THC-containing medications (dronabinol, nabiximols) are effective for cannabis withdrawal, dronabinol may help with opioid withdrawal, and rimonabant showed promise for smoking cessation but was pulled for psychiatric side effects.
Readers interested in pharmacological treatments for cannabis dependence and other addictions.
Dronabinol and nabiximols reduced cannabis withdrawal symptoms in RCTs; rimonabant helped smoking cessation but caused psychiatric side effects
What the researchers found
This review examined randomized controlled trial evidence for cannabinoid-based medications across different addictions.
For cannabis use disorder: THC-containing medications like dronabinol and nabiximols (Sativex) effectively reduced withdrawal symptoms. This agonist substitution approach parallels how methadone is used for opioid dependence. Dronabinol may also help reduce opioid withdrawal symptoms.
For tobacco: The CB1 inverse agonist rimonabant showed promising smoking cessation effects in clinical trials, but its psychiatric side effects (depression, anxiety, suicidal ideation) led to removal from the market. It was never approved in the United States.
For alcohol: Very few trials had investigated cannabinoid medications for alcohol use disorder at the time of this review, representing a significant gap.
The review highlighted emerging approaches: FAAH inhibitors (which boost anandamide) and neutral CB1 antagonists (which lack the psychiatric side effects of inverse agonists like rimonabant) as promising future options.
Why it matters
Addiction treatment options remain limited, and the endocannabinoid system's involvement in reward and dependence makes it a logical therapeutic target. This review provides a practical summary of what works, what failed, and what is coming next in cannabinoid-based addiction treatment.
The numbers in context
Dronabinol and nabiximols: effective for cannabis withdrawal (RCT evidence). Dronabinol: may reduce opioid withdrawal. Rimonabant: effective for smoking cessation but removed from market. Few RCTs for alcohol use disorder.
How the study worked
Narrative review of randomized controlled trials evaluating cannabinergic medications for substance use disorders, including cannabis, opioid, tobacco, and alcohol use disorders.
What this study cannot tell us
Narrative review without systematic search methodology. The evidence base for cannabinoid medications in addiction is still relatively small, with most RCTs having modest sample sizes. The review does not cover newer compounds that have entered clinical testing since publication.
How to read the evidence
Moderate evidence from a review of existing RCTs, though the underlying trial evidence is still limited in size.
When this study was published
Published in 2017. Novel cannabinoid-based addiction medications continue to be developed.
The bigger picture
The failure of rimonabant did not end the story of targeting the endocannabinoid system for addiction. Instead, it redirected research toward approaches that avoid brain CB1 blockade: peripheral antagonists, neutral antagonists, FAAH inhibitors, and agonist substitution strategies. The endocannabinoid system remains one of the most promising targets for developing new addiction medications.
Questions still open
- Will FAAH inhibitors or neutral CB1 antagonists prove effective for addiction without psychiatric side effects? Could nabiximols become a standard treatment for cannabis use disorder? Why has so little research addressed cannabinoid medications for alcohol use disorder?
Common questions
Can cannabinoid medications help people quit cannabis?
Why was rimonabant taken off the market if it helped with smoking cessation?
Read the original research
The endocannabinoid system as a target for addiction treatment: Trials and tribulations.
Neuropharmacology, 124, 73-83
Citation
Sloan, Matthew E; Gowin, Joshua L; Ramchandani, Vijay A; Hurd, Yasmin L; Le Foll, Bernard. (2017). The endocannabinoid system as a target for addiction treatment: Trials and tribulations.. Neuropharmacology, 124, 73-83. https://doi.org/10.1016/j.neuropharm.2017.05.031
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