Systematically Testing the Evidence on Marijuana

Search:

(Searched September 22, 2025)

• Ovid MEDLINE
• PsycINFO
• Cochrane Database of Systematic Reviews

Screening:

Key Questions

KQ1:  What are the benefits and harms of pharmacotherapy for CUD?

KQ2:  Are there known subpopulations for whom current pharmacotherapies are most or least effective for CUD?

Study Selection Criteria

Abbreviations. AE: adverse events; CBT: cognitive behavioral therapy; CUD: cannabis use disorder; PICOTS: population, interventions, comparators, outcomes, timing, setting; RCT: randomized controlled trial

• Studies (randomized controlled clinical trials) assessed the benefits and harms of pharmacotherapies, with or without adjunctive treatment, as potential treatments for known or suspected CUD in nonpregnant adults and adolescents.

Risk of bias:

• Cochrane Collaboration tool

Assessing the certainty of the body of evidence:

• Overall certainty of evidence for each outcome was determined using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach

Living systematic review updates:

• Search to be updated at regular intervals with new reports as needed

As of September 22, 2025:

• 34 eligible studies (4 published since the previous review)
  • 32 placebo-controlled trials
  • 1 comparative effectiveness trial of 2 antipsychotic medications and 1 head-to-head trial comparing an antidepressant to treatment as usual
• Very low- to low-certainty evidence for all GRADE outcomes: abstinence, cannabis use, treatment retention, dropouts due to adverse events, serious adverse events, and withdrawal symptoms
• Most included interventions did not differ significantly from placebo with respect to efficacy or harms in the treatment of CUD for adults and adolescents
• Antidepressants and cannabinoids provided the largest evidence bases in this review, and were analyzed by mechanisms of action and relative tetrahydrocannabinol (THC) concentrations, respectively
• 11 RCTs reported outcomes by subpopulation, but findings were insufficient to draw decisive conclusions

GRADE Outcomes Summary Table (Update Pending)

Abbreviations. CBD: cannabidiol; CM: contingency management; GRADE: Grading of Recommendations, Assessment, Development, and Evaluations approach; MAS-ER: extended-release mixed amphetamine salts; RCT: randomized controlled trial; SARI: serotonin antagonist and reuptake inhibitor; SNRI: serotonin-norepinephrine reuptake inhibitors; SSRI: selective serotonin reuptake inhibitor; THC: tetrahydrocannabinol.

Direction of effect: Light grey: no difference from comparator; green: significant improvement with intervention; red: increased risk of harm with intervention; orange: mixed or conflicting results; —: outcome not reported or not

GRADE certainty of evidence: Very low ⨁◯◯◯; Low ⨁⨁◯◯; Moderate ⨁⨁⨁◯; High ⨁⨁⨁⨁

• It remains uncertain whether pharmacotherapy can improve CUD-related outcomes despite a growing body of evidence examining a variety of medications.
• Certain cannabinoid formulations may hold promise for treatment of CUD, but results would need to be replicated in additional studies and across outcomes before being adopted in clinical practice.
• There is a need for more research to identify effective pharmacological treatments for this condition given the increasing use of cannabis in the general population and high prevalence of CUD among current cannabis users.

• Longer-term, large-scale replication studies would improve our understanding of previously assessed pharmacotherapies for CUD.
• We found limited evidence of the effect of pharmacotherapies for CUD by important subgroups (e.g., age, race or ethnicity, people with comorbidities or other substance use disorders).
• High-quality RCTs are needed to understand the use of pharmacotherapeutics to relieve withdrawal symptoms.