A rigorous 11-week trial of 122 cannabis-dependent adults found that combining dronabinol (synthetic THC) with lofexidine (an alpha-2 agonist) was no better than placebo at achieving cannabis abstinence.
Read this if you are looking for medication options for cannabis dependence or are interested in addiction treatment research.
27.9% medication vs. 29.5% placebo achieved 3 weeks abstinence (no difference)
What the researchers found
With no approved medications for cannabis use disorder, researchers tested a combination approach: dronabinol (synthetic THC, to ease withdrawal by providing cannabinoid receptor stimulation) plus lofexidine (an alpha-2 agonist, to reduce noradrenergic symptoms of withdrawal).
One hundred fifty-six cannabis-dependent adults were enrolled, with 122 randomized after a placebo lead-in week. Participants received either dronabinol 20 mg three times daily plus lofexidine 0.6 mg three times daily, or matching placebos, for 8 weeks with a 2-week taper and 1-week monitoring.
The result was clearly negative. The proportion achieving 3 weeks of abstinence during the maintenance phase was virtually identical: 27.9% for the medication group versus 29.5% for placebo. Both groups showed reduction in cannabis use over time, suggesting the behavioral therapy component (weekly motivational enhancement and relapse prevention) was driving improvement, not the medications.
Why it matters
This well-designed negative result is important because it eliminates a promising pharmacotherapy approach and redirects research efforts. The fact that both groups improved equally underscores the value of behavioral interventions for cannabis use disorder even in the absence of effective medication.
The numbers in context
156 enrolled, 122 randomized. 3-week abstinence: 27.9% medication vs. 29.5% placebo. Dronabinol 20 mg TID + lofexidine 0.6 mg TID for 8 weeks. Both groups showed reduction in use over time. Weekly behavioral therapy provided to all.
How the study worked
Randomized, double-blind, placebo-controlled, 11-week trial. 156 enrolled, 122 randomized after 1-week placebo lead-in. Dronabinol 20 mg TID plus lofexidine 0.6 mg TID versus matched placebo. All participants received weekly motivational enhancement and relapse prevention therapy. Primary outcome: 3 weeks abstinence during maintenance phase.
What this study cannot tell us
The dronabinol dose may not have been high enough to fully replace the cannabinoid stimulation from heavy cannabis use. Lofexidine targets only the noradrenergic component of withdrawal. The placebo lead-in may have selected for participants less likely to respond to medication.
How to read the evidence
Well-designed randomized double-blind placebo-controlled trial with adequate sample size. Strong methodology producing a clear negative result.
When this study was published
Published in 2016. Research on cannabis use disorder pharmacotherapy continues, with no FDA-approved medications as of this review.
The bigger picture
Cannabis use disorder is the second most common drug use disorder bringing people into treatment after alcohol. The continued failure to find effective medications highlights both the complexity of cannabis dependence and the importance of behavioral treatments.
Questions still open
- Would higher doses of dronabinol alone perform differently? Is the agonist replacement strategy (like methadone for opioids) fundamentally different for cannabis? What alternative pharmacological approaches might be more effective?
Common questions
Is there a medication to help quit cannabis?
Why is it so hard to find a medication for cannabis dependence?
Read the original research
Dronabinol and lofexidine for cannabis use disorder: A randomized, double-blind, placebo-controlled trial.
Drug and alcohol dependence, 159, 53-60
Citation
Levin, Frances R; Mariani, John J; Pavlicova, Martina; Brooks, Daniel; Glass, Andrew; Mahony, Amy; Nunes, Edward V; Bisaga, Adam; Dakwar, Elias; Carpenter, Kenneth M; Sullivan, Maria A; Choi, Jean C. (2016). Dronabinol and lofexidine for cannabis use disorder: A randomized, double-blind, placebo-controlled trial.. Drug and alcohol dependence, 159, 53-60. https://doi.org/10.1016/j.drugalcdep.2015.11.025
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