bodies.

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23. Hassan Azari, DOD. Cannabinoids Acidic for the treatment of Glioblastoma.

24. Hassan Azari, NIH. Acidic cannabinoidsfor the treatment of high-grade glioma.

25. Hassan Azari, The Florida Center for Brain Tumor research (FCBTR). Effects of cannabigerolic acid containing hemp NPs on glioma tumor progression.

26. Jacqueline Sagen (Co-Is: Stanislava Jergova, Mandip Sachdeva), Department of Defense SCIRP. Harnessing naturally-derived cannabinoid potential in development of neuropathic SCI pain treatments.

27. Jacqueline Sagen, NCCIH. Combination analgesic evaluation of minor cannabinoids and terpenes with exercise in chronic spinal cord injury pain.

28. Jennifer Attonito (Co-I; PI and Co-I- Karina Villalba, Mario De la Rosa, Lou XiangYang, Omar Martinez, Sharon Nichols, Ruben Perez Antezana, Angelica Torres Quintero), NIDA. Determining Pathways to Cannabis Use Disorder for Multilevel Intervention Strategies among At-Risk Youth in Bolivia and Colombia.

29. Jenny Wilkerson, NCCIH. Terpenes and minor cannabinoids as novel analgesics.

30. Jenny Wilkerson, NIDA. Terpenes and minor cannabinoids as novel analgesics.

31. Joshua Brown, NIH, Cannabis use and adverse drug events in older adults.

32. Lori Knackstedt (MPI; Setlow -MPI; Schwendt co-I), NIH/NIDA. Risks and benefits of cannabisopioid co-use.

33. Mandip Sachdeva (Co-I; PI-Seth Ablordeppey, Co-Is-John Cooperwood, John Copland). Florida Cancer innovation Fund (DOH). Consortium for Drug Discovery, Optimization and Pipelining to Clinical Trial. This is a consortium grant between FAMU and Mayo Clinic. Funded from June 1, 2024 to May 30, 2025 for $1.2 million.

34. Mandip Sachdeva, DDRFA Foundation. Exosomal Delivery of Cannabinoids for the Treatment of DMG/DIPG. 35. Mandip Sachdeva, James and Esther King Foundation. Role of Exosomal Formulations of CDB for Treatment of Cancer-related Peripheral Neuropathy.

36. Mandip Sachdeva, NIH. Preclinical evaluation of minor cannabinoids in chemotherapy induced peripheral Neuropathy.

37. Mandip Sachdeva, NIH. Role of Exosomal Formulations of CDB for Treatment of Cancer-related Peripheral Neuropathy, Funded April 2023-March 2027 for $540,000.

38. Mandip Sachdeva, NIH. Tetrahydrocannabivarin (THCV) and cannabidiol (CBD) combination treatment for paclitaxel induced neuropathy.

39. Mariola Edelmann, NIH. The regulatory functions of the endocannabinoid system in the innate immune responses against Gram-negative pathogens.

40. Mariola Edelmann, NIH. Unlocking the Impact and Mechanism of Cannabinoids on Intracellular Infection.

41. Nicole Ennis, Sherrilene Classen, NIDA. MMJ Use and Driving Performance: A Test of Psychomotor Functioning in Adults 50 and Older, Funded for $205,662 from 09/15/2020 – 09/14/2022.

42. Paul Borsa (Co-Is-Mark Bishop, Abhisheak Sharma, Arkaprava Roy), NCCIH. CBD treatment for musculoskeletal pain.

43. Rodrigo Cristofoletti (Co-PI; Asley Brown PI), Emulate. Using Organ-On-Chips to assess the impact of cannabinoids on the SARS-CoV-2 infection in the digestive system.

44. Rodrigo Cristofoletti (PI), NIDA. Transporter-mediated interactions at the blood-brain barrier: can opioids and cannabinoids affect brain penetration of antiretroviral drugs?

45. Simone Marini (Co-Is: Yan Wang, Kimberely Sibille), NIH. Medical Marijuana and chronic musculoskeletal pain in older adults: a multi-level, precision medicine analysis. Funded from September 30, 2024, to August 31, 2026, for $405,401.

46. Simone Marini (Contact PI; MPIs Wang and Sibille), NIH/NIA. Medical Marijuana and chronic musculoskeletal pain in older adults: a multi-level precision medicine analysis.

47. Yan Wang, (MPIs: Jennifer Hu), NIH/NCI. Assessing benefits and harms of medical cannabis and cannabinoid use in breast cancer patients during and after treatments. Funded 09/2024-08/2028 for $3,264,626.

48. Yan Wang, NIA. Real-Time and Long-Term Effects of MMJ on Older Adults: A Prospective Cohort Study. Funded from 2/15/2022-11/30/2026 for $2,940,426.

49. Yan Wang, NIH/NIA. R01 AG071729-01A1S1 Administrative Supplement, Real-time and longterm effects of MMJ on older adults: A prospective cohort study, Funded 02/2022-11/2026 for $375,000.

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MEDIA COVERAGE AND INVITED TALKS 1. Dr. Amie Goodin provided expert insight in an article for a women’s lifestyle platform, xoNecole.com: Is weed having an effect on your mental health. Here’s how to cut the habit.

2. Dr. Amie Goodin, the National News Desk, Daily marijuana use outpaces daily drinking in the US, a new study says.

3. Dr. Amie Goodin, AP News, Florida Sen. Rick Scott says he’ll vote against recreational pot after brother’s death.

4. Dr. Almut Winterstein, UF From Florida podcast, What is Florida’s MMJ research consortium studying – and what has it found so far?

5. Co-author with Jennifer Attonito and consultant, Melanie Bone MD was invited as a testifying physician in the DEA cannabis rescheduling hearings in 2025. This article was included in her affidavit. “Acceptance of and Access to Medical Marijuana among patients and providers in Florida residential long-term care facilities” was re-published in South Florida Hospital News.

6. Dr. Dvorak RD, Paulson D. Is the Grass Really Greener? An Examination of Medical Cannabis in Older Adults. Invited Talk at Orange County Higher Education Conference.

7. Dr. Jenny Wilkerson, Medscape, How Cannabis- Based Therapeutics Could Help Fight COVID Inflammation, Medscape.

8. Dr. Joshua Brown, Slate, Can weed protect you from COVID? 9. Dr. Joshua Brown, Medium, Are THC and CBD actually safe for everyone?

10. Dr. John Markowitz presented talk at a CE Program “Navigating Cannabis Use in Psychiatric Populations: Drug-Drug Interactions and Other Pharmacologic Considerations” 10th Annual Psychopharmacology Update 2024, Hollywood, FL, (included findings from this funded project).

11. Dr. Mariola Ferraro. Distinct Roles of Bioactive Lipid Signaling and Extracellular Vesicle Antigen Trafficking in Host Defense Against Bacterial Infections, George Mason University, DC, September 10, 2024 12. Dr. Robert Cook, the Alligator, Can medical marijuana help Gainesville seniors manage dementia?

Book Chapter: Muschett M, Brown JD. Profile of Older Users of Medical Cannabis and Cannabinoids.

In: Martin, Patel, & Preedy (editors). Medicinal Usage of Cannabis and Cannabinoids. 1st ed. Elsevier.

2022 (In press).

PATENTS AND INDs 1. Hasan Azari, Patent filed: “Cannabinoid containing plant derived extracellular vesicles and therapeutic methods using the same…”

2. Mandip Sachdeva, Patent filed: Cannabinoid composition and method of treating diabetic and chemotherapy induced neuropathic pain.

3. Paul Borsa, IND approved for investigational product manufactured and processed through a Florida-based CBD company (SunFlora, Inc, St. Petersburg, FL) 4. Walter Steigelman, IND 167819 approved for a full spectrum CBD product IND with less than 0.3% THC from SunFlora.

5. Catalina Lopez-Quintero, IND 171489 for SunFlora’s hemp derived CBD extract, an oily solution containing 100 mg/mL CBD.

CLINICAL TRIALS REGISTERED AT CLINICALTRIALS.GOV Catalina Lopez-Quintero, Use of CBD in the Treatment of Anxiety, (NCT06672666); is currently recruiting participants.

Simone Marini, Single-cell CBD Biomarkers of Inflammation Reduction in People Living With HIV (NCT05209867); completed.

Walter Steigleman, Cannabinoid vs Opioid for Photorefractive Keratectomy Pain Control (NCT05477875); completed.

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CONSORTIUM RESEARCH PLAN 2025-2026

Since its inception in July 2019, the Consortium has made great strides towards facilitating and conducting research that informs clinical care and policy about the medical use of marijuana. In the coming year, the Consortium will continue these efforts within the five original Consortium research program pillars: the Grants program, MEMORY, the Clinical Core, the Evidence Core, and outreach activities. The specific goals and plans for each pillar have been updated and are described below.

Two recent developments will play an important role in the coming year: the completion of MEMORY core components will allow formal observational studies on MMJ safety and effectiveness. Consortium work with the FDA has generated a host of evidence syntheses on MMJ effectiveness for select conditions and a host of safety outcomes, which will be published and integrated into patient and clinician info sheets this coming year.

The following describes the Consortium Research Plan for 2025-2026.

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GRANTS PROGRAM The Consortium grant funding program was restructured in 2022 to support level-two studies at $130,000 over a total of two years, where the second-year funding is committed if intermediate research goals for the first year have been accomplished and adequate funding is available. An additional fund for one-year projects as offered previously has been retained.

We will continue these funding structure changes in the coming year.

The Consortium Board has revised research priorities to emphasize the focus on clinical research, the impact of MMJ on pain management and opioid use, and an expanded scope on epidemiologic research, which will be the focus for this next grant awards cycle.

The Research Priorities for the 2025 award cycle include (unchanged priorities from the previous award cycle are shown in grey):

Consortium Research Priorities 2024 • E xpanded RP#1. Clinical Outcomes of Medical Marijuana Use: to include populations critical to monitor, including: pregnant people (and exposed infants); youth and young adults (with emphasis on the impacts on developing brain); veterans (PTSD, mental health); older adults and adults with chronic conditions.

• R P#2 Effect of Medical Marijuana Use in Reducing Opioid Dependence: human subjects research on the effectiveness of MMJ as an analgesic/adjuvant in pain management and reduction in opioid use.

• R P#3 Routes of Administration: effect of dosing and routes of medical marijuana use on efficacy and safety; of particular interest are studies that evaluate effects of smoking and vaping.

• R P#4 Interactions of Medical Marijuana with Other Drugs/Medications • M odified RP#5. Public Health Outcomes of Cannabis Laws and Regulations: studies on how state and local cannabis regulations, such as those related to licensing, zoning, product types, product additives, advertising, product labeling, and pricing influence public health outcomes, including health service use, disparities in treatment access, and health equity.

• Expanded RP#6. Evaluating Components of Medical Marijuana/Cannabis and contrast their clinical outcomes: to include-health effects of emerging synthetic and semisynthetic cannabinoids and high-concentration products.

• N ew RP#7. Mitigation of the Risks of Cannabis Use by evaluating risk-mitigation strategies for cannabis use and their effectiveness in reducing problematic use and minimizing harm.

The Consortium launched its seventh grants cycle in October 2024 with the release of its RFP with the above research priorities. The intent is to complete the application reviews by the end of the fiscal year to expedite funding of prioritized proposals, upon approval of the FY 2026 Consortium budget.

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MEMORY With the release of regular data updates and planned new linkages to other data sources, MEMORY development will continue, with refreshed data sets available every 6 months. This includes substantial effort for data curation, linkage of databases and development of analytical cohorts for access by Consortium researchers.

Specific new planned linkages for the new year include UF Electronic Health Record data, which will provide clinical detail such as pain scores, symptoms and laboratory data not contained in claims data; and linkage to the OMMU Seed to Sales data. Seed to Sales data provide detail on the exact MMJ product that has been purchased, whereas the MMUR dispensing information only identifies the dosage form and amount (THC content) that has been dispensed. Availability of Seed to Sales data in MEMORY would eliminate guesses on THC content in purchased flower, which is critical to study the effects of high-concentration products. It would further support product-specific assessments and facilitate active surveillance of product safety. Communication with FL DoH about data access have commenced.

As envisioned, MEMORY will continue to support studies on MMJ effectiveness and safety, and utilization and access. Ongoing studies conducted by Consortium faculty include studies on utilization, safety and effectiveness outcomes.

WORK IN PROGRESS IN MEMORY

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CLINICAL CORE Goals for the clinical core include the continued support of prospective studies. This includes guidance on DEA licensure and assistance with other relevant state and federal regulations, consultation for research study design and data analytic support for pilot studies. It will also work on planning expansion of M3 toward examination of MMJ use for specific conditions, including patients with cancer, and pregnant women.

The team will also continue analysis of the existing M3 data (cross-sectional and longitudinal data) and collaborate with researchers interested in analyzing the data for publications or grant applications. The clinical core has established a cannabis working group for this purpose and is facilitating collaboration for cannabis research by inviting national experts to share their experiences conducting research on cannabis and creating potential venues for collaboration, and present findings from our work at national and international conferences.

EVIDENCE CORE In the coming year, the evidence core will complete publication and dissemination of its evidence synthesis that was conducted in collaboration with the FDA. The Consortium will also continue to publish its evidence in context series, support evidence dissemination via the Consortium-organized CCORC, and survey and evaluate emerging evidence to inform Consortium research priorities.

OUTREACH Building on the success of our first four Cannabis Clinical Outcomes Research Conferences (CCORC), the Consortium plans to hold its fifth annual CCORC in May 2025. Other outreach activities through the Consortium website, its quarterly newsletter and participation in scientific conferences will continue. The Researcher Spotlight Series will be developed further to promote Consortium activities and disseminate research outcomes.

The board and Consortium faculty and staff would like to conclude this report by expressing strong continuing support and enthusiasm to advance the Consortium research program. The Consortium addresses an urgent and critical need to provide patients, clinicians, and regulators with the necessary evidence on the safe and effective use of MMJ. The medical use of marijuana must be guided by the same level of scientific evidence that is available for prescription medications, and MMJ products should be monitored with similar surveillance methods. The Consortium is devoted to establishing infrastructure and conducting research to accomplish these goals.

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APPENDICES APPENDIX A: THE CONSORTIUM FOR MMJ CLINICAL OUTCOMES RESEARCH BOARD MAX C. E. OREZZOLI, PHD CHAIR OF THE CONSORTIUM BOARD Associate Professor of Healthcare, School of Arts & Sciences, Florida Memorial University

Max C. E. Orezzoli, Ph.D. is an Associate Professor of Healthcare in the Department of Health & Natural Sciences at Florida Memorial University.

He holds a doctorate in Sociology (Medical) with an emphasis on quantitative analysis from Florida International University. His expertise and research focus are centered on community-based interventions that positively impact the health of underrepresented communities. Dr. Orezzoli has over 15 years of experience in minority health disparities research, including substance use disorder (SUD), marijuana use, nutrition, violence, and HIV research. Additionally, Dr. Orezzoli has provided experimental and instrument design, data collection trainings, evaluation, statistical and methodological consulting and assistance to institutions, biomedical, educational, and healthcare organizations.

Dr. Orezzoli is bilingual and fluent in Spanish. He has extensive experience in formative and summative program evaluation using quantitative and qualitative methods which are regionally and culturally appropriate. Additionally, due to his research/evaluation experience, including SAMHSA projects, Dr. Orezzoli is well equipped to conduct research involving human participants and, addressing sensitive issues/topics of focus (MMJ, diet research, HIV, SUD, violence, etc.) while adhering to all confidentiality and privacy requirements. Dr. Orezzoli served as the Co-chair of the Institutional Review Board (IRB) at Florida Memorial University from 2018-2022.

DINENDER K. SINGLA, PHD, FAHA, FIACS, FAPS VICE CHAIR OF THE CONSORTIUM BOARD Professor of Medicine, Cardiovascular Division Leader, Florida Hospital Chair in Cardiovascular Science, University of Central Florida

Dr. Dinender Singla is a translational scientist. His team investigates the role of stem cells and its derivative exosomes in anti-cancer drug induced cardiac toxicities and diabetes-induced muscle myopathy and cardiomyopathy.

He is continuously serving to review the grants for various NIH, AHA, ministry of Italian health, and Hong Kong study sections. He is an Academic Editor for PLOS one, Associate Editor for the Canadian Journal of Physiology and Pharmacology, as well as an editorial board member for different journals such as American Journal of Physiology: Heart and Circulatory. He has served as a chair for the TPIG committee and the American Physiology Society, and a general secretary for the North American section of the International Academy of Cardiovascular Sciences. He is President of the International Society for Adaptive Medicine. He is a fellow at the International Academy of Cardiovascular Sciences, American Physiological Society and American Heart Association. Dr. Singla has served as a chair for various scientific sessions throughout the world with experience in organizing scientific conferences. He has published a book on stem cells and is an author/coauthor for more than 100 peer-reviewed papers.

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WILLIAM (BILL) ANDERSON, PHD Associate Vice President of Research, Florida International University

Associate Vice President William (Bill) Anderson leads initiatives that expand FIU’s efforts in research development for faculty, doctoral students and postdoctoral scholars. Additional areas of leadership focus include research labs, core facilities, research integrity, and laboratory safety, among others. Dr. Anderson joined FIU in 2000 as Assistant Professor and has risen to the rank of Professor. Administratively, he has served as Chair of the Department of Earth & Environment and Associate Dean of Faculty in the College of Arts, Sciences & Education where he most recently served as the Vice Dean.

He received a doctorate of Natural Sciences from the Swiss Federal Institute of Technology (ETH-Zentrum), a M.S. in Geology from Syracuse University and a B.A. in Geology from the University of Kansas. His research has been published in top tier journals; he has presented in national and international conferences; and he has received funding from the NSF, the American Chemical Society, and the U.S. Department of the Interior, among others.

KEN DAWSON-SCULLY, PHD, MSC, FRES Sr. Vice-President, Associate Provost, and Professor, NSU Division of Research and Economic Development, Nova Southeastern University

Dr. Dawson-Scully is the Senior Vice-President and Associate Provost for the Division of Research and Economic Development (DoR) at Nova Southeastern University leading research administration for the university. NSU has over $160M in active external grants, where the DoR manages the Office of Sponsored Programs, the Office of Clinical Research, compliance, research development, the Office of Technology Transfer, and the Center for Collaborative Research.

Prior to his current position, Dr. Dawson-Scully has been in several leadership roles at Florida Atlantic University (FAU) and the Max Planck Florida Institute (MPFI) for Neuroscience over 13 years including Head of Institutional Partnerships at MPFI and the Associate VicePresident for Strategic Initiatives at FAU. He is also currently a professor of Psychology and Neuroscience at NSU with academic affiliations with Florida Atlantic University, the Max Planck Florida Institute, and the University of Florida/Scripps Research Institute. He has extensive experience in the areas of neuroscience, pharmacology, and genetics with a scientific focus on neurodegeneration with his active NIH funded laboratory on the NSU Palm Beach campus. He has published numerous articles in high impact journals, given invited talks both nationally and internationally, and has served as a reviewer for numerous journals and federal granting agencies.

PETER J. HOLLAND, MD, FACOEM, DLFAPA Director of Clinical Research, Florida Atlantic University

Prior to joining FAU in 2003, Peter Holland founded Boca Raton Psychiatric Group and Boca Raton Medical Research — a clinical trial organization with a national reputation. Since joining FAU, he has been the principal investigator of numerous, double-blind, placebo-controlled clinical trials. He is currently the medical director of the FAU Clinical Research Unit. Dr. Holland is also a founding faculty member of FAU’s Schmidt College of Medicine where he directs medical student education in psychiatry.

Dr. Holland earned his medical degree at the University of South Florida College of Medicine. He completed his internship in Medicine and Psychiatry at the University of South Florida and continued his residency training and fellowship in Psychiatry at the University of North Carolina-Chapel Hill. Dr. Holland is board-certified in Psychiatry with

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additional qualifications in Geriatric Psychiatry. He is a Distinguished Life Fellow of the American Psychiatric Association and a Fellow of the American College of Occupational and Environmental Medicine.

ERIC H. HOLMES, PHD Assistant Vice President for Research, Florida State University

Eric Holmes has a PhD in Biochemistry from the University of California, Davis. Since 2013 he has been an Assistant Vice President for Research in the FSU Office of the Vice President for Research. He currently also serves as the Interim Director for the FSU Office of Human Subjects. Prior to joining FSU, he was Director of Research at the University of Hawaii’s John A. Burns School of Medicine.

Dr. Holmes has a long track record of directing NIH-funded research in biochemical oncology. He is an author of approximately 100 research publications and is an inventor on over 30 issued US and foreign patents. Dr. Holmes has also worked in the Biotech industry in development-stage pharmaceutical companies located in the Pacific Northwest focused on antibody therapy and drug delivery technologies, and has designed and managed clinical trials related to the development of these technologies.

CHRISTOPHER R. MCCURDY, BSPH, PHD, FAAPS Associate Dean for Faculty Development, Professor, Departments of Medicinal Chemistry and Pharmaceutics, The Frank A. Duckworth Eminent Scholar Chair, Director, UF CTSI Translational Drug Development Core, College of Pharmacy, University of Florida

Dr. McCurdy serves as Associate Dean for Faculty Development and Professor in the Departments of Medicinal Chemistry and Pharmaceutics; and The Frank A. Duckworth Eminent Scholar Chair in Drug Research and Development at the University of Florida College of Pharmacy. He is also the Director of the UF Translational Drug Development Core. Dr. McCurdy completed his training as a pharmacist at Ohio Northern University and moved on to complete his PhD in medicinal chemistry from the University of Georgia, followed by a three-year postdoctoral fellowship at the University of Minnesota. McCurdy began his academic career in 2001 at the University of Mississippi where he rose to the rank of full professor (with tenure). He moved to the University of Florida in January of 2017.

He is a broadly trained pharmaceutical scientist, and pharmacist whose research focuses on the design, synthesis, and development of drugs to treat pain, anxiety, and substance use disorders. He is an internationally recognized expert on kratom (Mitragyna speciosa).

He also has developed a PET/MR imaging diagnostic agent for visualizing the origins of chronic neuropathic pain. Phase 1 and 2 human clinical trials are currently underway. He has published more than 200 manuscripts and holds 8 patents. He is currently funded by multiple NIH grants and the Florida Department of Health. Dr. McCurdy serves as a consultant to the US Food and Drug Administration’s Drug Safety and Risk Management Advisory Committee and previously served as President of the American Association of Pharmaceutical Scientists (AAPS).

MARTHA S. ROSENTHAL, PHD Professor of Neuroscience/Physiology, Director of the Cannabis Research, Education, and Workforce Initiative, Florida Gulf Coast University

Dr. Martha Rosenthal is a Professor of Neuroscience & Physiology at Florida Gulf Coast University, where she teaches courses in cannabis, drugs and society, neuroscience, human physiology, and human sexuality. Dr. Rosenthal received her bachelor’s degree in biology from the University of Virginia, her master’s degree in neuropharmacology from Brown University, and her Ph.D. in neuroscience from

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UCLA. She began her career teaching in the College of Pharmacy at the University of Florida, and then moved to Fort Myers to be one of the founding faculty members of FGCU. Dr. Rosenthal is the Director of the Cannabis Research, Education, and Workforce initiative (CREW) at FGCU, and runs the cannabis professional certificate program. She is the author of a number of textbooks, including Drugs: Mind, Body, and Society. Dr. Rosenthal has been honored to receive the Teacher of the Year award at both the University of Florida and at FGCU and to have presented a TED talk about sex and gender.

JACQUELINE SAGEN, PHD Professor of Neurological Surgery, University of Miami

Dr. Jacqueline Sagen is a Professor of Neurological Surgery at the Miami Project to Cure Paralysis, University of Miami Miller School of Medicine. She received her B.A. in Neuroscience from Northwestern University, Ph.D. in Pharmacology from the University of Illinois College of Medicine in 1984 and an M.B.A. in Entrepreneurship from University of Illinois at Chicago in 1994. She completed a postdoctoral fellowship in 1986 and joined the faculty at University of Illinois College of Medicine in the Department of Anatomy and Cell Biology as Assistant/Associate Professor through 1995. From 1995-1998 she was Associate Director, Pharmacology and Behavioral Research, CytoTherapeutics, Inc and Adjunct Associate Professor of Cellular Technology, Brown University, prior to her current position at University of Miami.

Research in Dr. Sagen’s laboratory over the past 35 years has been focused on exploring novel therapeutic strategies for chronic pain management that have the potential to provide sustained relief on a long-term or permanent basis. As chronic pain syndromes are often resistant to traditional pain interventions and/or limited by untoward side effects and possible analgesic dependence, the long term goal of work in her lab is to identify and develop more potent interventive approaches to improve the quality of life of these patients.

A primary initiative in her lab is the generation of gene therapies and cell transplantation that can provide a continually renewable source of pain-reducing substances. The identification of superior alternatives to opioids, such as cannabinoids, is a current focus of her research. She has published over 150 articles and book chapters and holds 6 patents in the field of novel pain therapies. She serves on numerous scientific review panels for NIH, DoD, VA, CIRM, and private foundations, and is faculty representative on the FDP.

CHARLES A. WEATHERFORD, PHD Vice President for Research, Florida A&M University

Charles Weatherford is the Vice President for Research at Florida A&M University (FAMU). Dr. Weatherford is also the Director of the FAMU Industrial Hemp Pilot Project, Principal Investigator on the FAMU MMJ Education and Research Initiative, Director of the FAMU Center for Plasma Science and Technology, as well as a Professor in the FAMU Department of Physics.

He received his Ph.D. in Atomic and Molecular Physics from Louisiana State University in 1974. Dr. Weatherford is a Fellow of the American Physical Society and a Fellow of the National Society of Back Physicists. Dr. Weatherford has a Patent Disclosure 2018: “FieldAssisted Muon-Catalyzed Fusion,” 224 journal publications, 5 book articles, and 2 books.

He was PI or Co-PI on $60.5 million in Research Grants and Contracts. His research interests include Materials and Energy for National Security, Correlation in Many-Body Quantum Chemistry, Laser-Matter Interactions, High-Energy Density Science, Field-Assisted MuonCatalyzed Fusion, and Computational Science.

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APPENDIX B: CORE FACULTY, STAFF, AND TRAINEES OF THE CONSORTIUM FOR MMJ CLINICAL OUTCOMES RESEARCH ALMUT G. WINTERSTEIN, RPH, PHD, FISPE CONSORTIUM DIRECTOR Distinguished Professor, Pharmaceutical Outcomes & Policy, Dr. Robert and Barbara Crisafi Chair in Medication Safety, College of Pharmacy, Director, Center for Drug Evaluation and Safety, University of Florida

Almut Winterstein is Distinguished Professor in the Department of Pharmaceutical Outcomes and Policy at the College of Pharmacy, the founding Director of the Center for Drug Evaluation and Safety, and affiliate professor in epidemiology at the University of Florida. In 2017, she was named the Dr. Robert and Barbara Crisafi Chair for Medication Safety in recognition of her research on drug safety and on devising ways to improve medication use. Since 2019 she serves as director of the Consortium.

She received her pharmacy degree from Friedrich Wilhelm University in Bonn, Germany and her PhD in Pharmacoepidemiology from Humboldt University in Berlin. Since joining the University of Florida in 2000, Winterstein has served as principal investigator on extramurally funded grants and contracts totaling more than $20 million and published more than 400 manuscripts and conference abstracts. Her research interests center on the post-marketing evaluation of drugs in pediatrics and pregnancy, infectious disease and psychiatry and the evaluation and improvement of quality surrounding medication use using real-world data. As expert in drug safety, she has chaired the Food and Drug Administration’s Drug Safety and Risk Management Advisory Committee from 2012-2018. Recognizing her contributions in pharmacoepidemiology, Dr. Winterstein was inducted as a fellow of the International Society of Pharmacoepidemiology in 2013 and served as president of the society from 2019-2020. In 2022 she was inducted in the Academy of Science, Engineering and Medicine in Florida. She has chaired more than two dozen PhD committees and was awarded the UF-wide Dissertation Advisor/Mentoring award for her excellence in graduate training.

ROBERT L. COOK, MD, MPH CONSORTIUM ASSOCIATE DIRECTOR Professor, Epidemiology, Medicine, Director, Southern HIV & Alcohol Research Consortium (SHARC), College of Public Health & Health Professions, University of Florida

Robert L. Cook, MD, MPH is a Professor of Epidemiology at the University of Florida, with a joint appointment in the Division of General Internal Medicine.

Dr. Cook has expertise and experience in a range of research methods, including randomized clinical trials, cohort studies, and qualitative research.

Over the past 20 years, Dr. Cook’s research has focused on strategies to improve health outcomes related to HIV and sexually transmitted diseases. He is the Director of the Southern HIV Alcohol Research Consortium (SHARC), which supports collaborative research and training related to alcohol and HIV infection across the state of Florida.

Dr. Cook has also been engaged in a range of research related to clinical outcomes and MMJ. He recently completed a 5-year NIH-supported project on the effects of marijuana use on clinical outcomes in persons with HIV, including cognitive function and systemic inflammation. Since 2021, Dr. Cook has been a co-author on 19 peer-reviewed journal articles related to medical cannabis and 5 additional publications that are commentaries or conference proceedings. Dr. Cook’s research is translational, ranging from basic science to

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implementation science, and he is currently the PI or MPI of 3 major NIH grants and a T32 training program that supports PhD students and postdoctoral scholars. Mentoring is also an important aspect of Dr. Cook’s academic career. He has served as PhD dissertation chair for 15 students, PhD committee member for over 34 students, and mentor for numerous additional trainees, post-docs and junior faculty.

AMIE J. GOODIN, PHD, MPP CONSORTIUM ASSISTANT DIRECTOR, EVIDENCE Assistant Professor, Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida

Amie J. Goodin, PhD, MPP is an Assistant Professor within the Department of Pharmaceutical Outcomes and Policy (POP) at the University of Florida.

Dr. Goodin completed her Master of Public Policy and Doctor of Philosophy degree at the University of Kentucky, with specialization in pharmaceutical outcomes and policy and an additional Certificate in Informatics. She completed a Postdoctoral Fellowship at University of Florida POP, specializing in pharmacoepidemiology methods.

She is the lead for Pharmaceutical Health Services Research track within POP’s graduate program and serves on the advisory board for the Center for Drug Evaluation and Safety (CoDES). She is a Fellow of the Center for Public Health Law Research. Her research evaluates the impact of policy changes and controlled substance regulations on treatment access, utilization, and care quality.

MD MAHMUDUL HASAN, PHD, MSC CONSORTIUM ASSISTANT DIRECTOR, MEMORY Assistant Professor, Pharmaceutical Outcomes & Policy, Information Systems and Operations Management, College of Pharmacy, University of Florida

Md Mahmudul Hasan, PhD is an assistant professor in the Department of Pharmaceutical Outcomes and Policy (POP) with a joint appointment in the department of Information Systems and Operations Management (ISOM) at the University of Florida. His appointment is a part of the UF’s larger AI initiative. Prior to joining UF, Dr. Hasan worked as an Oak Ridge Institute for Science and Education (ORISE) Postdoctoral Fellow of Drug Safety and Artificial Intelligence Methods in the Center for Drug Evaluation and Research (CDER) at the United States Food and Drug Administration (FDA). Dr. Hasan has completed PhD and worked as a postdoctoral research scientist at the Decision Analytics Lab at Northeastern University, Boston, Massachusetts. He was also an active member of Northeastern’s Center for Health Policy and Healthcare Research.

Dr. Hasan conducts data-driven interdisciplinary research to address complex challenges in public health, contributing to healthcare decision-making, policy, and management.

Funded by CDC in collaboration with Massachusetts Department of public health (MDPH), he has collaborated in several interdisciplinary research projects that address critical issues surrounding opioid use disorder and opioid overdose epidemic. His current research lies in the intersection of pharmaceutical outcomes and health service utilization with a focus on substance use and mental health disorder, opioid related adverse drug events, and chronic diseases. His primary research interests include developing (i) fair, trustworthy, and equitable AI-driven and evidence-based Clinical Decision Support Systems (CDSS) to help predict adverse health outcomes; and (ii) prescriptive decision analytic models to improve medication adherence and effectiveness of personalized interventions to better manage the chronic health conditions. From a methodological standpoint, Dr. Hasan leverages data science, in particular AI/machine learning, statistical modeling, and management science techniques.

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YAN WANG, PHD CONSORTIUM ASSISTANT DIRECTOR, CLINICAL CORE Associate Professor, Epidemiology, College of Public Health & Health Professions, University of Florida

Yan Wang, PhD is an Associate Professor of Epidemiology at the University of Florida. Her research interests focus on leveraging advanced technologies and methods (e.g., wearable sensors, ecological momentary assessment/EMA) to improve the understanding of etiology and outcomes of substance use (e.g., alcohol, MMJ). Dr. Wang is the PI/MPI of two prospective cohort studies funded by NIH (R01AG071729, PI: Wang; U01CA286810, MPIs: Hu & Wang) which will utilize technology-based assessments to investigate health effects of medical cannabis on older adults with chronic pain and breast cancer patients, respectively. Dr. Wang is currently the PI or Co-I on multiple NIH projects focusing on alcohol use among persons with HIV that involve the use of wrist-worn alcohol biosensor (R01AA030481, MPIs: Cook & Wang; P01AA029547, MPIs: Naar & MacDonald; P01AA029543, MPIs: Cook & Cohen), and she is Co-I on several NIH projects (R01 AA030481, PI: Weafer & Leeman; R21AA029489, PI: Jaffe; R34AA031379, PI: Scaglione) to contribute her expertise on alcohol biosensors or EMA. Additionally, Dr. Wang has also served as Co-I on several NIH or FDA funded projects such as a U24 grant for biomedical data repository (U24 AA029959, PI: Wu & Cook).

JEEVAN JYOT, PHD, PMP CONSORTIUM ASSISTANT DIRECTOR, RESEARCH ADMINISTRATION College of Pharmacy, University of Florida

Dr. Jyot received her PhD in Microbiology and Molecular Biology from the Institute of Microbial Technology (India) and completed her postdoctoral fellowship and was an Assistant Scientist at Division of Infectious Diseases and Global Medicine, Department of Medicine, University of Florida. In addition, she has Project Management Professional credentials.

Dr. Jyot has previously served as Research Program Coordinator at Division of Research Program Development (DRPD) at Office of Research at University of Florida. Currently, Dr. Jyot is part of the Department of Pharmaceutical Outcomes and Policy (POP) at the University of Florida and serves the MMJ Clinical Outcomes Research Consortium.

CATALINA LOPEZ-QUINTERO, PHD, CONSORTIUM FACULTY, CLINICAL CORE Assistant Professor, Epidemiology, College of Public Health & Health Professions, University of Florida

Dr. Lopez-Quintero’s research program over the past 18 years has focused on developing a comprehensive and interdisciplinary understanding of the mechanisms that generate and sustain disparities in drug use transitions and trajectories, with the aim to inform drug use policy. Based on the eco-social theory of disease distribution, her research examines the complex interactions between drug use and neuropsychological processes, socio-cultural factors, and systemic-level factors. Dr. LopezQuintero aims to contribute to the design of effective and developmentally appropriate drug use prevention and treatment interventions, as well as public health policy. Her federally and state-funded research on cannabis and medical cannabis spans several key areas, including epidemiological studies among diverse population groups (e.g., racial-ethnic minorities, older adults, individuals with mental health disorders, and pregnant women), as

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well as clinical trials investigating whether medical cannabis is a safe and effective option for improving mental health and treating other medical conditions. Through her research, she aims to provide a balanced understanding of both the benefits and risks associated with cannabis and medical cannabis use.

NICOLE E. SMOLINSKI, PHARM.D., PHD RESEARCH ASSISTANT PROFESSOR, PHARMACEUTICAL OUTCOMES & POLICY. College of Pharmacy, University of Florida

Nicole E. Smolinski is a research assistant professor within the Department of Pharmaceutical Outcomes and Policy (POP). Dr. Smolinski completed her Doctor of Pharmacy at Midwestern University in Downers Grove before completing her Doctor of Philosophy degree at the University of Florida. Her research focuses on child and maternal health with a focus on appropriate antibiotic prescribing and safety of medications during pregnancy and childhood.

ALLISON VELIZ CONSORTIUM COMMUNICATIONS SPECIALIST College of Pharmacy, University of Florida

Allison is the Communications Specialist of the Consortium for MMJ Clinical Outcomes Research. Allison attended the University of Florida, earning a Bachelor of Science in Journalism and a Master of Arts in Mass Communication. Before joining the Consortium for MMJ Clinical Outcomes Research, Allison worked for the University of Florida International Center and the University of Miami.

SHEILA AUSTIN, MS, ACRP-CP REGULATORY SPECIALIST Clinical and Translational Science Institute, University of Florida

Sheila works with Investigators to negotiate the FDA Investigational New Drug (IND) and Investigational Device Exemption (IDE) submission and approval process. Sheila is also a part of the admin team for UF ClinicalTrials.gov.

MATTHEW MUSCHETT, PHARM.D. DATA ANALYST III Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida

Matthew Muschett is a Data Management Analyst at the Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida. Matthew is a pharmacist by training, whose research with the Consortium involves the analysis of data obtained from Florida’s Medical Marijuana Use Registry to estimate average daily doses of MMJ in a variety of subpopulations.

KANNOP MITSANTISUK, M.SC. DATA MANAGEMENT ANALYST III Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida

Kannop Mitsantisuk is a Data Management Analyst at the Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida. For the Consortium, Kannop designs and manages data file systems, as well as establishes linkages between databases.

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DONALD PORCHIA, PHD, CLINICAL CORE Research Design and Date Coordinating Center, Department of Biostatistics, College of Public Health and Health Professions, University of Florida

Dr. Porchia is a Data Manager and Analyst within the Department of Biostatistics at the University of Florida. He has recently joined the Clinical Core and is currently working to help analyze the M3 study data.

CONSORTIUM GRADUATE STUDENTS AND POST-DOCS JABED AL FAYSAL, MS Graduate Assistant, Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida

Jabed Faysal worked as a graduate assistant within the Department of Pharmaceutical Outcomes & Policy and is currently a volunteer. He serves as a data analyst for MEMORY studies.

SEBASTIAN JUGL, MS, RPH Ph.D. Student, Student Volunteer, Evidence Core & MEMORY, Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida

Since joining the Consortium in 2019 as a research assistant and is currently a volunteer. Sebastian has contributed to multiple projects within MEMORY and the Evidence core.

JUAN PEREZ, MD, CLINICAL CORE Ph.D. Student & Research Coordinator, Epidemiology, College of Public Health & Health Professions, University of Florida

Dr. Juan Perez is a predoctoral graduate assistant in the Department of Epidemiology at the University of Florida. He serves as a data analyst and research coordinator for the Clinical Core. His dissertation will focus on the impact of cannabis on the cardiovascular system.

PRIYANKA KULKARNI, MPH, B. PHARM. Ph.D. Student, Graduate Assistant, Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida

Priyanka Kulkarni works as a research assistant on the MEMORY project, conducting research and analysis of data to determine the utilization of MMJ and its impacts on medically certified patients in Florida.

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APPENDIX C: REVIEWERS OF THE 2024 RESEARCH GRANTS PROGRAM

*reviewers who reviewed more than one proposal Aaron Murnan

University of Cincinnati

Assistant Professor

Brian Soher*

Duke University

Associate Professor

Caroline Arout*

Columbia University Irving Medical Center

Assistant Professor

Carrie Cuttler

Washington State University

Assistant Professor

Charles Leonard*

University of Pennsylvania

Assistant Professor

Chris Delcher*

University of Kentucky

Associate Professor

Claire Hulsebosch*

University of Texas Health Sciences Center

Research Professor

Denise Walker

University of Washington

Research Professor

Emeka Okafor

Baylor College

Assistant Professor

Geoffroy Laumet*

Michigan State University

Assistant Professor

Gregory Tung*

University of Colorado

Associate Professor

James White

Duke Molecular Physiology Institute

Assistant Professor

Joanna Jacobus

University of California San Diego

Associate Professor

John Streicher

University of Arizona

Professor

Joseph Ditre

Syracuse University

Professor

Juan M Hincapie-Castillo

University of North Carolina

Assistant Professor

Kate Lapane

University of Massachusetts

Professor

Kelly Naugle

Indiana University

Associate Professor

Kelly Young-Wolff*

University of California San Francisco

Assistant Professor

Matthew S Freiberg*

Vanderbilt University

Professor

Mercy N Mumba

University of Alabama

Associate Professor

Michael Hoane

Tennessee Technical University

Professor

Natacha M De Genna

University of Pittsburgh

Associate Professor

Omayma Alashaarawy*

Michigan State University

Assistant Professor

Rahi Abouk*

William Patterson University

Assistant Professor

Rajiv Radhakrishnan

Yale School of Medicine

Assistant Professor

Ryan McLaughlin*

Washington State University

Associate Professor

Samer Narouze

Northeast Ohio Medical University

Professor

Steven Kinsey*

University of Connecticut

Professor

Sylvia Fitting

University of North Carolina Chapel Hill

Assistant Professor

Tally M Largent-Milnes

University of Arizona

Associate Professor

Tim Moran

Johns Hopkins University

Professor

Tory Spindle*

Johns Hopkins University

Associate Professor

Tracy Baker

University of Wisconsin

Associate Professor

Vijay Sivaraman

North Carolina Central University

Associate Professor

Xuan-Zheng Shi*

University of Texas Medical Branch

Associate Professor

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APPENDIX D: A SUMMARY BROCHURE FOR CANNABIS CLINICAL OUTCOMES RESEARCH CONFERENCE (CCORC) 2024

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