Dronabinol did not help cannabis-dependent adults quit but did improve treatment retention and withdrawal symptoms | Research

The takeaway

In 156 cannabis-dependent adults, dronabinol (synthetic THC) did not increase abstinence rates compared to placebo, but significantly improved treatment retention (77% vs 61%) and reduced withdrawal symptoms.

Read this if you are trying to quit cannabis and are interested in medication-assisted treatment options.

77% retention on dronabinol vs 61% on placebo (p=0.02)

What the researchers found

This was the first clinical trial testing an agonist substitution strategy for cannabis dependence, similar to how methadone is used for opioid dependence.

156 cannabis-dependent adults were randomized to dronabinol (20 mg twice daily) or placebo for 12 weeks, with all participants receiving weekly therapy. There was no significant difference in the primary outcome: 17.7% of dronabinol patients achieved 2 weeks of abstinence versus 15.6% on placebo.

However, dronabinol showed two significant secondary benefits. Treatment retention at the end of the maintenance phase was significantly higher with dronabinol (77%) compared to placebo (61%, p=0.02). Withdrawal symptoms were also significantly lower on dronabinol (p=0.02).

Both groups reduced marijuana use over time, but there were no between-group differences in overall reduction.

Why it matters

While dronabinol did not increase abstinence, the improved retention and withdrawal management established proof of concept for agonist substitution in cannabis dependence, informing future medication development.

The numbers in context

156 participants. Abstinence: 17.7% dronabinol vs 15.6% placebo (not significant). Retention: 77% vs 61% (p=0.02). Withdrawal symptoms lower on dronabinol (p=0.02). Dose: 20 mg BID.

How the study worked

Randomized, double-blind, placebo-controlled, 12-week trial. 156 cannabis-dependent adults. 1-week placebo lead-in, then dronabinol 20 mg BID or placebo for 8 weeks maintenance, 2-week taper. Weekly motivational enhancement and relapse prevention therapy for all. Timeline followback for marijuana use assessment.

What this study cannot tell us

Abstinence rates were low in both groups. Dronabinol dose may have been insufficient. Relapse often occurred during the taper/post-taper period. Self-reported marijuana use as primary outcome.

How to read the evidence

Well-designed RCT with adequate sample size, though the primary outcome (abstinence) was not met.

When this study was published

Published in 2011. Cannabis dependence pharmacotherapy research has continued with combination strategies.

The bigger picture

The study opened the door for testing higher doses, combination medications, and more potent behavioral interventions alongside agonist substitution for cannabis dependence.

Questions still open

Would higher dronabinol doses produce better abstinence outcomes? Could dronabinol be combined with other medications for additive effects?

Common questions

Can medications help you quit cannabis?

Dronabinol (synthetic THC) did not significantly increase abstinence rates in this trial. However, it kept more people in treatment (77% vs 61%) and reduced withdrawal symptoms, suggesting medication-assisted approaches have potential but need refinement.

What is agonist substitution?

Similar to using methadone for heroin addiction, agonist substitution gives a controlled dose of a similar drug (dronabinol, which is synthetic THC) to manage withdrawal and cravings while the person works on behavior change.

Read the original research

Dronabinol for the treatment of cannabis dependence: a randomized, double-blind, placebo-controlled trial.

Drug and alcohol dependence, 116(1-3), 142-50

View on PubMed ↗Publisher’s paper ↗

Citation

Levin, Frances R; Mariani, John J; Brooks, Daniel J; Pavlicova, Martina; Cheng, Wendy; Nunes, Edward V. (2011). Dronabinol for the treatment of cannabis dependence: a randomized, double-blind, placebo-controlled trial.. Drug and alcohol dependence, 116(1-3), 142-50. https://doi.org/10.1016/j.drugalcdep.2010.12.010