Buspirone Showed Modest Promise for Treating Marijuana Dependence in a Small Trial

In a 12-week placebo-controlled trial, buspirone showed a trend toward more negative drug tests compared to placebo, with a significant effect among participants who completed the full trial.

McRae-Clark, Aimee L et al.·Drug and alcohol dependence·2009·Preliminary EvidenceRandomized Controlled Trial
RTHC-00374Randomized Controlled TrialPreliminary Evidence2009RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Randomized Controlled Trial
Evidence
Preliminary Evidence
Sample
N=23

What This Study Found

Fifty participants with marijuana dependence received either buspirone (up to 60 mg/day) or placebo for 12 weeks alongside motivational interviewing.

In the full intent-to-treat analysis, the buspirone group had 18 percentage points more negative urine drug screens than placebo, though this did not reach statistical significance (p=0.071).

Self-reported marijuana-free days did not differ between groups (45.2% vs 51.4%).

However, among participants who completed all 12 weeks, buspirone produced a significantly higher percentage of negative drug tests (p=0.014) and a trend toward reaching the first negative test sooner (p=0.054).

Retention in the study was a major challenge, limiting statistical power.

Key Numbers

23 buspirone, 27 placebo. 12-week trial. 18 percentage point difference in negative drug tests (not significant, p=0.071). Among completers: significant difference (p=0.014). Self-report showed no difference.

How They Did This

Randomized, double-blind, placebo-controlled trial. 23 participants received buspirone (maximum 60 mg/day) and 27 received placebo for 12 weeks. Both groups received motivational interviewing. Outcomes included urine drug screens and self-reported use.

Why This Research Matters

No FDA-approved medication exists for cannabis use disorder. This was an early exploration of whether an anti-anxiety medication could help, based on the idea that anxiety contributes to continued cannabis use.

The Bigger Picture

Finding effective medications for cannabis dependence remains an ongoing challenge. This trial, while underpowered, suggested buspirone warranted further study, though retention problems highlighted the difficulty of conducting cannabis cessation trials.

What This Study Doesn't Tell Us

Small sample with high dropout rates. The completer analysis showing significance is subject to selection bias. Self-report and urine test results conflicted. Buspirone dose was variable up to 60 mg/day.

Questions This Raises

  • ?Would a larger trial with better retention confirm buspirone efficacy?
  • ?Is the discrepancy between urine tests and self-report a measurement issue?
  • ?Would combining buspirone with different behavioral interventions improve outcomes?

Trust & Context

Key Stat:
18 percentage point improvement in drug tests with buspirone (p=0.071 overall, p=0.014 in completers)
Evidence Grade:
Small randomized controlled trial (n=50) with high dropout rates that limited statistical power. Intent-to-treat analysis did not reach significance.
Study Age:
Published in 2009. Subsequent cannabis cessation medication trials have explored other compounds, but no FDA-approved pharmacotherapy for cannabis use disorder has been established as of the time of this writing.
Original Title:
A placebo-controlled trial of buspirone for the treatment of marijuana dependence.
Published In:
Drug and alcohol dependence, 105(1-2), 132-8 (2009)
Database ID:
RTHC-00374

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled TrialGold standard for testing treatments
This study
Cohort / Case-Control
Cross-Sectional / Observational
Case Report / Animal Study

Participants are randomly assigned to treatment or placebo groups to test cause and effect.

What do these levels mean? →

Frequently Asked Questions

What is buspirone?

Buspirone is an anti-anxiety medication that works differently from benzodiazepines. It was tested for cannabis dependence because anxiety often drives continued cannabis use, and reducing anxiety might help people quit.

Why did self-report and drug tests give different results?

Self-reported drug use is often unreliable, particularly in treatment settings where participants may underreport use. Urine drug screens provide objective confirmation but only detect use within a limited time window.

Read More on RethinkTHC

Cite This Study

RTHC-00374·https://rethinkthc.com/research/RTHC-00374

APA

McRae-Clark, Aimee L; Carter, Rickey E; Killeen, Therese K; Carpenter, Matthew J; Wahlquist, Amy E; Simpson, Stacey A; Brady, Kathleen T. (2009). A placebo-controlled trial of buspirone for the treatment of marijuana dependence.. Drug and alcohol dependence, 105(1-2), 132-8. https://doi.org/10.1016/j.drugalcdep.2009.06.022

MLA

McRae-Clark, Aimee L, et al. "A placebo-controlled trial of buspirone for the treatment of marijuana dependence.." Drug and alcohol dependence, 2009. https://doi.org/10.1016/j.drugalcdep.2009.06.022

RethinkTHC

RethinkTHC Research Database. "A placebo-controlled trial of buspirone for the treatment of..." RTHC-00374. Retrieved from https://rethinkthc.com/research/mcrae-clark-2009-a-placebocontrolled-trial-of

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.