Natural Medicine Journal Cognition + Mental Health Special Issue 2023

OCTOBER 2023 SUPPLEMENT

SPECIAL ISSUE

Cognition and Mental Health

Psilocybin: Psychological and Psycho-spiritual Applications β-Alanine’s Effects on Cognition, Mood, and Physical Function in Older Adults

Naturopathic Approaches to Mental Health Concerns EVOO for Mild Cognitive Impairment Choline and Cognitive Functions in Healthy Middle-Aged Adults

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SPECIAL ISSUE

COGNITION AND MENTAL HEALTH OCTOBER 2023 VOL. 15, NO. 101 (SUPPL)

Contents 4

Contributors

5

A Message from the Publisher

ABSTRACTS & COMMENTARY

6

Egg Yolk Choline and Cognitive Function

10

Beta-Alanine Applications for Older Adults

14

Olive Oil Prevents Cognitive Decline

EXPERT INTERVIEW

18

Research Update on Psilocybin

22

Addressing Mental Health Issues from a Naturopathic Perspective

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Contributors KAROLYN A. GAZELLA is the founder of the Natural Medicine Journal and the host of the Natural Medicine Journal Podcast. She also cohosts the Five to Thrive Live weekly radio show on the Cancer Support Network, which is also widely available as a podcast.

She has been writing and publishing integrative health information since 1992 and is the author or ­coauthor of several books and booklets on a variety of holistic health topics.

ADAM RINDE, ND, is a Bellevue, Washington–based naturopathic physician. He has been based in the Seattle area since graduating from Bastyr University in 2006 and completing a residency at the Bastyr Center for Natural Health.

His practice is focused on gastrointestinal disorders, autoimmunity, and metabolism. He hosts a podcast called The One Thing Podcast with Dr. Adam Rinde, which features integrative health topics and guests. He enjoys speaking on digestive health and related topics. You can find him at www.soundintegrative.com.

4

JACOB SCHOR, ND, FABNO, is a graduate of National College of Naturopathic Medicine (since renamed National University of Naturopathic Medicine), Portland, Oregon, and recently retired from his practice in Denver, Colorado. He served as president to the Colorado Association of Naturopathic Physicians and is a past member of the board of directors of the Oncology Association of Naturopathic Physicians and American Association of ­Naturopathic Physicians. He is recognized as a fellow by the American Board of Naturopathic Oncology. He serves on the editorial board for the International Journal of Naturopathic Medicine, Naturopathic Doctor News and Review (NDNR), and Integrative Medicine: A Clinician’s Journal. In 2008, he was awarded the Vis Award by the American Association of Naturopathic Physicians.

His writing appears regularly in NDNR, the Townsend Letter, and Natural Medicine Journal, where he is the past Abstracts & Commentary editor.

KATIE STAGE, ND, RH (AHG), FABNG, is a naturopathic physician, registered herbalist, and Fellow of the American Board of Naturopathic Gastroenterology. She practices family medicine and teaches at Sonoran University of Health Sciences (formerly SCNM). Stage graduated with high honors from the Sonoran University of Health Sciences and then completed a residency at Sonoran University Medical Center. She serves as director of therapeutics and is a member of the Ric Scalzo Institute for Botanical Research.

©2023 NATURAL MEDICINE JOURNAL. ALL RIGHTS RESERVED. NMJ, OCTOBER 2023 SUPPLEMENT—VOL. 15, NO. 101 (SUPPL)

Copyright © 2023 by the Natural Medicine Journal. All rights reserved.

Tina Kaczor, ND, FABNO

A Message from the Publisher

Editor In Chief

Lise Alschuler, ND, FABNO

Editor, Abstracts & Commentary

Deirdre Shevlin Bell

VP of Content and Communications

Karolyn A. Gazella

Founder and NMJ Podcast Host

Avery St. Onge

Content Specialist

On behalf of the Natural Medicine Journal, I am thrilled to present this special issue on cognition and mental health. Millions of Americans experience mental illness or struggle with cognitive impairment. This issue offers perspectives in brain, mind, and mood research, and I hope the findings offer new ideas and insights that you can take back to your practice.

This issue of the journal highlights the effects of egg yolk choline intake on cognitive functions and plasma choline levels; the role of β-Alanine supplementation on cognitive function and mood in older adults; and how extra-virgin olive oil enhances the blood-brain barrier function in mild cognitive impairment. We’ve also included two fascinating podcast discussions: One on psilocybin with Emily Whinkin, ND, and the other on addressing mental health issues from a naturopathic perspective with Tara Peyman, ND.

Kristin Bjornsen, MA Copyeditor

Karen Sperry Designer

Katherine Shagoury

Digital Product Director

Kelcey George

Marketing Manager

As I reflect on this edition of the journal and the year we’ve had at the Natural Medicine Journal, I want to take a moment to thank first and foremost our dedicated authors, editorial board, and staff members, without whom these publications would not be possible. I would also like to recognize our sponsors, advertisers, and industry partners for their continued support of the journal.

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PUBLISHED BY Diversified Communications 121 Free St Portland, ME 04101 Natural Medicine Journal (ISSN 2157-6769) is published 13 times per year by Diversified Communications. Copyright © 2023 by Diversified Communications. All rights reserved. No part of this publication may be reproduced in whole or in part without written permission from the publisher. The statements and opinions in the articles in this publication are the responsibility of the authors; Diversified Communications assumes no liability for any information published herein. Advertisements in this publication do not indicate endorsement or approval of the products or services by the editors or authors of this publication. Diversified Communications is not liable for any injury or harm to persons or property resulting from statements made or products or services referred to in the articles or advertisements.

Lastly, I cannot close without thanking you, our readers and community members. Your engagement is the reason we publish this journal, and we are grateful for your support. With that in mind, we invite you to share your feedback with us at Natural Medicine Journal, along with our digital online resource Integrative Practitioner and annual in-person conference the Integrative Healthcare Symposium. Our virtual door is always open should you have questions or feedback on how we can better support you and your practice. Please email editor@naturalmedicinejournal.com with your comments.

In health,

Katherine Shagoury Director Natural Medicine Journal Integrative Practitioner

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ABSTRACT & COMMENTARY

Egg Yolk Choline and Cognitive Function Results from a randomized, controlled trial REFERENCE

Yamashita S, Kawada N, Wang W, et al. Effects of egg yolk choline intake on cognitive functions and plasma choline levels in healthy middle-aged and older Japanese: a randomized double-blinded placebo-controlled parallel-group study. Lipids Health Dis. 2023;22(1):75.

STUDY OBJECTIVE

To investigate the effect of egg yolk choline supplementation on cognitive function in Japanese adults aged 60 to 80 years with signs of memory decline but without diagnosis of dementia or depression KEY TAKEAWAY

Dietary choline supplementation for 3 months seems to support beneficial cognitive changes in adults with mild cognitive decline.

DESIGN

Randomized, double-blind, placebocontrolled, parallel-group study lasting 12 weeks PARTICIPANTS

Investigators enrolled 60 male and female adults aged 60 to 80 years.

Thirty participants were in the intervention group and 30 in the control group; researchers ensured there were no significant differences between participants based on their age, gender, body mass index (BMI), blood pressure, pulse, MMSE (mini-mental status exam score), GDS (geriatric depression scale), Cognitrax score, plasma free choline, and egg consumption per week.

All participants had a score of at least 26 points on the MMSE (which excluded dementia diagnosis) and a GDS ≤6 6

(which excluded a depression diagnosis). Other exclusion criteria included psychiatric disease, cerebrovascular disease, other serious diseases (not specified), use of medications with central nervous system (CNS) effects, impaired vision or hearing, excessive alcohol or tobacco use, regular use of foods/supplements high in antioxidants or with nootropic claims, and very irregular dietary habits.

INTERVENTION

The study group took a supplement of egg yolk oil containing 300 mg choline; the placebo group took a supplement of egg yolk oil without choline. The 300-mg egg yolk came in 7 capsules that participants took after breakfast daily for 12 weeks.

Placebo and choline capsules were standardized to contain the same calories, protein, fat, carbohydrates, and salt; choline supplements contained 2,027.2 mg phosphatidylcholine, calculated to be 271.6 mg choline (vs 0 in placebo supplements).

The supplements were manufactured

by Aliment Industry Co, Ltd (Yamanashi, Japan); Kewpie Corporation supplied the egg yolk oil, both with and without choline.

STUDY PARAMETERS ASSESSED

Investigators assessed cognition changes at 0, 6, and 12 weeks using: • Cognitrax, a digitized assessment of composite memory, verbal and visual memory, psychomotor speed, reaction time, complex attention, cognitive flexibility, processing speed, executive function, attention, and motor speed.

• Trail-making tests (TMT), to assess executive function.

By Katie Stage, ND, RH (AHG), FABNG Investigators assessed quality-of-life changes at 0, 6, and 12 weeks using: • Short Form 36 (SF-36, which assesses health outcomes such as social function, bodily pain, and mental health).

• World Health Organization–Five Well-Being Index (WHO-5, which assesses recent emotions, such as feeling cheerful, calm, and/or rested).

Blood samples were taken at 0, 6, and 12 weeks to assess plasma free and fat-soluble choline levels.

Safety evaluations were done at 0 and 12 weeks and included a diet survey (to evaluate for under/overeating), medical interview, vitals, urine, and blood (complete blood count [CBC], complete metabolic panel [CMP], lipids, hemoglobin A1c, and urinalysis [UA]).

PRIMARY OUTCOME

The primary outcome consisted of changes compared to baseline in Cognitrax test results including individual areas of assessment.

Secondary outcomes included changes in test results for: • TMT • SF-36 • WHO-5 • Plasma free and fat-soluble choline levels • Brief diet history questionnaire (BDHQ) • Safety: blood pressure, weight, CBC, CMP, lipids, hemoglobin A1c, UA

©2023 NATURAL MEDICINE JOURNAL. ALL RIGHTS RESERVED. NMJ, OCTOBER 2023 SUPPLEMENT—VOL. 15, NO. 101 (SUPPL)

“

Other dietary sources of choline include chicken liver, soy, salmon, and quinoa, though eggs are the richest source of choline by volume.

KEY FINDINGS

”

Verbal memory scores were higher at 6 weeks (P=0.003) and 12 weeks (P=0.043) in the choline group compared to placebo.

Serum choline levels were higher in the choline group at 6 weeks and 12 weeks, but levels were only statistically significant at 6 weeks (P=0.039).

TRANSPARENCY

IRB approval through Nihonbashi Cardiology Clinic Institutional Review Board (approval NJI-021-07-01) and registered with University Hospital Medical Information Network (UMIN) Center (UMIN 000045050).

Research was funded by Kewpie Corporation (Tokyo, Japan).

Seven of the authors (SY, NK, WW, KS, YT, MK, and RM), including the PI, are employees of Kewpie Corporation. The other 3 authors stated no conflicts.

PRACTICE IMPLICATIONS & LIMITATIONS Dementia (recently renamed major neurocognitive disorder, MND1) is a common and growing problem as the population ages. There are 47 million people worldwide with MND and 5 million in the United States;2 numbers are expected to increase substantially in the next 20 to 30 years.1

There is evidence that dietary choline plays a role in animal cognition. Mice placed on a choline-enriched diet for 4.5 months performed similarly to mice 1 year younger, whereas those on the choline-deficient diet performed similarly to mice 1 year older.9 Mice with induced dementia who were given choline for 4.5 months showed increased memory performance and improved levels of choline and acetylcholine in their brains.10 This Risk factors for MND include cardiovas- suggests that, at least in mice, dementia is cular disease, female gender, age, obesity, not due to malabsorption of choline but, diabetes, depression, tobacco use, physical perhaps instead, lack of dietary sources. inactivity, hearing loss, and the apolipoThe most common dietary source of protein E4 genotype (APOE4).2,3 choline, in the form of phosphatidylMild cognitive impairment (MCI) is a choline (sometimes confusingly called condition in which there are some cogni- “natural choline”13), is chicken egg tive deficits but with the ability to main- yolks.11 There is evidence that chicken tain activities of daily living.4 While there egg consumption has a supportive effect isn’t a clear path from MCI to dementia, on cognition. A relatively large study of within 3 years, approximately 22% of male Finns found that increased dietary those with MCI will progress to a diag- egg consumption, but not increased nosis of dementia.5 Thus, there is a tremen- cholesterol consumption, over 4 years’ dous interest in interventions to treat time was associated with higher scores on cognitive changes at this phase or decrease the trail-making tests (TMT) and verbal the rate of progression. fluency tests.2 These tests assess executive and frontal-lobe function. The protecAcetylcholinesterase inhibitors are the tive effects of egg consumption were also mainstay of MND treatment, though conferred on those with APOE4 gene, they are not usually used for MCI due which is generally considered an “unmodto side effects.6 The use of natural acetyl- ifiable” risk factor for MND. cholinesterase inhibitors, such as Salvia rosmarinus (rosemary),7 huperzine A This study aimed to further elucidate (from Huperzia serrata), and Salvia offi- whether there was a component in the cinalis (sage),8 is supported by clinical chicken egg other than choline responresearch and traditional use. These herbs sible for cognitive changes. The choline are generally very safe for even long-term and placebo egg yolk oil supplements were use. A complementary approach would be standardized to be equivalent in terms of to address availability of the major dietary kCal, protein, fat, and salt. The researchers substrate of acetylcholine: choline. also assessed safety, including increases in cholesterol, at the beginning and end

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ABSTRACT & COMMENTARY

of the 3-month protocol. This is not an insignificant dietary intervention: Because 1 egg contains about 17 grams of yolk,12 the amount of phosphatidylcholine needed to provide 300-mg choline in an egg yolk oil supplement is equivalent to approximately 17 eggs.

The egg yolk oil supplements, both placebo and cholinecontaining, increased daily dietary fat by 10.5 g. There was a mild but insignificant increase in total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) in both groups after 3 months. There were no adverse events in either group.

The choline group demonstrated increased plasma free choline.

This choline is presumed to reach brain tissue and serve as an acetylcholine precursor.

There were some conflicting results, possibly due to the relatively short duration of the study. Tests for simple attention and motor speed were not different between the groups.

At 6 weeks, the processing rate score (P=0.045) and correct response on SDC test (symbol digit coding, P=0.021) were higher in the placebo group but were not statistically different between groups at 12 weeks. The reason for this is unclear but may have been a transient effect. There were also differences in the PCS score (physical component score) in the choline vs placebo groups, which the authors postulate may have been related to changes in activity due to the Covid-19 pandemic.

The study supports the intervention of 300 mg dietary choline over 3 months to positively affect verbal memory in adults with memory decline but not dementia. The choline intervention also appeared to support increased processing speed (number of correct hits, delayed). The study also demonstrated safety of this intervention.

Limitations include the relatively short duration of the study and a limited population of healthy Japanese people. Because choline content of food is not listed on nutritional labels, investigators did not analyze or standardize the amount of dietary choline that participants consumed outside of the intervention.

However, the intervention was well-tolerated. Evaluating patient diets for choline (the Institute of Medicine defines 8

adequate intake as 435 mg/day for women and 550 mg/day for men aged ≥ 19 years12), and addressing deficiencies through diet or supplementation seems to be a reasonable approach for supporting the cognition of our patients with MCI. Other dietary sources of choline include chicken liver, soy, salmon, and quinoa, though eggs are the richest source of choline by volume.12 Patients following a vegan diet or who, for other reasons, are not consuming eggs might consider supplementation. However, choline (in the form of phosphatidylcholine) seems to be better absorbed compared to lab-manufactured choline bitartrate.13 The company that sponsored the study, Kewpie Corporation, is well-known in Japan (and has a cult following in other countries) as a manufacturer of mayonnaise. Could cholineenhanced mayonnaise be the next functional food for the aging population?

REFERENCES 1

2 3 4 5 6 7 8 9

Emmady PD, Schoo C, Tadi P. Major neurocognitive disorder (dementia). In: StatPearls. Treasure Island (FL): StatPearls Publishing; November 19, 2022.

Rolandi E, Zaccaria D, Vaccaro R, et al. Estimating the potential for dementia prevention through modifiable risk factors elimination in the real-world setting: a population-based study. Alzheimers Res Ther. 2020;12(1):94.

Ylilauri MP, Voutilainen S, Lönnroos E, et al. Association of dietary cholesterol and egg intakes with the risk of incident dementia or Alzheimer disease: the Kuopio Ischaemic Heart Disease Risk Factor Study. Am J Clin Nutr. 2017;105(2):476-484.

Jutkowitz E, Kane RL, Gaugler JE, MacLehose RF, Dowd B, Kuntz KM. Societal and family lifetime cost of dementia: implications for policy. J Am Geriatr Soc. 2017;65(10):2169-2175.

Gabryelewicz T, Styczynska M, Luczywek E, et al. The rate of conversion of mild cognitive impairment to dementia: predictive role of depression. Int J Geriatr Psychiatry. 2007;22(6):563-567.

Matsunaga S, Fujishiro H, Takechi H. Efficacy and safety of cholinesterase inhibitors for mild cognitive impairment: a systematic review and meta-analysis. J Alzheimers Dis. 2019;71(2):513-523.

Habtemariam S. The therapeutic potential of rosemary (Rosmarinus officinalis) diterpenes for Alzheimer’s disease. Evid Based Complement Alternat Med. 2016;2016:2680409.

Dos Santos TC, Gomes TM, Pinto BAS, Camara AL, Paes AMA. Naturally occurring acetylcholinesterase inhibitors and their potential use for Alzheimer’s disease therapy. Front Pharmacol. 2018;9:1192.

Bartus RT, Dean RL, Goas JA, Lippa AS. Age-related changes in passive avoidance retention: modulation with dietary choline. Science. 1980;209(4453):301-303.

10 Chung SY, Moriyama T, Uezu E, et al. Administration of phosphatidylcholine increases brain acetylcholine concentration and improves memory in mice with dementia. J Nutr. 1995;125(6):1484-1489.

11 Zeisel SH, da Costa KA. Choline: an essential nutrient for public health. Nutr Rev. 2009;67(11):615-623.

12 Eggs, grade A, large, egg yolk. FoodData Central website. https://fdc.nal.usda.gov/ fdc-app.html#/food-details/748236/nutrients. Accessed August 20, 2023.

13 Smolders L, de Wit NJW, Balvers MGJ, Obeid R, Vissers MMM, Esser D. Natural choline from egg yolk phospholipids is more efficiently absorbed compared with choline bitartrate; outcomes of a randomized trial in healthy adults. Nutrients. 2019;11(11):2758.

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ABSTRACT & COMMENTARY

Beta-Alanine Applications for Older Adults Effects on cognition, mood, and physical function REFERENCE

Ostfeld I, Ben-Zeev T, Zamir A, et al. Role of β-alanine supplementation on cognitive function, mood, and physical function in older adults; double-blind randomized controlled study.

Nutrients. 2023;15(4):923.

By Adam Rinde, ND

Exclusion criteria included any supplementation with β-alanine in the 6 months prior to the study and any neurological condition (eg, dementia, movement disorders).

INTERVENTION

To determine if supplementation with beta-alanine (β-alanine) affects cognition, mood, or physical function in an elderly population

Participants took 2.4 g of slow-release β-alanine orally in 2 600-mg tablets twice daily for 10 weeks. The placebo was identical and contained hydroxypropyl methylcellulose in lieu of β-alanine. Natural Alternatives International (Carlsbad, California) provided the tablets and placebo.

KEY TAKEAWAY

Investigators made all assessments at 3 separate time points:

STUDY OBJECTIVE

β-alanine did not improve physical function in older adults compared to placebo; however, it may have had some benefit for depression and cognitive dysfunction, especially in those with borderline or below-normal cognitive function at baseline.

• MID-test (week 5) • POST-test (week 10) STUDY PARAMETERS ASSESSED

DESIGN

Randomized, placebo-controlled study PARTICIPANTS

Original recruitment garnered 100 volunteers from various clinics across Israel (aged 60–80 years; 15 men and 35 women in the β-alanine group and 14 men and 36 women in the placebo). Twenty-one participants dropped out, leaving 79 participants for final analysis (38 in the intervention group; 41 in the placebo group).

“

• Montreal Cognitive Assessment (MoCA) detects mild cognitive impairment in adults.

• Stroop test, which measures cognitive and executive function • Profile of Mood States (POMS), measuring tension, depression, anger, vigor, fatigue, and confusion • Geriatric Depression Scale (GDS) • Geriatric Anxiety Scale (GAS) • Hand-grip dynameter • Sit-to-stand test

PRIMARY OUTCOME

It is most helpful to create a concerted exercise program alongside the supplementation of β-alanine rather than provide the dietary supplement alone.

10

• PRE-test

”

Do 10 weeks of slow-release β-alanine supplementation affect cognitive function and improve executive function in older adults?

KEY FINDINGS

MoCA: Both groups improved MoCA (F=5.4, P=0.005). Pre to post hoc analysis revealed MoCA scores were significantly greater for β-alanine (BA) than for placebo (PL) at both MID (P=0.009) and POST (P=0.016) time points. When MoCA scores were examined in participants with borderline or below-normal MoCA scores (ie, ≤26), a significant interaction was found (F=3.37, P=0.042).

Stroop: All groups improved in time (F=8.83, P<0.001). Reaction times also improved from PRE to MID (P=0.027) and from (continued on page TK) PRE to POST (P<0.001).

©2023 NATURAL MEDICINE JOURNAL. ALL RIGHTS RESERVED. NMJ, OCTOBER 2023 SUPPLEMENT—VOL. 15, NO. 101 (SUPPL)

However, no significant interactions between BA and PL were noted for reaction time (F=0.343, P=0.711). Both groups improved in speed accuracy (F=15.1, P<0.0001).

Behavioral measures: There were no differences between groups in tension (P=0.571), depression (P=0.559), anger/ hostility (P=0.103), vigor (P=0.101), fatigue (P=0.164), or confusion (P=0.131). In addition, no differences between BA and PL were noted in total mood score.

There was a significant group difference in Geriatric Depression Scale (P=0.037) but only a trend toward a difference in Geriatric Anxiety Scale (P=0.096). Post hoc analysis for Geriatric Depression Scale indicated that the mean rank for depression scores was significantly lower at MID (P=0.012) and POST (P=0.002) compared to PRE in the BA group. No significant differences from PRE were noted in the PL group.

There were no differences noted between groups for total mood score (P=0.131).

Hand/grip strength: Analysis of changes in hand grip strength revealed a trend toward an improvement with both groups combined (F=2.933, P=0.66) but no significant interaction (F=0.258, P=0.773).

Sit to stand: Examination of performance in the sit-to-stand test revealed a significant main effect for time (F=22.1, P<0.001) with both groups combined but no significant interaction (F=0.320, P=0.727). Improvements were observed from PRE to MID (P<0.001) and from MID to POST (P=0.005). Although no significant main effect was noted for peak power during the sit-to-stand assessment (F=1.103, P=0.335), a trend for an interaction was observed (F=2.554, P=0.093). No main effects for time or interactions were observed in mean power output (F=1.46, P=0.235 and F=1.312, P=0.272, respectively) or fatigue rate (F=0.326, P=0.723 and F=1.081, P=0.342, respectively) during the 5 sit-to-stand repetitions.

TRANSPARENCY

This research was funded by Natural Alternative Inc (Carlsbad, CA, USA), a manufacturer of the supplement used in the study. However, the funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

PRACTICE IMPLICATIONS & LIMITATIONS Strength loss, cognition changes, and mood changes are all concerns of aging. These aging processes can be exacerbated if individuals are inactive as they age. More rapid progression of these symptoms can be caused by sarcopenia (muscle loss)1,2 and/or brain-function loss secondary to oxidative stress and brain atrophy.3 It seems reasonable to consider β-alanine as a supplement to address these concerns in aging populations. β-alanine is a nonessential amino acid naturally present in the body. It combines with L-histidine to form the dipeptide beta-alanyl-L-histidine, aka carnosine. This reaction is catalyzed by carnosine synthase. L-histidine is an essential amino acid present in the serum only after consumption.4 Carnosine accumulates in its highest concentrations in the skeletal muscle.5 Many trials have investigated the effects of β-alanine supplementation on muscle carnosine content and exercise performance.6 In one study, oral BA supplementation increased muscle carnosine content and improved anaerobic exercise performance in rowers. Improved performance was attributed to the buffering capacity of carnosine, which helps to reduce the accumulation of lactic acid during high-intensity exercise.5 A meta-analysis by Hobson et al further supported the positive effects of BA supplementation on exercise performance. The analysis included multiple studies and found that β-alanine supplementation improved exercise lasting 60 to 240 seconds and exercise lasting more than 240 seconds but did not provide benefits for exercise lasting less than 60 seconds.6 Further, BA has been studied for its enhancement of combat-specific performance in military subjects, showing benefits in 50-meter casualty carry time and cognitive performance.7 The Ostfeld et al study under review here was helpful in addressing 2 commonly overlapping scenarios in aging populations: strength decline and cognitive changes.8 Cognitive

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ABSTRACT & COMMENTARY

decline, when progressive, is a major cause of morbidity in aging populations.9 Sarcopenia can also be a significant cause of morbidity, especially in aging orthopedic patients.10 It is most helpful to create a concerted exercise program alongside the supplementation of β-alanine rather than provide the dietary supplement alone. It is possible that the study end points (in particular, strength) may reflect improvements not seen in the current study design.

While the addition of exercise may improve results, it is important to note that studies have shown that BA supplementation can improve exercise performance in inactive 60to 80-year-olds.11

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Of note, 21 participants dropped out of the study, but the paper gives only an annotation saying that “participants were no longer interested in participating.” Precisely why they dropped out was not mentioned. This implies inconvenience of the intervention at the very least. Paresthesia (tingling of the skin) and temporarily increased alanine aminotransferase (ALT) have been described in the medical literature as possible side effects. There was no indication of these or any other untoward effects in this study.

Finally, it would be interesting to see if a higher dosage might have been more effective. Doses as high as 6.4 g/day have been used for 24 weeks safely.12 Future studies may also look at increased dosing, as many studies have used 4.8 g/day of BA for physical performance enhancement.5 Perhaps this is needed in older populations due to generally poorer absorption with advanced age.

REFERENCES 1

Powers SK, Jackson MJ. Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol Rev. 2008;88(4):1243-1276.

2

Stiklioraitis K, Stiklioraitis S, Sereikaitė L, Jasinskaitė M, Krivickas Ž, Aldujeli A. Sarcopenia of aging. Health Sci. 2021;31(2):232-235.

3

Nunomura A, Perry G, Aliev G, et al. Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol. 2001;60(8):759-767.

4

Jukić I, Kolobarić N, Stupin A, et al. Carnosine, small but mighty—prospect of use as functional ingredient for functional food formulation. Antioxidants.

2021;10(7):1037.

5

Derave W, Özdemir MS, Harris RC, et al. β-alanine supplementation augments muscle carnosine content and attenuates fatigue during repeated isokinetic contraction bouts in trained sprinters. J Appl Physiol. 2007;103(5):1736-1743.

6

Hobson RM, Saunders B, Ball G, Harris RC, Sale C. Effects of β-alanine supplementation on exercise performance: a meta-analysis. Amino Acids.

2012;43(1):25.

7

Hoffman JR, Landau G, Stout JR, et al. β-alanine ingestion increases muscle carnosine content and combat specific performance in soldiers. Amino Acids.

2015;47(3):627-636.

8

Ostfeld I, Ben-Zeev T, Zamir A, et al. Role of β-alanine supplementation on cognitive function, mood, and physical function in older adults; double-blind randomized controlled study. Nutrients. 2023;15(4):923.

9

Melis RJF, Marengoni A, Rizzuto D, et al. The influence of multimorbidity on clinical progression of dementia in a population-based cohort. PLoS One. 2013;8(12):e84014.

10 Fauzi A, Idrial D, Rizki A, Asdi B. Clinical importance of sarcopenia and how it impacts orthopaedic-trauma patients and the surgical outcomes. Folia Medica Indonesiana. 2022;58(4):355-363.

11 Del Favero S, Roschel H, Solis MY, et al. Beta-alanine (CarnosynTM) supplementation in elderly subjects (60-80 years): effects on muscle carnosine content and physical capacity. Amino Acids. 2012;43(1):49-56.

12 Holeček M. Side effects of amino acid supplements. Physiol Res. 2022;71(1):29-45.

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ABSTRACT & COMMENTARY

Olive Oil Prevents Cognitive Decline Extra virgin vs refined REFERENCE

Kaddoumi A, Denney TS Jr, Deshpande G, et al. Extra-virgin olive oil enhances the blood-brain barrier function in mild cognitive impairment: a randomized controlled trial. Nutrients.

2022;14(23):5102.

STUDY OBJECTIVE

To prove or disprove that the phenolic fraction of extra virgin olive oil (EVOO) is responsible for the cognitive benefits of olive oil by comparing its effects with those of refined olive oil (ROO) in participants diagnosed with mild cognitive impairment (MCI) KEY TAKEAWAY

Both refined olive oil and extra virgin olive oil show benefit against cognitive decline, but EVOO has broader effects.

DESIGN

This study examined the effect of daily consumption of ROO and EVOO for 6 months on blood-brain barrier (BBB) permeability (assessed by contrast-enhanced magnetic resonance imaging [MRI]) and brain function (assessed using functional MRI) in subjects with MCI as the primary outcomes in a randomized, controlled trial. Investigators also assessed cognitive function and Alzheimer disease (AD) blood biomarkers as the secondary outcomes.

PARTICIPANTS

Investigators recruited individuals with MCI from the community and assessed them for eligibility at Auburn University MRI Research Center, in Auburn, Alabama. Participants underwent neuropsychological evaluations for inclusion. Eligible participants were randomly assigned to either the EVOO or ROO group.

Twenty-six participants enrolled in the study. One did not complete the postintervention session and so was excluded from analysis. Thirteen participants were enrolled in the EVOO group and 12 participants in the ROO group. There were 5 men in the EVOO group and 3 in the ROO group. Those in the ROO group were slightly younger on average, 65.5 years vs 67.5.

Otherwise, the 2 groups were comparable.

INTERVENTION(S):

Both groups received 30 mL (2 tablespoons) of their olive oil per day. The EVOO group received an oil called The Governor 14

By Jacob Schor, ND, FABNO from the Kyoord company. This EVOO contains 1,200 mg/ kg of total polyphenols (see Kyoord.com). Those in the ROO group received Bertolli® Extra Light Olive Oil. STUDY PARAMETERS ASSESSED

Blood-brain barrier permeability (assessed by contrast-enhanced MRI) and brain function (assessed using functional MRI) were the primary outcomes assessed.

Cognitive function and AD blood biomarkers were also assessed as secondary outcomes. These markers included plasma concentrations of Aβ40, Aβ42, tau, and p-tau181, along with serum neurofilament light chain (NFL) levels. Investigators also used the Clinical Dementia Rating (CDR) to assess patients.

PRIMARY OUTCOME

This proof-of-concept study was designed to evaluate EVOO in MCI participants and compare its effect with that of ROO (null in phenolic fraction).

KEY FINDINGS

EVOO significantly improved clinical dementia rating (CDR) and behavioral scores. EVOO also reduced BBB permeability and enhanced functional connectivity. While ROO consumption did not alter BBB permeability or brain connectivity, it also improved CDR scores and increased functional brain activation to a memory task in cortical regions involved in perception and cognition. EVOO and ROO significantly reduced blood Aβ42/Aβ40 and phosphorylated (p)-tau/total (t)-tau ratios, suggesting that both altered the processing and clearance of Aβ. In conclusion, EVOO and ROO improved CDR and behavioral scores; only EVOO enhanced brain connectivity and reduced BBB permeability, suggesting it was the EVOO phenols that contributed to this effect.

TRANSPARENCY

The authors declare no conflict of interest. However, the lead and corresponding author, Amal Kaddoumi, is a cofounder and equity shareholder in Oleolive, LLC. This company produces and markets polyphenol concentrates from olive oils; specifically they hope to commercialize a specific phenol called oleocanthal. This company did not supply either of the olive oils used in the current study.

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PRACTICE IMPLICATIONS & LIMITATIONS At this point in time, we are well aware that olive oil is good for you. Higher intakes of olive oil are associated with significant improvements in total mortality and disease-specific deaths from cardiovascular, cancer, neurodegenerative, and respiratory diseases.1 Recent studies suggest that EVOO also has a significant effect on memory and alters blood markers for Alzheimer disease for the better. In her study published in 2020, Magda Tsolaki reported that in volunteers given 50 mL EVOO/ day for a year, both high and moderate levels of phenols were associated with improved scores for those with mild cognitive impairment and also with a significant reduction in the AD marker APOEɛ4.2 In December 2021, Elena E Tzekaki provided further follow-up on this group of study participants.

Those who had received EVOO had experienced drops in their AD markers so that their levels were no longer distinguishable from the healthy study controls who did not display symptoms of cognitive impairment.3

“

There is a significant difference in cost between the 2 oils used in this study that must be acknowledged.

”

The authors of this current study, Kaddoumi et al, have in recent years reported that EVOO has a beneficial effect on Alzheimer disease in mice, reducing various biomarkers of the disease and improving memory function.4,5 These results led to their current trial in humans. The trial is interesting as the authors compare the effect of a high-phenolic-content olive oil (EVOO) with a refined olive oil (ROO) in which the phenolic content was negligible. This current study lasted only 6 months.

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15

ABSTRACT & COMMENTARY

The EVOO appeared to have significant advantages over the ROO. It was associated with enhanced functional connectivity and reduced BBB permeability. Past research suggests that the blood-brain barrier begins to breakdown before the brain atrophy or dementia of Alzheimer disease are apparent.

Alterations in blood-vessel morphology appear to even precede changes in BBB permeability. The EVOO appears to have protected against these changes, whereas the refined oil did not. While the EVOO may be superior in these aspects, both oils were associated with some benefit. Both oils were associated with significant improvements in memory based on the CDR rating.

There is a significant difference in cost between the 2 oils used in this study that must be acknowledged. The EVOO used, a product called The Governor from Kyoord Company, is currently sold online for $80/500 mL bottle. The refined olive oil, Bertolli® Extra Light, sells online for $60/2,000 mL. In this study, participants consumed 50 mL/day. The EVOO would cost $8/day to take, while the ROO would cost just $1.50 per day. While the EVOO may have greater benefit, it may be challenging, based on current evidence, to convince patients to invest this much money in olive oil.

My immediate reaction is to wonder if there might be other sources of olive polyphenols that would provide high levels of polyphenols at a lower cost than the high-priced EVOO used in this study? Olive trees increase production of polyphenol chemicals to defend themselves against insect attack, fungal, bacterial, or viral infections, excessive sun exposure, and lack of water. Such stressors are common in the Mediterranean environment where olive trees originated and are grown. It might be possible to manipulate the trees’ growing environment to increase the polyphenol content of their oils. Actually, some companies already advertise that they purposefully stress their olive trees to increase polyphenol content.

Olive trees also produce and accumulate stores of polyphenols in other parts of their structures. Efforts are well-underway to use both the leaves and olive pits as a source of polyphenols for nutraceutical extracts. It makes ecological sense to 16

repurpose the olive leaves, which are traditionally trimmed from olive trees but not used afterwards, and which typically end up as waste material.6 Up to this point, I’ve made the common assumption that the dose/response curve between polyphenol exposure and prevention of cognitive decline is a straight line—that is, the higher the dose of polyphenols administered, the greater their effect at protecting the brain. Consider, though, that the action of many biologically derived substances we employ in our practices are not straight lines but rather U-shaped curves with a sweet spot at which a specific dose produces an optimum response that lessens at lower or higher concentrations. Such U-shaped dose responses are sometimes referred to as hormetic responses. Nothing in the data reported in these recent studies argues that more is better, only that some polyphenols are more helpful than almost none. This study by Kaddoumi et al compared olive oils at either extreme, from highest polyphenol content to lowest. Nothing in their data excludes the possibility that some intermediate concentration of polyphenols might be even more effective. At this point, all we can say is that daily doses of olive oil are helpful, and so far, the higher polyphenol content in EVOO has superior effect.

Until there are results from clinical trials using a range of oils with varying polyphenol contents, we can only guess what to tell patients as to how much money they need to spend on their oil to achieve the best cost/benefit balance.

REFERENCES

1

Guasch-Ferré M, Li Y, Willett WC, et al. Consumption of olive oil and risk of total nd cause-specific mortality among U.S. adults. J Am Coll Cardiol. 2022;79(2):101112.

2

Tsolaki M, Lazarou E, Kozori M, et al. A randomized clinical trial of Greek high phenolic early harvest extra virgin olive oil in mild cognitive impairment: the MICOIL pilot study. J Alzheimers Dis. 2020;78(2):801-817.

3

Tzekaki EE, Tsolaki M, Geromichalos GD, Pantazaki ΑA. Extra virgin olive oil consumption from mild cognitive impairment patients attenuates oxidative and nitrative stress reflecting on the reduction of the PARP levels and DNA damage.

Exp Gerontol. 2021;156:111621.

4

Al Rihani SB, Darakjian LI, Kaddoumi A. Oleocanthal-rich extra-virgin olive oil restores the blood-brain barrier function through nlrp3 inflammasome inhibition simultaneously with autophagy induction in TgSwDI mice. ACS Chem Neurosci.

2019;10(8):3543-3554.

5

Batarseh YS, Kaddoumi A. Oleocanthal-rich extra-virgin olive oil enhances donepezil effect by reducing amyloid-β load and related toxicity in a mouse model of Alzheimer’s disease. J Nutr Biochem. 2018;55:113-123.

6

Peršurić Ž, Saftić L, Klisović D, Pavelić SK. Polyphenol-based design of functional olive leaf infusions. Food Technol Biotechnol. 2019;57(2):171-182.

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EXPERT INTERVIEW

Research Update on Psilocybin

A discussion with integrative mental health expert Emily Whinkin, ND Interest and research regarding psilocybin has grown considerably over the past several years. In this interview, Emily Whinkin, ND, discusses the latest research and provides clinical guidance on the use of psilocybin. Whinkin is a naturopathic physician with the Advanced Integrative Medical Science Institute in Seattle, where she also conducts research and explores altered states of consciousness.

Karolyn A. Gazella: Can you tell us a bit about what psilocybin is and how it works?

Emily Whinkin, ND: Psilocybin is a tryptamine that is a constituent of many species of fungal spores and fruiting bodies that are native to the Americas. Most psilocybin-containing species of mushrooms contain an average of about 1% of this tryptamine, but up to 2.25% of a dried, fruiting body of a mushroom could be the psilocybin constituent. The active constituent is actually its metabolite, psilocin, which is found itself in several fruiting bodies as well, but the human body can transform psilocybin into psilocin.

Psilocin is active at the 5-HT2A receptor, commonly known as the serotonin receptor. This receptor is found in the central nervous system, throughout the cardiovascular system, and in the gut tissue. We think that through agonism of this 5-HT2A receptor, psilocin impacts learning, mood, memory, and neurogenesis in the central nervous system. It also seems to reduce blood flow and therefore function of the default mode network, a kind of a neural network in the brain that is responsible for self-referential thinking and internal processing. The default mode network is also most active when we are retrieving memories about ourselves, as well as imagining our future and our place in it. So if this area of the brain or this network of the brain is getting less blood flow, if it’s de-emphasized as our background way of thinking and being, there are novel ways to experience the world and ourselves and to imagine ourselves in the world. We think that this has to do with what’s been shown to be powerful about psilocin and psilocybin in terms of treatment for mood disorders, including depression and anxiety.

Gazella: You coauthored a paper about psilocybin and palliative care that was recently published in the journal Current Geriatrics Report. Tell us about that paper and its conclusions.

18

Listen to the full podcast here.

Approximate listening time: 34 minutes

Whinkin: This was a 5-year review that looked at papers from 2017 to the point of publication (early 2023) to better understand if there was a role for psilocybin in palliative care specifically. Our definition of palliative care included total pain, which is not just physical pain, but includes psycho-spiritual pain, emotional pain, and the disconnection from community that patients can sometimes experience because of a condition that warrants palliative care medicine. We wanted to explore the role with psilocybin for each of these concerns independently—physical pain, existential distress that can come with a life-limiting illness, and cognitive issues. We found some compelling research to support each of these targets.

Psilocin seems to support neuroplasticity that can promote novel modes of thinking and problem solving. It can help with rebuilding of neuronal tissue, so it can be helpful for people who have suffered traumatic brain injury or cognitive injury as well as readdressing someone’s interpretation of their of their own pain. For pain that has become centralized in the nervous system, psilocin offers almost a rebranding of the person’s interpretation of that and sometimes reduces the secondary impact of being seen as a palliative care patient.

Gazella: Interesting. How does psilocin help other conditions?

Whinkin: The way we think psychedelics work, including psilocybin-containing fungi, is they seem to have 2 central modes of action. One is more neurochemical. As I mentioned, the 5-HT2A receptor seems to be prominent in psilocybin effect. The other mode is more of a psycho-spiritual or

©2023 NATURAL MEDICINE JOURNAL. ALL RIGHTS RESERVED. NMJ, OCTOBER 2023 SUPPLEMENT—VOL. 15, NO. 101 (SUPPL)

psychological benefit. The ways that those 2 things are helpful are how they work together. When we think about where psilocybin and other psychedelics have been suggested to be particularly beneficial, we think about major depressive disorder, generalized anxiety disorder, obsessive compulsive disorder (OCD), and problematic substance use. These are all situations where there’s extra rigidity in the mind. So we’re thinking about the depth of neuronal grooves where people seem to suffer from thinking the same thoughts, feeling the same feelings, or pursuing the same behaviors over and over again, and there becomes this rigidity internally. Psychedelics open up an opportunity to have a different experience internally based on new thinking pathways, new opportunities to connect memories to emotions, novel ways of interpreting our somatic cues, and reflecting on our own experience. So overall, psychedelics seem to help in particular with rigid types of thinking and feeling states by facilitating more openness, more access to novel connections in the mind—and that reflects more hope or the ability to shift our own perspective about what could be possible for healing.

Gazella: It’s fascinating. What does the research tell us about the safety of psilocybin?

Whinkin: We need more long-term data. Psilocybin is still a Schedule 1 drug in the United States, and under the Controlled Substances Act of 1970 is restricted in terms of how we can access and appropriately study some of the long-term effects. So whereas ketamine, for example, has been used and studied robustly since the 1970s and we have a lot of data about its safety, we don’t have the benefit of 50 years of data for psilocybin. What we do know, based on its function at the 5-HT2A receptor is that it may have some cardiovascular adverse events or effects with longer term use. We know that when this receptor is targeted by other pharmaceuticals, there can be some damage to the endothelial cells along the vascular system and potentially some damage to heart valves. But contrary to other pharmaceuticals that target that receptor, research suggests that psilocybin doesn’t need to be used even multiple times for durable effect. So we’re measuring weeks of benefit after a single dose of psilocybin. That’s very different than other medications for similar concerns, like

antidepressants or anxiolytics. There is probably a lesser risk of damage, but we just don’t have the long-term data.

Gazella: The term “microdosing” comes up a lot with psilocybin. Can you tell us more about that?

Whinkin: I’ll start with macrodosing as a comparison. We think that between 2 and 5 grams of whole fruiting body of a mushroom, which is the above-ground part of the fungus dried, appears to be a macro-dose. Most of the single-dose studies isolate 25 mg of psilocybin to determine the outcomes that they’re tracking. That equates at the 1% profile average that I mentioned earlier—maybe a 2.5 gram whole, dried mushroom equivalent. Microdosing is about a fifth of that, maybe 1 to 5 mg psilocybin. The reason we’re using ranges is because there’s a lot of variety in the extracts, the strains within the psilocybin-containing mushrooms, and the way the mushroom is prepared. Microdosing is more regular use, which tends to be a few days a week. Common protocols are 3 days on in a row and then 4 consecutive days off, for example, with the goal being a subperceptual effect. With microdosing, there’s not a cognitive impairment so we are able to function, go about our day, and show up to our lives. But there may be some benefits, including feeling a little uplifted, feeling a little more clearheaded. Some people microdose for the creative benefits and the neuronal neurogenesis, promoting novel ways of thinking and problem-solving.

Gazella: Is there a way to standardize psilocybin extract?

Whinkin: I think that’s coming. There are certainly ways to measure the amount of psilocybin and psilocin. And there are efforts to extract and standardize just those constituents.

As a naturopathic doctor, I am curious about that because in other facets of herbalism, we know that using the whole herb has its own benefits. There are likely other constituents within these fungal fruiting bodies and these organisms that probably mediate the effects of psilocybin and psilocin and probably complicate the interaction with the human body in a way that I think should be studied. We don’t necessarily know if that’s harmful to us or if it facilitates some of the benefits of microdosing and macrodosing.

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19

EXPERT INTERVIEW

Gazella: Do you have concerns about the quality of the psilocybin products that are presently on the market or people who are doing their own thing with it?

which connects people who are independently choosing to and sourcing psilocybin to trained guides for integration work or answering questions regarding these substances.

Whinkin: I do have concerns. I practice from a harm reduction model with most of my patients who report to me that they’re using what they believe to be psilocybin. I can’t verify that’s what they’re ingesting. Sometimes they don’t know what strain they’re using or how much they’re taking. So it’s a challenge to practice in a way that ethically respects that person’s agency from a harm reduction model, while also trying to give them as much information as I can about how to use this in a safer way. I do hear stories where harm has occurred. Not medical harm, but people are underprepared for the experience of ingesting and being with a psilocybin-containing substance or a psychedelic in general, and there’s not enough appropriate support afterward for what we call integrating the experience or making sense of a big shift in perception. Sometimes there are new insights or confrontation with pre-existing belief models that can occur during that experience. So it’s more of a psychological risk that I’m hearing about and kind of concerned about. Of course, there’s also a chance for a more physiological or medical concern to arise.

Gazella: For people without mental health concerns, are there any potential benefits to psilocybin?

Gazella: It does seem like there are a lot of people using psilocybin, sometimes without proper guidance or any guidance. How do you advise people get the proper support when using psilocybin?

Whinkin: It’s a great question. One part is making sure the medical community is well informed so they can field questions from their patients appropriately and without shame or judgment. From a harm reduction lens, we ask, “If this person, in their own agency, is going to use the substance, how can we work together to not just reduce the harm, but consider that there might be benefit for this person and try to optimize the benefits?” So one part is clinician education, and that includes psychotherapists and counselors, as well as other traditional healing routes like chaplains. The other piece is making sure that if we are not able to provide the support, then making an appropriate referral, just like we do for any other concern.

I often refer people to a website called Psychedelic Passage, 20

Whinkin: There may be benefits to psilocybin-containing mushrooms in a way that’s not contained within a medical model. That is to say that there are there are potential psychospiritual, psycho-emotional benefits to consulting these plant medicines. Taking an open stance towards what would happen, maybe what I confront, what is something that maybe I haven’t even thought of, to ask myself or look at internally that that could facilitate some personal growth. I like that there is interest in that realm and it’s not so contained within a clinical model where people have to meet criteria in order to access these medicines. They’ve been used traditionally for eons— originally, we think by the Mayan and Aztec people in what is now the Amazonian region. Were they thinking through the DSM-V and vetting people and diagnosing people before they could access these plant medicines and the insights therein?

No. I think that should certainly be part of the conversation about how we move forward.

Gazella: As you mentioned, psilocybin is a Schedule 1 drug, so what is the exact legal status regarding its use for therapeutic purposes?

Whinkin: Federally, it’s still Schedule 1, which means there’s basically no acknowledged therapeutic benefit out of out of federal level. But we do have some examples within the United States, specifically in Oregon and Colorado, where they’re creating policy and pursuing the belief that this should be accessible to some extent and should be regulated so people can receive the potential benefits in an above-ground way. In Oregon, this is regulated by measure 109, which has a 3-pronged approach. First is that there’s regulation of the growth and distribution of the psilocybin-containing mushroom itself. Second, there’s regulation of the Certified Service Centers where a psilocybin experiential session could occur.

That means there are sites and venues specifically certified,

©2023 NATURAL MEDICINE JOURNAL. ALL RIGHTS RESERVED. NMJ, OCTOBER 2023 SUPPLEMENT—VOL. 15, NO. 101 (SUPPL)

meaning it’s not legal to use psilocybin in somebody’s house or out in the woods. Third is regulation of who can facilitate a psilocybin session, so they have accredited training programs and an exam to pass.

Gazella: What would you like to see next when it comes to psilocybin?

Whinkin: I would love to see more science around the whole fungus. What can we learn about the other constituents? Can we assume there’s an intelligence in the way that psilocybin has been used as a whole plant for thousands of years and also consult some people who are who are familiar with whole plant extracts within other mushrooms? There’s a lot of good evidence and clinical herbalism with other mushroom species, so why not? I think this also reflects more of the real world, what people tend to be utilizing for microdosing, or when they source their own mushrooms. I’d love to see more research on the phenomenology of these altered states, including acknowledging what we know and what we don’t. The results we get are only as thorough as the questions we’re asking and what we’re able to measure. So almost liberating ourselves from a strict medical monitor model and appreciating that there might be a lot of other planes of change that people are experiencing by utilizing these substances.

For the percentage of folks who don’t respond as expected, or maybe the duration of the benefit doesn’t last, I want to know why that is. Are we not measuring the change that they do experience? Or is it different type of depression, for example, that would be better benefited from a different tool? Or are there things like single nucleotide polymorphisms or other changes in the enzyme that converts psilocybin to psilocin and that, for example, could explain why certain people benefit more in the ways we’re able to measure?

I think there are a lot of questions around who is really a good fit for this as a tool within the medical model, but also branching out and thinking a little bit more broadly about the benefits outside of a medical model.

This is an edited and condensed version of our interview. Listen to the full interview on the Natural Medicine Journal podcast.

ABOUT THE EXPERT EMILY WHINKIN, ND (she/they), is an integrative mental health practitioner, researcher, and psychonaut currently practicing at the Advanced Integrative Medical Science Institute in Seattle. She holds Washington and Oregon licenses in naturopathic medicine and graduated with a master of science degree in integrative mental health from the National University of Natural Medicine in Portland, OR. Clinically, Whinkin works to provide person-centered, relationally informed care at the confluence of entheogenic spiritual medicine, mental health, and reproductive/ generative health. As an undergraduate, she studied both biology and religious studies, formally launching her work to explore and affirm the interdependence of mind, body, and spirit with a focus on cycles, transitions, and environment. Community connection, belonging, and collective transformation are central to Whinkin’s vision of being well in the world. She works to reflect this framework in caring for each patient’s foundational vitality, resilience, and health contexts as ‘root cause’ approaches to healing. She is certified in perinatal mental health (PMH-C) by Postpartum Support International and Holistic Pelvic Care™ with Tami Kent, and she often weaves mindful somatic therapy and botanical medicine within psycho-spiritual work with all genders across the lifespan.

RESOURCES

• AIMS Institute in Seattle: https://www.aimsinstitute.net/ • Oregon.Gov: https://www.oregon.gov/oha/ph/preventionwellness/pages/psilocybin-­ license-facilitator.aspx • Psychedelic Alpha for tracking legal status in the US: https://psychedelicalpha.com/ data/psychedelic-laws • Podcast: The Revolution will not be Psychologized: https://podcasts.apple.com/us/ podcast/the-emerald/id1465445746 • Psychedelic Passage (Connecting with a guide): https://psychedelicpassage.com/

STUDIES

• Whinkin E, Opalka M, Watters C, Jaffe A, Aggarwal S. Psilocybin in palliative care: an update. Curr Geriatr Rep. 2023;12(2):50-59. https://www.ncbi.nlm.nih.gov/pmc/ articles/PMC10106897/ • Whinkin E, Eparwa TRJ, Julseth MC, Schneider A, Aggarwal SK. Reductions in anxiety and depression symptoms in a subset of outpatients with problematic substance use who received ketamine-assisted psychotherapy: a two-year retrospective chart review. Front Psychiatry. 2023;14:1160442. https://www.ncbi.nlm.nih. gov/pmc/articles/PMC10498542/

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EXPERT INTERVIEW

Addressing Mental Health Issues from a Naturopathic Perspective An interview with Tara Peyman, ND

Mental health issues are on the rise, with 37% of Americans rating their mental health as poor or fair according to the American Psychiatric Association.1 There’s a need to address mental health issues holistically, taking into account all aspects of an individual’s health and lifestyle. Naturopathic doctors are uniquely suited to help address the root causes of mental health issues and not just the symptoms.

In this podcast interview, we talk with Tara Payman, ND, vice president of the Psychiatric Association of Naturopathic Physicians, to understand the current state of mental health treatment and how naturopathic doctors can address mental health in clinical practice.

NATUROPATHIC DOCTORS ARE IN A UNIQUE POSITION TO HELP When dealing with the rising prevalence of mental health issues like depression, anxiety, posttraumatic stress disorder, and eating disorders, conventional medicine often falls short.

A naturopathic approach, on the other hand, takes a multifaceted approach that shows promising results. “One of the most important things that differentiates a naturopathic doctor from a conventionally trained doctor when we’re talking about mental health is that we look at things really holistically,” she says. “We look at all of the aspects of a person’s life, from their economics, their environment, and their lifestyle, to their nutrition and their emotional and spiritual well-being. We also look at biochemical and physiological imbalances, and how they may be contributing to the current state of mental health.”

With this holistic approach, naturopathic doctors can develop comprehensive treatment plans that may include both conventional and natural methods.

Those natural methods are aimed at root causes and can include herbal medicine, nutritional supplements, diet and lifestyle counseling, IV therapy, hormone therapies, acupuncture, homeopathic medicine, and mindfulness strategies.

Payman explains, “My approach with these patients is to first

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Listen to the full podcast here.

Approximate listening time: 45 minutes

start with that foundation, that basic good naturopathic care, and then start them on a holistic protocol.”

In the case of patients already on prescription medication, Payman stresses the importance of a careful approach. “My first job when it comes to managing or considering tapering medications is to assess the medications based on the history of that patient.”

“As naturopathic doctors, we do have training in medication, and we also have training in all sorts of natural alternatives.

So we can provide a wide array of treatment options,” Payman notes. “Our goal is to help people find the most effective and natural treatments to improve their mental health.”

PRELIMINARY RESEARCH AND THE FUTURE OF CARE Payman cites several studies demonstrating the potential ­benefits of naturopathic treatments for mental health. For instance, one study found that individualized homeopathic medicines were successful in treating severe depression and led to sustained remission.2 As president of the Psychiatric Association of Naturopathic Physicians, Payman aims to expand the field of naturopathic mental healthcare and establish standards within it. She highlighted the association’s resources, continuing education

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events, and its upcoming certification process for eligible naturopathic doctors.

“We’re in the final stages right now of establishing a certification process for eligible naturopathic doctors to be recognized for meeting a specified standard of experience and knowledge in the field of naturopathic mental health,” Payman says.

This certification will allow more people to benefit from naturopathic mental health treatment, while also encouraging practitioners to expand their knowledge and experience. The certification process will ensure that practitioners are providing the highest level of care and that they are following the highest ethical standards.

Listen to the full interview here.

REFERENCES 1

Americans anticipate higher stress at the start of 2023 and grade their mental health worse. https://www.psychiatry.org/News-room/News-Releases/­ Americans-Anticipate-Higher-Stress-at-the-Start-of.

2

Adler UC, Paiva NMP, Cesar AT, et al. Homeopathic individualized Q-potencies versus fluoxetine for moderate to severe depression: double-blind, randomized non-inferiority trial. Evid Based Complement Alternat Med. 2011;2011:520182. doi:10.1093/ecam/nep114.

ABOUT THE EXPERT TARA PEYMAN, ND, is a licensed naturopathic doctor and the clinical director of Integrative Mental Health Center in Scottsdale, Arizona. She has a focus in the homeopathic and integrative treatment of mental illness, with a particular interest in bipolar disorder, schizophrenia, and OCD. She has additional training as a PESI-Certified Clinical Trauma Professional. She is well-versed in the use of psychiatric medications and can assist patients in either reducing the need for prescriptions, or safely integrating them with naturopathic care if that is best for the patient. Peyman found inspiration to focus her medical practice on homeopathic treatment of mental health after she overcame her own depression and panic disorder, which started when she was in college. She found total relief with homeopathic medicine, under the care of a doctor who was later one of her homeopathy teachers in medical school. Bipolar disorder runs in her family, so she has a personal perspective on this condition that allows her to have a level of compassion and understanding that patients can really feel. Her experiences motivate her to help as many people as she can to reach a place of healthy remission.

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