CLiR No. 5 Cannabis. A new way to make science

CONTENT

3 EDITORIAL LATEST NEWS 4 Pandemic adverse events: underdiagnosis of other diseases, the case of tuberculosis in America 4 Drexel University in Philadelphia opens medical Cannabis research center 5 Chocolate Health Claims 5 Adverse financial events can be a sign of dementia THE EXPERT’S OPINION 6 Cannabis, beyond the myth. Marco A. Cid 7 Let us all build a solid industry! Israel Madrid 8 Cannabis’ new appraisal in Mexico. Midalia Denisse Arias 9 Cannabis old and new, risks and opportunities. Thor Nissen 11 Our Cages. Dante Alducin

CANNABIS. A NEW WAY TO MAKE SCIENCE

EDITION ENQUIRY 12 Does cannabis really have a medicinaluse? Why? INTERVIEW 14 Mexico, a paradise for Cannabisresearch and development

YEAR TWO

MAR-APR

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Interview to Lorena Beltrán, one of the most prominent investigators and activists of Cannabisin Latin America.

NEWS IN MEDICAL RESEARCH 22 “A journey to Nashville” – Quality of life is sometimes more important than life itself: use of Cannabis as a potential treatment for Intestinal inflammatory disease. Ana Villaseñor-Todd RESEARCH 28 Cannabis in Latin America: the bloom of an industry under a new paradigm. Gerardo Garza Villarreal et al.

30 Legal cannabinoid-based medicine in Mexico: challenges and perspectives.

Luis David Suárez Rodríguez

34 Morphology and physiology between subspecies and sexes of Cannabis.

Raúl Porras Gutiérrez de Velasco et al.

40 Cannabis, the controversy updated. Guillermo Caletti 44 The creative and inventive boom of Cannabis. Enrique U. Alcázar CLINICAL RESEARCH & PHARMACOLOGY 50 Tetrahidrocannabidol (THC), genetic variability and viariavility in pharmacological response. Javier Esquivel Vargas et al.

GADGETS 55 Cannabis and technology: The new non-stigma of the 21st century. Mauro Orozco REVIEW 58 How to smoke marijuana and have a good trip. A sociological look.

Orígenes Romero

PROFILE 60 Viola Brugnatelli: Scientific research, innovation, and awareness.

Karen González

ART & LITERATURE 63 “Chewing the soul” poem by Marco Antonio Gabriel 64 CLIRTOON

S TA F F DIRECTORY

•DIRECTION

•COMMERCIAL

GENERAL DIRECTOR

Francisco de Landero Gerardo Garza Luis David Suárez Rodríguez Raúl Porras Izaizel Libertad Cruz Gómez Alejandra Nayeli De Olarte Carbajal Guillermo Caletti Enrique U. Alcázar Israel Madrid Lozano Javier Esquivel Vargas Diana Vega Perea Darío Morales Martínez Miriam Morales Mtz Alberto García González Alionka Citlali P. Ángeles Midalia Denisse Arias Vergara Mauro Orozco Orígenes Romero Porras Karen González Vega Marco Antonio Gabriel Francisco Hernández Rick Ruíz-Dana

CO MME RCIA L DIREC TO R

Marco A. Cid

Fabián Villegas

EXECU TI VE D I R EC TO R

CO MME RCIA L MA N AG E R

Ivette Venegas

Jorge Castro

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EDITOR IN CHIEF

Antonio Padua

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Marco A. Limón del Toro Natalia Robles Cabrera

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Carmen de la Rocha Jennefer Iveth Mercado Marco A. Cid Thor Nissen Dante Alducin Lorena Beltrán Ana Villaseñor-Todd Ana Lucía González Allegra Piaccentini

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Advertising information Contact: antonio.padua@cidvid.com.mx Cel: (33) 3250 6078 CLiR Clinical Research Insider, year 2, no. 5, March-April 2021 is a trademark of CRPS, Clinical Research Professional Services, LLC. All rights reserved. CLiR Clinical Research Insider is a bimonthly publication, published in Calle Volcán Popocatépetl No. 3352, Colli Urbano, Zapopan, Jalisco, C.P. 45070. Tel. 33 20 02 86 97. Website: clirinsider.com. Editor in Chief Carolina Villanueva López, email: carolina.villanueva@cidvid.com.mx. Reservation of Rights to the Exclusive Use: in process. ISSN: pending at the National Copyright Institute. Title and Content Lawsuit: pending. The content of the articles and advertising is the responsibility of their authors and sponsors. CLiR Clinical Research Insider is not responsible for the information in the advertising content.

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EDITORIAL

Mexico at the forefront: paradise for the Cannabis research and development «If there is any country in the world with the perfect conditions for the development of the Cannabis industry and the greatest need for its implementation, that would be Mexico.

Our country deserves the opportunity to legally take advantage of the economic, social and environmental benefits of an ancestral plant nowadays considered as the green gold» – Lorena Beltrán

Science has the virtue of transforming prejudices into accurate knowledge, in the same way, clinical studies and protocols carried out on Cannabis break down taboos, thus generating unimaginable benefits for humanity. The medical-therapeutic use of Cannabis dates back millennia but Mexico specifically has an ancestral tradition in the use of the plant; our history and culture are infused with it.

With sails unfurled and favorable wind, Mexico will undoubtedly become the plant’s largest market globally. In addition to the possibility for recreational use of cannabis and its largescale manufacturing, the medical use of the plant presents as the ultimate solution, an optimal treatment for multiple conditions affecting millions of people around the world.

However, more clinical studies and promoting the development and investment in the field are needed. Thus, Mexico is at the vanguard with the financial resources, investors, croplands, and the capacity for global-scale exporting; as well as researchers and healthcare professionals

Carolina Villanueva, EIC Editor and content creator with a Degree in Hispanic Literature.

with the expertise and infrastructure needed to research and develop drugs that would potentially improve the quality of life for humans.

We still have a lot to learn about the use of Cannabis, therefore CLiR presents you the research and expert opinions on the matter: members of the Mexican Commission for Cannabis and Hemp, pioneers in the research of the plant; an interview with Lorena Beltrán, one of the biggest cannabis researcher and activist in Latin America; as well as several articles written by chemists, biologists and physicians dedicated to the development and study of the plant.

We face a turbulent century where humanity has gotten by, we begin a new era for Mexico; this is a unique moment where political regulations, the power of raw materials, economic prosperity and the Mexican creativity and hard work converge to skyrocket our country into true modernity.

These are our roots, we have the industry, this is our time. Cannabis is now Mexican.

EDITORIAL |

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DREXEL UNIVERSITY IN PHILADELPHIA OPENS MEDICAL CANNABIS RESEARCH CENTER After Pennsylvania’s medical cannabis law set forth that medical schools could be designated as Academic Clinical Research Centers (ACRC), Drexel University started operations at the Medical Cannabis Research Center in 2020, aiming to conduct clinical, public health and translational research studies along with Argonomed Biologics LLC, these two organizations entered into an 8-year, 15.5-million-dollar contract.

In addition, funding for annual pilot trials is being considered in order to explore the efficacy of Cannabis as a treatment for other conditions such as autism and opioid addiction.

This research center leads to the possibility of using Cannabis as a consolidated treatment for several diseases and to study on a larger scale the safety and efficacy analysis of the plant.

Source: https://drexel.edu/about/glance/, https://drexel.edu/cannabis-research/about/mission-goals/

PANDEMIC ADVERSE EVENTS: UNDERDIAGNOSIS OF OTHER DISEASES, THE CASE OF TUBERCULOSIS IN AMERICA On March 24 of this year, the World Health Organization along with the Pan American Health Organization issued an alert regarding the diagnosis of tuberculosis in the American continent; due to the pandemic caused by COVID-19, a decrease of approximately 20% has been observed in the diagnosis of the disease, no information is yet available on the effect on tuberculosis-associated mortality.

Tuberculosis is an infectious bacterial disease caused by Mycobacterium tuberculosis, which

primarily affects the lungs. It is and airborne disease transmitted from person to person. These bacteria are released when a person with TB in lungs or throat coughs, sneezes, talks, or sings.

In 2019, approximately 290,000 new cases and 22,900 deaths were reported in America. Brazil, Peru, Mexico, Colombia, and Haiti account for 70% of the reported cases.

Therefore, it is imperative to address this problem in line with the strategy of reducing deaths by tuberculosis, up to 95% by 2035.

Source: https://www.paho.org/en/news/24-3-2021-diagnosis-new-tbcases-americas-reduced-15-20-during-2020-due-pandemic

| LATEST NEWS

Written by Dr. Carmen de la Rocha D. in Plant Biotechnology, CINVESTAV-Irapuato - Master of Science in Biochemical Engineering, ITC - Bachelor of Science in Nutrition and Food Science, IBERO, León Supervisor of the Department of Development CidVID - Professor of Subject B, CUCS UdeG Member of the National System of Researchers, level I.

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CHOCOLATE HEALTH CLAIMS Love chocolate? 73.9% of the United States population likes chocolate. It is a delicious snack that provides a boost after a long day. You have probably heard that dark chocolate has health benefits, but is that scientifically true or false?

Clinical studies have found that cocoa may have health benefits, this is possible because of the amount of nutrients in cocoa that could improve heart health and boost brain function, especially in adult cells.

Written by Jennefer Iveth Mercado Cerda.

Student of the Master of Public Health, Bachelor of Public Health, Researcher in the Department of Development at CidVID.

Baker L.D. et al. conducted a study to assess the design and baseline characteristics of the cocoa supplement and multivitamin for the mind. The study found that cocoa health benefits derived from flavonoids; cocoa beans and dark chocolate contains high levels of such components.

Baker et al. study is still ongoing to evaluate whether cocoa supplement help preventing cognitive impairment in older adults, if there is an impact in short-term memory and what benefits provide to overall brain function.

More than 2,000 older adults have been recruited over three years; however, investigators consider it’s too soon to drag final conclusions on the benefits for brain health.

Another article supporting these benefits in an investigation carried out in Kuna, near to the coast of Panama, where the population consumes high amounts of cocoa. This population consumes hot chocolate like water, lots of cups throughout the day. Consequently, the population consuming high amounts of this product had a lower incidence of heart disease, compared to the neighboring region not consuming such high amounts of cocoa.

Researchers are currently studying the exact dose of cocoa flavonoids that help improving general health, from eye problems to heart and cognitive diseases.

References: Baker, L. D., Rapp, S. R., Shumaker, S. A., Manson, J. E., Sesso, H. D., Gaussoin, S. A., ... & COSMOS-Mind Research Group. (2019).

Design and baseline characteristics of the cocoa supplement and multivitamin outcomes study for the Mind: COSMOS-Mind.

Contemporary clinical trials, 83, 57-63. DOI: 10.1016/j.cct.2019.06.019 https://newsinhealth.nih.gov/2021/02/chocolate-health-claims

ADVERSE FINANCIAL EVENTS CAN BE A SIGN OF DEMENTIA A group of investigators carried out a study that discovered that financial problems could be an indicator of early dementia. Some older adults had these types of problems before being diagnosed with Alzheimer’s disease or other neurodegenerative diseases.

Nicholas L.H. et al. examined the medical records of 80,000 adults between 1999 and 2018, they found that people over 65-year, living in singleperson households and receiving medical care, missed bill payments 30 or more days late, and

drops in subprime credit scores as early as 6 years prior to diagnosis of dementia or a related condition.

The investigators state that this is the first largescale study providing scientific and quantitative evidence of the relationship between dementia and financial education of the elderly; the investigators conclude that dementia causes a negative impact on daily-life activities, including the ability to manage bills and finances.

Reference: Nicholas, L. H., Langa, K. M., Bynum, J. P., & Hsu, J. W. (2021). Financial presentation of Alzheimer disease and related dementias.

JAMA internal medicine, 181(2), 220-227. DOI: 10.1001 / jamainternmed.2020.6432

LATEST NEWS |

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CANNABIS , BEYOND THE MYTH

Marco A. Cid, Director Chemist-pharmacist from La Salle University, MBA from ITESO and a senior management degree from the IPADE Business School.

Expert in medical research and development, entrepreneur and founder of several non-profit and for-profit associations; he us also the creator of a private investment fund.

We are living controversial and interesting times.

Mexico has crossed the threshold on the issue of legalizing the use and research of Cannabis. A few decades ago, in 1940 to be precise, the use of marijuana was banned, regulated, and in some cases demonized; arguing psychoactive effects to its users, the plant surrounded itself with myths and legends, therefore dissolving any possibility for its study or research. For many years, it was not possible to further study the plant, its real effects or its importance in modern therapies.

Today the world has changed, the laws are trying to give the plant the opportunity that stigmatized generations for its consumption. This April, Mexico approved its use for Cannabis research, thus opening the doors to new horizons. There has never been before an opportunity to deep research the plant and to find out all the possible benefits for the human beings. Mexico has a great responsibility in its hands; there has been a tirelessly fight to legislate on the matter, however, we still don’t know how to make the most out of this advantage we’ve received.

Over time, various types of miracles have been conferred to the plant: the cure for cancer and for the so-called rheumatism, pain relief and, even against COVID-19; however, little has been consistently and accurately studied to demystify

| THE EXPERT’S OPINION

or to support generalized theories. TODAY, we have the opportunity to make a quantum leap and go to the insides of CANNABIS, therefore seeking for its true applications in neurology, oncology, rheumatology and in many diseases afflicting modern man.

It is time for this country, in pain and bloodstained, to join the efforts in the field of research, development and marketing of the plant that for years connected us with our ancestors! The road is hard and has not yet been drawn, we will need an international and multicultural scenario to take on this complex task. But I do believe that with everyone’s effort, we can find the optimal uses for CANNABIS in our everyday life.

The ancient gods have returned to connect the ancient wisdom with modern man. Cannabis is the beginning of the reencounter between our ancestral medicine, brought to us by divine voices, and modern medicine, fruit of the hand and effort of men. Great horizons are looming in a future where only humanity wins; innovation and development always begin as a glimmer of hope and end up becoming an infinite flame of wisdom.

The new laws that grant us the right to search for the truth will always be welcome.

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LET US ALL BUILD A SOLID INDUSTRY! For decades, Mexico has faced an alienated and imposed war, which increasingly moved Cannabis from the transparency to the underground within a prohibitionist strategy that only created a lair for the worst leftovers of society: violence and intolerance. Our social subconscious is always dwelling around the myths of drug dealing and narcos. Ideas arisen from poor educational programs and dogmas crashed against a crude reality that cannot be paid with blood anymore.

It appears that necessity and congruence are prevailing on stigmas and dogmas. With the potential legalization of Cannabis for adults, we face a historical opportunity to change rooted paradigms, developing a new industry resulting in welfare and income along with adequate educational and innovation programs. The timing could not have been better, with the Mexican economy so desperate for results.

With the decree of Law for the control of Cannabis and its derivatives, a range of possibilities opens before us for a new industry that, according to estimations, could reach a market of about five billion pesos by 2025. Although the expectancy is huge, contrary to expectations, the incorporation to this segment is being slow. Despite the recent regulation for the medical use of Cannabis, only a handful of companies have taken action to enter the market.

It is true that the rules are not yet clear and that there is a long road towards the standardization and legislation of Cannabis, however since the structure has not been built yet, then, it is the perfect time to enter into action. We are before a potential opportunity to design a new industry from

the foundations, built upon socially responsible models addressing not only an entrepreneurial vision but a socially sustainable development.

The objective is to integrate proven business models into a completely new industry. For example, we have this accelerator, a Fintech fully standardized model that five years ago impacted and transformed the financial environment. This model can be replicated in the new Cannabis industry, so needed for actions and resolutions.

Furthermore, the new legislation creates a new and underrated business arm: industrial hemp.

An agriculture project, designed with sustainable processes within a socially responsible economy would result in sustainable raw materials for sectors like fabrics, bioenergy, pharmaceutical, construction, and bioplastics.

One hectare of hemp can yield up to three times more fiber than one hectare of cotton while requiring only a quarter of the water used in the latter. With potentially high biomass and its suitability to adapt to current crop rotations, hemp could not just complement but overcome other current energetic crops that require high levels of water for its cultivation.

Israel Madrid New Business Management Commission. Israel is an Industrial Engineer, a specialist in the creation of new businesses with more than 10 years of experience in the operation and development of productive models, franchises, start-up programs, business incubation, and strategic planning for SMEs. He currently develops several commercial and communication initiatives for the Cannabis business sector.

From the CMCC we encourage all entrepreneurs to enter the business now, this is a perfect time; at the Board, we account for the human and technical tools to guide them through this road, blurry though. Still, we know that it will be a success for those who decide to take the risk. In some years, we will see those who took that risk turned into well-established companies.

THE EXPERT’S OPINION |

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CANNABIS’ NEW APPRAISAL IN MEXICO

Midalia Denisse Arias Vergara Bachelor’s degree in Chemistry and Biology by the Veracruz University, Master Science’s degree in pharmacology with Specialty in Molecule design with biological activity in the molecular modeling and bioinformatics laboratory – Medical School, IPN postgraduate unit. She currently works at the Department of Clinical resolution and analysis of the Cardiology Hospital “Centro Médico Nacional Siglo XXI” of the Mexican Institute of Social Security and the Mexican Academy of Cannabis Medicine (AMMEDCAN).

Overall, Cannabis has been considered a plant with different implications in terms of politics, economy, science, and culture. Having said that, it is interesting to imagine a clear scenario to enforce a balanced use and management of the plant. Although in most of the countries around the world, scientists have researched the use and management of Cannabis in terms of human health, for decades in Mexico, the stigma spawned on the myths of Cannabis or marijuana has limited the management of this plant for scientific or biomedical researching, restraining the advance to obtain more information and awareness on the medicinal and pharmacological potential of the active ingredients produced by Cannabis. It is to note that in Mexico City, on January 12, 2021, the Official Federation Journal published the Health Law on Medicinal Cannabis, which allows the management of several researching and development process to generate specific information on Cannabis in terms of particular characteristics presented by the metabolites of the plant. This represents a huge advance in Mexican legislation.

Is not easy to start the road to the development and evaluation of medicinal trials on phytocannabinoids (active ingredients) and terpenes (molecules that confer the smell and flavor of Cannabis). However, it will be necessary to limit the myriad of activities ruled by this law, as well as estimating the new scopes on innovation and development, but also, determining new adequate applications evaluated by quality controls and regulatory criteria that allow traceability and validation, from raw materials to the standardization of Cannabis derivatives, developed through Mexican investigations, and other derivatives introduced to the country. The dimension on research, education, health, nutrition, business, agronomy, etc., must be considered since the adapting of these sectors will be essential to play a critical role in the technological development applied to Cannabis cultivation in Mexican fields. Crops can be derived to produce cellulose, paper, fibers, textiles, bioplastics, textile industry derivatives, nutritional supplements, and pharmacological products, to mention some applications. Taking into account the wide range of possibilities that Cannabis offers for its use and management in the social fabric, it is necessary to have a new appraisal on the plant, which potential benefits give us a glimpse to the applicative universe that Cannabis offers, allowing us to foresee the vast future that Mexico can implement with the development, knowledge, research, and innovation of Cannabis.

| THE EXPERT’S OPINION

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CANNABIS OLD AND NEW, RISKS AND OPPORTUNITIES Almost every paper dealing with the topic of cannabis includes a reference to its millennial presence in the history of humanity, a comment distinguishing between its recreational and medicinal uses, and the notion of its geographical legality.

Traditionally, drugs used to treat medical conditions were derived from plants and other natural sources. The first synthetic drug was introduced late in the XIX century1 as chemistry knowledge from other industries gave birth to the first pharmaceutical companies, later on. Drug design became more and more intricate as the molecular size and complexity of the components started to grow. And then came biologics.

In an era where sophisticated technology and artificial intelligence has proven their efficacy and led to the development of a new vaccine for the COVID-19 virus in a record time, the two main cannabinoids found in the cannabis plant, delta-9tetrahydrocannabinol (THC) and cannabidiol (CBD) are still news and topic of harsh debate.

Aside from its recreational and non-prescription, legal or illegal uses, cannabis therapeutic role has been the object of recent publications in wellrecognized scientific sources. Patients’ interest in the use of cannabis products guided the discovery of what was identified as a cannabinoid system in the human brain and body. These findings relate the system with the control of functions, such as cognition, memory, pain, sleep, and immune performance.2 Its potential indications spread into different chronic diseases.

The anti-emetic efficacy of cannabinoids in cancer patients receiving chemotherapy is probably one of the most known indications. It has been featured in some medical television series. Even if Cannabis-based medications have shown to be useful in this setting, some of the available studies present a risk of bias, they were mostly conducted by the end of the previous century, and do not include a comparison with newer antiemetic drugs. “Further research reflecting current chemotherapy regimens and newer anti-emetic drugs is likely to modify these conclusions.”3

Thor Nissen Doctor, graduate in Clinical Pharmacology and MBA in Quality Management. He has managed to collaborate for the development of medicines in world leading pharmaceutical companies both in medical matters and in clinical research in new drugs, regulation, marketing and sales departments.

Jones AW. Early drug discovery and the rise of pharmaceutical chemistry. Drug Test Anal. 2011 Jun;3(6):337-44. doi: 10.1002/ dta.301. PMID: 21698778.

European Monitoring Centre for Drugs and Drug Addiction. Medical use of cannabis and cannabinoids: questions and answers for policymaking. Publications Office of the European Union, Luxembourg, 2018. http://www.emcdda.europa.eu/system/files/ publications/10171/20185584_TD0618186ENN_PDF.pdf 3 Smith LA, Azariah F, Lavender VT, Stoner NS, Bettiol S. Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy. Cochrane Database Syst Rev. 2015 Nov 12;2015(11):CD009464. doi: 10.1002/14651858.CD009464.pub2. PMID: 26561338; PMCID: PMC6931414.

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THE EXPERT’S OPINION |

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Other supported indications for medicinal use of cannabis-based products and cannabinoids are chronic pain, multiple sclerosis, and treatment of resistant epilepsy.4 The quality of evidence to support its use in chronic pain and spasticity is modest.5 Still more debatable is the effectiveness of cannabis-containing products in appetite and weight loss associated with weakening conditions such as HIV/AIDS. The list of reviewed settings in which these products might find some benefit extends to, for example, Tourette syndrome, anxiety, post-traumatic stress disorder, and schizophrenia, as much as the evidence shortens.

With more or less scientific support or clinical evidence, cannabis and cannabinoid drugs are used to treat disease or alleviate symptoms in different scenarios. The way of these drugs into acceptable medicinal use should account for their high abuse potential as well as concerns for dependence. If qualified information of its use under well-controlled environments may arise, it will have to deal with a stigma surrounding it as a potential gateway to other uncontrolled and more harmful substances.

One thing for sure is that the place of cannabis in the medical field has been and will continue to be controversial.6

Freeman T P, Hindocha C, Green S F, Bloomfield M A P. Medicinal use of cannabis based products and cannabinoids BMJ 2019; 365 :l1141 doi:10.1136/ bmj.l1141 Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, Keurentjes JC, Lang S, Misso K, Ryder S, Schmidlkofer S, Westwood M, Kleijnen J. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA. 2015 Jun 23-30;313(24):2456-73. doi: 10.1001/jama.2015.6358.

Erratum in: JAMA. 2015 Aug 4;314(5):520. Erratum in: JAMA. 2015 Aug 25;314(8):837. Erratum in: JAMA. 2015 Dec 1;314(21):2308. Erratum in: JAMA. 2016 Apr 12;315(14):1522. PMID: 26103030.

6 Bridgeman MB, Abazia DT. Medicinal Cannabis: History, Pharmacology, And Implications for the Acute Care Setting. P T. 2017;42(3):180-188.

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Informes: 33 2048 7741

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OUR CAGES “Kif, good quality, cheap, good deal my friend...”.

My new pal, who introduced himself as Hassan, took what looked to me like an eternity attempting to sell his precious Kif to me when he saw me seating in a coffee shop in Chefchaouen, a town in the Rif mountains of Morocco. Kif a.k.a. Hashish, is what could be identified as the Cannabis resin and differentiates from marijuana because the last is essentially the dried leaf of the plant, therefore, less strong. Hashish is a brown paste that is generally smoked, and in some cases, it is consumed as is, like the notorious “stuffed” brownies. “Shukran Hassan, Shukran”.

Overall, these are the magic words in Northern Africa if you want to get rid of an annoying dealer, which is quite frequent.

However, Hassan was persistent, and he knew better since the Rif region in Morocco is better known for being the main Hashish-producing zone that reaches Europe. Chefchaouen, besides its cultural singularity, is one of the temples of this Cannabis derivate. So, dealers like Hassan invade the streets looking for foreign clients, seeking the same deed. This is illegal of course, but authorities use to turn a blind eye in certain zones such as Chefchaouen; however, in the rest of the region, this causes instability and insecurity, like in Ketama, a town frequently visited by “hardcore” Europeans, which locals persuaded me not to go. The legend tells that the term “Assassin” comes from the Arab “Hashshashin” or Hashish smoker, a member of an Ismaili Muslim sect who populated what is now known as Iran. The word was that they kidnapped children to turn them into addicts and killing machines.

It is unlikely that the Hashish effects would turn those children into angels of death since

Tetrahydrocannabinol or THC, the active ingredient of Cannabis that produces more relaxing and somnolence effects. But the bone was rolled for Hashish; likewise, other substances considered addictive, its approval over the centuries has come and gone. The question is whether is worthy to prohibit this drug in Morocco and the rest of the world since it happens that anyone can invent themselves their addictions: compulsive gambling, alcohol, sex, smoking, working, etc.

The stigma bore by these substances comes from early studies in rats where their addiction grew unabated, however, a small detail was not considered: rats were alone in their cages; they had nothing to do but get high. When the experiment was repeated sometime later with groups of rats, the situation changed: an overwhelming majority preferred the social interaction than the consumption of addictive substances. With this, I do not attempt to simplify the complex problem of addictions, but to assess the kind of society we live in and the requirements imposed on us since, in many cases, a lonely cage is the outcome.

Dante Alducin Q.F.B. with the Specialization in Leading People and Teams program by the University of Michigan. He has 12 years of experience in Clinical Research.

Founder of Blast! Academy and host of the Ruido Blast! podcast.

Why do we work until chronic exhaustion? why drinking or smoking until death? why smoking is cool? is it necessary to eat snacks only because it represents our typical cuisine? Depression, violence, burnouts, diabetes, hypertension, and some other consequences from our addictions make look the Hashish effects negligible, however, the drug is publicly condemned. The Cannabis era is coming, go ahead with it. I am more concerned about having a more balanced and human experience; to stop killing each other for alien demands and enjoying life.

THE EXPERT’S OPINION |

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EDITION INQUIRY SOCIAL MEDIA RESPONSES

Does cannabis really have a medicinal use? Why?

| PREGUNTA DE LA EDICIÓN

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SEAIRRA ROBERTS

CHAMPIÑÓN HERNÁNDEZ

Cannabis has helped me with my scoliosis, I have no cure and doctors in the United States recommended lifetime pain pills, I did so for years but when I used marijuana it instantly numbed the pain; I could sleep face down again or simply sleep, lift and carry things, stand or sit for long periods. I am thirty years old now and I feel perfectly fine.

Because it helps me against the pain in hands and knees and without affecting my liver!

JUAN HERNÁNDEZ ISRAEL OLIVAREZ ¡¡Porque ya NO me dan convulsiones!!

Personally, I started using Cannabis recently as ointments and edibles to treat gastritis in myself and other two family members. It helps with gastritis-related inflammation and additionally reduces pain, it has helps us to deal with the stress and anxiety, it allows me to be more relaxed, I can sleep, and reduces body aches in general; in several friends it has helped them with bumps, sores, amputation, and psoriasis; we use it as ointment and also as handmade oil.

OSWALLDO TORRES My wife suffers from bronchial asthma and only Cannabis helps to control it and sleep at night. She got COVID-19, we thought the worst would happen but inexplicably the virus did not reach her lungs. It was a miracle, but I do know what prevent the disease from reaching her lungs.

MICKEY CORTÉZ OTZ It is an effective treatment for headaches and insomnia; I have retinal detachment, the pain in the eyeball is strong and Cannabis helps getting rid of it.

JO ADRIÁN AG TA RORRO BARRI Yes, I use Cannabis for severe pain, migraines and seizures.

When I was 15 years, I was diagnosed with epilepsy and they gave me medicine for life, approximately when I was 20 years, I started it just out of curiosity, but it didn’t take me long to realize that seizures disappear when I used marijuana, so I started smoking right when the auras appear, on many occasions that allowed me avoiding seizures and since that day I always carry some with me.

アメリア 利光 I am still very ignorant about it, however, I have done some research and I believe CBD and CBG are the best components and those considered for medicinal use due to their properties, since THC is the one with psychotropic effects, unlike the other two that have anti-inflammatory and anesthetic effects among numerous other beneficial properties. My mother suffers from chronic migraine since she was a child and fibromyalgia for 2 years now; she has taken a lot of medications, some of were prescription drugs, for many years and they were never truly effective nor helped her being functional; They had less and less effect and for the fibromyalgia the medication helped her only about 10%. Since she takes CBD drops, her quality of life has improved dramatically and without any psychotropic effect; as to her functionality it even helped her being able to leave the house and be more active; one of the great things of Cannabis is that its positive features are not limited to these diseases, people with cancer, autism, epilepsy, Parkinson’s disease, insomnia, depression, colitis, colic, anorexia can also benefit from the plant. I wish doctors could prescribe these components, the best of all is that it is natural.

PREGUNTA DE LA EDICIÓN |

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INTERVIEW

Mexico, a paradise for Cannabis research and development Besides positioning the country as one of the main players in the Cannabis industry around the world, Lorena is an excellent, reliable, and always up-to-date source to clarify any question on marijuana.

Interview to Lorena Beltrán, one of the most prominent investigators and activists of Cannabis in Latin America

Lorena Beltrán CannabiSalud CEO She started her career in the Cannabis industry in Denver, Colorado in 2014. By that time, she founded CannabiSalud, the first international congress on medicinal Cannabis for healthcare professionals in Mexico, which has positioned itself as one of the most important educational platforms for both health and business sectors. In 2018 she moved to Mexico City and co-founded Endonatura Labs S.A. de C.V., a company focused on research, advisory, and activities within the legal framework. Lorena continues her education by participating as a speaker in major foreign congresses, such as CannaTech in Israel and Panamá, MjBiz in Las Vegas and Bogotá, ExpoMedeWeed in Medellín, and many more in the United States and Canada. Currently, she leads the movement for the Legalization 4/2020, a coalition of associations and companies, formalized and constituted in the Alianza Latinoamericana de la Cannabis A.C.

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Dear Lorena, can you tell us WHAT IS THE LEGAL REGULATION POSTULATED BY THE GOVERNMENT ON THE USE OF CANNABIS IN MEXICO? WHICH ARE THE PERMITTED USES IN THE COUNTRY? Currently, Cannabis regulation in Mexico is addressing the medicinal issue. In 2017, the first law was approved, amending the General Health Law as well as the Federal Penal Code to allow the importation of derivatives of Cannabis intended for medical or therapeutic purposes and the domestic production from the seeding to the final product. Having all this production in Mexico is also possible, but only for the development of medicinal products. This law was submitted, approved, and issued in 2017, but it had to wait for regulation or guidelines for more than three years though. Recently, in January 2021, COFEPRIS and the Ministry of Health issued the regulations for this law, i.e., the rules of the game, which essentially refer to which type of licenses will be granted by COFEPRIS. Also, the basic information related to importation and domestic production can be requested. At this time, the categories of permitted products under this regulation are only two: herbal and pharmaceutical medicines. So, with this regulation, we can expect that universities, private, public institutions, or companies request these licenses to start up the medicinal use industry. There is another discussion that is taking place in both the Chamber of Deputies and the Senate about a new law that would expand the use of Cannabis that we have permitted until now, which is only medicinal. In this new law draft, it is proposed to liberate the use and production of Cannabis for recreational use. Also, the use of hemp for industrial use was declared and established. This proposal is not yet law but a draft, since it was authorized by the Senate and the Chamber of Deputies, but the approval by the Executive power, i.e., the signature of the President is needed in order to publish the law in the Official Federation Journal. Once the law is published, from that day, the government will have 180 days to implement the guidelines for the law. In the meantime, we currently work with the significantly -limited medicinal use law; we believe that the guidelines are even more restrictive than a general law since it does not include food, beverage, and cosmetics, although in a previous discussion

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it was mentioned that those products will be permitted, provided they had less than 1% of THC –the plant’s psychoactive agent– since that percentage no longer implies a risk for the health, and therefore, the goods could be free sale products. However, this was not established in the guidelines and we only have products available for sale with a medical prescription, provided the product meets the requirements, i.e., when clinical investigations support the product.

Therefore, this type of Cannabis drug product is not available in the market. I think we still need to see more participation and investment in this subject since we know that, for the pharmaceutical industry, the development of these products is costly.

So, at this time, there is no expedited, safe, or efficient access to these products for patients, who remain in the line.

On other occasions you have spoken about the compounds of the Cannabis plant, could you please tell us WHAT IS THE RELATIONSHIP BETWEEN HUMANS AND CANNABINOIDS? The compounds contained in this plant are the phytocannabinoids “Phyto” since it is a plant, but it happens that humans and mammals also produce remarkably similar compounds to phytocannabinoids, called endocannabinoids. Then, during the ‘60s, research led by Israeli physicians and scientists discovered that these two molecules are almost identical and that humans and mammals have an endocannabinoid system with specific receptors for those molecules. Thus, our relationship with the plant is much more direct and tighter than we expected. It happens that, having these receptors over our cells, the receptors call the

endocannabinoids when a cell gets swollen.

When this happens, the cell “asks for help” since these compounds whether cannabinoids or phytocannabinoids have antioxidative and neuroprotective functions hence, helping to deflate the cell.

According to your extensive knowledge WHICH IS SOME OF THE BENEFITS OF CANNABIS? After being scientifically and anecdotally proven, and with ancestral evidence, now we know that the plant has plenty of benefits for health, as well as for the environment and many other applications, still probable unknown for our society.

Basically, the Cannabis plant, marijuana, or hemp are the same plant, and the scientific term is Cannabis. Then, we have two more denominations to differentiate the psychoactive Cannabis from the

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non-psychoactive. The psychoactive Cannabis with high percentages of THC (the compound that triggers the psycho-activity) is known as marijuana, and the non-psychoactive Cannabis is called hemp since it contains a lower percentage of THC. In Mexico, the law states that a Cannabis plant with less than 1% of THC is considered hemp.

We know that these compounds help to mitigate pain and many conditions since 80% of diseases attacking humans involve cell inflammation.

From there, we can infer that the compounds of this plant fit perfectly with the receptors of our endocannabinoid system like a lock and key, reducing inflammation or avoiding many diseases that we endure as humans. The plant may not be a miracle drug, but its functions –scientifically proven– help patients with conditions such as multiple sclerosis, fibromyalgia, cancer, arthritis, anxiety, depression, pain, and many more. The huge therapeutic potential of this plant is out of the question, and only a third of the plant’s phytocannabinoids have probably been studied.

There is still a long road in researching, but this is the perfect time for Mexico. Being Cannabis’

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medicinal use legalized at the Federal level, a gate for the so-needed investigations in Mexico opens with all the potential to develop and discover new findings on the plant, our body, and our relationship with the plant.

In both, social and political, WHICH ARE THE TABOOS, PREJUDICES, OR STIGMAS THAT YOU HAVE FACED ON THE USE OF MARIJUANA FOR MEDICINAL PURPOSES? The Cannabis plant was prohibited about 101 years ago; before, it was a common-use plant. Both oils and flowers –where the cannabinoids, CBD, THC, etc. concentrate– were used for therapeutic uses, long time ago. In fact, the Cannabis plant was found in the American and Mexican Pharmacopoeias, and in the Mexican Book of Herbalism. However, when Prohibition started in the United States in the 40s–50s, the plant was removed from these books and from any scientific and investigational papers to wipe the slate clean because Cannabis started to become a threat to other several industries. The most impacted industry was the pharmaceutical, although several more were

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affected, such as the oil industry, paper, and car manufacturing since the plant also has industrial uses.

Its stem contains cellulose, a very resistant fiber that, after being transformed into raw materials can produce paper, plastic, biological fuel, construction materials, among others. Then, this plant became a threat to other industries, so aggressive lobbying took place against Cannabis, including a media campaign launched to demonize the plant. There were documentaries like Reefer Madness, where they explained that marijuana was only consumed by illegal Mexican immigrants coming to the United States and by African Americans; that the plant turned people crazy, violent, and suicidal with trends to commit sexual assault. However, these behaviors had nothing to do with the actual effect of the plant; at the end of the day, joint lobbying with the government enacted the prohibition of this ancestral plant, which always had been in contact with humanity. From there, massive stigmatization, demonizing the plant started. The United States prohibited marijuana about the same time that the DEA agency was created – very convenient, I would say. We also know that these political bodies generate substantial income for fighting drug dealers given the drug prohibition.

Many things occurred during those years that promoted the prohibition of the plant, however, they had nothing to do with the psychoactive effect. A long time ago, our families grew up under an absolute prohibition; us too, but it is recently that we are glimpsing the transition from the illegal use to the legal consumption, so it would not be fair to judge people who continue demonizing the plant because they probably grew-up under those banning circumstances. Now, it is our turn to re-educate and re-learn ourselves, and to recognize the true benefits that this plant holds for humankind and the environment.

Little by little, we are breaking those chains. Evidently, Mexico is a country with a very conservative, religious, and double-standard population, inflamed by lies about this plant broadcasted by notorious media corporations, maintain the fear on the plant. It is to note that the drug prohibition, including the Cannabis plant, and the war against drug dealers have caused more deaths than the consumption of the drug by itself.

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It is important to mention that Cannabis, being a plant, contains compounds almost identical to those produced by humans, as well as the phytocannabinoids receptors of the plant, so no death for the consumption or excess of Cannabis has been reported, there is no such thing. We often confuse things and use to hear our granny or mom saying: “here comes that pothead-drunkard neighbor of yours” or “be careful, those guys are junkies”. The truth is people who look that intoxicated or out of their minds is because they are not only on Cannabis, otherwise, their behavior would be totally different.

But we use to label everyone as a pothead although this person uses other harder drugs. Alcohol is much more harmful to the body, smoking too. Then, we still have to do a lot to share and educate.

May people have the will to learn. Information is a click away, not watching conservative TV shows that still demonize the plant. But, if we surf through scientific websites, there are numerous papers and literature, published a long time ago. Thus, I invite people to not be blurred by double standards and for whatever our relatives had instilled us in the past for we are evolving, the science never stops, and we are realizing of many things that we thought never would be real, but recently, have been scientifically proved. Unfortunately, now humans require that everything be demonstrated by science.

We even need that science tells us that fruits and vegetables are

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healthy to believe it. As humankind, I think we have lost some common sense because, we are talking about a plant, not materials transformed with external chemical components like cocaine. The last is produced from a plant, but if we chew some coca plant, the effect would not be as deadly as the one posed by the chemically processed coca powder. The danger lies there. On the other hand, the Cannabis plant is overall consumed in its natural form. If cannabinoids are to be extracted, the processes to obtain the resin would be basically natural; the resin is the only compound to be consumed with no further additions. When more ingredients are added we talk about a combination e.g., olive or coconut oil, to be administered sublingually. Mexico treasures a great knowledge in herbal remedies and combining the plant would have an even better effect on the health of persons. So, it is as simple as that, to recover our common sense recognizing that this is just a plant, do some research and stop believing what we watch in soap operas and the news. Currently, elections are coming, which means, a political clash between parties. Cannabis case is being delayed and used as a weapon to attack each other; parties favoring the use of Cannabis and others not. Well, we need to disregard this electoral war and continue advancing with a fair, inclusive regulation with a true social, environmental, and economic impact in our country for Mexicans.

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As part of your formation and involvement in the Cannabis case, you have traveled to several countries like Israel, United States, Canada, Colombia, etc., learning the positive aspects of the use and management of medicinal Cannabis. Thus, and thinking about the future of Mexico, WHAT POSITIVE ASPECTS YOU CONSIDER COULD BE REPLICATED IN MEXICO OR WHAT SHOULD BE IMPLEMENTED? Mexico, after legalizing the use of Cannabis at the federal level, would be the third country in the world to do so. There are many countries with regulations only for medicinal use, others for hemp industrial use, but countries with a full federal law for medicinal, recreational, and industrial use of Cannabis there are only three: Uruguay, Colombia, and soon, Mexico.

However, there is a significant learning curve that we observe from these countries, examining what worked and what did not.

For example, Uruguay, a relatively small country, allowed a full regulation on the use of Cannabis mainly driven by human rights and social justice. That was the true reason to legalize it, rather than an economic or business point of view. So, there was not too much fuss about it, and the huge economic impact is yet to be seen since the legalization only allowed people to have their plants at home for self-cultivation, so the consumer would not

be prosecuted, and some other minor changes. But then, you have Canada, a much larger and visible country where all uses were legalized too; however, we can see things that did not work so well, like taxation. A high taxation regime for both processes and final product discourages individuals from working illegally and transit into a legal industry since they would be not willing to pay high taxes; they rather prefer continuing their operations in the black market without contributing to the authorities and still generate the same income, or even more. This is an error not only observed in Canada but also in the United States where there is no federal law either. Instead, the government is legalizing Cannabis state by state, which happens to be extraordinarily complex since every state has its own regulations and turns to be quite different.

In such a case, a market saturation arises, leading to a significant illegal market and the transportation of materials from one state to another. We are witnesses of all these events, so, we insist that here in Mexico, the incoming law be relaxed in terms of taxation for recreational and industrial use. This task corresponds to the Chamber of Deputies and shall be discussed in the upcoming parliamentary period, starting in September. We insist on a progressive tax like those of alcohol and tobacco because many of the regulations they pretend to apply to Cannabis are similar

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to those of tobacco. If an initial extremely high tax is established, people would be discouraged to participate in the legal market where many of the so-needed taxes would be lost since increased taxation is generated from the recreational products and industrial use while taxes for medicinal products are extremely low or inexistent. It may not be possible to affirm that, whatever had worked overseas is going to work in Mexico, a complex and different country, scarred by a history of drug dealing, a narco-war, corrupted governments, and social conservativeness mindset. So, Mexico faces a challenge to implement a regulation that fits like a glove.

To conclude, WHICH ARE THE ADVANTAGES OF CONVERTING MEXICO INTO A PARADISE FOR THE RESEARCH AND DEVELOPMENT OF CANNABIS? Mexico has been one of the main producers of Cannabis around the world; and now that we are entering into the legal industry, many opportunities are open for the research and development of technologies, as well as discovering more findings on the plant and the development of Cannabis-based products. Currently, there are lots of nutrition supplements, cosmetics, food, etc.; however, products supported by formal clinical research are just a few. The FDA and MTA have approved about four, as much; in the European Union, I think there are two. Globally, the only products endorsed by clinical research, proving that they work on something specific are no more than ten. Mexico faces an awesome opportunity to develop such Cannabis clinical pharmaceutical investigation to produce this type of goods, which shall include all the relevant information about how many milligrams must be taken or to have a more established parameter to start a dosage for a specific condition. For example, among the products approved by the FDA, there is one specifically for epilepsy, one for cancer, another for pain, but imagine if we would have the ability to produce goods for 80% of the diseases suffered by humans. The above represents a huge opportunity for our country, particularly since we will have a federal regulation, something that even the United States lack of. Therefore, there is a lot of interest from companies and foreign investors to take the stake in Mexico, on our people, and the development of new technologies. Likewise, the interest is not only for medicinal use, but the industrial applications, a milestone for the country since its future looks prominent. With all this, it is not a surprise that the eyes of the world are over Mexico now.

The interview was generated by the publishing house of the Clinical Research Insider.

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“A JOURNEY TO NASHVILLE” – QUALITY OF LIFE IS SOMETIMES MORE IMPORTANT THAN LIFE ITSELF: USE OF CANNABIS AS A POTENTIAL TREATMENT FOR INTESTINAL INFLAMMATORY DISEASE

Music is a fascinating journey that undoubtedly has to be pursued. However, when attempting to describe places that you had traveled while listening to something so sui géneris, history repeats itself and becomes complex.

Dra. Ana Villaseñor-Todd Mexican scientist recognized by her research on minimal hepatic encephalopathy, oxidative stress, quality of life, and social cognition.

As a professional physician, she completed her postgraduate studies at Texas A&M University; currently, she is a candidate to receive the Medical Doctor degree by the UANL.

TECHNICAL COMMITTEE Bastán-Fabián, Daniel; GarridoTreviño, Luis Felipe; MartínezVázquez, Manuel. School of Medicine and Health Sciences – Monterrey Institute of Technology and Higher Education. Institute of Digestive Health, Clinic of Inflammatory Disease.

Once upon a summer night in the south of Athens, illuminated by the psychedelic reflex of the city lights, on the southern shore of the Cumberland river, packed rooftops with lovers of Country music enjoy at the Lower Broad; a piano duel, the smell of lavender-colored sunflowers, a couple of beers at Tootsies... Submerged into Taylor Swift’s hometown, an Elvis Presley’s building stands in the background, and just when I thought that it could not be better, the voice of a passionate, sophisticated, and quiet woman with a British accent started to sound. Her lyrics dwell on dreams and small victories, but more importantly, the redeeming power of love. The folk creator of “Something More Beautiful” is back after six years of absence, probably caused by some exacerbation of her intestinal inflammatory disease. She is Elizabeth Caroline Orton. Several years have gone by since the beginning of her career and that intricate landscape of sounds she created.

Today, I start my day with the song in a playlist capable of starting my engine’s car while playing a little prelude of synth, pianos, guitars, and distortion pedals from “I wish I never saw sunshine”. Every time I listen to Orton, I perceive her unique, intact, and consistent style. She emphasizes her potential as a composer; however, she recurrently expresses true moments of pain, that she uses to forget and heal. In the eve of #WorldIBDday, #breakthesilence and #ibdsmile, under the empathy and influence of the wonderful realm of Cortázar, I meditate on: “You could not, he said: You think too much before doing nothing. I assume that the reflection must precede the action”.

Intestinal Inflammatory Disease (IID) comprises two main conditions: Crohn’s disease (CD) and Chronic Idiopathic Ulcerative Colitis (CIUC). Both diseases commonly manifest themselves as abdominal pain and diarrhea. An important difference between these conditions is the affection topography: CD trends affecting any section of the gastrointestinal tract, while CIUC involves only the colon and rectum. The current epidemiology reports an increased incidence of IID up to 5-fold more in the last 15 years; on the other hand, in Mexico, CIUC is 4-fold more frequent than CE. In the first Latin American study of the epidemiology of IID, the current prevalence of IID, CIUC, and CD were of 1.83, 1.45, and 0.34 for every 100,000 years/person, respectively. (1)

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Throughout history, the denominated marijuana plant Cannabis sativa has been used as a symptomatic remedy for certain ailments (multiple sclerosis, chronic pain, glaucoma, epilepsy, among others), but also to perform religious rituals and as a recreational drug.

Nevertheless, several studies suggest that this plant has antiemetic, antidiarrheal, analgesic, and anti-inflammatory effects. Marijuana contains two primary components: cannabidiol (CBD) and tetrahydrocannabinol (THC); the last is the main psychoactive compound while CBD is the anti-inflammatory agent. The human body also produces two important cannabinoids denominated endocannabinoids: anandamide and N-arachidonoyl-ethanolamine. (2-6) This paper aims to explain the multiple benefits provided by the marijuana plant, as well as to clarify whether the benefits modify the disease, not only affecting the symptoms. Likewise, the non-desirable effects of marijuana are mentioned. It is to note that several studies have demonstrated that between 6.8 - 17.6% of patients that consume Cannabis, only 12.8% have discussed it with their physicians. This highlights the importance of patient-physician communication to guide their decisions and improve the long-term results.

Arguments in favor of the use of Cannabis as treatment The endocannabinoids have demonstrated to play a significant role in the regulation of inflammation and permeability of the gastrointestinal tract mucous. Two critical receptors regulate the Cannabis components’ action: CB1 and CB2. The CB1 receptor is responsible for decreasing pain perception and intestinal motility, nausea, and mitigating the secretion of digestive acid. CB2 is responsible for increasing the interleukin-10 yield, decreasing inflammation, as well as creating anti-nociception. Because of this, multiple assays have been performed attempting to demonstrate the capabilities of this plant on IID. Despite this, a clear effect on the regulation of inflammation on these diseases has not been proved, based on clinical trials properly randomized. In patients with IID, a decreased concentration of anandamide has been demonstrated, which can be supplemented with exogenous cannabinoids. (1, 2, 3, 4)

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Some studies showed an improvement in the CD symptoms perception, measured on a scale named Chron’s Disease Activity Index (CDAI).

In this study, a group of patients was supplied with a certain amount of marijuana cigars for 8 weeks, followed by a 2-weeks withdrawal period, while the other patients received a placebo. The benefits reported by patients in the marijuana arm were lost during the withdrawal period. In another study, Picardo et al. used Cannabis in an arm of patients and the placebo in other. Then, through a questionnaire, improvement of their symptoms was recorded. Most of the Cannabis arm reported an improvement in abdominal pain (83%), 74% reported relief in abdominal cramps, 48% reported improvement in arthralgias, and almost 25% reported relief in diarrhea. (1,5) In addition, studies in adolescents and young adults have been performed where improvements in the quality of life of patients with IID have been demonstrated. These studies are comprised of questionnaires where patients report the improvement of their symptoms and other aspects, such as quality of sleeping,

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appetite, mood, etc. The American Academy of Pediatrics acknowledges that the medical use of Cannabis can be an alternative for the symptomatic treatment of patients with IID, especially in terms of quality of life. (5)

Arguments against the use of Cannabis as treatment The most common adverse effects of the use of marijuana are headache, nausea, somnolence, and dizziness. Also, short-term effects can be described, such as episodic memory disorder, increased impulsiveness, disruption of the ability to make decisions, and behavioral disinhibition.

In the long-term, there could be neuropsychiatric symptoms, such as cognitive disorder and dependency, as well as fertility impairment, increased myocardial infarction, chronic bronchitis, hyperemesis by Cannabis, among others.

The mental health of patients must be assessed before allowing marijuana consumption since there can be underlying anxiety or depression

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condition which can be exacerbated or masked by its use. Furthermore, there is a relationship between schizophrenia and substance abuse, especially marijuana. However, more studies are needed to demonstrate if there is a causality.

Although it is believed that marijuana is not addictive, the chronic use of this plant can also result in addiction. (1,6,7) Several observational studies have reported benefits, but no randomized clinical trials demonstrating that these benefits were induced by the placebo or other reasons have been carried out. The use of Cannabis must not substitute the medical therapy but complement it since IID represents a disease with a high impact on the quality of life of patients. (4) In addition, there is evidence that shows that the use of Cannabis during pregnancy may result in infant cognitive alterations. The official stance of the American Association of Obstetricians and Gynecologists is that the use of Cannabis is not recommended during pregnancy; however, no reports on preterm delivery, low birth weight, or decease have been posted. Likewise, it is to note the fact that many patients opt to quit the conventional

treatment by Cannabis therapy. Nevertheless, in the long-term, this may result in an exacerbation of the IID since the anti-inflammatory effect of marijuana is not as significant as the treatment with biologicals or aminosalicylates. (2-5)

Conclusion Currently, evidence supporting the use of marijuana in the management of IID is limited; however, some studies support its consumption as an adjunct or complementary therapy for the relief of psychosomatic symptoms. The stance of several associations, such as the Crohn and Colitis Foundation states: “although marijuana may help to control the symptoms and quality of life of patients with IID, the plant has not yet demonstrated that modifies the disease behavior”. Furthermore, the Canadian Gastroenterology Association (CAG) declares that: “marijuana does not appear to alter the course of the disease, for the better or worse, based on current and available evidence, and must not replace the approved medical treatments for IID”.

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Inflammatory intestinal diseases (IID) indeed impact and disrupt severely the quality of life of patients. The use of marijuana in IID management is a controversial issue, and although current evidence suggests that the plant does not modify the natural evolution of the disease, it is important to discuss the use of marijuana within a multidisciplinary program for the potential improvement of the patient’s quality of life. In order to define the applications, doses, routes, strength, and frequency to standardize the use of marijuana in IID, more studies are needed, since this group of people, besides facing their IID every day, also have limited access to medical care, education, employment, and personal relations. The world has changed reducing mobility, social distancing and the pandemic contention procedures have increased the unsatisfied needs of patients with IID; this ought to be better demonstrated and communicated to the public in general, as well as the scientific community, healthcare providers, and decision-makers. To make up our minds not only the present situations they face but to take immediate further actions in some key issues in the IID management. Because, like Julio Cortázar says: “Probably, from all of our feelings, the only one that is not truly ours, is hope. Hope belongs to life; it is life defending itself”.

References: 1. Yamamoto-Furusho, J. K., Sarmiento-Aguilar, A., Toledo-Mauriño, J. J., Bozada-Gutiérrez, K. E., Bosques-Padilla, F. J., MartínezVázquez, M. A., Marroquín-Jiménez, V., García- Figueroa, R., Jaramillo-Buendía, C., Miranda-Cordero, R. M., Valenzuela-Pérez, J. A., Cortes-Aguilar, Y., Jacobo-Karam, J. S., Bermudez-Villegas, E. F., & EPIMEX Study Group (2019).

2. Quezada SM, Cross RK. Cannabis and Turmeric as Complementary Treatments for IBD and Other Digestive Diseases. Curr Gastroenterol Rep. 2019;21(1).

3.- Carvalho, A., Souza, G., Marqui, S., Guiguer, É., Araújo, A., & Rubira, C. et al. (2020). Cannabis and Canabidinoids on the Inflammatory Bowel Diseases: Going Beyond Misuse. International Journal Of Molecular Sciences, 21(8), 2940. doi: 10.3390/ ijms21082940 4. Incidence and prevalence of inflammatory bowel disease in Mexico from a nationwide cohort study in a period of 15 years (2000-2017). Medicine, 98(27), e16291. https://doi.org/10.1097/MD.0000000000016291 5. Kienzl, M., Storr, M., & Schicho, R. (2020). Cannabinoids and Opioids in the Treatment of Inflammatory Bowel Diseases. Clinical and translational gastroenterology, 11(1), e00120. https://doi.org/10.14309/ctg.0000000000000120 Complementary Treatments for IBD and Other Digestive Diseases. Current Gastroenterology Reports, 21(1),

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CANNABIS IN LATIN AMERICA: THE BLOOM OF AN INDUSTRY UNDER A NEW PARADIGM With the legalization of Cannabis and hemp cultivation in several countries of Latin América occurring at frantic speed, it is important to discuss the impact of this type of cultivation on the environment; currently, in other productive regions, indoor cultivation has been privileged with the elaboration of products considered as Premium, which may result in both economic and environmental high costs.

Ana Lucía González, Allegra Piaccentini, Francisco de Landero and Gerardo Garza Sustainable Development Committee – Cannabis and Hemp Mexican Board Gerardo Garza Villarreal.

Founding entrepreneur of Biodynamics Lab, a company specialized in the research and development of molecular biology applications and advanced materials. Co-inventor of an agrobiotechnology patent.

Currently developing projects for the cannabis sector.

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In some states of the US such as Colorado, it has been observed that the indoor Cannabis cultivation sector pollutes even more than the coal industry. According to greenhouse effect gas emission studies on Cannabis production, 1 kg of indoorcultivated dried Cannabis flower delivers between 2,283 and 5,184 Kg of CO2. This significant variation in numbers is directly attributed to the different power sources used in the cultivation.

It is recommended to invest in sustainable power sources to reduce the carbon footprint since CO2 discharges caused by indoor farming systems can be reduced by 42% using greenhouse systems and up to 96% implementing open-field production systems.

Reducing the carbon footprint is not the only issue to resolve in order to achieve a sustainable industry. Besides measuring and mitigating the polluting gas discharges, it is critical to maintaining the Sustainable Development Global Objectives, raised in the United Nations’ 2030 Agenda as a comprehensive reference in the plotting of the regulatory strategy for this new industry.

The transition towards a bio-economy will be the path to achieve the change of structural paradigm in Latin America and the rest of the world, needed to fulfill the Sustainable Development Global Objectives on schedule. This transition must be driven by efficient agricultural and rural development policies aimed to intelligently specialize lands.

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It is expected that the regulation of sustainable Cannabis and hemp production works as an environmental, social, and economic-change vehicle, developing replicable models that facilitate the transition for these and other types of cultivations, as well as the inclusion of productive communities that require a deep process of social structure renovation and repair of damage caused by the prohibition.

To this effect, regulations and standards must be adapted to the new market regions, considering the geographic conditions of countries near the equator, not only for the profit, but for the regulatory challenges facing the plant’s farming under enhanced ideal conditions, such as hemp cultivated in the open field that, under direct, consistent, and prolonged sunlight exposure trends to increase the levels of THC, which, in case of reducing the allowed limit of 1% in order to standardize it with other regions closer to the poles, where the allowed limit is kept at 0.3%, would cause the loss and waste of great amounts of biomass. Only in 2019, near 60% of the United States crops were classified as “hot hemp” and processed to be wasted.

We face the opportunity to design parameters adjusted to the reality of Latin America, which permit that social justice works hand in hand with sciences to fulfill a better future for the agricultural sector and the individuals involved in this industry, who participate in the share of profit, food, and environmental recovery.

Supporting references: 1 - The greenhouse gas emissions of indoor cannabis production in the United States Hailey M. Summers, Evan Sproul & Jason C. Quinn https://doi.org/10.1038/s41893-021-00691-w 2 - Bioeconomía en América Latina y el Caribe Contexto global y regional y perspectivas Adrián G. Rodríguez Andrés O. Mondaini Maureen A. Hitschfeld https://www.cepal.org/es/publicaciones/42427-bioeconomiaamerica-latina-caribe-contexto-global-regional-perspectivas 3 - Naciones Unidas Objetivos y metas de desarrollo sostenible: 17 objetivos para transformar nuestro mundo https://www.un.org/sustainabledevelopment/es/sustainabledevelopment-goals/ 4 - Economic Viability of Industrial Hemp in the United States: A Review of State Pilot Programs ers.usda.gov/webdocs/publications/95930/eib-217.pdf 5 - Dr. Ethan Russo 1% THC Limit for Hemp World-renowned neurologist and cannabis and endocannabinoid scientist explains why increasing hemp’s allowable THC content makes sense. https://www.hempgrower.com/article/dr-ethan-russo-1-is-ascientifically-defensible-thc-limit-for-hemp/

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LEGAL CANNABINOIDBASED MEDICINE IN MEXICO: CHALLENGES AND PERSPECTIVES Luis David Suárez Rodríguez, M.D. Specialist in Functional Medicine.

Graduated from UNAM with a Medical Specialty in Acupuncture and Phytotherapy and another specialty in Physiological Regulation Medicine. He is a member of the American Conference for the Advancement of Medicine and of the Mexican and Spanish Association for Ozone Therapy.

Since 2015, he has been part of the Scientific Advisory Committee of the International Scientific Committee in Ozone therapy. He has practiced functional medicine for over 12 years and has been working with medical Cannabis in his private practice for 8 years.

Since 2011, he has been a member of the International Association of Cannabinoid Medicines (IACM).

In 2018, together with other healthcare professionals, he founded the Mexican Association of Cannabinoid Medicine (AMMCann AC), a non-profit institution whose objective is the education of physicians and other healthcare professionals in the correct use of cannabinoid medicine in our country. He is currently the chair of the AMMCann AC. He is the author of several scientific articles on functional medicine and cannabinoid-based medicine, gives courses and conferences on these topics in both national and international forums.

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Since last January 12, 2021, Mexico finally has a Regulation to prescribe Cannabinoid-Based Medicine (CBM) for thousands of patients and their families that have been waiting since 2017 for the publication of these so called “game rules”; that are nothing more than a set of rules and ordinances allowing them to access, via medical prescription, to drugs made from Cannabis and some of its more than 500 pharmacologically active compounds (including cannabinoids, terpenes, terpenoids and flavonoids).

We consider that the published regulations are a valuable instrument for the development of the national CBM industry and the clinical practice of this kind of therapy, as it lays the foundation for scientific research and medical use of the plant in our country. The regulation considers the production of Cannabis in our territory and ensures the exploitation and protection of the national Cannabis species’ genomics. The regulation also allows the importation of raw material for CBM as isolated cannabinoids (including psychotropic such as Tetrahydrocannabinol, THC), molecular complexes or herbal medicines, while preventing the importation of Cannabis flower.

With these rules, national farmers / producers are protected, and the opportunity arises to detonate the development of the Mexican fields. Additionally, these regulations allow the prescription of CBM by those professionals who are already prescribers, in accordance with the General Health Law (Mexican GHL) in force, i.e. physicians, homeopaths, dentists and veterinarians. In order to prescribe CBM, the use of the existing controlled drugs formulary and classified as Group I (narcotic drugs) according to Article 226 of the GHL (available to any of the aforementioned professionals at COFEPRIS) is proposed. The preparation of master formulas using CBM is also regulated which will allow from this moment on to have safe and affordable medicines, manufactured using good manufacturing practices and, what is most important from our patients’ point of view, available for immediate prescription.

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The regulation is not, however, free of problems. For example, it does not differentiate psychotropic cannabinoids such as THC from non-psychotropic like CBD and CBG, or from the acidic forms of these (THCA, CBDA, CBGA) that also lack psychotropic activity and that, in addition, as is the specific case of CBD, have very promising therapeutic properties; a reclassification would allow this compounds to be used in the cosmetic industry and would also exempt them from being prescribed through the narcotics formulary, which in turn would make it more accessible for a greater number of patients. To be fair, the issue of cannabinoids’ reclassification is not in the scope of CBM regulations since it derives from the GHL current wording, specifically Articles 234 and 245. The opportunity to modify such articles is a power of the Legislative, who could modify the GHL while the General Cannabis Law is issued (whose controversial verdict was approved by the lower chamber representatives on March 8, the ratification or subsequent amendment corresponds to the Senate) in order to recognize the wide nature of cannabinoids, among which Δ8, Δ9 THC, CBN, and Δ9 THCV are the main psychotropics, and others like CBD, CBG, CBC, CBDV and non-decarboxylated acid forms like THCA, CBNA, THCVA, CBDA do not have a psychotropic effect and thus should not be considered narcotics. This reclassification is in line with the recommendation of the UN INCB, distinguishing between non-psychotropic Cannabis (better known as hemp, cultivated for the fiber to make textiles, among many other uses, and rich in CBD) and psychotropic Cannabis (which has been illegally cultivated to provide the highest possible effects, high in THC).

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The published regulations do not allow the preparation of herbal remedies with Cannabis plant, requiring that such be registered instead as herbal medicines. Although this angle of the regulation is one of the most controversial in the public eye, our position is in favor of herbal medicines and against herbal remedies. The difference is significant: an herbal remedy can be labeled in such a way that the precise content of the active ingredients is not clearly specified, it is only enough to indicate the common names of the plants the remedy contains. As opposed to this, in an herbal medicine the concentration of the active ingredient must be precisely labeled. Especially in the case of CBM, it is neither desirable nor safe to ignore the contents of the active ingredients in the product, precisely because there are some cannabinoids psychotropic with potentially harmful effects for the patients.

In the CBM, as with any other medicine or product intended for human use, we must demand traceability from the seed to the finished product, where each step is according good agricultural practices, which are the good manufacturing practices to elaborate herbal medicines and also with analytical controls to demonstrate the cleanliness and safeness of the medicine as to its level of microorganisms, absence of pesticides or herbicides, absence of heavy metals and other contaminants commonly found in Cannabis flowers. This represents a major challenge for the new CBM industry in Mexico, which must invest a substantial amount of financial and human resources to comply with these regulations. We believe this is the greatest challenge facing this

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nascent: the injection of resources to produce CBM must equal the investment to finance controlled, randomized, blind clinical trials, with the greatest number of participants; controlled clinical trials contributing to raise the quality of clinical evidence for the use of CBM in various pathologies; if we thoroughly analyze the evidence, it is not conclusive to recommend the use of CBM in many clinical contexts, where patients and physicians expect to see a positive effect of including these drugs in the clinical equation. The research cannot be ignored: critical steps cannot be overlooked if we aim to determine the efficacy and safety of these products for the Mexican population, with its genetic and geographic peculiarities that differentiate how we metabolize cannabinoids (or any other drug).

It would be unfortunate to repeat in Mexico the scenarios of Canada and Uruguay, where upon regulating the adult use of Cannabis, companies have focused their economic resources towards the production of CBM and have left forgotten to accompany such productive effort with a greater investment in high-quality clinical research, disguising the old pharmaceutical marketing model as “training” for healthcare professionals. Therefore, education becomes more of a talent recruitment for an industry that requires the medical profession to ensure the marketing of its products.

This leads us to another similar challenge for the new CBM industry in Mexico: ensuring that the training of healthcare professionals

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includes the endocannabinoid system, which as to date is not part of the health sciences curriculum; this training needs to be both academically and scientifically sound, as well as ethical and humanistic, in a relevant way for a country like Mexico, this meaning it should be free and available to most interested physicians and healthcare professionals.

In addition, it is necessary to invest considerable material and human resources in educating the Mexican society on the uses and limitations of Cannabis, both in the medicinal context and for adult use, since the stigma and misinformation still influence many of the opinions about the plant, and poorly informed society makes bad decisions.

It is our responsibility as physicians to demand from the Cannabis industry the level of safety and efficacy that we would demand from any other pharmaceutical industry, as well as sufficient investment in research to match the projected astronomical profits from the use of these products. As physicians, we are facing an invaluable opportunity to contribute to the education of our patients and their families with accurate, updated, and contextualized information on the use of this wonderful plant in the clinical context, and so contribute to destigmatize its adult use. Hopefully, we will know how to take advantage of it.

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MORPHOLOGY AND PHYSIOLOGY BETWEEN SUBSPECIES AND SEXES OF CANNABIS PROMOTION AND DEVELOPMENT OF EDUCATION, RESEARCH, AND DISSEMINATION OF THE MEDICAL APPLICATIONS OF CANNABIS CANNABIS IS A MONOTYPIC GENUS PLANT THAT HAS THREE SUBSPECIES, ALTHOUGH NOWADAYS THERE IS MORE TALKING OF HYBRIDIZATION IN THE GENUS AND HERMAPHRODITISM IN THE SEX. THUS, IT IS IMPORTANT TO MAKE BOTH MORPHOLOGICAL AND PHYSIOLOGICAL DISTINCTIONS BETWEEN SUBSPECIES, AS WELL AS A MORPHOLOGICAL DIFFERENTIATION BETWEEN THE SEXES. LA CANNABIS, UNA PLANTA DE GÉNERO MONOTÍPICO CON TRES SUBESPECIES, AUNQUE HOY EN DÍA SE HABLA MÁS DE HIBRIDACIÓN EN EL GÉNERO Y HERMAFRODITISMO EN EL SEXO. POR ELLO, ES IMPORTANTE RECONOCER LAS DIFERENCIAS TANTO MORFOLÓGICAS COMO FISIOLÓGICAS ENTRE LAS SUBESPECIES, ASÍ COMO LA DIFERENCIACIÓN MORFOLÓGICA ENTRE LOS SEXOS.

Dr. Raúl Porras

Pro Secretary of the Consejo Mexicano de Cannabis y Cáñamo.

Medical Surgeon, PhD in Biomedical Sciences at the Instituto Nacional de Enfermedades Respiratorias (INER).

Certified in Cannabis medicine; he applies his knowledge advising patients under cannabis treatment.

Member of the International Association of Cannabinoid Medicine (IACM). Founder and president of Cannapeutas A.C. Social service:

Izaizel Libertad Cruz y Alejandra Nayeli De Olarte

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Cannabis is considered as a monotypic genus plant part of the Cannabaceae family.

This meaning that there is only one species in the genus, although it is commonly spoken of three: indica, sativa and ruderalis. These are actually subspecies, but each one has unique characteristics. Being in fact the same species, they can be easily crossbred, thus resulting in uncountable hybrids with a greater or lesser genetic similarity to one or the other, that is why is very odd to find pure indica or sativa genetics, since most of the existing varieties are hybrids of the two subspecies that have mixed over the years, these are commonly and commercially know as strains.

Additionally, indica and sativa are the most chosen varieties, since ruderalis is low in THC, but thanks to its shorter cycle it integrates auto-flowering varieties in a certain percentage (we will discuss this in another publication). Therefore, the two most popular subspecies are indica and sativa. Their main characteristics are mentioned below.

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Figura 1 y 2. Cannabis sativa in the vegetative stage, its long and thin leaves can be observed from the early stage as a seedling (left side photo).

SIZE

Because sativa is native to tropical areas, the plants are taller and tend to grow more, making them ideal for outdoor growing; while indica plants are small and shrubby, more suitable for indoors.

LEAVES

ORIGIN

a) The leaves of sativa plants are characterized for being longer and thinner. They usually have 7 to 9 leaflets (subdivisions of a leaf) (see Fig. 3).

Indica varieties come from the Central Asian and Indian subcontinent (Pakistan, Afghanistan, India, Tibet, Nepal, etc.) regions, due to its mountainous origin they are more resistant to low temperatures and extreme conditions.

Sativa, meanwhile, is typical of tropical climates such as Thailand, South India, Jamaica, or Mexico (McPartland, 2017).

b) The leaves of the indica plants are characterized for being shorter, narrower, and having 5 leaflets. (see Fig. 4).

The rudelaris species is little known, its origin goes back to Siberia and Kazakhstan; scarce light intensity in these areas made the plant adapt to its environment and to not depend on light exposure for flowering, thus making it extremely interesting for indoor growers who do not have sufficient hours of natural light; It is small and with few branches, its effect is usually more of intoxication.

Sativa is mainly characterized for its great height, long branches and nodes clearly separated one from the other, a widely extended root system and big and thin leaves; it usually produces an energetic, fast, and euphoric effect (see Fig. 1 and 2). On the other hand, indica is small, short, and compact, its root system is compact as well, is has robust stems with wide dark green leaves as well as dense and heavy flowers that produce a physically relaxing powerful narcotic effect, it is commonly used for medicinal purposes.

Figure 1

Figure 2

Figure 3 C. sativa, the thin leaves can be observed.

Figure 4 C. indica leaf with 5 leaflets.

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GROWTH

SEX-DEPENDENT DIFFERENCES

1. Indica tends to grow in clusters around the branches and stem nodes. Plants are more branched with thicker stems.

Cannabis plants are characterized for being dioecious, this meaning that there are female and male plants in different specimens. For this reason, you need to unequivocally identify the sex of the plants, if you are interested in smoking the flowers (marijuana) you must identify the female individuals and get rid of the males to avoid pollination, so female plants canalize all their energy on cannabinoid generation and not seed production.

2. Sativa distributes its growth over the branches, with longer internodal spaces and fewer branches.

FLOWERING 1. Indica is more robust and compact, with heavier and more compact buds.

2. Sativa, meanwhile, tends to have larger buds.

HARVEST 1. Indica plants are used to less time of optimal light and heat conditions and thus, they present a faster flowering of about 45 to 60 days (6-8 weeks).

2. ) Sativa plants, usually needing a stable warm temperature and around 12 hours of light per day year-round take longer to complete flowering: between 60 and 90 days (10-16 weeks).

EFFECTS Indica contains more CBD and less THC than sativa, hence indica is more used in medical treatments without significant psychoactive effects. These species can cause relaxation and alter the senses, more specifically: touch, hearing, and taste. At high doses they have direct somniferous, sedative, and relaxant effects; additionally, they can relieve pain, reduce stress and anxiety with a completely physical effect (McPartland, 2017). Sativa variety produces a “getting high” sensation with a more energetic, euphoric, and creative effect, enhances concentration, helps fighting depression, and stimulates appetite; it also has a more mental-cerebral effect.

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SEX-DEPENDENT MORPHOLOGICAL IDENTIFICATION:

MALE When male plants reveal their sex, they show a cluster of little spheres at the base of the lateral branches called pollen sacs, when these open, they release the pollen responsible for fertilizing the female plants. Thus, when you see a male plant you need to remove it immediately before fertilization occurs (see Fig. 5).

FEMALE The protagonists for a good “high” are female plants, for they produce the flowers known as “buds” and it is there where the plant concentrates its THC production.

To identify female plants, you need to identify some small calyces from which some white hairs will protrude, these are the style (a prolongation of the plant’s ovary) and the stigma, both are part of the gynoecium commonly known as “pistil”.

Their function is to capture pollen (stigma) and to be the conduit (style) through which pollen reaches the plant’s ovules (see Fig. 6).

Avoiding your plants pollination is important because if the pistil comes into contact with pollen, the calyx will become the ovary and it will devote its energy to produce fruits (dried, inedible) and subsequently seeds, instead of buds.

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The spontaneous development of hermaphroditic inflorescences (pistillate flowers containing anthers) on female plants during commercial farming of marijuana creates a problem for growers as the resulting seed formation reduces the quality of the harvested flower (Small, 2017).

Also, female plant’s resource allocation to pollen production, followed by seed production, can result in disproportionately lower levels of terpenes and essential oils (up to 56%) in pollinated flowers compared to unfertilized female flower (Punja and Holmes, 2020).

Flowers: Figure 5 Male plant, pollen sacs can be observed under the leaves.

Pistillate flowers are accompanied by anther formation, leading to the formation of unwanted seeds. In the young terminal inflorescences papillae are developed (stigmatic hairs).

Inflorescence development: It converts into many anthers’ clusters. In mature inflorescences, it originates from a central nucleus.

Mature inflorescence: Individual anthers produced in hermaphroditic inflorescences.

Consists of an outer wall (epidermis and endothecium) with a sulcus (stomium) that expands when mature and opens to release pollen grains. Trichomes develop along the anthers’ stomium.

Figure 6 Female plant, the style (white threads) can be observed in the apical part, the gynoecium is found below it.

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HERMAPHRODITES Harvest: it has collapsed stigmas and swollen carpels; it also presents pollen grains.

TRICHOMES Trichomes are extensions of the plant epidermis that have several functions such as absorbing water, regulating temperature, protecting against the sun and predators; Cannabis has special glandular trichomes that secrete resins (sticky compounds) that uses to trap insects or substances that irritate them. They are mainly found in the inflorescences and it is right inside them where the most cannabinoids and terpenes are stored. (MatillaPlant, 2019) (see Fig. 7, 8 y 9).

Through the trichomes we can determine the point of maturity of the plant and so find out when it is best to harvest, depending on the personal interest; trichomes go through four color changes that allow us to know their maturation status, whitish trichomes are the most desirable.

(MatillaPlant, 2019).

Transparent trichomes show us that cannabinoid biosynthesis has started and that the plant is not ready to be harvested yet. They look whitish when they have reached the maximum level of cannabinoid, specifically THC (Δ 9- tetrahydrocannabinol); at this precise moment it will provide the maximum psychoactive effects; this of course, only after being dried and “cured”. The amber colored trichomes reach maturity but can only be collected when there are about 10-20% mature; at that moment there is a mixed cannabinoid effect. When it shows a amber / brown color, it is said that the harvest time has passed, since the levels of THC (Δ 9-tetrahydrocannabinol) and CBD (cannabidiol) have greatly decreased; however, other cannabinoids such as CBN (cannabinol) increase, thus offering a more narcotic herb with a relaxing effect (MatillaPlant, 2019).

Figures 7 / 8 / 9 Indoor cultivation plants, hybrids, predominantly sativa, female, in flowering stage, many glandular trichomes can be observed in the apical leaves.

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CHEMICAL COMPOSITION AND PHYSIOLOGY Overall, plants produce two types of metabolites: primary, which are essential for survival, and secondary, which are synthesized by plants for the ecological interaction between the plant and its environment. They are classified into three groups, depending on their biosynthetic origin: terpenes (derived from the IPP compound (Isopentenyl diphosphate or “5-carbon isopentenyl diphosphate”)), phenolic compounds and their derivatives (synthesized by the shikimic acid route or by the malonate / acetate), and alkaloid or nitrogenous compounds (synthesized from amino acids) (Croteau, R., et al, 2000). Furthermore, many of these metabolites have a very restricted distribution, to only a single species or group, such is the case of cannabinoids that can only be found in our favorite plant, Cannabis.

Cannabis has around 500 secondary metabolites derived from different biosynthesis, among which: cannabinoids, terpenes, flavonoids, alkaloids, stilbenes, phenolic amicides and lignanamides (Ángeles López et al., 2014). All of them have important roles for the plant, and we have been able to make the most out of them.

The terpenes in Cannabis are hydrocarbons that differ from complex terpenes by having more diversity of TPS (terpene synthase) enzymes, this provides them greater variety of monoterpenes to synthesize, which gives our plant certain characteristics, like the smell, that helps characterizing our strains; Monoterpenes such as myrcene and sesquiterpenes β-caryophyllene and α-humulene appear to be present in most cannabis “strains”, some others like α-pinene, limonene and linalool, as well as the sesquiterpenes bisabolol and (E) -β -farnesene are responsible for the characteristic smell of each “strain”: Lemon Skunk or Purple Kush, among others (Nikfar and Behboudi, 2014; Booth and Bohlmann, 2019).

Cannabinoids have been extensively studied due to its great biomedical importance. There are about 70 cannabinoids

known, D9-THC-a, CBD-a, CBN-a stand out; followed by CBG-a, CBC-a, CBND-a and other compounds in smaller quantities. The “a” at the end, means “acidity”, after decarboxylation it will reach its final form as THC, CBD, CBN, CBG, CBC, and CBND. These are crucial because of their interaction with the endocannabinoid system (discussed later); besides, when synthesized by terpene route, they generally concentrate in the resins produced in trichomes.

Their psychotropic effect is also documented, but we will discuss this in further publications (Flores Sánchez and Verpoorte, 2008; Ángeles López et al, 2014).

Flavonoids are aromatic compounds mainly found in leaves, some of them, like canflavin A and B, have shown pharmacological activity inhibiting the production of prostaglandin E, while other studies suggest they regulate the action of cannabinoids (Ángeles López et al, 2014).

Other chemical components such as alkaloids are mainly found, although to a lesser extent, in roots, stems, leaves, pollen and / or seeds, but due to their low concentrations they have not been evaluated for ther pharmacological activity. The stilbenes lignanamides and phenolic amides work together as defense mechanisms; antibactericide, antifungal, anti-inflammatory and neuroprotective properties, among others, have also been attributed to them. Lastly, different lignanamides and phenolic amides with cytotoxic, anti-inflammatory, antineoplastic and analgesic activity have been identified (Ángeles López et al, 2014).

Finally, we would like to emphasize that Cannabis is a exceptional and medically important plant due to its botanical and chemical characteristics for it produces a unique metabolite very useful against several diseases; knowing more about Cannabis could be helpful, since it is of great interest not only for adult recreational purposes use but also for medical uses; therefore, its regulation should be of benefit for most of population.

References: 1 - The greenhouse gas emissions of indoor cannabis production in the United States. Hailey M. Summers, Evan Sproul & Jason C. Quinn https://doi.org/10.1038/s41893-021-00691-w 2 - Bioeconomía en América Latina y el Caribe Contexto global y regional y perspectivas. Adrián G. Rodríguez Andrés O. Mondaini Maureen A. Hitschfeld https://www.cepal.org/es/publicaciones/42427-bioeconomia-america-latina-caribe-contexto-global-regional-perspectivas 3 - Naciones Unidas. Objetivos y metas de desarrollo sostenible: 17 objetivos para transformar nuestro mundo https://www.un.org/sustainabledevelopment/es/sustainable-development-goals/ 4 - Economic Viability of Industrial Hemp in the United States: A Review of State Pilot Programsers.usda.gov/webdocs/publications/95930/eib-217.pdf 5 - Dr. Ethan Russo 1% THC Limit for Hemp World-renowned neurologist and cannabis and endocannabinoid scientist explains why increasing hemp’s allowable THC content makes sense. https://www.hempgrower.com/article/dr-ethan-russo-1-is-a-scientifically-defensible-thc-limit-for-hemp/

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CANNABIS, THE CONTROVERSY UPDATED Guillermo Caletti, MD, PhD. Chief of Clinical Operations at Boehringer Ingelheim for Mexico and Central America.

It is interesting reading the great number of publications related to the use of Cannabis as a medicinal and recreational product and the worldwide controversy for the authorization, and regulation for its medicinal and recreational use.

The history of Cannabis in Mexico is at least 5 centuries old, beginning with the introduction of hemp upon the arrival of Spaniards in the 16th century. Since then, hemp has had a continuous presence in Mexican society, economy, and national culture, either in the form of hemp products, as medicine for traditional use, and/or as a psychoactive substance. However, hemp had not been considered an unhealthy product until the 20th century, particularly during the ‘80s, when, due to pressure from the United States, the Mexican government was forced to start a fight against the Cannabis business, along with the illegal trade of cocaine from Colombia, increasing the levels of corruption within the government institutions, as well as the rise of organized crime and violence, linked to these unlawful businesses.

Nevertheless, this national reaction had nothing to do with local problems of diseases related to the use of Cannabis, but rather to the Cannabis’ illegal trade in the United States and the flight of capital that this market represents. It should be noted that, according to the 2011 Annual Report of the United Nations Office on Drugs and Crime (UNODC), the United States has the highest annual consumption of marijuana (13.7%), while in Mexico, the consumption is barely 1%, only higher than in Ecuador (0.7%) and the Dominican Republic (0.3%). So, whose problem it is?

From a health perspective, is marijuana a harmful substance? When a person learns that a relative or friend is consuming any type of drug,

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one of the major concerns is the risk of a fatal overdose. However, it has been discussed that marijuana overdose may not be possible because of all the factors involved for it to be experienced and still be fatal.

The scientists have demonstrated that, in order to enter a state of overdose, an individual requires at least 750 kg of marijuana. And there is more, that amount must be present in the body for 15 minutes. So, is it possible to smoke that amount of drug in such a short time?

To prove this risk, scientists decided to overdose animals. They provided an amount equivalent to 40,000 marijuana cigars; still, none of the animals died. Therefore, the risk of death for marijuana overdose is marginal.

Now, a consumer may never experience an overdose, however, there are long-term effects that would compromise his/her health if marijuana is consumed for a prolonged period and in high doses.

RESPIRATORY PROBLEMS Lungs are damaged when a person smokes, therefore, if this activity is done regularly for a long period, the potential risk of pulmonary irritation due to marijuana smoke is to be considered since the consumer would suffer the same consequences as those who smoke tobacco.

Chronic cough and some of the most common lung diseases, such as Chronic Obstructive Pulmonary Disease (COPD) and the increased risk of infections are the most frequent conditions suffered from users. However, there is no evidence of lung cancer in Cannabis consumers.

ACCELERATED HEART RATE Cannabis consumption accelerates the heartbeat, increasing the workload of the cardiac muscle. At least, four hours must pass for the heart rate to normalize after smoking marijuana. This is a feared effect since it can provoke a heart attack under specific conditions of physical or mental stress, hence, marijuana could be a secondary cause of death.

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AGGRESSIVENESS DUE TO CANNABIS CONSUMPTION There is no scientific evidence proving that Cannabis consumption increases aggressiveness in people. Many of us already knew it. It is as simple as attending a reunion with friends who consume Cannabis. They may have laughing attacks, reciting deep reflections that they may never do being sober, then got hungry or lethargic due to the Cannabis secondary effects, but we will never see them in an aggressive posture. Recently, for the most skeptical, this was scientifically proved.

Using a validated test of aggression behavior in response to provocation, subjective aggression increased significantly after drinking alcohol and decreased after ingesting Cannabis. The study performed at the Maastricht University, The Netherlands, included heavy alcohol users (n = 20), Cannabis regular consumers (n = 21), and controls (n = 20). Alcohol and Cannabis users received single doses of alcohol and placebo, or Cannabis and placebo, respectively. Then, the grade of aggressiveness was measured and tested.

Aggressive feelings increased significantly after provocation in all arms while being sober. Alcohol consumption increased subjective aggression while Cannabis decreased it post-provocation. Aggressive responses during PSAP (point-subtraction aggression paradigm) increased after alcohol consumption and decreased after consuming Cannabis compared to placebo. The authors concluded that “alcohol stimulates aggressive feelings while Cannabis decreases them in heavy alcohol users and regular Cannabis consumers, respectively”.

So, if Cannabis causes neither health, physical nor mental issues, why its legalization is taking so long?

The main discussion of the drug legalization promoters in Mexico, including Cannabis lies in the assumption of a decreased violence, not explaining the issue of increased consumption though, especially among young people under 18 years old, who would be trapped in the black-market mafias that provide the consumer groups that exist with or without legalization.

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What should we do to solve the issue without failing in the radicalization of stances?

The answer, as for many controversial topics, is researching.

The good news is that on January 12, 2021, the Official Federation Journal published the “Ministry of Health Regulation in terms of the sanitary control for the production, research and medicinal use of Cannabis and its pharmacological derivatives”, allowing the legal cultivation of Cannabis to provide material for the relevant research programs, but not for commercial purposes. Only physicians would be able to prescribe Cannabis drug products through a unique recipe book with code bars. Also, only pharmacies will be able to market these products, provided they have the relevant COFEPRIS authorization.

This is a huge advancement in the recognition of the use of Cannabis in Mexico that will benefit from the outcome of the researches, as well as from the legally available Cannabis products in the international market.

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THE CREATIVE AND INVENTIVE BOOM OF CANNABIS The intellectual property, established within the group of economic, social, and cultural rights, or 2nd. generation human rights, safeguard the creative and inventive expression of the human being, granting privileges and rights of exclusive use, operation, disclosure, transfer, etc., to authors, artists, inventors, and improvement enhancers. The protection covers the rights related to artwork, distinctive signs, new creations, and even vegetable varieties.

Enrique U. Alcázar Treasurer of the Consejo Mexicano de Cannabis y Cáñamo.

Entrepreneur, leader and reference in franchise structuring, business acceleration and high impact incubation. Promoter of culture, defense and protection of intellectual property. Founder of Project 72 and Alcázar y Compañía.

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In terms of Cannabis, we are facing the regulation of the plant for multiple uses, such as medical, recreational, industrial, and some others.

Likewise, the social, political, economic, sanitary, and cross-cutting impact on different sectors has been on the public agenda for some years ago.

Although little discussed, the correlation and deep bonding between intellectual property and Cannabis development in all its potentialities are not surprising.

In Mexico we are at the gates and opening of a myriad of possibilities for the use and operation of the Cannabis species, expecting a systematic and regulated standardized framework, but also, prevailing the common good, safety, and liberties of the consumer or user. Besides motivating a healthy competition, the new legislation eradicates abusive, unfaithful, and deceiving practices under a legal framework of warranties for the stakeholders, which will only be possible with clear rules and even opportunities for the private sectors that produce, manufacture, and provide services. Also, the bond between these sectors and the health authorities must be comprehensive, as well as the understanding and acceptance of the value and impact of the intellectual property of this

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What is the value of Cannabis? In recent years we have been immersed in a new digital and technological revolution, where the value of companies, services, and consumer goods is originated, integrated, and based on creativity, originality, design, technology, and innovation while the production activities are relegated to the background. Whoever controls the trade channels owns the market, so for footwear and textile products, the site of manufacture is irrelevant for the consumer, who chooses the product by design and brand. Compared to agricultural products, the trade chain or the transformation process is more important. Do you know who produces the coffee that you drink in your favorite coffee shop, or where is the manufacturing site?

origin, as well as the natural and cultural factors involved in the creation of the good. In Mexico there are 18 designations of origin, being Tequila the most renowned of them, although more beverages are being included such as Mezcal, Sotol, Bacanora, Raicilla, Charanda, or food like Morelos’ rice, Veracruz and Chiapas’ coffee, Papantla’s vanilla, Mango Ataulfo, Grijalva’s cocoa, Yahualica’s pepper, and the notorious Yucatan’s Chile Habanero; and even handcraft like Talavera porcelain, Olinalá’s woodcraft, and Chiapas’ amber. So, we are convinced that, in the case of Cannabis, soon we will have our designations of origin. This provision is protected under the Lisbon Agreement, where Mexico, along with other 30 countries, is a member. However, for non-member countries, the protection is extended through a geographical indications program, included in most of the international treaties.

The claiming of certain products and production processes is through the declaration of designation of origin, which bonds the product to a specific geographic area from which it originates, provided the quality, characteristics, or reputation are due to exclusively and essentially the raw materials and production processes natives of the geographic

Recently, I have found several studies, treaties, articles, presentations, conferences, and more about Cannabis, some more substantial and formal than others. Suddenly, lots of experts, cartoons, videos, methods, farming, and watering processes, and more have flourished, all of them protected under copyright, e.g., primal, derived, collaborative or on-

whole new cultivation, and the implementation of better compliance practices and policies.

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demand works. The bottom line is to identify and respect the rights that imply both moral and property values for their authors. Even the last amendment to the Federal Law of Copyright includes effective and protective technological measures, as well as information on the management of rights on the Internet and digital platforms in order to enforce such rights.

Another relevant role in the Cannabis market is the vegetable varieties and the rights of their holders for their exclusive or temporary use by themselves or third parties without their consent. A vegetal variety is a species’ subdivision with similar characteristics from its parents, and both stable and homogeneous. The vegetal variety, dissemination material, production, re-processing, distribution, marketing, as well as the production of other varieties and hybrids for commercial purposes are critical, therefore in terms of Cannabis, the relevant characters, phenotype, and genotype expressions (as the case of three plant species, Cannabis sativa, C. indica y C. ruderalis), have origins, applications, effects, and even different farming methods. Based on different methods, new stables varieties have been and will be developed.

The seed origin, plant traceability, and cultivation method will also be critical not only for the producer in terms of industrial or commercial issues, but for backyard planting, Cannabis clubs, or self-cultivators, who also demand safety, transparency, and knowledge on the origin of the product that cultivate and eventually consume. Mexico has a great potential to develop new

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vegetal varieties and become an exporting leader of seeds, plants, and manufactured products.

One of the most important issues are the medical and therapeutic applications of the Cannabis, derived from the cannabinoids, being the most renowned the THC and CBD because of their applications and effects; however, there are six more of them with different effects and applications, some less studied though: CBC, CBG, CBN, CBDa, THCa, and THCv. There are research and development protocols that assess new molecules and active substances with the ability to develop drug products with different indications, and under the provision of an invention patent, these products can be protected and marketed within the pharmaceutical industry.

In addition to drug products, greenhouses, watering and farming technologies, the transformation processes, equipment, instrumental, devices and other apparatus, provided they are new, resulting from the inventive activity and subject to industrial applications, could be deemed as inventions or innovations, protected, and marketed as patents or models of utility.

Packaging, trade channels, establishments, drug stores, coffee shops, clinics, spas, medicines, supplements, collection and processing centers, food (human and animal), goods, snacks, accessories, and memorabilia related to Cannabis, all of them shall comply with the required regulation, but also all these brands shall distinguish themselves from each other, conveying their

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values, characteristics, and essence, and interacting with their market target.

This can only be achieved through the proper protection of their brands, slogans, corporate image, and all those elements that allow identify and distinguish the products and services from each other, including all the nonevident information which will pose economic and competitive advantages in terms of confidentiality, property, priority, and privileges, protected under the industrial secrecy.

It is evident that intellectual property impacts essentially all our business, industrial, production, and daily activities. With the opening of the Cannabis sector, there will be a boom of creative and inventive options; however, the winners will be only those with the vision to protect their intellectual and intangible assets.

In the beginning, or even before, we would see the rising of products, business opportunities, investments, etc., not all of them legitimate, formal, or serious though. It is required to respect and guarantee the consumer’s safety and liberty

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as well as the healthy competition, and the intellectual property rights involved. So, we would be witness, players or co-creators of a new pushing sector into the economy, with the potential described above, and even more.

Overall, regulations are imperfect but necessary. A starting point is required to evaluate and test the sector development and performance and increasingly improving the opportunities areas. Bodies like the Mexican Board of Cannabis and Hemp must be facilitators between the agricultural and business sector, and the authorities, seeking to establish better practices.

The different players that participate in the chain of valor, from the producer to the user, including laboratories, industry, traders, distributors, services providers, companies, and authorities must observe the sector’s safety, legality, traceability, and formality to avoid practices that undermine the free competition, compromise the safety and warranties of the user, and represent a risk for the public health.

Thus, the recognition, respect, protection, and defense of intellectual property rights will be critical in the rise of this high-impact booming industry, outlining differentiators and innovative and original elements.

Derived from the R&D and entrepreneurship, we are to witness a creative and inventive surge of technological products and services, commercial channels, and layouts, immersed in a market where many would like to participate; however, only those prepared, advised, and properly related shall succeed.

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TETRAHIDROCANNABINOL (THC), GENETIC VARIABILITY AND VARIABILITY IN PHARMACOLOGICAL RESPONSE The most frequent drug of consumption in the world is marijuana, with a 3.8% prevalence (around 183 million people), followed by amphetamines and amphetamine-type stimulants(1).

In Mexico, there is an estimated 14.0% of men and 3.7% of women who uses it; Additionally, it is the drug with the highest increase in consumption, both in men and women. The risk perception of marijuana use is involved in this growth, it has fallen below 40%, while in other substances such as cocaine or inhalants it reaches values above 62%(2).

Javier Esquivel Vargas, Diana Vega Perea, Darío Morales Martínez, Miriam Morales Mtz., Alberto García González, Alionka Citlali P. Ángeles Grupo Phi Innovación y Desarrollo Científico, S.A.P.I. de C.V.

Cannabis is a plant native to Mongolia and southern Siberia. America’s first contact with it was through Christopher Columbus, who transported in his boats an estimated 80 tons of sails and ropes made of hemp. Later, during the conquest period (~ 1521), Hernán Cortés imported several plants from Europe and Asia, including C. sativa and C. indica, to boost the economy of New Spain(3).

The Cannabis Sativa plant belongs to the Cannabaceae family (4), it is composed for more than 545 substances (5) from 18 types of chemical compounds (4), where at least 120 phytocannabinoids have been identified (6).

Phytocannabinoids can be divided into 11 classes, depending on their chemical structure: cannabigerol, (-) - 19-tetrahydrocannabinol, cannabidiol, cannabichromene, cannabinol, (-) - 18 tetrahydrocannabinol, cannabicyclol, cannabinodiol, cannabielsoin, cannabitriol and miscellaneous (7). Most of the biological properties of cannabinoids lie in their interaction with the human endocannabinoid system. This system includes two G protein coupled to cannabinoid receptors, CB1 and CB2, as well as two endogenous ligands, anandamide and 2-arachidonylglycerol (8).

Among cannabinoids, Δ9-Tetrahydrocannabinol (THC) has the highest psychoactive strenght(9). It has shown analgesic, immunosuppressive and muscle relaxant, antiinflammatory, appetite modulator, antidepressant, antiemetic, bronchodilator, neuroleptic, antineoplastic and antiallergen effects (10); however, it has also been associated with some side effects, including anxiety, cholinergic deficit, severe immunosuppression, hallucinations, paranoia, and tachycardia. These adverse effects have been commonly associated with car accidents, work injuries, and hospitalizations (11).

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The primary metabolic pathway for THC involves cytochrome CYP2C9. THC hydroxylates to its active form (OH-THC) still with significant psychoactive activity, it is later oxidized by CYP2C9 to its acidic carboxylic form (COOH-THC), which is pharmacologically inactive (11).

Cytochromes P450 (CYP 450) constitute a family of hemoproteins found in organisms from all biological kingdoms, from bacteria to mammals.

In humans, 18 families and 48 subfamilies of CYP450 have been described, encoded by 57 genes expressed in different organs and tissues.

In the nomenclature of these cytochromes, the number followed by CYP designates the family, the letter the subfamily and the number the gene (CYP1A1, CYP2E1) (12).

Families 1, 2 and 3 include the enzymes responsible for biotransforming xenobiotics. Only CYP1A, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4 and CYP3A5 metabolize 90% of the drugs for human use (12).

CYP2C9 is one of the most abundant enzymes in the adult human liver, it metabolizes a significant number of drugs: cannabinoids, antibiotics, anticancer, antidiabetic, antiepileptic, antihypertensive, among others (13); this corresponds to 10 %-20% of the commonly prescribed drugs (14). To date, 42 alleles have been identified in the CYP2C9 gene (13).

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Polymorphisms with reduced activity increase the risk of toxicity and side effects (15). The CYP2C9 * 2 variant is the most prevalent and has been suggested to affect the P450 interaction between the enzyme and P450 reductase; this could explain the slow metabolism of some CYP2C9 substrates (13) (enzyme activity of 12% compared to the wild variant) (16).

Genetic epidemiology trials have shown that 15-20% of the population has the CYP2C9 * 3 allele. This gene variant results in a much slower communication of THC with its non-psychoactive form compared to the “normal” CYP2C9 * 1 allele’s variant. Therefore, individuals with * 3 allele can accumulate THC levels 200-300% higher than those with the normal allele (11).

The frequencies of allelic variants of the CYP2C9 gene differ depending on the population. The CYP2C9 * 2 polymorphism in the European population occurs at a frequency of 16% in Spaniards, 10.7% in Swedes, 12.5% in British, and 11.2% in Italians; this frequency is very similar to that reported in Americans (15%). In the East Asian population, this polymorphism is considered rare as it occurs at a frequency ≤ 0.1% (17).

CYP2C9 * 3 presents less frequently than CYP2C9 * 2. The highest frequency of this polymorphism is observed in Europeans (7.4-9.2%), also in Iranians (9.7%) and Turks (10%) in West Asia. The frequency of this polymorphism

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in East Asia widely varies, Chinese population presents a greater frequency compared to Japanese and Koreans. In the Mexican population, this polymorphism is observed in 1.5% of the Mexican-Tepehuano and Mexicomestizo population and in 6% of the Mexican-American population (17).

An important characteristic in the Mexican population is the miscegenation between the Amerindian and Caucasian groups from Europe and Africans brought in as slaves in the 16th century as a result of the conquest (14). In addition to the mestizo population, it is of note that in Mexico there are currently 70 indigenous groups that represent 6.1% of the total population (18). Due to this particularity, it is necessary to know which alleles are present in our population and what are their frequency in order to find out the relationship and efficacy of the drugs prescribed.

In Mexico, pharmacogenomics has not yet been fully extended to the daily clinical practice; there are however different research groups that have taken on the task of elucidating genetic variations within our population.

The following graph shows different pharmacokinetic curves that may present the same dose of THC, given by the variations in CYP isoforms, in such a way that low doses of THC will yield in some people levels resulting in unwanted side effects, while the expected effect will be attained in people who metabolize it in a “normal” way.

Concentration (ng/mL)

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Time (hrs)

It is estimated that genetics explains 20 to 95% of the variability in the disposition and effects of drugs (19), including THC; thus, knowing the frequency of genetic variants within populations will lead to predictive applications and more effective treatments.

BIBLIOGRAPHY: 1.United Nations Office on Drugs and Crime. (2017). World Drug Report 2017 (E.14.XI.7).

2.Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz; Instituto Nacional de Salud Pública, Comisión Nacional Contra las Adicciones, Secretaría de Salud. (2017). Encuesta Nacional de Consumo de Drogas, Alcohol y Tabaco 2016–2017: Reporte de Drogas. INPRFM. https://www.ind.com 3.Leal Galicia, P., Betancourt Ocampo, D., González González, A., & Romo Parra, H. (2018). Breve historia sobre la marihuana en Occidente. Revista de Neurología, 67(04), 133. https://doi.org/10.33588/rn.6704.2017522 4.Barrales-Cureño, H. J., López-Valdez, L. G., Reyes, C., Cetina-Alcalá, V. M., Vasquez-García, I., Diaz-Lira, O. F., & Herrera-Cabrera, B. E. (2020). Chemical Characteristics, Therapeutic Uses, and Legal Aspects of the Cannabinoids of Cannabis sativa: A Review.

Brazilian Archives of Biology and Technology, 63, 20. https://doi.org/10.1590/1678-4324-2020190222 5.Gonçalves, J., Rosado, T., Soares, S., Simão, A., Caramelo, D., Luís, N., Fernández, N., Barroso, M., Gallardo, E., & Duarte, A. (2019). Cannabis and Its Secondary Metabolites: Their Use as Therapeutic Drugs, Toxicological Aspects, and Analytical Determination. Medicines, 6(1), 31. https://doi.org/10.3390/medicines6010031 6.Hanuš, L. O., Meyer, S. M., Muñoz, E., Taglialatela-Scafati, O., & Appendino, G. (2016). Phytocannabinoids: a unified critical inventory. Natural Product Reports, 33(12), 1357–1392. https://doi.org/10.1039/c6np00074f 7.Citti, C., Linciano, P., Panseri, S., Vezzalini, F., Forni, F., Vandelli, M. A., & Cannazza, G. (2019). Cannabinoid Profiling of Hemp Seed Oil by Liquid Chromatography Coupled to High-Resolution Mass Spectrometry. Frontiers in Plant Science, 10. https://doi. org/10.3389/fpls.2019.00120 8.Andre, C. M., Hausman, J. F., & Guerriero, G. (2016). Cannabis sativa: The Plant of the Thousand and One Molecules. Frontiers in Plant Science, 7, 8. https://doi.org/10.3389/fpls.2016.00019 9.Sociedad Española de Investigación sobre Cannabinoides. (2002). Guía básica sobre los cannabinoides. Departamento de Bioquímica y Biología Molecular. Facultad de Medicina Universidad Complutense de Madrid.

10.Covarrubias-Torres, N. (2019). Uso medicinal de la Marihuana. Anestesia en México, 31(2), 49-58. Recuperado en 07 de abril de 2021, de http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S244887712019000200049&lng=es&tlng=es.

11.Papastergiou, J., Li, W., Sterling, C., & van den Bemt, B. (2020). Pharmacogenetic-guided cannabis usage in the community pharmacy: evaluation of a pilot program. Journal of Cannabis Research, 2(1). https://doi.org/10.1186/s42238-020-00033-1 12.Perales-Caldera E, Uribe-Campo GA, Orozco-Orozco L. (2019). Análisis de la frecuencia de polimorfismos del CYP2C19 (*2,*3,*17) en población Mexicana. ISSN 2448-8771. Anestesia en México 31 (3). 3-12 13.Hirota, T., Eguchi, S., & Ieiri, I. (2013). Impact of Genetic Polymorphisms in CYP2C9 and CYP2C19 on the Pharmacokinetics of Clinically Used Drugs. Drug Metabolism and Pharmacokinetics, 28(1), 28–37. https://doi.org/10.2133/dmpk.dmpk-12-rv-085 14.Flores-Tufiño A. (2014). Identificación de mutaciones en CYP2C9 asociadas con la resistencia a anticoagulantes orales. [Tesis de licenciatura]. México, D.F. UNAM. Facultad De Estudios Superiores Zaragoza.

15.Frías AG, Hierro OS, Jiménez AJ, et al. (2007). Farmacogenómica y sus aplicaciones clínicas. Dermatol Rev Mex;51(3):99-111.

16.Fricke-Galindo, I., Jung-Cook, H., LLerena, A., & López-López, M. (2018). Farmacogenética de reacciones adversas a fármacos antiepilépticos. Neurología, 33(3), 165–176. https://doi.org/10.1016/j.nrl.2015.03.005 17.Lazalde Ramos B. (2012). Polimorfismos De Relevancia Farmacogenética De Las Familias 1A2, 2C Y 3A En Poblacion Indígena Del Noroeste De México. [Tesis doctoral]. Universidad De Extremadura. Facultad De Medicina.

18.Pueblos indígenas por estado. (2020). Sistema de información Cultural México. https://sic.cultura.gob.mx/lista. php?table=grupo_etnico&disciplina=&estado_id= 19.Castelán-Martínez, O. D., Hoyo-Vadillo, C., Sandoval-García, E., Sandoval-Ramírez, L., González-Ibarra, M., Solano-Solano, G., Gómez-Díaz, R. A., Parra, E. J., Cruz, M., & Valladares-Salgado, A. (2013). Allele frequency distribution of CYP2C9*2 and CYP2C9*3 polymorphisms in six Mexican populations. Gene, 523(2), 167–172. https://doi.org/10.1016/j.gene.2013.03.128

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CANNABIS AND TECHNOLOGY:

THE NEW NON-STIGMA OF THE 21ST CENTURY Probably one of the great differentiators of each century is how beliefs change. When we think of concepts such as “nineteenth-century thinking”, we understand that we are referring to the whole set of “philias and phobias” that societies had in the nineteenth century, both social and cultural, political, scientific, artistic and all the other things we can think of. Much of this during the twentieth century was broken, evolved or, failing that, reincarnated in new beliefs, stigmas, ideologies and also more etcetera. It is normal that living in the present we do not notice these ruptures as they are, in Braudel’s words, “long-lasting processes”, but the 21st century has also brought its own new ways of thinking. While this continues to lend itself to much debate, we have one unquestionable maxim: the stigma of marijuana is rapidly fading and legalization in more and more parts of the world is a reality. Science and medicine have found great benefits in the use of cannabidiol, especially in the fields of neurology and mental health. On the other hand, the much feared recreational use has ceased to be this social “satan” as it is increasingly present in academic, professional and scientific circles.

Likewise, organized crime would be avoided in a certain sense by putting into practice activities such as self-cultivation. Faced with this panorama, brands and companies dedicated to technology have been taking action on the matter for some years now.

Mauro Orozco Moreno Communicologist and historian graduated from the University of Guadalajara. Since 2019 he is dedicated to journalism and content creation about video games, technology and “geek culture” on the internet. He was co-founder of the page Operación Gamer and currently his content appears on his page Totherland on Facebook Gaming.

GADGETS |

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LEVO

One of the great proposals of this new century in which we live is that of urban gardens. The self-cultivation of plants and vegetables is one of the activities that have become more common among young adults and this also includes cannabis.

What happens when I do not have the conditions for a garden at home, but I want to grow my own plant? Well, several brands have put this hydroponic technology on the market. One popular brand is SeedoLab. This device has and does everything you need for your plant to grow in the best conditions. It has LED light and interior lighting adjustment to simulate day and night, irrigation system, temperature and humidity control, hermetic sealing system to create an ecosystem free of pests and CO2 and, as if that were not enough, it can be linked to your cell phone to receive notifications about the status of your plant or even to see your little sprout in stream.

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APPS

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Let’s start with a product that we can have in the kitchen, next to the coffee maker. This LEVO machine is used to make butter, honey or oil from the plant. The procedure is simply to put the plant in the machine, press the button of what we want and in a few minutes we will have cannabis butter to prepare brownies, honey for a smoothie or oil to make sweets, among other things. Such technology is priced at $300 on the LEVO website or a $160 model with perhaps fewer options, but ideal for those looking for a simpler and more economical alternative.

02.

SEEDO LAB

Vamos a comenzar con un producto que podemos tener en la cocina, A very well known app, especially in places where marijuana has already completely decriminalized, junto a la cafetera.

Esta máquina de labeen marca LEVO sirve para hacer is Leafly. This app is very useful to know all the distribution centers, dispensers or smoke shops consiste that you mantequilla, miel o aceite de la planta. El procedimiento have nearby, in addition to giving you information about the type of plant you need for your simplemente en poner la planta en la máquina, presionar el botónhealth de lo condition and in which of these to getyit.enWe alsominutos have GrowBuddy that serves as andeadvisor for queplaces deseamos unos tendremos mantequilla cannabis the cultivation of the plant, giving you reminders for watering and alerts about the status of your plant. para preparar brownies, miel para algún smoothie o aceite para hacer dulces, entre algunas cosas más. Tal tecnología tiene un precio de 300 Another very interesting onedólares is EazeMD, has thede function being able de to contact doctors at en lawhich página web LEVO oofun modelo 160 dólares quizá the moment that can give you consultations regarding the use of the plant for any health problem you con menos opciones, pero ideal para quien busca una alternativa más may have. In addition to those mentioned, there are many other apps that serve to tell you if you are sencilla y económica. in conditions to, for example, drive after consuming marijuana or even to weigh the amount you have tried, so that the dealer gives you grams that are not grams.

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BECOMING A MARIHUANA USER. A SOCIOLOGICAL LOOK Howard Becker is an American sociologist born in 1928, he belongs to the “second Chicago school” and, among his most outstanding works, is Becoming a Marihuana User. This work was published in 1953, in the context of an American society not open to discussing legalization. Although the author himself calls for a responsible use of the term “context” so as not to fall into the simplistic generalization that marijuana consumers engage in this practice due to problematic “contexts”, it is imperative to recognize the society that received this work.

In the 1950s, American society was concerned about

Humberto Orígenes Romero Porras Holds a degree in history from the Universidad de Guadalajara. A former Paralympic athlete (20062017), he won a medal at the 2015 Parapan American Games held in Toronto, Canada. A partisan of worthy causes, he is interested in the interconnections between history, literature, and soccer.

“crime, mental illness, gangs: things like these were social problems.

But relatively few people used marijuana and it didn’t cause too much disruption, so despite the efforts of some authorities, no section of public opinion was clamoring to be rid of the practice.”

By the 1960s, marijuana use was widespread among middle-class college students. Among them, some enterprising farmers decided to experiment with growing weed, in the purest style of Savages, the 2012 film directed by Oliver Stone. It is easy to imagine young Californians trying to be enterprising and have fun.

In Becker’s historical context, the use of opiates already existed, which gave rise to the word Junkie, which, incidentally, is the name of a novel by William S. Burroughs, an author of the Beat Generation, a subject that is beyond the scope of this article. The use of these substances was studied a few years before the publication of Becker’s study on marijuana by a colleague of his in the Department of Sociology at the University of Chicago, Alfred Lindesmith, who wrote Opiate Addiction (1947), a book that “attributed addiction to opiates to the fact that the consumer got the idea that he had to take the drug to avoid intensely displeasing physical symptoms.”

It was clear to Howard Becker that marijuana did not produce these symptoms, so he decided to think of it as non-addictive. He interviewed several university students and discovered that “a good trip” depends on the interpretation of the traveler, so that the same experience, interpreted differently, leads to different sensations. Becker starts from the conceptualization of what he calls “deviance studies”, to present the marijuana user as someone who does not live with a psychological pathology, but who has become a “deviant” for

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goal should be to have fun and experiment with perception. He relies on the notion of “consumption for pleasure”, i.e., the subject does not feel obliged by his own body to smoke marijuana.

According to the author, for those who are experienced in the subject, it is necessary to know the symptoms in order to know that they are “stoned”, otherwise it would seem that nothing is happening. When they are not aware that they are under the effects of cannabis, they can have experiences that border on the ridiculous, with episodes of paranoia in which they presume not to feel anything, but at the same time they are shouting and boasting about their supposed sobriety.

In Becoming a Marihuana User, the reader will find a slight disappointment as it is a little less than the 92 pages promised, since several images intersperse the text. Nor will you find a psychiatric cause for the use of this herb. However, you will find the reason for the continued use of it, because with Becker we learn that, to become a professional smoker and not quit at the first puff, the consumer had to go through a process of teaching and resignification of experiences to recognize the characteristics of a trip that often does not meet previous expectations. a society; or rather, a hegemonic social group that has the power to impose that label.

In this text there is a shift from why to how. While he does not consider the consumer as sick, Becker leans towards the process that leads the individual to become a regular user of cannabis. The habit of smoking marijuana is perceived in the essay not as a sick act, but as a socially learned activity. The sociologist abandons the idea of a “genetic predisposition” to marijuana use.

Among those interviewed by Becker, a certainty emerges: the first time was neither good nor pleasant. The first use of marijuana is perceived as something common because nothing happens or it is unpleasant because they do not like the effects it produces. The user needs the guidance of more experienced users to learn how to get hooked, otherwise they would give up marijuana.

For Becker, the “disposition” to use marijuana occurs through the learning process and not before. What changes in the subject is the attitude towards the drug, which leads him to experience it.

One must learn to have a good trip, says the sociologist. Whoever smokes marijuana for the first time must resignify his experience to try it again and thus become a regular consumer. Becker does not speak of medicinal uses but of pure recreation. The smoker’s

What is most interesting is what can be intuited about the use of other more dangerous substances. Although it is true that a text from 1953 is unable to foresee the development of future situations or the discovery of increasingly aggressive substances, the issue of the re-signification of experiences should not be overlooked.

When the user (in 1953 and today) stops feeling something pleasant and is not able to make sense of continued use, he/she has two options: to stop using marijuana or to turn to another substance in search of better effects. Moving from marijuana use to non-use has to do with the consumer’s conception of marijuana. When someone argues that marijuana no longer has an effect, what they really mean is that they no longer find the same pleasurable experiences.

It is likely that the transition to another drug is due, following Becker’s analysis, to the fact that the user cannot find a pleasurable effect in repeated use, either because of unfulfilled expectations or because of ignorance of the correct use of marijuana. It is noteworthy that there are cases in which users interviewed by Becker report having abandoned marijuana and returned months or years later, with much more satisfactory results. Perhaps to avoid experimentation with other drugs we should first learn to have a good trip.

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VIOLA BRUGNATELLI: SCIENTIFIC RESEARCH, INNOVATION, AND AWARENESS

Karen Beatriz González Vega Holds a bachelor’s degree in Hispanic Letters from the University of Guadalajara. Since 2020 she works as a proofreader in the marketing industry.

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Medicine is a science in constant evolution, reinventing itself with treatments, alternatives, and discoveries related to the human body. This evolution cannot occur but through research. Someone who understands the importance of sharing insights is Viola Brugnatelli, a prominent scientist with a proven record of investigator in the medicinal Cannabis field. Brugnatelli studied Neurosciences at the Dundee University in Scotland. During her education, she completed an internship in the Neurosciences department, which allowed her to get closer to her current career objective at that time: the endocannabinoid system.

Following this appeal, she started working at the Neurosciences Center of the Ninewells Hospital and Faculty of Medicine, where

she could strengthen her knowledge on the endocannabinoid system and the orphan cannabinoid receptors, leading to the completion of her thesis project on the cannabinoid derivative receptors related to pain perception. Given her tenacious work on medicinal Cannabis, Dr. Brugnatelli was designated a member of the International Cannabinoid Research Society. Furthermore, she is the Italian ambassador of the International Association of Cannabinoid Medicines.

Brugnatelli has performed multiple investigations on cannabinoids and their effects on the nervous system. For example, she investigated the anti-inflammatory effects of CBD and the interaction of the essential Cannabis oils. Another of her

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passions is teaching and sharing her insights. In Ireland, she worked as a teaching assistant on subjects like Adjuvant Pharmacology, Phytotherapy, and Endocannabinoid System. In addition, she was a tutor in the Neurosciences laboratories of the same institution. Viola shares her work through different media: she participates in seminaries, imparts workshops, and is a member of the Joint Board of the CANNA Foundation, a non-profitable Spanish organization dedicated to Cannabis scientific studies and its effects on the human body.

Dr. Brugnatelli is the head of the Cannabiscienza Scientific Committee, one of her most interesting projects to date. It is about a webpage that provides information with scientific evidence on the medicinal Cannabis and the endocannabinoid system. This platform is more than just a discussion forum for members of the scientific community: it is a site fully

dedicated to medicinal Cannabis with several online curses on Cannabis and its clinical, pharmaceutical, and even veterinary applications.

Doubtless, Viola Brugnatelli’s work has been a milestone for investigations about medicinal Cannabis. Brugnatelli has participated and supported several media for the dissemination of knowledge, and she even created an educational platform for other physicians and students can learn more about medicinal Cannabis, with access to information upto-date. Definitively, Viola Brugnatelli has contributed to the scientific community with a myriad of options to distribute information on medicinal Cannabis, and therefore, she has globally contributed to scientific innovation.

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CHEWING THE DAYBREAK When I woke up, daybreak was pouring with its warm waters, the implosive stones of the streets, the human rivers.

The roads dismantled the world, into bittersweet waves light as, at some point, and everything counted and throbbed the presence.

My affluent sight with drowsy iris recapped, over and over, the passage of light, I saw myself like a new man, discovering the earth, and I’d like to name the wind, throbbing scar and to the stones, hearts of iron nonetheless, the smell of aged liquor rested in my maw. a smooth sweat lied on my skin, the feeling of having loved, forever, dwelled in my bones.

I am chewing the daybreak, it means the path I must follow, waves of sound made by a sweet tone, started to take me, and the daybreak, enter through the mountains of my mouth

Marco Antonio Gabriel Guadalajara, Jalisco, Mexico, 1977. He holds a bachelor’s degree on Hispanic Letters from the University of Guadalajara, author of the poetry book Tornasol y Fuego by Editorial Paraíso Perdido. He has been published in the Anthologies Poesía viva de Jalisco and 101 poetas - 101 pintores. Internship of the Program for the Artistic Promotion, Creation, and Development, 2008-2009. He is the editor of Ediciones el Viaje.

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