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North America is currently experiencing an opioid overdose crisis driven mainly by fentanyl and fentanyl analogs, such as carfentanyl.

fatalities involving opioids in the United States

 The COVID-19 pandemic has only heightened the 

 of opioids on individuals who use the drugs, their families, and communities across 

 Novel solutions are needed for this complex problem.

Much is already being done. In an effort to mitigate the overdose crisis, both Canada and the United States have implemented multiple public health and treatment strategies. Extant strategies include providing opioid agonist therapies (OAT), naloxone for reversing fatal opioid overdoses, and access to harm reduction services. In addition, injectable/implantable buprenorphine is available in both countries. However, the opioid receptor antagonist naltrexone, while available in the oral formulation in both Canada and the United States, is not available in the depot formulation in Canada. Currently, OAT with methadone or buprenorphine/naloxone are the first-line interventions for individuals with moderate to severe 

 Although buprenorphine/naloxone is preferable over methadone in terms of its superior safety profile, there are many limitations to these treatments. Moreover, in Canada, there are barriers to accessing OAT, including reduced access to OAT prescribers in rural areas, and the shortage of pharmacies offering on-site OAT.

OAT clinics often lack psychosocial supports, and there are often high out-of-pocket expenses that prove problematic for individuals with OUD who have limited financial means.

 Similar economic, geographic, attitudinal, and organizational barriers exist in the United States.

 Additionally, in the United States, health insurance barriers, where public insurance providers favour methadone while private insurance favours buprenorphine/

, have caused rampant racial and economic disparities in OAT access across the United States.

Since the start of the opioid crisis, Canada has taken several novel harm reduction approaches to combat the opioid crisis. Harm reduction refers to a wide array of public health policies intended to reduce the adverse consequences of human behaviours, including—but not limited to—substance use. In the context of the opioid crisis, harm reduction interventions have included rapid access addiction medicine services, providing take-home naloxone kits, supervised consumption facilities (SCFs), and education around overdose risk mitigation.

Historically, the success of harm reduction services for OUD has been difficult to quantify; most studies have small sample sizes and poorly defined outcome measures. These studies have limited generalizability to most individuals with OUD, who respond to first-line treatments. However, there is mounting evidence that demonstrates proof of efficacy and effectiveness for a range of harm reduction services. Recent studies have shown that they can reduce opioid overdose mortality, infection-related complications, and crime amongst individuals with treatment-refractory OUD (TR-OUD).

In recent years the Canadian health care providers have implemented 3 critical harm reduction measures that have curtailed opioid-related fatalities: (1) heroin-assisted therapy, (2) hydromorphone-assisted therapy, and (3) supervised consumption facilities (SCFs). A summary of each of these novel treatments is provided in 

Following the Canadian example, we advocate for the provision of 

 in the United States that could save countless lives by increasing access to evidence-based treatment options for OUD.

Heroin-assisted treatment (HAT), or heroin maintenance, is an evidence-based intervention for managing the symptoms of treatment-refractory OUD (TR-OUD). While there are varying definitions of TR-OUD, most studies refer to the failure to respond meaningfully to 1 or more first-line treatments for OUD (eg, methadone or buprenorphine/suboxone). HAT is available in Canada (eg, Vancouver and Montreal) and in some European countries (eg, Germany, Switzerland, and the United Kingdom) and has shown efficacy in select groups experiencing TR-OUD. To receive HAT, individuals with TR-OUD must visit designated 

, where they will receive injectable medical-grade heroin (diacetylmorphine) up to 3 times daily under strict nursing and medical supervision.

 In essence, most HAT clinics operate under a supervised consumption model.

Results from randomized controlled trials have shown promising findings for individuals with TR-OUD. In one trial, HAT reduced illicit heroin use, improved treatment retention, reduced criminal activities, and improved mental and physical health compared with methadone therapy.

 While HAT is more expensive than oral methadone treatment, the social and economic benefits justify its provision for select patients with TR-OUD who have not benefited from first-line therapies. Nonetheless, studies have shown an association between HAT and a higher risk of adverse events such as seizures and opioid overdoses11 than methadone or buprenorphine/naloxone. While HAT carries a more dangerous safety profile than other forms of OAT, HAT administration typically occurs in supervised clinical settings, which lessens these risks. Thus, while HAT carries an increased absolute risk of adverse events—including opioid overdose—it is still a harm reduction measure as it lessens the risk relative to the unsupervised consumption of street-sourced heroin or fentanyl.

Given the regulatory restrictions in providing HAT, investigators in Vancouver, Canada, considered alternative strategies for treating individuals with TR-OUD. The search for alternative OAT led to hydromorphone, a synthetic opioid used to treat chronic pain. Consequently, researchers at St Paul’s Hospital in Vancouver conducted the Study to Assess Longer-term Opioid Medication Effectiveness (SALOME) trial.

In brief, the SALOME trial was an innovative study investigating the use of injectable hydromorphone (IH) as an alternative to intravenous diacetylmorphine (eg, HAT) for TR-OUD. The researchers aimed to establish the noninferiority of IH to HAT. Ultimately, the researchers found that delivering the 2 interventions under the same conditions (eg, supervised consumption facilities) led to positive outcomes in both groups. For example, participants receiving either treatment showed improved treatment retention, greater global functioning, reduced illicit opioid use, and diminished illegal activities.

 The SALOME trial was one of the first to establish the efficacy of these harm reduction measures for a population of individuals with TR-OUD. Consequently, the SALOME trial suggests that when diacetylmorphine is unavailable or other treatments are unsuccessful, IH can be a suitable alternative for treating severe TR-OUD.

In January 2019, Vancouver started the first hydromorphone tablet distribution program, based on the promising results of the SALOME trial. A qualitative study evaluated its effects, suggesting that it can decrease illicit drug use, overdose risk, engagement in illegal activities, and address social inequalities surrounding drug use.

, take-home hydromorphone has been permitted, and the effects of this expansion can be promising for the wide-scale implementation of similar programs in rural, suburban, and urban settings.

 However, further study of injectable and oral hydromorphone in TR-OUD patients in diverse settings is warranted.

Supervised consumption facilities (SCFs) are safe and clean indoor facilities where individuals can use pre-obtained drugs under the supervision of trained medical professionals to ensure safe injection or other consumption (eg, oral or smoked) methods. In parallel, SCFs can implement rapid responses in opioid overdoses, such as by providing intranasal or intramuscular naloxone.

 SCFs have emerged in Canadian cities such as Toronto, Ottawa, and Halifax as grassroots initiatives to address unmet needs for special populations with TR-OUD or other substance use disorders. These SCF initiatives can also assist in different ways by providing counselling and psychosocial supports, referrals to social services, and access to medical and psychiatric treatment where necessary.

SCFs were first developed in response to the HIV epidemic in Vancouver when Insite—North America’s first SCF—proved to be a tremendous asset in combating the 

 One of the additional benefits of SCFs is that they can provide a multifaceted opportunity to address comorbidities, such as psychiatric illness, HIV/AIDS, and other infectious diseases. As individuals with TR-OUD frequently experience co-occurring medical and psychiatric disorders, SCFs have created critical opportunities to engage with a population that is difficult to reach otherwise. Various studies have demonstrated their myriad benefits, such as decreasing overdose deaths, crime, and infectious disease transmission while remaining cost-effective.

A recent study estimated the cost and impact of establishing SCFs in New York City. It showed that an SCF can prevent 19 to 37 opioid overdose fatalities per year in New York City and between $831,700 and $2.9 million in costs would be saved by the healthcare system.

 However, this remains a controversial topic in the United States, and advocacy for drug policy changes must continue.

The overdose crisis has negatively affected all Canadian provinces and territories, with British Columbia, Ontario, and Alberta recording the highest number of opioid-related overdose deaths in 2019.

 The United States has also seen a widespread increase in the number of opioid-related deaths since the 2000s, with the Northeast, Mid-Atlantic, and Mid-Western states being most impacted.

 Currently, most of the overdose fatalities involve synthetic opioids such as fentanyl and its analogues,

 (> 90%) appear to be accidental. The high prevalence of fentanyl as an adulterant in the illegal supplies of heroin and other injectable drugs (eg, cocaine and crystal methamphetamine) are the major factors accounting for the growing number of overdose-related deaths.

The most commonly used opioid agonist therapies (OAT) in Canada and the United States are methadone and buprenorphine/naloxone. However, their availabilities vary across regions and by insurance coverage.

The rising number of opioid-related fatalities is a call to action to implement sustainable measures to prevent overdose occurrences beyond acute naloxone administration. Canada has implemented multiple harm reduction measures since the beginning of its opioid crisis, which have reduced overdose mortality. For example, the current safe supply programs focus on prescribing pharmaceutical-grade opioids, such as injectable hydromorphone and diacetylmorphine, to individuals at high risk of 

. These can be powerful aids to reducing the harm of fentanyl-related opioids from the illicit drug market, and as a result, prevent overdose events and decrease overdose mortality.

 Canadian and international SCF studies have shown effectiveness in reducing overdose fatalities and decreasing needle sharing, unsafe injection practices, and involvement in criminal activities.

 As Canada and the United States take action to combat the current opioid crisis, they can learn from the collective expertise and strategies implemented on either side of the border to search for comprehensive, collaborative, and evidence-based approaches to the opioid crisis.

is a 3rd-year medical student at Touro College of Osteopathic Medicine in New York, NY, USA.

is a Fellow in Addiction Psychiatry in the Cumming School of Medicine at the University of Calgary, Calgary, Canada.

is a Staff Psychiatrist in the Addictions Division at the Centre for Addiction and Mental Health (CAMH) and Lecturer in Psychiatry, Temerty Faculty of Medicine, University of Toronto.

is an Advanced Practice Clinical Leader at CAMH, and a PhD candidate in the Bloomberg School of Nursing at the University of Toronto.

is Professor of Anthropology and Psychiatry, and Research Chair in the Social Medicine Theme, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

is Professor of Psychiatry in the Temerty Faculty of Medicine at the University of Toronto, and Clinician-Scientist in the Addictions Division at CAMH in Toronto, Canada. He also serves as Deputy Editor of the journal Neuropsychopharmacology (NPP).

The constructive and critical comments of Dr Eric C. Strain of John Hopkins University on the manuscript are gratefully acknowledged.

1. Ivsins A, Boyd J, Beletsky L, McNeil R. Tackling the overdose crisis: The role of safe supply. 

2. Government of Canada. Opioid- and Stimulant-related Harms in Canada (Maps). Accessed March 24, 2021. 

https://health-infobase.canada.ca/substance-related-harms/opioids-stimulants/maps

3. National Institute on Drug Abuse. Overdose death rates. January 29, 2021. 

https://www.drugabuse.gov/drug-topics/trends-statistics/overdose-death-rates

4. Government of Canada. (March 24, 2021). Opioid- and Stimulant-related Harms in Canada (Key Findings). 

https://health-infobase.canada.ca/substance-related-harms/opioids-stimulants

5. Centers for Disease Control and Prevention. Overdose deaths accelerating during COVID-19 – expanded prevention efforts needed. December 18, 2020. 

https://www.cdc.gov/media/releases/2020/p1218-overdose-deaths-covid-19.html

6. Schuckit MA. Treatment of opioid-use disorders. 

7. Priest KC, Gorfinkel L, Klimas J, et al. Comparing Canadian and the United States opioid agonist therapy policies. 

8. Hansen HB, Siegel CE, Case BG, et al. Variation in buprenorphine and methadone treatment by racial, ethnic, and income characteristics of residential social areas in New York City. 

9. Young S, Fairbairn N. Expanding supervised injection facilities across Canada: lessons from the Vancouver experience. 

10. Drug Policy Alliance. Heroin assisted treatment (HAT). February 2016. 

https://drugpolicy.org/sites/default/files/DPA%20Fact%20Sheet_Heroin-Assisted%20Treatment_(Feb.%202016).pdf

11. Oviedo-Joekes E, Brissette S, Marsh DC, et al. Diacetylmorphine versus methadone to treat opioid addiction. 

12. Oviedo-Joekes E, Guh D, Brissette S, et al. Hydromorphone compared with diacetylmorphine for long-term opioid dependence: A randomized clinical trial. 

13. Timko C, Schultz NR, Cucciare MA, et al. Retention in medication-assisted treatment for opiate dependence: A systematic review. 

14. Ivsins A, Boyd J, Mayer S, et al. "It’s helped me a lot, just like to stay alive": a qualitative analysis of outcomes of a novel hydromorphone tablet distribution program in Vancouver, Canada. 

15. Behrends CN, Paone D, Nolan ML, et al. Estimated impact of supervised injection facilities on overdose fatalities and healthcare costs in New York City. 

How can understanding the opioid crisis in Canada inform strategies in the United States?

Lessons from Novel Harm Reduction Methods

Vaping—one word, but not one behavior. 

 is a method of substance inhalation that delivers anything from blueberry-flavored vitamin D to delta-9-tetrahydrocannabinol (THC) into the body. While health professionals often refer to electronic cigarettes (e-cigarettes) and vaping synonymously, e-cigarettes represent only a small fraction of the growing market for 

 products available to consumers of all ages. So, why all the fuss?

 tar and asbestos is risky, but what about zinc, lead, chromium, manganese, and copper?

 All have been identified as components in various vaping products (ie, e-liquids, vape juice), although the long-term health consequences of these ingredients are not well-defined. E-liquid ingredients that are safe to be ingested and processed in the gut may be thought to be benign (eg, vegetable glycerin [VG] and propylene glycol [PG]), but may cause 

 Beyond lung damage, aerosol inhalation may increase cardiovascular risk.

Nicotine vaping products increase the risk for the same health consequences as any other nicotine exposure: subsequent development of a nicotine addiction; priming for use of other substances; changes in attention, cognition, and impulse control; and increased risk of developing mood disorders.

 The risk is compounded by the ready availability of vape juices and e-liquids with high concentrations of nicotine, beyond what is found in traditional tobacco products.

Young children and developing fetuses may also be prone to indirect health consequences of vaping products. There are reports of vaping liquids being swallowed and absorbed through the skin and eyes, resulting in poisoning. Fetal exposure can result in multiple adverse health consequences, including sudden infant death syndrome.

Given the potential for harm, why do individuals vape nicotine and other harmful chemicals for purposes other than 

 cessation? Among youth, the most common reason for vaping is curiosity.

 Vaping may be seen an act that brings social benefit—friends use what their friends use.

 Available online and in neighborhood stores, vaping products are perceived as both fashionable and convenient.

 Vape systems can be discreet (ie no visible aerosol) or flashy (ie production of large vape clouds). With advanced features such as voice control, accent lighting, and Bluetooth compatibility, there is a vaping device to appeal to almost any subculture and customer.

The ability to customize vape systems and liquids carries additional risks. Most samples obtained from the e-cigarette liquid of individuals being treated for e-cigarette or vaping product use-associated lung injury (EVALI), contained THC. Vitamin E acetate was identified in all samples, and glycerin, propylene glycol, diacetyl, aldehydes, formaldehyde, terpenes, organic compounds, and trace metals may have contributed to the over 

2800 EVALI cases and 68 associated deaths

 In our investigation of college student vaping using data collected from the 2018 to 2019 Health Minds Study survey, we found that almost 1 in 4 students who vaped used THC,

 and a study of the 2018 National Youth Tobacco Survey found that about 1 in 4 of the middle and high school student sample had vaped marijuana.

The short answer is yes. A few US states, tribal governments, and some countries have broadened prohibitions against smoking in public places to include vaping, but most have not. The US Food and Drug Administration (FDA) 

, predominantly when marketed to children and youth, sold without age-verification or without limiting number.

 Menthol, previously considered an adult flavor, is 

While vaping products are being used by nonsmokers, vaping has utility as a smoking cessation aid for adult consumers.

 Given the undeniable harms of smoking, vaping provides an option for people who are ready to quit smoking.

 However, among youth, vaping is more often initiated as an addition to, or a gateway to smoking; in one typical study, only 7.3% of 12th graders who vaped did so for smoking cessation

 and people with dual use (smoking and vaping) are exposed to increased harms.

“Paul” was a smoker for over 30 years; despite use of numerous quit methods, Paul’s frequent attempts to stop 

 were curtailed by his anxiety and disrupted concentration. Finally, his primary care provider convinced him to give vaping a 2-week try. Cynical about anything helping, Paul was relieved when he discovered vaping worked for him. In addition, he was thrilled to find products that were within his budget. But vaping has not been 100% panacea. One day while working at his computer, Paul felt a sudden flash of pain and his pant leg burst into fire. A visit to the emergency department and a skin graft were required after his battery exploded in his pocket. Nevertheless, Paul is still vaping. He says he will never return to smoking cigarettes, although he misses it. He is scheduled to see a pulmonologist; he is certain that vaping has been better for his health than the 2 packs a day he used to smoke. However, family and friends are concerned, he reports, because he is never without his vape pen, and he realizes he hits it with no conscious knowledge of doing so, regardless of where he is.

Assessing the clinical significance of vaping.

 Talking to a patient about vaping may require some investigation (

). Frequency of use and the types of products used influence the safety and clinical significance of the behavior. If the client is distressed by their behavior, experiences functional impairment, or reports poor health outcomes including symptoms of tobacco or cannabis use disorders, you may decide to provide assistance and help your client quit, or reduce, vaping behavior.

Resources to help your client quit vaping.

 The US Department of Health and Human Services

 In-person and online classes and/or support groups, tailored text messaging services, a free QuitGuide app, and information related to nicotine replacement products are available. Patients can consult and access these resources when they want to quit smoking or vaping. While vaping cessation research is scant

 and is primarily limited to nicotine vaping, methods used to quit are likely amenable to those used in smoking cessation.

 US Preventive Services Task Force recommendations for clinicians are to ask about use, advise quitting, and provide behavioral interventions and pharmacotherapy.

 Teens and adolescents may require niched interventions, whether consuming nicotine via vaping or other methods.

 funded the development of a text-to-quit mobile application as an addition to their quit program for teens. This program is based on research of vaping patterns, quit attempts, and cessation motivation; interventions should be tailored to address social influences, outcome expectancies, and intentions to quit.

 Expecting mothers also need a tailored approach to quit vaping; counseling techniques, including relaxation activities,

 and monetary incentives improve outcomes.

 Nicotine Replacement Therapy may also be helpful.

is an associate professor and Director in psychiatric epidemiology at the University of Florida.

is a PhD student in epidemiology at the University of Florida.

1. Stratton K, Kwan LY, Eaton DL. Public health consequences of e-cigarettes: consensus study report. 

Public health consequences of e-cigarettes: consensus study report

https://www.cabdirect.org/cabdirect/abstract/20183318811

2. US Department of Health and Human Services. E-Cigarette use among youth and young adults. A report of the surgeon general

 US Department of Health and Human Services; 2016. 

https://e-cigarettes.surgeongeneral.gov/documents/2016_SGR_Full_Report_non-508.pdf

3. Buchanan ND, Grimmer JA, Tanwar V, et al. Cardiovascular risk of electronic cigarettes: a review of preclinical and clinical studies. 

4. Goniewicz ML, Boykan R, Messina CRet al. High exposure to nicotine among adolescents who use Juul and other vape pod systems (‘pods’). 

5. Romijnders KAGJ, van Osch L, de Vries H, Talhout R. Perceptions and reasons regarding e-cigarette use among users and non-users: A narrative literature review. 

6. Jarmul S, Aherrera A, Rule A, et al. Lost in e-cigarette clouds: A culture on the rise. 

7. Outbreak of lung injury associated with the use of e-cigarette, or vaping, products. Centers for Disease Control and Prevention. Updated February 25, 2020. Accessed May 11, 2021. 

https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html

8. Griffiths A, Rauzi A, Stadheim K, Wheeler W. Lung injury associated with e-cigarette or vaping product use. 

9. Striley CW, Nutley SK. World vaping update. 

10. Ben Taleb Z, Kalan ME, Bahelah R, et al. Vaping while high: Factors associated with vaping marijuana among youth in the United States. 

11. FDA finalizes enforcement policy on unauthorized flavored cartridge-based e-cigarettes that appeal to children, including fruit and mint. US Food and Drug Administration. March 24, 2020. Accessed May 11, 2021. 

https://www.fda.gov/news-events/press-announcements/fda-finalizes-enforcement-policy-unauthorized-flavored-cartridge-based-e-cigarettes-appeal-children

12. FDA commits to evidence-based actions aimed at saving lives and preventing future generations of smokers. US Food and Drug Administration. April 29, 2021. Accessed May 11, 2021. 

https://www.fda.gov/news-events/press-announcements/fda-commits-evidence-based-actions-aimed-saving-lives-and-preventing-future-generations-smokers

13. Hartmann-Boyce J, McRobbie H, Lindson N, et al. Electronic cigarettes for smoking cessation. 

14. Wang RJ, Bhadriraju S, Glantz SA. E-cigarette use and adult cigarette smoking cessation: A meta-analysis. 

15. Evans-Polce RJ, Patrick ME, Lanza ST, Miech RA, O'Malley PM, Johnston LD. Reasons for Vaping Among U.S. 12th Graders. 

. 2018;62(4):457-462. doi:10.1016/j.jadohealth.2017.10.009

16. Prochaska JJ, Benowitz NL. Current advances in research in treatment and recovery: Nicotine addiction. 

17. QuitGuide. Smokefree.gov. Accessed May 11, 2021. 

https://smokefree.gov/tools-tips/apps/quitguide 

18. Tobacco information and tips for quitting smoking. BeTobaccoFree. Accessed May 11, 2021. 

19. Smoking—Medicines to help you quit. US Food and Drug Administration. 2019. Accessed May 11, 2021. 

https://www.fda.gov/consumers/free-publications-women/smoking-medicines-help-you-quit

20. Smoking cessation information & programs. Tobacco Free Florida. Accessed May 11, 2021. 

21. Berg CJ, Krishnan N, Graham AL, Abroms LC. A synthesis of the literature to inform vaping cessation interventions for young adults. 

22. Cuccia AF, Patel M, Amato MS, et al. Quitting e-cigarettes: Quit attempts and quit intentions among youth and young adults. 

23. Amato MS, Bottcher MM, Cha S, et al. “It’s really addictive and I’m trapped:” A qualitative analysis of the reasons for quitting vaping among treatment-seeking young people. 

24. US Preventive Services Task Force, Krist AH, Davidson KW, et al. Interventions for tobacco smoking cessation in adults, including pregnant persons: US preventive services task force recommendation statement. 

25. This is quitting. The Truth Initiative. Accessed May 11, 2021. 

https://www.thetruth.com/article/this-is-quitting

26. Chamberlain C, O’Mara-Eves A, Oliver S, et al. Psychosocial interventions for supporting women to stop smoking in pregnancy. 

27. Notley C, Gentry S, Livingstone‐Banks J, et al. Incentives for smoking cessation. 

28. Livingstone‐Banks J, Norris E, Hartmann‐Boyce J, et al. Relapse prevention interventions for smoking cessation. 

Healthy lungs are at risk—what can you do as a clinician to help patients quit vaping?

Vaping: What Psychiatrists Need to Know

 and autism spectrum disorders is in its infancy, there has been much controversy and confusion. Over the years, more patients and their families are seeking guidance from doctors on using cannabis to alleviate symptoms. From preventing seizures to calming aggression, a slow trickle of research is suggesting that cannabidiol (CBD), a component of cannabis, may be the wonder drug families have been searching for. But does it hold up to this standard? Should we be recommending it to patients? How do we weigh the benefits and the risks?

Unfortunately, many clinicians lack adequate training on the subject, making them unprepared to have a meaningful discussion with patients and families. Efforts to advance research have been limited for technical and logistical reasons, often leaving doctors with just as many questions as patients.

is a genus of flowering plants belonging to the family Cannabaceae that includes 3 species: cannabis sativa, indica, and ruderalis. Marijuana specifically refers to the parts of the cannabis plant that contains high amounts of delta-9-tetrahydrocannabinol (THC). Medicinal use of the cannabis plant dates back thousands of years in cultures all around the world. Today, it is used to treat an assortment of conditions, such as arthritis, cancer, HIV/AIDS, glaucoma, seizures, and more.

Used recreationally, it produces a high or mind-altering effect when smoked or consumed. It is also used therapeutically. The National Institute on Drug Abuse 

 as “using the whole, unprocessed marijuana plant or its basic extracts to treat symptoms of illness and other conditions.”

The plant produces more than 500 different chemical substances. These include 100 unique cannabinoids, which bind to the CB1 and CB2 receptors in the body’s endocannabinoid system. CB1 receptors are more common in the central and peripheral neurons, while CB2 receptors are expressed only in peripheral tissues, predominating the immune system.

THC and CBD are 2 cannabinoids found in cannabis that have particular clinical importance.

In medical applications, THC is typically used to relieve pain, nausea, insomnia, and poor appetite. THC is a partial agonist of the CB1 and CB2 receptors.

, which is why it is included in so many recreational marijuana products.

CBD is less controversial than THC because it does not produce mind-altering or euphoric effects. It has low affinity for CB1/CB2, acting as an antagonist.

 It affects various receptor systems in the body (TRPV1, GPR55, PPAR.) Of note is its agonism on the 5HT1A (serotonin) receptor at high concentrations to help with anxiety, sleep, pain perception, and nausea.

 It also appears to be a partial dopamine receptor agonist, pointing toward its possible antipsychotic properties. Additionally, CBD appears to influence the glutamate-GABA system.

Endocannabinoids are naturally occurring lipid mediators in the body that bind to the cannabinoid receptors. Unlike other neurotransmitters, they are produced on demand in the body and are quickly inactivated. The most common ones include: N-arachidonoylethanolamine (anandamide), 2-arachidonylglycerol (2-AG), and 2-arachidonylglyceryl ether.

Anandamide, also known as the “bliss molecule,” is currently one of the most-studied endocannabinoids.

 The cannabinoid receptor system has a very complex role in the body, which includes regulation of cell function, maintenance of homeostasis, motor coordination (basal ganglia), brain reward system, stress response, memory function (hippocampus), appetite, modulation of pain, and reduction of inflammation. 

Anandamide causes inhibition of the release of neurotransmitters such as glutamate and gamma aminobutyric acid (GABA). It also affects norepinephrine, dopamine, serotonin, histamine, prostaglandins and opioids.

 An imbalance in the GABA and glutamate system is often linked with 

Autism spectrum disorder (ASD) is a neurodevelopmental disability characterized by impairment in 3 major domains: social interaction, communication, and behavior patterns. It is called a spectrum disorder because it has a broad range of severity and symptom type. These usually appear within the first few years of life, although it can be diagnosed at any age.

In 2016, 1 in 54 children by the age of 8 was diagnosed with ASD, according to 

Centers for Disease Control and Prevention statistics

. This was a 10% increase over 2014, when the estimate was 1 in 59. Boys are 4 times more likely than girls to be diagnosed.

The causes of autism are not clearly understood. It is a complex disorder thought to be multifactorial in origin, involving genetic and environmental factors.

 It is associated with several conditions, such as Fragile X, Rett syndrome, tuberous sclerosis, phenylketonuria, and certain genetic conditions involving the deletion or duplication of chromosomes. Additionally, roughly 20% to 25% of individuals with autism are diagnosed with epilepsy at some point during their lives. Intellectual disability is also highly prevalent in autism, and there is a close association with seizure risk in autistic individuals.

Environmental factors being explored by research include viral infections, air pollutants, dietary factors, medications, and perinatal complications. Other common risk factors include children born to older parents, siblings of affected children (especially in the case of identical twins), and a family history of autism.

There are no medications that address autism’s core symptoms. Existing medications are used to target comorbid symptoms such as anxiety or mood symptoms and aggressive behavior. But these may not be very effective and often cause several side effects, limiting their use.

With autism cases on the rise, the need for effective treatments is rising too. Treatments in childhood carry special risks and potential rewards. Because a child’s brain is still developing, it is a good opportunity to make significant changes, but for the same reason, it is a dangerous time to experiment with certain compounds like THC and cannabis. Many of us have encountered desperate families who have found traditional treatments inadequate or resulting in undesirable side effects. At their wit’s end, they are willing to try just about anything. By not approaching the topic, patients and families may seek unsubstantiated advice on the Internet, leading them to use substandard and potentially dangerous products in an unregulated market.

Today, cannabis is easily accessible and popular with millions of Americans, but as noted, cannabis can be a mixture of many things. While the federal government considers cannabis a Schedule I drug, it has been legalized in 33 states and Washington, DC. Meanwhile, CBD is a schedule 5, the lowest degree of regulation by the US Food and Drug Administration. As a treatment for autism, cannabis has been prescribed in 14 states since 2019, according to the 

Whether we accept cannabis as a psychiatric treatment or not, our patients and their families are curious and interested in learning about all options. That is why it is vital for us as psychiatrists to educate ourselves on the use of cannabis to treat autism spectrum disorder (ASD), recognizing that the both the risks and benefits of use in ASD are indirect and insufficient. This might be the only way we can guide our patients to weigh all the facts before making a treatment choice.

Research on cannabis’ impact on autism is still very much in its infancy, but there are several important studies to consider, with more on the way. In a 2018 Stanford University study, anandamide concentration was significantly lower in children with ASD as compared to controls.

 Research studies have suggested that anandamide produces effects similar to, but less intense than, those associated with THC.

 Because of this similarity, researchers theorize THC has therapeutic potential in the treatment of autism.

Another study in 2013 found an increased expression of CB2 receptors in peripheral blood mononuclear cells in autistic children, suggesting an imbalance in the endocannabinoid system.

 Oxytocin is a neuropeptide crucial for social behavior, and studies indicate the oxytocin-driven anandamide signaling system may be defective in autism patients, leading researchers to theorize whether CBD can correct this.

Terpenoids are aromatic compounds present in the cannabis plant that give each strain its unique smell. Cannabinoids and terpenoids are thought to interact with each other as well as the brain in an entourage effect to produce synergistic results. This effect potentially increases the therapeutic value and tames the mind-altering effects of THC in a product. Similarly, there is some evidence proposing that the simultaneous use of THC and CBD is more effective than either alone. While still theoretical, it explains why both are often used together in medical applications.

 Further, the ratio of THC to CBD in a preparation determines the fine balance between its therapeutic use and mind-altering effects.

Epidiolex is the first CBD prescription approved by the US Food and Drug Administration (FDA) in 2018 to treat seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis (TS) in patients as young as 1 year old. It does not contain THC. This approval was based on 3 double-blind randomized controlled trials (RCT) and an open label extension study for LGS and DS, and one RCT for TS, all with 

 About 25% of children with treatment-resistant epilepsy have comorbid ASD. Both LGS and DS have been commonly linked to ASD.

It is important to note that medical cannabis has its own significant side effects 

 found that persistent users of cannabis had reduced neuropsychological functioning, with adolescent onset users experiencing greater decline in IQ and executive functioning.

 These effects did not reverse fully on stopping cannabis use for one year or more, suggesting it has potential neurotoxic effects.

cannabis use in adolescence can significantly increase the risk of developing psychotic symptoms

Cannabis is prescribed as a treatment for autism in 14 states. Is it the wonder drug patients and families have been waiting for? 

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