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Special Report Chairperson: Tony P. George, MD, FRCPC

In the United States, cannabis is a Schedule I drug. However, legislative matters have effectively allowed each state to manage legalized recreational cannabis. This patchwork has led to disparities in state versus federal regulations regarding recreational 

 that, coupled with myths about its psychological benefits, increase confusion for our patients. This article will summarize changes in cannabis legislation and provide an update for psychiatrists on the evidence both for and against its clinical utility.

Eighteen states (and Washington, DC, and Guam) have adopted legalized recreational cannabis use, and 37 (plus DC, Guam, Puerto Rico, and the US Virgin Islands) have approved medicinal use. While this patchwork leads to disparities in medical care and arrests across states, it allows for comparisons in mental health trends related to legalization. Longitudinal analysis of 505,796 respondents found an increased diagnosis of cannabis use disorder (CUD) in individuals aged 12 to 17 years (2.2% to 2.7%) and 26 years and over (0.9% to 1.2%) after legalization, which was not mirrored in states where it remains illegal.

 However, there was no increase in CUD prevalence for respondents aged 18 to 25 years.

Evidently, for consumers to make informed choices and to reduce potential harms, legalization alone may be risky and should be coupled with increases in evidence-based education and access to treatment, especially for at-risk groups such as adolescents and individuals with mental illnesses.

CUD refers to continuous excessive use, characterized by a loss of control, psychological and social impairments, and risky behavior. The prevalence of CUD (ages 12+) is around 2.9% in the United States,

 with males having rates twice that of than females.

 However, in psychiatric patient samples, CUD prevalence reaches ~25%.

 Individuals with mental illnesses and other SUDs may be more susceptible to CUD because of shared genetic and environmental factors increasing vulnerability,

 or because of overuse in an effort to manage symptoms (ie, coping with negative affect).

 There is the popular perception that cannabis is an effective tool in managing anxiety, mood, and eating disorders, but evidence to support self-medication is minimal.

 in cannabis are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is known to produce the characteristic “high” from inhalation of cannabis because of its high-affinity for cannabinoid type 1 (CB1) receptors in the mesolimbic dopamine system; CBD antagonizes these effects, but the exact mechanism is unclear.

The acute effects of THC intoxication, including at higher doses, are outlined in the 

. Cannabis misuse is associated with first-episode psychosis, longer psychotic episodes, more positive symptoms, and poorer psychosocial functioning in individuals with schizophrenia.

 Such effects directly correlate with THC dose and potency; evidence suggests a dose-dependent relationship between cannabis use and schizophrenia that cannot be explained by use of other psychoactive substances.

 Similarly, in bipolar disorder, cannabis use is associated with earlier onset of depressive, manic, and psychotic episodes and more frequent suicide attempts,

 with high THC as the culprit. Moreover, longitudinal studies on bipolar disorder show lower rates of treatment adherence and greater symptom severity, particularly mania and psychosis, in bipolar cannabis users.

Less clear is the interaction between THC and depression. While cannabis prevalence in depression is high,

 longitudinal studies have provided modest evidence on whether 

 Infrequent use may not be related to depression, whereas heavy use is more likely to increase symptoms.

 Similarly, evidence on cannabis as a risk factor for anxiety disorders is modest, with some prospective studies showing greater risk of developing anxiety disorders and more anxious symptoms in cannabis users,

 while others have failed to replicate such findings.

 These inconsistencies might be explained by genetic differences

 or the dose-dependent nature of THC intoxication, with low doses eliciting feelings of relaxation and euphoria, while higher doses result in dysphoria, panic, and paranoia. Moreover, extensive exposure to THC over time may paradoxically increase anxiety via changes in allostatic load.

 Despite claims that cannabis helps reduce depression and anxiety, we found no controlled clinical trials suggesting its effectiveness. In fact, in a recent study of 28 days of cannabis abstinence in people with 

, there was a significant improvement in depressive and anxiety symptoms, sleep problems, and anhedonia with extended cannabis abstinence, which argues against self-medication of mood symptoms by cannabis use.

 Conversely, CBD does not produce intoxication. Rather, it has been shown to antagonize CB1 and CB2 receptors, thus opposing effects of THC. Preclinical models suggest a range of potential therapeutic benefits of CBD as a function of antipsychotic, neuroprotective, anxiolytic, and sedating properties.

 For example, animal models suggest that 

 might produce antidepressant effects via serotonergic neurotransmission, in particular activation of 5-HT1A receptors.

Preliminary evidence in human studies is similarly encouraging: CBD may produce antianxiety and antidepressant effects.

 Interestingly, increased doses are not associated with dysphoria or anxiety as is found with increased THC doses. One study found that administration of CBD produced functional changes in anxiety-related limbic and paralimbic cortical areas that were further associated with a reduction in state anxiety.

 Moreover, there is evidence that CBD 200 to 1500 mg daily may alleviate psychotic symptoms through inhibition of anandamide metabolism and reduce cognitive impairments through CB1 and CB2 receptor agonism in schizophrenia.

One case study even found improvements in symptoms of 

where the individual had previously failed to respond to olanzapine, clozapine, or haloperidol.

 Even where findings are null, CBD is well tolerated and does not worsen symptoms.

 Thus, emerging evidence on anxiolytic, antipsychotic, and antidepressive effects of CBD is promising. Of note, there are a number of drug interactions between CBD and common psychiatric medications that need to be considered when prescribing CBD.

In addition, some studies have found support for the use of CBD in treating cannabis-related issues. Specifically, CBD at 40 to 100 mg daily has been shown to improve cannabis withdrawal symptoms,

 which may help participants avoid using to alleviate withdrawal. Other open-label studies have found that CBD increased rates of abstinence and reduced the amount of cannabis used by participants.

Unfortunately, trends observed in concentrations of THC and CBD in cannabis in licit and illicit markets have seen the former increasing from an average of 4% to as high as 25% to 30%, and the latter decreasing from 0.28% to less than 0.15% (1995-2014).

 This imbalance precludes the opposing effects of CBD on THC intoxication, increasing the risk of experiencing harms associated with 

Cannabis Legalization and the Opioid Toxicity Crisis

The rapidly increasing rates of opioid-related poisonings has galvanized health care providers, advocates, and governments to find solutions to overprescription of 

 and the toxicity of the illicit opioid market (eg, carfentanil). It has been proposed that legalization of cannabis may play a role in curbing the opioid crisis.

A few studies have attempted to answer this question. Initially, Bachhuber et al

 suggested that in states with medical cannabis laws, rates of fatal opioid overdoses were reduced after implementation of these laws. However, more recent studies have suggested the opposite

 and that frequency of cannabis use, in fact, correlates with the severity of opioid use disorder.

 These studies, although methodologically sound, are not entirely sufficient to answer the question of whether cannabis legalization may curb the opioid crisis—a broad and somewhat vague claim. Examining a few scenarios will help highlight the importance of defining the potential role of cannabis legalization in reducing opioid overdoses.

, prescription of high-dose opioids long term may increase the risk of developing opioid use disorder

 that may in turn result in transition to use of illicit opioids (eg, heroin, fentanyl).

 In these cases, prescribing cannabis for pain management may, in fact, reduce the chances of introduction to and dependency on opioids.

It has also been suggested that recreational cannabis use may act as a “gateway drug” that encourages transition to use of other drugs, such as opioids. In states where cannabis remains illegal, 1 potential mechanism of this transition (if it occurs) is introduction to the illicit market, criminal networks, and potentially the judicial system if one were arrested. In this instance, legalization of cannabis means individuals could access regulated amounts without having to go through illicit sources.

However, for individuals who already have an 

 that has arisen from a complex array of biological, psychological, and social circumstances, legalization of cannabis may not affect their use of opioids. Rather, as suggested by Olfson et al,

 we may see that individuals continue to use opioids alone or with cannabis and thus would likely benefit more from a specific and targeted opioid use disorder intervention.

As such, well-controlled longitudinal studies are needed to adequately investigate the clinical and public health relationships between cannabis use and opioid toxicity.

While there remains a dearth of clinical research on the benefits of cannabis, particularly in individuals with mental illnesses, the evidence suggests they are likely outweighed by the harms of (high-THC) cannabis. However, the question is no longer should cannabis be legalized? The question is how can we effectively promote evidence-based public health messaging around cannabis, regulate available supplies to achieve an appropriate balance of THC and CBD, and increase access to CUD treatment?

is a research analyst at the Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada. 

 is an associate professor of psychiatry at Harvard Medical School, and director of addiction psychiatry at Beth Israel Deaconess Medical Center (BIDMC) in Boston, Massachusetts.

is professor of psychiatry, Temerty Faculty of Medicine, at the University of Toronto, and senior physician-scientist at CAMH in Toronto, Ontario, Canada. He is currently deputy editor and incoming coprincipal editor of Neuropsychopharmacology (NPP).

Acknowledgements: This work was funded in part by NIH grant R21-DA-043949 to Dr George.

1. Cerdá M, Mauro C, Hamilton A, et al. 

Association between recreational marijuana legalization in the United States and changes in marijuana use and cannabis use disorder from 2008 to 2016.

US epidemiology of cannabis use and associated problems.

A systematic review and meta-analysis of sex differences in cannabis use disorder amongst people with comorbid mental illness.

4. Lowe DJE, Sasiadek JD, Coles AS, George TP. 

Diversity of molecular targets and signaling pathways for CBD.

6. D’Souza DC, Pearlson GD, Selloni A, et al. A review of cannabis and cannabinoids in schizophrenia and psychotic disorders. 

7. Polkosnik GL, Sorkhou N, George TP. Effects of cannabis use on psychotic and mood symptoms: a systematic review. 

8. van Rossum I, Boomsma M, Tenback D, et al; EMBLEM Advisory Board. 

Does cannabis use affect treatment outcome in bipolar disorder? A longitudinal analysis.

Association of cannabis use in adolescence and risk of depression, anxiety, and suicidality in young adulthood: a systematic review and meta-analysis.

 Exploring the association between cannabis use and depression.

11. Otten R, Huizink AC, Monshouwer K, et al. 

Cannabis use and symptoms of anxiety in adolescence and the moderating effect of the serotonin transporter gene.

12. Lucatch A, Kloiber S, Meyer J, et al. Effects of extended cannabis abstinence in major depressive disorder. 

The therapeutic role of cannabidiol in mental health: a systematic review.

14. Silote GP, Sartim A, Sales A, et al. 

Emerging evidence for the antidepressant effect of cannabidiol and the underlying molecular mechanisms.

15. Zieba J, Sinclair D, Sebree T, et al. 

Cannabidiol (CBD) reduces anxiety-related behavior in mice via an FMRP-independent mechanism.

16. Crippa JA, Derenusson GN, Ferrari TB, et al. 

Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report.

17. Leweke FM, Mueller JK, Lange B, et al. 

Role of the endocannabinoid system in the pathophysiology of schizophrenia: implications for pharmacological intervention.

The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial.

19. Hill KP, Gold MS, Nemeroff CB, et al. 

Risks and benefits of cannabis and cannabinoids in psychiatry.

20. ElSohly MA, Mehmedic Z, Foster S, et al. 

Changes in cannabis potency over the last 2 decades (1995-2014): analysis of current data in the United States.

21. Bachhuber MA, Saloner B, Cunningham CO, Barry CL. 

Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010.

Association of state policies allowing medical cannabis for opioid use disorder with dispensary marketing for this indication.

23. Olfson M, Wall MM, Liu SM, Blanco C. 

Cannabis use and risk of prescription opioid use disorder in the United States.

24. Hoffman KA, Ponce Terashima J, McCarty D. 

Opioid use disorder and treatment: challenges and opportunities.

25. National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Sciences Policy; Phillips JK, Ford MA, Bonnie RJ, et al, eds. 

Pain Management and the Opioid Epidemic: Balancing Societal and Individual Benefits and Risks of Prescription Opioid Use.

 National Academies Press (US); 2017. ❒

What's the latest update on cannabis legislation and its clinical utility?

Cannabis Legalization: What Psychiatrists Need to Know

The juxtaposition of 2 recent research reports should give us pause for concern. In September, the National Institute on Drug Abuse reported that 

 use among college students reached 44% in 2020, a significant increase from 38% in 2015 and at its highest level since the 1980s.

 currently available is more potent than that used in the past. This follows a July report from researchers in Denmark who claim that the increasing use of cannabis is a likely cause of increasing incidence of schizophrenia noted in that country over the past 2 decades.

 An increasing incidence of schizophrenia, or psychosis in general, has also been reported in England, Switzerland, and Canada, especially among young people.

 Since 19 US states have already legalized the recreational use of cannabis and other states are considering doing so, a possible relationship between cannabis use and increasing 

 is potentially very important and needs to be confirmed.

The National Institute of Mental Health (NIMH) website describes itself as “the lead federal agency for research on mental disorders.” Schizophrenia is generally considered to be the most disabling mental disorder and in 2013 was estimated to cost the US $155.

 One would therefore expect NIMH to have accurate information on the incidence and prevalence of schizophrenia and some idea whether they are increasing, decreasing, or constant over time. However, when a health reporter asked NIMH for its reaction to the report on cannabis and 

 from Denmark, a NIMH spokesperson had little to offer other than to say that “it’s hard to obtain accurate estimates of the prevalence of schizophrenia because diagnosis is complex and it overlaps with other disorders.”

In fact, NIMH says that it does not know the prevalence of schizophrenia in the US other than within broad limits.

 For the last 4 years, the NIMH website has combined schizophrenia with other “related psychotic disorders” and claimed that together, their prevalence is “between 0.25% and 0.64%” of the population, which translates to between 772,000 and 2.0 million individuals. For every other mental disorder, except schizophrenia, NIMH provides a precise prevalence number.

Part of the problem is that NIMH has not undertaken a serious study of the incidence or prevalence of 

 or other major mental illnesses in 40 years. At that time, it reported the 1-year prevalence of schizophrenia among adults in the US to be 1.1%, equivalent to 2.6 million adults based on 2010 census data.

 NIMH used that percentage as its official estimate for the prevalence of schizophrenia until 2017. At that time, for reasons it has yet to explain, NIMH declared that the true prevalence of adult schizophrenia was really only 0.3%, or 704,000 individuals. As justification for this new number, NIMH cited a study from 2005that only counted people with schizophrenia who were living at home (including college students); those residing elsewhere—including hospitals, group homes, 

 Since NIMH had effectively made 2 million people with schizophrenia disappear without justification, the number was publicly ridiculed.

 NIMH’s response was to acknowledge that it really does not know the prevalence and to offer the range of numbers cited above.

In order to ascertain whether any disease is increasing or decreasing over time, one needs a reliable baseline number as well as repeated surveys. Since NIMH has never repeated the prevalence survey for the 40-year-old study or established another reliable baseline number, it has no way to tell whether schizophrenia is increasing or decreasing. In fact, since the 1990s, there are suggestions that it may be increasing. The number of seriously mentally ill individuals who are homeless or incarcerated has appeared to increase in recent years, and schizophrenia is a significant part of that population. Schizophrenia is a major, and apparently increasing, contributor to the cost of the Medicaid and Medicare programs. And the “mental disorders” diagnostic category has been 1 of the fastest-growing parts of the Supplemental Security Income and Social Security Disability Income programs.

It is an embarrassment to American medicine that NIMH has so little to contribute on such an important question. At a minimum, NIMH should issue a request for proposals to try and confirm the Danish study in another country which has appropriate data so that we will have a definitive answer to this question.

is the founder of the Treatment Advocacy Center and the author of 

American Psychosis: How the Federal Government Destroyed the Mental Illness Treatment System

1. Marijuana use at historic high among college-aged adults in 2020. National Institute on Drug Abuse. September 8, 2021. Accessed December 22, 2021. 

https://www.drugabuse.gov/news-events/news-releases/2021/09/marijuana-use-at-historic-high-among-college-aged-adults-in-2020

2. Hjorthøj C, Posselt CM, Nordentoft M. 

Development over time of the population-attributable risk fraction for cannabis use disorder in schizophrenia in Denmark.

3. Boydell J, Van Os J, Lambri M, et al. 

Incidence of schizophrenia in southeast London between 1965 and 1997.

4. Ajdacic-Gross V, Lauber C, Warnke I, et al. 

Changing incidence of psychotic disorders among the young in Zurich.

Increase in schizophrenia incidence rates: findings in a Canadian cohort born 1975-1985.

6. Cloutier M, Aigbogun MS, Guren A, et al. 

The economic burden of schizophrenia in the United States in 2013.

7. Hunt K. Schizophrenia linked to marijuana use disorder is on the rise, study finds. CNN Health. July 22, 2021. Accessed December 22, 2021. 

https://www.cnn.com/2021/07/22/health/marijuana-schizophrenia-study-wellness/index.html

8. Gordon JA. On the prevalence of schizophrenia-and transforming care through research. 

https://www.psychiatrictimes.com/view/prevalence-schizophrenia-and-transforming-care-through-research

9. Gordon JA. Letter to Senator Bernard Sanders. February 6, 2019.

10. Regier DA, Narrow WE, Rae ES, et al. 

The de-facto US mental and addictive disorder system. Epidemiologic Catchement Area retrospective 1-year prevalence rates of disorders and services.

11. Kessler RC, Birnbum H, Demler O, et al. 

The prevalence and correlates of nonaffective psychosis in the National Co-Morbidity Survey Replication (NCS-R).

12. Torrey EF, Sinclair E. Hocus pocus: how the NIMH made 2 million people with schizophrenia disappear. 

https://www.psychiatrictimes.com/view/hocus-pocus-how-nimh-made-2-million-people-schizophrenia-disappear

13. Torrey EF, Simmons W. Where did the schizophrenics go? 

. March 26, 2019. Accessed December 22, 2021. 

https://www.wsj.com/articles/where-did-the-schizophrenics-go-11553640973

14. Torrey EF. Severe psychiatric disorders appear to be increasing. 

https://www.psychiatrictimes.com/view/severe-psychiatric-disorders-may-be-increasing

Is cannabis’ effect on schizophrenia being downplayed? 

Is Cannabis Use Increasing Schizophrenia? 

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The rising rate of teen cannabis use and its potential causes.

The effects of smoking marijuana on brain development.

How other psychiatric illnesses can lead to substance abuse disorders.

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is a child and adolescent psychiatry fellow at New York-Presbyterian Hospital.

Thanks to Columbia University Department of Psychiatry for allowing us to present the Caring for Teens and Tweens podcast with experts in the field of psychiatry.

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Prior to my decision to attend medical school, I was planning to become a basic science researcher. I studied biochemistry in college at a time when it was a relatively young field. My bachelor of science curriculum included 7 semesters of chemistry; 5 semesters of biochemistry, physics, microbiology, and zoology; and a senior honors thesis that entailed designing, completing, and defending a novel research project. I successfully defended my thesis, “An Analysis of the Fate of the Escherichia coli 4.5S RNA Gene in Yeast Using a Recombinant Plasmid,”

 and was planning to attend graduate school in genetics at the University of Washington in Seattle.

Between completing my senior thesis and my planned move to Seattle, I suddenly panicked and wondered: Is this truly the career path for me? Ultimately, I realized I did not have what it took to be a basic science researcher, so I worked for a year as a biochemical technician and applied to medical school—a decision I have never regretted.

Yet, I do not regret my background in biochemistry either. It is the foundation upon which all I have learned of medicine and psychiatry is built. The field of neuropsychopharmacology has evolved over the past 30 years, and I am filled with pride, awe, and excitement to have witnessed the clinical advancements that basic science researchers have made possible. However, in my opinion, there is 1 significant exception to all my accolades for how good science has advanced medicine: the research on cannabis.

The scientific method is used in medicine and has been the established paradigm for scientific inquiry since the 1600s. Thus, all clinical trials submitted to the US Food and Drug Administration (FDA) are meticulously designed to answer a primary outcome question about the drug under investigation. A necessary requirement of the study design is to ensure that the variables in the various arms of the study are identical except for one: drug A at dose X compared with placebo. If multiple doses of drug A or multiple drugs are being compared, each arm is precisely characterized so the conclusions drawn from the primary outcome will be highly accurate and reliable.

Over the past 10 years, I have read numerous articles in the psychiatric literature that draw conflicting conclusions about the effect of cannabis on cognition, its attendant risk of psychosis, its addictive potential, and its effect on suicidality, and about its impacts on depression, anxiety, pain relief, and apathy. (There appears to be only 1 consistent finding: Heavy cannabis use during brain development increases the risk of psychosis and cognitive impairment, especially when other risk factors are present.) A likely explanation for the wide-ranging discrepancies is that cannabis is the product of a plant that is not a single molecule or pure substance. Many articles with the word cannabis in the title can be discarded as meaningless unless the authors took the additional step of testing all of the cannabis used by their study subjects for the quantitative and qualitative molecules present.

It is well established that cannabis contains 

 These constituents include more than 100 cannabinoids, more than 200 terpenoids (terpenes), and numerous flavonoids. Two cannabinoids are most prevalent in cannabis: Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), both of which exist in an extremely wide range of ratios depending on the specific strain of cannabis assayed. Significantly, these 2 cannabinoids are oppositional in their clinical effects and have dramatically different pharmacodynamic effects. In reviewing the literature on cannabis, a consistent finding is that potency of cannabis is a proxy for the amount of THC. Although this is likely a result of the psychoactive effects of cannabis that have been noted for more than 6000 years,

 CBD has surfaced as an important cannabinoid with many positive medicinal properties. Notably, cannabis remains a Schedule 1 drug by the Drug Enforcement Administration (DEA), while CBD is unscheduled.

documents some of the significant differences between THC and CBD. Despite these differences, the vast majority of publications on cannabis draw conclusions based on participants’ self-reports of quantity and frequency of cannabis use. In these studies, the molecular components of the cannabis used are not known, nor is the important ratio of THC to CBD.

A fair analogy would be to evaluate a new drug; let us call it Sedalant. Sedalant contains a wide-ranging ratio of 2 molecules with different mechanisms of action: one a sedative, and one a stimulant. Without knowing the exact ratios and concentrations of each of these molecules in clinical studies of Sedalant, no evidence-based conclusions could be drawn from the drug studies.

Naturally occurring cannabis plants produce roughly an equal ratio of THC to CBD, containing approximately 2% of each. However, over the decades, with selective breeding in some strains, THC has been increased significantly while CBD has been virtually bred out. 

 analyzed the concentrations of THC and CBD from 38,681 samples of illegal cannabis seized by the DEA between 1995 and 2014. The authors found a clear trend of increased THC in cannabis over time, with an average concentration of 4% in 1995 that increased to 12% in 2014. Simultaneously, CBD concentration steadily declined, from 0.5% in 2004 to less than 0.2% in 2014. The investigators concluded that the ratio of THC to CBD increased from 14-fold in 1995 to 80-fold in 2014.5 Some strains of cannabis today may contain up to 30% THC with virtually no CBD, while other strains have high concentrations of CBD with minimal THC.

To further complicate the cannabis story, very few of the other cannabinoids in cannabis plants have been characterized pharmacodynamically or pharmacokinetically. The characterization of 3 of these more than 100 cannabinoids—Δ-9-tetrahydrocannabivarin, cannabichromene, and cannabigerol—tells us that they are 

Interestingly, the odors (skunk is a common description) often associated with cannabis are largely due to the complex combination of terpenes, another compound that complicates the study of cannabis. (Cannabinoids are odorless.) An extensive literature documents the essential role terpenes play in the biology of the cannabis plant, the plant’s production of cannabinoids, and the properties of a specific strain of cannabis that help determine its market value. Terpenes likely also contribute pharmacodynamic and pharmacokinetic effects that impact the neuropsychopharmacology resulting from ingestion of each different strain of 

Several publications since 2018 have appropriately concluded that we know very little about the range of pharmacological effects from cannabis due to the large variability of cannabinoids, terpenes, and flavonoids that are present in 

For this very reason, it would be contrary to the scientific method of research to attempt to gain FDA approval of cannabis.

Only 1 of the more than 100 cannabinoid components in cannabis has been sufficiently studied to receive FDA approval: CBD. Following a comprehensive analysis as well as clinical trials of pure CBD, it received 

 for the treatment of seizures in Dravet syndrome and in Lennox-Gastaut syndrome in children and adults.

 We may see additional approvals in the future for this well-studied compound, as a growing and consistent body of evidence shows that pure CBD in defined dosages has antipsychotic effects in patients with schizophrenia.

The practice of medicine is built upon evidence-based treatments that have been appropriately vetted by well-established protocols. CBD traveled this path to become an FDA approved drug, and so should any other component of the 500-plus molecules in cannabis. Accordingly, clinical publications should be held to a higher standard of identifying and defining what components of cannabis are relevant in any article being submitted for publication.

With each passing year, more US states legalize cannabis for medical use, recreational use, or both. It is likely that federal laws will eventually make cannabis use legal on a national level. That will create an opportunity to require a comprehensive analysis and disclosure of all the components of the numerous strains of cannabis currently being sold in state dispensaries or on the streets. Concurrently, the individual molecular components of the cannabis plant should be identified and pharmacologically characterized. This would create a treasure trove of possible drug candidates for specific clinical indications, and it would allow for a more informed choice when choosing a cannabis product.

In this scenario, cannabis should be regulated federally similar to tobacco products and alcohol. Both of these have significant risks, and both are tightly controlled. Ideally, the taxes imposed on federally regulated cannabis could help fund the extensive research needed to allow a more competent understanding of the complex combination of molecules that different strains of cannabis contain.

1. The word cannabis should not be used casually in medical literature, as it is nonspecific and includes varying molecular combinations of diverse cannabinoids, terpenes, and flavonoids.

2. Future research involving cannabis should use a single strain in each study; each strain used should be analyzed quantitatively and qualitatively for biologically active components.

3. If multiple strains are used in a clinical trial, they should be analyzed (as noted in #2), and each strain should be studied as a separate arm compared with placebo.

4. Increased funding is needed to accurately characterize the 500-plus molecular components of the cannabis plant, including the pharmacokinetics and pharmacodynamics of each component.

5. A public education campaign should aggressively disseminate the molecular facts about cannabis, especially the oppositional effects of THC and CBD. Similarly, the risks of increased psychosis and cognitive impairment with heavy regular use of THC in the developing brain should be explained, much like disclaimers on alcohol about drinking during pregnancy.

6. Cannabis should be federally legalized and regulated similarly to alcohol and tobacco products.

7. Cannabis should not be regulated by the FDA due to its extreme heterogeneity of components and the associated unpredictable pharmacological properties.

8. Cannabis should not be prescribed by medical practitioners. However, as molecular components of cannabis are developed and garnish FDA approval, those components should be prescribed appropriately.

9. Pharmacological exploration and development of cannabis components that demonstrate medical benefits should be continued. CBD is a successful model of such.

10. Medical practitioners should discuss cannabis with their patients only after they have attained competence in understanding the science and factual risks/benefits/adverse effects of cannabis, similar to how a practitioner would discuss alcohol or tobacco use.

With this structure in place, we have the ability to inform and support our patients appropriately. And, with more information, we can help end the cannabis confusion.

10 keys to understanding the science of cannabinoids. 

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