Pharmacotherapy for the Treatment of Cannabis Use Disorder. A Systematic Review, Karli K. Kondo et al., 2020,

Pharmacotherapy for the Treatment of Cannabis Use Disorder. A Systematic Review

Karli K. Kondo, PhD; Benjamin J. Morasco, PhD; Shannon M. Nugent, PhD; Chelsea K. Ayers, MPH; Maya E. O’Neil, PhD; Michele Freeman, MPH, and Devan Kansagara, MD, MCR

Annals of Internal Medicine, 2020, 172, 398-412.

doi : 10.7326/M19-1105


Background : Cannabis use disorder (CUD) is a growing concern, and evidence-based data are needed to inform treatment options.

Purpose : To review the benefits and risks of pharmacotherapies for the treatment of CUD.

Data Sources : MEDLINE, PsycINFO, Cochrane Database of Systematic Reviews, and clinical trial registries from inception through September 2019.

Study Selection : Pharmacotherapy trials of adults or adolescents with CUD that targeted cannabis abstinence or reduction, treatment retention, withdrawal symptoms, and other outcomes.

Data Extraction : Data were abstracted by 1 investigator and confirmed by a second. Study quality was dually assessed, and strength of evidence (SOE) was determined by consensus according to standard criteria.

Data Synthesis : Across 26 trials, the evidence was largely insufficient. Low-strength evidence was found that selective serotonin reuptake inhibitors (SSRIs) do not reduce cannabis use or improve treatment retention. Low- to moderate-strength evidence was found that buspirone does not improve outcomes and that cannabinoids do not increase abstinence rates (moderate SOE), reduce cannabis use (low SOE), or increase treatment retention (low SOE). Across all drug studies, no consistent evidence of increased harm was found.

Limitations : Few methodologically rigorous trials have been done. Existing trials are hampered by small sample sizes, high attrition rates, and heterogeneity of concurrent interventions and outcomes assessment.

Conclusion : Although data on pharmacologic interventions for CUD are scarce, evidence exists that several drug classes, including cannabinoids and SSRIs, are ineffective. Because of increasing access to and use of cannabis in the general population, along with a high prevalence of CUD among current cannabis users, an urgent need exists for more research to identify effective pharmacologic treatments.

Primary Funding Source : U.S. Department of Veterans Affairs. (PROSPERO: CRD42018108064)

Social, medical, and legal acceptance of cannabis has grown dramatically during the past 15 years, and cannabis use—for medical and recreational purposes—has also increased. According to the National Survey on Drug Use and Health, from 2002 to 2014, the prevalence of past-year daily cannabis use in the United States nearly doubled, with an increase from 1.3% to 2.5% (1). Meanwhile, the potency of readily available cannabis has also increased (2, 3), and the proportion of the public that perceives important harms from cannabis use has decreased (2, 4). A recent national survey found that about 1 in 5 persons reporting past-year cannabis use perceived addiction to be an associated risk (5).

A growing body of evidence shows that addiction is a concern. Among regular users, cannabis use may
lead to physiologic dependence with withdrawal symptoms similar to those of other substance use disorders and may include dysphoric mood, disturbed sleep, gastrointestinal symptoms, and decreased appetite (6, 7). The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, defines cannabis use disorder (CUD) as clinically significant impairment or distress in more than 1 realm (such as tolerance; social, interpersonal, or occupational challenges; or continued use despite adverse consequences) (8). Among U.S. adults in 2012 to 2013, the overall prevalence of 12-month CUD was 2.5% and that of lifetime CUD was 6.3% (9). Furthermore, among persons reporting past-year cannabis
use, 36% met criteria for CUD during the previous year (10). Nearly half of those with CUD have moderate or severe CUD, and the risk is greatest in young adults and socioeconomically disadvantaged groups (9).

Although CUD is more prevalent and severe than many recognize, most persons with this disorder do not
seek treatment. Only 5% of those with CUD have sought treatment from a health care provider (9). Standard treatment of CUD includes psychotherapy, such as cognitive behavioral therapy (CBT), motivational enhancement therapy (MET), or contingency management (CM). However, these treatments may be inaccessible to many and are time and resource intensive.

Pharmacotherapy might offer additional treatment options for the growing number of patients with CUD. Currently, no pharmacotherapies for CUD have been approved by the U.S. Food and Drug Administration, although several (including cannabinoids, antidepressants, anxiolytics, and glutamatergic modulators) have been proposed for off-label use (2). The purpose of this systematic review was to examine the benefits and harms of pharmacotherapies used off-label to treat CUD.