Hero

Videos

Slideshows

Articles

Podcasts

Poll

Patients increasingly ask about cannabis and whether it can be useful for sleep, PTSD, pain, and even dementia. In this video, Timothy W. Fong, MD gives a brief overview on emerging issues in cannabis. On Monday, May 3, Dr Fong and colleagues will speak at this year’s APA meeting in a presentation titled “

Facing the Challenge of Cannabis Legalization: Psychiatry’s Role

Dr Fong is Professor of Psychiatry & Director, UCLA, and Co-Director of UCLA’s Gambling Studies. The presentation is in collaboration with Laurence Westreich, MD; Kevin Allen Sevarino, MD; and Frances Rudnick Levin, MD.

Timothy W. Fong, MD, touches on our current understanding about cannabis use for psychiatric disorders.

Addressing Myths and Facts About Cannabis Use

For the full report of survey results, see 

You Spoke, We Listened. Psychiatry's Cannabis Survey

Clinical Management of Cannabis Complications


Thomas R. Kosten, MD, and Christopher D. Verrico, PhD

The Age of Cannabis Has Arrived: Issues for Older Adults

Cannabis 2021: What Clinicians Need to Know

Cannabis and Psychosis: A Synthesis of Quantitative Reviews

How to Discuss Cannabis With Your Patients

Infographic: A Snapshot of Psychiatrists' Attitudes Toward Cannabis

Research on psychiatrists' attitudes on the potential of cannabis in psychiatry.

Infographic: A Snapshot of  Psychiatrists' Attitudes Toward Cannabis

Enlightening survey results reveal what psychiatrists think about medical marijuana/cannabis use, how or whether to discuss with their patients, and what biases might get in the way of such conversations.

A new question must be added to the list that mental health clinicians ask their older patients while taking a history, regardless of age: “Have you used any cannabis products recently?”

I learned this lesson during a follow-up appointment with an 82-year-old man with Alzheimer disease. He reported some rather abrupt cognitive decline, and I asked him and his wife about recent medical changes without finding any clear precipitant. Finally, his wife sheepishly confessed that their son had sent them a grab bag of cannabis-derived products that the patient was taking. The family was desperate for anything to help his cognitive decline and they had heard that cannabis was a miracle cure for Alzheimer disease and many other conditions. Unfortunately, the patient received no benefit but did experience some mild, noticeable adverse effects. Without my probing, I never would have known. The next patient I asked explicitly about using cannabis products responded in an equally explicit manner: “No I haven’t,” he said, “but can you get me some?” It was clear that the age of cannabis had arrived.

Older individuals with psychiatric disorders are increasingly using cannabis, largely in the form of prescribed medical marijuana and cannabidiol (CBD). This trend has been driven by several factors: reduced stigma, lifted restrictions on possession and sale by most states, and the enormous proliferation of articles and ads that tout supposed benefits of 

 for many conditions that afflict the elderly, including chronic pain, peripheral neuropathy, stress, anxiety, depression, insomnia, headaches, and the adverse effects of chemotherapy.

 As a result, medical marijuana use by individuals 65 or older has increased more than 8-fold in recent years, from less than 0.5% in 2006 to 4.2% in 2018

). In a survey of 345 adults in Colorado, 16% had used medical marijuana since legalization, with half the users being 75 or older.

 CBD has seen a particularly enormous surge in interest and availability after it was exempted from federal regulations in the 2018 US Farm Bill. Since then, it is estimated that 6.4% of adults aged 45 to 55 and 3.7% of those 55 or older have used CBD at least once.

Although the cannabis sativa plant contains hundreds of chemicals known as cannabinoids, the 2 main active chemicals are Δ-٩-tetrahydrocannabinol (THC) and CBD. THC has both psychotropic and euphoric properties and confers the high associated with marijuana, while CBD is noneuphoric because it does not activate the cannabinoid 1 receptor like THC does. The same plants that produce THC also produce CBD. Both THC and CBD come in a variety of forms; they can be smoked, vaped, eaten, ingested as liquids, used as oils, and applied via creams and cosmetics.

The psychotropic effects of both THC and CBD are mainly because of their interaction with endogenous cannabinoid receptors in the brain, as well as activation of a variety of other cannabinoid and noncannabinoid receptors (ie, serotonergic, glutaminergic, µ-opioid, and α1-adrenergic) in the central nervous system and on immunologic cells. Based on their known and theorized properties, marijuana and CBD have been proposed as remedies to modulate symptoms of stress, insomnia, pain, inflammation, and cognitive impairment, particularly in older individuals. As a result, there are many unsubstantiated claims that THC and/or CBD can treat Alzheimer disease, Parkinson disease, schizophrenia, and anxiety and mood disorders.

Several small case series have suggested a tentative basis for some of these claims. For example, a study looked at the use of an oral spray containing THC and CBD for peripheral nerve pain and found that it was well tolerated and showed a trend toward improvement in pain and sleep.

 Medical marijuana use has been associated with some improvement in both movements and neuropsychiatric symptoms in individuals with Parkinson disease.

 One small case series found improvement in behavioral and psychological symptoms of dementia from cannabis oil containing THC.

 A related randomized control trial of 50 individuals with dementia and associated neuropsychiatric symptoms did not see any benefit from THC, but did find it was well tolerated and with no appreciable effect on memory.

 Despite these limited data, agitation associated with dementia is a qualifying condition for medical marijuana in several states.

Gruber and colleagues studied a sample of middle-aged individuals using medical marijuana over 3 months and found improvements in 

 and reductions in depression, insomnia, and impulsivity.

 They also saw a reduction in the use of benzodiazepines and opioids as well as a normalization of brain activation waves to states seen in normal controls. It is not clear, however, if these neurocognitive results were the direct result of the medical marijuana or an indirect benefit of decreases in pain, anxiety, and 

Although there are many other in vivo, in vitro, and animal studies of THC and CBD, it is clear that evidence is limited, and there are few randomized controlled trials to support most of their theorized clinical benefits. In addition, these studies are based on a variety of cannabis products from multiple sources and with variable contents.

 The 2 exceptions include a Food and Drug Administration (FDA)-approved form of synthetic THC known as dronabinol, which is used for treating appetite and weight loss resulting from AIDS as well as nausea and vomiting from chemotherapy, and a medication containing CBD for the treatment of 2 rare childhood seizure disorders. Dronabinol has also been studied in Alzheimer disease to treat anorexia and agitation and was found to be well tolerated with variable efficacy for both conditions.

, a CBD-THC combination, has been approved for the treatment of muscle spasms associated with multiple sclerosis.

The use of medical marijuana and CBD in older adults must be approached with caution because there are several potential adverse effects. It has been well established that heavy marijuana use in both young and middle-aged adults can cause mild functional and structural brain impairments affecting attention, 

, motor coordination, verbal memory, and executive function.

 Although these effects may be more variable with lighter use in older adults, they may be amplified by preexisting brain impairment as well as by underlying pulmonary and cardiovascular conditions, especially when medical marijuana is smoked or vaped.

 One review of 184 older patients (median age, 82) who were on medical marijuana for 6 months found that approximately 80% reported some benefit for the treated symptoms, but one-third reported adverse effects, including dizziness (12%) and sleepiness and fatigue (11.2%).

 Other reported adverse effects from a national epidemiologic survey included changes in mood and cognition, psychosis, increased heart rate and blood pressure, urinary retention, and blurred vision.

 In addition, THC has been associated with impaired driving in young adults, which could also be a problem in older drivers who may be impaired at baseline.

 of CBD use found that it is generally well tolerated with few adverse effects, the most common one being diarrhea.

 Other adverse effects associated with CBD include nausea, drowsiness, fatigue, dry mouth, and mood changes. Keep in mind that CBD is an inhibitor of several cytochrome P450 enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2D6, and CYP3A4. CBD can lead to drug-drug interactions with several commonly used medication groups in older patients, including blood thinners, antibiotics, anticonvulsants, antidepressants, and antipsychotics.

What To Ask Patients, and What To Tell Them

In this new era of medical marijuana and CBD, there are several important takeaways for clinicians working with older patients. Do not assume that because a patient is elderly and has physical or cognitive limitations that they do not fit the profile of a cannabis user. To the contrary: Every older patient along with their caregivers should be queried as to their use of cannabis, whether recreationally, from mail order or friends and family, or through a prescription. To this end, every clinical history should include questions about the use of cannabis products, including the stated reasons for use, the type of marijuana or CBD being used, and observed benefits and adverse effects. Concomitant medical conditions must be reviewed for potential vulnerabilities, such as an individual with hypertension using a product that increases blood pressure or heart rate, or an individual with chronic obstructive pulmonary disease using vaping oils. Potential 

 also need to be considered, with a focus on the categories of medications discussed in the article.

Patients and their caregivers need to understand that nearly all benefit claims are largely unsubstantiated, as they lack a rigorous scientific basis. Slick articles and ads generally exaggerate potential benefits, or they refer to in vitro or animal studies and anecdotal reports, making them sound as if they constitute direct evidence of clinical effects. They also need to understand the differences between THC and CBD, along with the fact that production is largely unregulated, so products can have many different ingredients and properties. Several studies have found wide discrepancies between labels for cannabis products and their actual contents, especially when it comes to the amount of THC or CBD.

 Thus, many products that claim only to have CBD actually have varying degrees of THC present. This lack of consistency often accounts for both inconsistent clinical effects as well as adverse effect issues, and these factors lead many older adults to discontinue use of cannabis products.

Finally, keep in mind that older patients with preexisting 

 such as in Alzheimer disease might be particularly vulnerable to adverse effects such as drowsiness, dizziness, fatigue, and mood changes, which in turn can account for significant and unpredictable fluctuations in cognition and behavior. Such unpredictability (in the amount of drug being ingested over time and the ensuing effects on brain and body) is exactly the sort of variability that can be hazardous in the older patient. Compounding these risks is the fact that many individuals will use products such as CBD oil without the knowledge and supervision of a knowledgeable clinician.

The bottom line is that more rigorous scientific study using randomized controlled trials is needed to substantiate the proposed benefits of cannabis and more fully understand the range and impact of common adverse effects.

is the chief medical officer at MIND Institute at Miami Jewish Health.

1. Gruber SA, Sagar KA, Dahlgren MK, et al. 

Splendor in the grass? A pilot study assessing the impact of medical marijuana on executive function

2. Grinspoon P. Older adults and medical marijuana: reduced stigma and increased use. 

Updated April 6, 2020. Accessed February 1, 2020. 

https://www.health.harvard.edu/blog/older-adults-and-medical-marijuana-reduced-stigma-and-increased-use-2-2020040119321

3. Han BH, Palamar JJ. Trends in cannabis use among older adults in the United States, 2015-2018. 

4. Reynolds IR, Fixen DR, Parnes BL, et al. Characteristics and patterns of marijuana use in community-dwelling older adults.

5. Oberbarnscheidt T, Miller NS. The impact of cannabidiol on psychiatric and medical conditions. 

6. Russo EB. Cannabis therapeutics and the future of neurology. 

7. Serpell M, Ratcliffe S, Hovorka J, et al. A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment. 

8. Shelef A, Barak Y, Berger U, et al. Safety and efficacy of medical cannabis oil for behavioral and psychological symptoms of dementia: an-open label, add-on, pilot study. 

9. van den Elsen GA, Ahmed AI, Verkes RJ, et al. Tetrahydrocannabinol for neuropsychiatric symptoms in dementia: a randomized controlled trial. 

10. Maust DT, Bonar EE, Ilgen MA, et al. Agitation in Alzheimer disease as a qualifying condition for medical marijuana in the United States. 

11. Gruber SA, Sagar KA, Dahlgren MK, et al. The grass might be greener: medical marijuana patients exhibit altered brain activity and improved executive function after 3 months of treatment. 

12. Britch SC, Babalonis S, Walsh SL. Cannabidiol: pharmacology and therapeutic targets. 

13. Antonsdottir IM, Makino KM, Porsteinsson AP. Dazed and confused: medical cannabis in Alzheimer disease. 

14. Crean RD, Crane NA, Mason BJ. An evidence-based review of acute and long-term effects of cannabis use on executive cognitive functions. 

15. Nader DA, Sanchez ZM. Effects of regular cannabis use on neurocognition, brain structure, and function: a systematic review of findings in adults. 

16. DeFilippis EM, Bajaj NS, Singh A, et al. Marijuana use in patients with cardiovascular disease: JACC review topic of the week. 

17. Abuhasira R, Ron A, Sikorin I, Novack V. Medical cannabis for older patients-treatment protocol and initial results. 

18. Benitez A, Lauzon S, Nietert PJ, et al. Self-reported cognition and marijuana use in older adults: Results from the national epidemiologic survey on alcohol and related conditions-III. 

19. Arkell TR, Vinckenbosch F, Kevin RC, et al. Effect of cannabidiol and Δ9-tetrahydrocannabinol on driving performance: a randomized clinical trial. 

20. Chesney E, Oliver D, Green A, et al. 

Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials

Cannabis use has prompted symptoms such as dizziness, sleepiness, and fatigue in older patients. Are there any benevolent effects?

Lost in the various public policy arguments fueling cannabis decriminalization and legalization 

 across the United States is the fact that a percentage of individuals who use cannabis will experience negative effects, ranging from bothersome to the catastrophic. These difficulties arise from a sharply decreasing perception of risk, easy availability of the drug, and increased potency of Δ-9-tetrahydrocannabinol (THC) preparations. The arithmetic of cannabis remains immutable: Best 

 are that about 9% of individuals who use cannabis will become dependent on the substance at some point in their life,

 and if the number of those who use cannabis goes up, the total number of those experiencing problems with the substance will rise also. Clinicians must learn to manage cannabis-related problems in this growing population.

 cannabis-dependent individuals face are serious, disheartening, and deserving of treatment. National Survey on Drug Use and Health (NSDUH) data on 505,796 Americans

 show that between 2008 and 2016 individuals aged 12 to 17, who met criteria for a cannabis use disorder (CUD), were 25% more common in states that had enacted Recreational marijuana laws (RMLs) as opposed to those who did not. In addition, the THC content of the various preparations of cannabis has risen over the past 10 years. Studies show that the mean THC concentration in smokable marijuana increased from 8.9% in 2008 to 17.1% in 2017,

 and half of those who frequently use marijuana ingest concentrates of at least 80% THC.

 in Colorado had an average THC percentage of 56.6%, while by 2017 the average was 68.6%, with some retail stores cheerfully advertising a 95% THC rate in their products.

Cannabis-related problems, like lack of motivation, usually become apparent after many years of use. Given cannabis’ pharmacological designation as a sedative-hypnotic substance, it is hardly surprising that common complaints on presentation to treatment include acute intoxication with high-potency 

; psychiatric phenomena such as depression, anxiety, and 

; and cannabinoid hyperemesis syndrome (CHS).

Clinicians should at least consider their patients’ cannabis use as a precipitating or exacerbating factor in any psychiatric or medical syndrome. Also, although the DSM-5

 contains a useful list of cannabis-related signs and symptoms, many individuals with cannabis-related problems do not meet the full criteria for CUD. For instance, while the casual cannabis smoker may present with a depressive picture but meet no other criteria for CUD, cessation of cannabis use may be necessary to achieve resolution of the patient’s dysphoria, anhedonia, and fatigue. CHS, cyclic episodes of nausea and vomiting often relieved with hot baths, can be a confusing emergency department presentation. Other medical presentations of heavy cannabis smoking include cough, bronchitis, lung hyperinflation,

 as well as acute lung injury from vaping.

 concerns related to cannabis may also generate first visits with a clinician.

, the DSM-5 criteria list the myriad problems that can arise from cannabis use. To fulfill criteria for CUD, the patient must demonstrate at least a yearlong “problematic pattern of cannabis use” and meet at least 2 of the criteria. However, the clinician would do well to consider any cannabis-related problem as a possible contributor to the patient’s reason for presentation.

The patient should be offered a coherent psychotherapy aimed at first minimizing the harms of cannabis use, and then achieving abstinence from the substance. Treatment of any co-occurring psychiatric conditions should be initiated concurrently with the below strategies, focused on cannabis cessation. Manualized techniques like cognitive behavioral therapy,

 have shown measurable, if modest, improvements in outcome criteria such as frequency of cannabis use, number of dependence symptoms, quantity of cannabis use, and negative consequences of cannabis use. These effective treatments share a good understanding of the addictive process, practical and easily deployed interventions, and a focus on small gains. Most clinicians use a mix of therapeutic techniques, which often include cannabis-specific

Peer-led support groups like Alcoholics Anonymous, although commonly recommended as an adjunct to the treatment of substance use disorders, should be carefully selected if recommended for the individual who uses cannabis. Members of peer support groups can be wrongly dismissive of those who only use cannabis. If possible, clinicians should recommend groups like 

 or specific groups which are known to understand the seriousness of CUD. Similarly, inpatient treatment or intensive outpatient programs should be carefully selected for their focus on or at least understanding of CUD.

A common—and counterproductive—fallacy about cannabis is that the substance does not cause withdrawal. In fact, the withdrawal syndrome from cannabis, though unlikely to cause serious medical problems, is uncomfortable and a leading reason that individuals who use cannabis do not stop their use of the substance. Withdrawal therefore requires treatment. Common phenomena associated with cannabis withdrawal include irritability, anxiety, depression, insomnia, disturbing dreams, anorexia, abdominal pain, tremors, sweating, fever, chills, headache,

A powerful first step in engaging the patient in treatment to beat their dependence on the drug is the clinician’s acknowledgement of the withdrawal syndrome and offer to find symptomatic relief. Patients should remain well-hydrated, eat a healthy diet, and exercise regularly during the withdrawal period. Although no medications have been approved by the US Food and Drug Administration (FDA) to treat cannabis withdrawal, symptom-relief medications like gabapentin

 to relieve anxiety and insomnia is indicated in some cases.

Treatment of cooccurring psychiatric illnesses with the appropriate medications is vital to the treatment of CUD. Although no medications have FDA-approved indications for the specific treatment of CUD, 2 have shown suggestive data in studies, and can be prescribed for patients needing additional pharmacological support. In small studies, the anticonvulsant topiramate

 demonstrated improved retention in treatment over placebo and gabapentin

 showed better treatment retention and a decrease in cannabis use and depressive symptoms. Various trials of dronabinol and nabilone, both THC analogues; nabiximols, a combination of THC and CBD; and N-acetylcysteine, a glutamatergic modulating dietary supplement, have shown little efficacy in the treatment of CUD.

Individuals who use cannabis may question any need for addressing their use by noting the ongoing success of cannabis legalization in the US, cannabis’ lack of lethality (as compared to opioids), and the natural provenance of the smokable varieties of cannabis. Clinicians should focus instead on the clinical issues that have brought the individual to treatment. Has the drug contributed to problems at work or school? Is there a psychiatric condition that would be better treated by psychotherapy or an actual medication? Have medical problems like hyperemesis developed? Although some individuals who use cannabis arrive in the clinic simply because a family member disapproves of cannabis use, the vast majority come in became they are being harmed in some way by their 

Despite the changing cultural ethos regarding cannabis, many individuals will suffer from problems related to their use of the substance. Some will meet criteria for CUD, and some will find their educational achievement, work lives, health, and relationships profoundly damaged by the drug. Along with the clinician’s attitude of encouragement and hope about recovery, effective relapse prevention therapies should be deployed. When necessary, medications for co-occurring psychiatric conditions should be used, as should the few available pharmacologic remedies for cannabis withdrawal. Clinicians engaging with patients should model a non-judgemental attitude about the substance, be realistic about the effects of cannabis, and encourage the path for reducing or stopping its use.

is an associate professor of clinical psychiatry in the Division of Alcoholism and Drug Abuse, Department of Psychiatry, New York University School of Medicine in New York, New York. He also serves as the consultant on behavioral health to the commissioner of Major League Baseball.

1. Lopez-Quintero C, Pérez de los Cobos J, Hasin DS, et al. 

Probability and predictors of transition from first use to dependence on nicotine, alcohol, cannabis, and cocaine: results of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC)

2. 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

3. Chandra S, Radwan MM, Majumdar CG, et al. New trends in cannabis potency in USA and Europe during the last decade (2008-2017). 

4. Bidwell LC, YorkWilliams SL, Mueller RL, et al. Exploring cannabis concentrates on the legal market: User profiles, product strength, and health-related outcomes. 

5. Colorado Department of Public Health and Environment. Colorado monitoring health concerns related to marijuana. Accessed January 22, 2021. 

The disproportionate rate of acute clinical illness associated with cannabis edible use

7. Hindley G, Beck K, Borgan F, et al. Psychiatric symptoms abused by cannabis constituents: a systematic review and meta-analysis. 

8. Galli JA, Sawaya RA, Friedenberg FK. Cannabinoid hyperemesis syndrome. 

Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)

10. Yayan J, Rasche K. Damaging effects of cannabis use on the lungs. 

11. Abeles M, Popofsky S, Wen A, et al. Vaping-associated lung injury caused by inhalation of cannabis oil. 

12. Mead A. Legal and regulatory issues governing cannabis and cannabis-derived products in the United States. 

13. Hazle MC, Hill KP, Westreich LM. Workplace cannabis policies: a moving target. 

14. Stephens RS, Roffman RA, Curtin L. Comparison of extended versus brief treatments for marijuana use. 

15. Stein MD, Hagerty CE, Herman DS, et al. A brief marijuana intervention for non-treatment-seeking young adult women. 

16. Budney AJ, Higgins ST, Radanovich KJ, Navy PL. Adding voucher-based incentives to coping skills and motivational enhancement improves outcomes during treatment for marijuana dependence. 

17. Marijuana Anonymous World Services. Service Manual. Updated 2012. Accessed January 22, 2020. 

https://madistrict4.org/docs/MAServiceManualrev4_1.pdf

18. Budney AJ, Stanger C. Cannabis use and misuse. In: Rey JM, ed. IACAPAP e-Textbook of Child and Adolescent Mental Health. International Association for Child and Adolescent Psychiatry and Allied Professions; 2012.

19. Lee D, Schroeder JR, Karschner EL, et al. Cannabis withdrawal in chronic, frequent cannabis smokers during sustained abstinence within a closed residential environment. 

20. Mason BJ, Crean R, Goodell V, et al. A proof-of-concept randomized controlled study of gabapentin: effects on cannabis use, withdrawal and executive function deficits in cannabis dependent adults. 

21. Levin FR, Mariani JJ, Brooks DJ, et al. Dronabinol for the treatment of cannabis dependence: A randomized, double-blind, placebo-controlled trial. 

22. Miranda R Jr , Treloar H , Blanchard A , et al. Topiramate and motivational enhancement therapy for cannabis use among youth: a randomized placebo-controlled pilot study. 

23. Kondo KK, Morasco BJ, Nugent SM, et al. Pharmacotherapy for the treatment of cannabis use disorder: a systematic review. 

24. SAMHSA. Brief counseling for marijuana dependence: a manual for treating adults. 2015. 

http://store.samhsa.gov/product/Brief-Counseling-for-Marijuana-Dependence-A-Manual-for-Treating-Adults/sma15-4211

25. Budney AJ, Roffman R, Stephens RS, Walker D. Marijuana dependence and its treatment. 

The sharply decreasing perception of risk and easy accessibility of cannabis has many patients turning towards it, despite the potential negative effects. 

This Special Report contains articles about cannabis use and its potential complications, including 

 highlights the use of cannabinoids among the geriatric population. Cannabis and cannabidiol (CBD) use in older adults has become more prevalent as a result of reduced stigma; leniency in state restrictions on possession and sale; and advertisements touting benefits for chronic pain, peripheral neuropathy, stress, anxiety, depression, insomnia, headaches, and the adverse effects of chemotherapy. Medical marijuana use by individuals 65 and older has increased more than 8-fold in recent years. The article nicely summarizes how heavy marijuana use can cause mild functional and structural brain impairments, affecting attention, processing speed, motor coordination, verbal memory, and executive function. Overall, every 

, along with their caregivers, should be queried as to their use of cannabis products. They should also be cautioned that those with preexisting neurocognitive impairment, such as Alzheimer disease, might be particularly vulnerable to adverse effects such as drowsiness, dizziness, fatigue, and mood changes.

We have a changing cultural ethos regarding cannabis acceptability; nevertheless, many users will suffer from its use. Some will develop CUD, and many can damage their educational achievement, work lives, health, and relationships. The 

 about the increasing number of cannabis users who experience negative effects, ranging from the annoying to the catastrophic. As noted, these effects arise from 3 sources: potential users’ sharply decreased perception of risk in recent years, easy availability of cannabis, and increased potency of Δ-9-tetrahydrocannabinol (THC) in legal and illegal cannabis sources. In recent years, THC concentrations in smoked cannabis doubled to 17.1% in 2017. Due to these high THC concentrations, clinicians need to recognize psychiatric complications of heavy repeated cannabis use, such as depression, anxiety, psychosis and, although rare, the cannabinoid hyperemesis syndrome.

Furthermore, although subtle compared with alcohol or opioid withdrawal, cannabis withdrawal does occur and includes irritability, anxiety, depression, insomnia, disturbing dreams, anorexia, abdominal pain, tremors, sweating, fever, chills, headache, and craving. Off-label use of medications for withdrawal are suggested and might include gabapentin and the THC analogue dronabinol, and limited amounts of benzodiazepines to relieve anxiety and insomnia. However, there has been little efficacy in the treatment of CUD.

 focuses on patients with schizophrenia. It synthesizes the large literature on cannabis and psychosis risk. The piece also reviews the literature on genetic associations, earlier age of onset, poorer treatment outcomes, and cognition. For example, a critical meta-analysis found an association between better cognitive performance and cannabis use in schizophrenia, a finding that merits careful replication because another analysis of first-episode schizophrenia found patients with psychosis and current cannabis use had significantly lower premorbid and current IQ scores.

We hope that you find that this educational 

 enhances your understanding of the rapidly changing field of cannabinoids and their clinical implications, particularly for our geriatric population and patients with schizophrenia.

is the Jay H. Waggoner Endowed Chair and co-founder at the Institute for Clinical and Translational Research. He is also a professor of psychiatry, neuroscience, pharmacology, and immunology at Baylor College of Medicine in Houston, Texas. 

 is an assistant professor of psychiatry research at Baylor College of Medicine. ❒

The rapidly changing field of cannabinoids and their clinical implications poses a particular challenge in psychiatry.

“Mr Green” is a 39 year-old African-American male with a history of chronic schizophrenia, cannabis use disorder, and alcohol use disorder. He started smoking cannabis almost daily at age 20. When he was 22, he was in a motor vehicle accident while under the influence of substances and suffered a head injury. Several months later, he was hospitalized for a first episode of psychosis (FEP). Thereafter, he participated in a long-term antipsychotic clinical trial.

For more than a decade, he has been maintained on a long-acting injectable antipsychotic and is adherent with appointments. He tends to get paranoid during stressful times, but he has not had any subsequent psychiatric hospitalizations. However, he has continued to use cannabis regularly—daily to weekly—for almost 20 years. Although he worked prior to the onset of his psychotic disorder, he has since been chronically unemployed. He lives at home with his parents, has never married, and does not have any children. He remains precontemplative regarding the need for treatment for alcohol and cannabis use disorder.

Mr Green’s case is (sadly) all too familiar for clinical practitioners in psychiatry. Substance use comorbidity in psychotic disorders has been described as the rule rather than the exception, and it is often deleterious to the clinical course of 

 Cannabis (marijuana) is one of the most commonly used substances by patients with schizophrenia and related psychoses. Modulation of the endocannabinoid system by the main psychoactive component in marijuana, Δ9-tetrahydrocannabinol, can induce acute psychosis and 

 Over the past 2 decades, there has been extensive research on the association between cannabis and psychosis.

To better understand the relationship, it is important to synthesize recent research—through the lens of systematic quantitative reviews—including associations between cannabis and psychosis risk; the epidemiology and phenomenology of psychosis and comorbid cannabis use; associations between cannabis use and clinical course; and outcomes in psychosis. Dichotomous outcomes are reported as odds ratios (OR) with 95% confidence intervals (95% CI). Continuous measures are reported as effect sizes (ES), where an ES of 0.2 is small, 0.5 is medium, and 0.8 is large.

 investigated cannabis use and psychotic experiences in a meta-analysis of 61 cohorts. They found a significantly increased prevalence (OR=2.41, 95% CI 1.84-3.43) and incidence (OR=1.77, 95% CI 1.20-2.61) of psychotic experiences in participants who used cannabis. This association is important given that 7.4% of people with psychotic experiences at baseline developed a psychotic disorder.

 meta-analyzed 29 studies of cannabis use and schizotypy (attenuated psychosis). Lifetime cannabis users had significantly greater scores for total (ES=0.42), positive (ES=0.44), negative (ES=0.18), and disorganized (ES=0.33) schizotypy versus never users. Furthermore, current cannabis users had significantly greater scores for total (ES=0.21), positive (ES=0.23), and disorganized (ES=0.27), but not negative schizotypy scores versus subjects that do not currently use cannabis.

 investigated the prevalence of cannabis use and its association with symptoms in participants at ultra-high risk (UHR) for psychosis. Across 30 studies (n=4205 UHR), there was a 27% current and 53% lifetime prevalence of cannabis use, and a 13% prevalence of cannabis use disorders (CUD). This corresponded to a 2.09-fold and 5.45-fold increased odds of lifetime use and CUD, respectively, in patients at UHR compared to n=667 controls. Furthermore, UHR cannabis users had a higher prevalence of both suspiciousness (ES=0.21) and unusual thought content (ES=0.27).

Furthermore, a recent comprehensive review by 

 which included 36 studies, found a 26% current and 49% lifetime prevalence of cannabis use, and a 15% prevalence of CUD in those at clinical high-risk for psychosis.

 reviewed the association between cannabis use and transition to psychosis in people at UHR across 7 studies. They found that lifetime cannabis use was not significantly associated with transition to psychosis in people at UHR (n=1171, OR=1.14, 95% CI 0.86-1.52). However, they found that current CUD was associated with significant, increased odds of transition to psychosis (OR=1.75, 95% CI 1.14-2.71).

 performed a meta-analysis of 7 case-control studies of cannabis use and risk of psychotic disorder. They found that cannabis use was associated with an almost 3-fold increased odds of psychosis (OR=2.9, 95% CI 2.4-3.6), with evidence that early cannabis use may confer even greater risk for psychosis outcomes. In a meta-analysis of 7 studies, Moore and colleagues,

 found a significant increased risk of any psychotic outcome in participants who had used cannabis (OR=1.41, 95% CI 1.20-1.65), with an even greater risk in those who used cannabis most frequently (3 studies = daily, 1 study each = weekly, >50 times, and cannabis dependence; OR=2.09, 95% CI 1.54-2.84).

 also investigated the magnitude of the dose-response relationship between cannabis use and risk of psychosis. In a meta-analysis of 10 studies (n=66,816), there was a significant, almost 4-fold increased odds of psychosis among the most severe cannabis users compared to non-users (OR=3.90, 95% CI 2.84-5.34).

 conducted a large genome-wide association study of those who use cannabis (n=20,916) and controls (n=363,116). They identified 2 loci with genome-wide significance: a novel locus on chromosome 7 (

; OR=1.11, 95% CI 1.07-1.15), and a previously identified locus on chromosome 8 (near 

; OR=0.89, 95% CI 0.86-0.93). Importantly, cannabis use and CUD were significantly, positively, and genetically correlated with schizophrenia in this study.

Epidemiology of Psychosis and Comorbid Cannabis Use

In a meta-analysis of 35 studies (n=5540), and found a 16% current and 27% lifetime median prevalence of CUD in patients with schizophrenia.

 The median prevalence of CUD was higher in FEP versus those with long-term schizophrenia (29% versus 22% for current, and 44% versus 12% for lifetime use). CUD was also more prevalent in studies with male predominance. A more recent systematic review of 69 studies in community and clinical settings found a 26% prevalence of current or lifetime cannabis use (36% in FEP samples).

 analyzed prevalence data on current cannabis use in FEP. In 10 samples, the pooled estimate for the time between initiation of regular cannabis use and onset of psychosis was 6.3 years. In 35 samples, the estimated prevalence of cannabis use at FEP was 34% (95% CI 31-39%), consistent with findings from an earlier meta-analysis.

 In 19 samples, cannabis use at follow-up (between 6 months and 10 years after FEP) declined about 50% over time (OR=0.56, 95% 0.40-0.79).

In a meta-analysis of 41 samples, Large and colleagues

 found that the age of onset of psychosis was 2.7 years younger (ES=0.41) for those who used cannabis than those who did not. Given that many cannabis users also smoke tobacco, Myles and colleagues

 compared the extent to which cannabis and tobacco use are associated with an earlier age of onset of psychosis. In 40 samples, the age of onset of psychosis was 32 months earlier for cannabis users than nonusers (ES=0.40, p<0.01), but 2 weeks later in tobacco smokers than non-smokers (ES<0.01, p=0.97). Sex was not a significant moderator of the association.

Psychopathology and Cognition in Comorbid Psychosis

Several reviews have investigated psychopathology in patients with comorbid psychosis and CUD. In pooled data from 2 studies, Potvin and colleagues

 did not find any difference in depressive symptoms in patients with schizophrenia with versus without cannabis use (ES<0.01). This same group found significantly greater levels of negative symptoms across 3 studies in patients with schizophrenia who used cannabis (n=102) than those who did (n=168) (ES=0.51).

 In a meta-analysis of 22 studies, Large and colleagues

 did not find any significant differences between positive, negative, and depressive symptoms, or social function in patients with psychosis and cannabis use versus those with psychosis and other non-cannabis substance use.

 conducted a meta-analysis of 10 studies (n=572) of the association between cannabis use and cognition in schizophrenia. They found significant better global cognition (ES=0.55), processing speed (ES=0.65), visual memory (ES=0.45), planning (ES=0.67), and working memory (ES=0.64) in individuals who used cannabis in their lifetime but not current/recent use . The association between better cognitive performance and cannabis use in schizophrenia may be driven by a subgroup of patients with less cognitive impairment who developed psychosis after a relatively early onset of cannabis use.

 further investigated the association between cannabis use and cognition, focusing on younger patients with psychosis (mean age 15-45). In a pooled analysis of 14 studies, patients with psychosis and current cannabis use had significantly lower premorbid (ES=0.40) and current IQ (ES=0.17), as well as worse scores on verbal learning (ES=0.39), working memory (ES=0.0.76), and motor inhibition (ES=0.19), but significantly better scores on conceptual set-shifting (ES=0.32) compared to patients with psychosis and no lifetime cannabis use.

Clinical Course and Outcomes in Psychosis

The duration of untreated psychosis (DUP) is a predictor of outcome in FEP. Burns

 analyzed 7 studies (n=1453) of DUP and cannabis use in FEP, 39% of whom were cannabis users. He found a non-significantly shorter DUP in those who used cannabis versus those who did not (28.4 vs 29.3 weeks).

In a meta-analysis of 15 observational studies (n=3678), Foglia and colleagues

 investigated the effects of cannabis use on antipsychotic adherence in patients with psychosis. At baseline, cannabis users had a 2.5-fold increased odds of antipsychotic nonadherence compared to non-users (OR=2.46, 95% CI 1.97-3.07, n=3055). At follow-up, there was an almost 6-fold increased odds of antipsychotic nonadherence in current cannabis users compared to nonusers (OR=5.79, 95% CI 2.86-11.76, n=175 subjects). By contrast, antipsychotic nonadherence was not significantly different between former cannabis users and non-users.

There is very limited data comparing antipsychotics head-to-head in patients with psychosis and comorbid cannabis use. Brunette and colleagues

 found significantly less cannabis use in n=15 patients treated with clozapine versus n=16 patients treated with other antipsychotics (ES=1.08), broadly consistent with evidence for efficacy of clozapine in patients with substance use comorbidity. Another small trial found significantly less cannabis use in n=20 patients on olanzapine versus n=21 patients on risperidone.

Despite the established association between cannabis use and psychosis, less is known about the effects of continued (versus discontinued) cannabis use after the onset of illness. Schoeler and colleagues

 identified 24 studies (n=16,565) in this area. Independent of illness stage, patients who continued cannabis use had a significantly greater risk of relapse of psychosis than both patients who discontinued cannabis use (ES=0.28) and non-users (ES=0.36). By contrast, there was no difference in relapse risk between patients who discontinued cannabis use and non-users (ES=0.02). Furthermore, patients with continued cannabis use had significantly longer durations of hospitalization than non-users (ES=0.36). In meta-regression analysis, continued cannabis use (versus discontinued use) was a significant moderator of more severe positive symptoms and lower level of functioning, but not negative symptoms.

, there are robust associations between cannabis use and psychosis risk, with evidence for a dose-response relationship, which supports the plausibility of a causal association. Comorbid cannabis use is highly prevalent in psychosis (especially FEP, with declining use over time), with strong evidence for an earlier age of onset of illness, as well as effects of psychopathology and cognition. In patients with psychosis, continued cannabis use is associated with antipsychotic nonadherence, illness relapse, and longer hospitalizations. These findings raise the possibility of a dose-response relationship between current cannabis use and transition to psychosis. Findings suggest that targeting cannabis use during the UHR period may confer significant benefits on long-term outcomes. Continued cannabis use is also a potential target for intervention to improve antipsychotic adherence and other outcomes in patients with psychosis. Future research in this area is clearly warranted to elucidate mechanisms and novel treatment strategies for relevant populations.

is professor in the Department of Psychiatry and Health Behavior, Augusta University, Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for 

The author reports that he receives research support from Augusta University, the National Institute of Mental Health, the Brain and Behavior Research Foundation, and the Stanley Medical Research Institute.

A synthesis of quantitative reviews on the relationship between cannabis use and psychosis.

Cannabis