Drug shows potential as treatment for cannabis use disorder

Key takeaways:

• AEF0117 decreased cannabis use and positive mood effects in daily users.
• The drug was also well tolerated and did not affect sleep or food intake.

A first-of-its kind drug demonstrated potential as a safe and effective treatment for cannabis use disorder, according to a phase 2a study published in Nature Medicine.

“We have tested over a dozen potential treatment medications in our cannabis research laboratory, and this is the first to decrease both the positive mood effects of cannabis and the decision to use cannabis by daily smokers,” Margaret Haney, PhD, a professor of neurobiology at the Columbia University Medical Center, said in a press release.

According to the CDC, approximately one in three cannabis users have cannabis use disorder (CUD). However, “there is no medication to facilitate CUD treatment,” Haney and colleagues wrote.

AEF0117 (Aelis Farma) is the first drug in a new pharmacologic class of signaling-specific inhibitors of the type 1 cannabinoid receptor (CB₁-SSi), the researchers reported. This class uses a “unique mechanism of action” that allows it to inhibit only cellular activity associated with CUD, as opposed to previous CB₁ receptors that block all receptor activity in CUD, leading to adverse effects, according to the release.

After finding that AEF0117 was safe and well tolerated in a phase 1 trial, Haney and colleagues conducted a phase 2a trial to further evaluate the drug in 29 healthy participants with CUD. The participants were given a 0.6 mg (n = 14) or 1 mg (n = 15) daily dose of AEF0117 over 5 days and placebo over another 5 days in a randomized order, with a minimum 14-day washout period in between treatments.

Haney and colleagues reported that AEF0117 reduced positive subjective effects of cannabis by 19% with the 0.6 mg dose and 38% with the 1 mg dose compared with placebo. The 1 mg dose also significantly reduced cannabis self-administration.

The drug was not associated with anoxia, sleep disruption or significant changes in food intake or mood ratings, nor did it precipitate cannabis withdrawal, according to the researchers.

Haney and colleagues wrote that one factor that likely contributed to AEF0117’s successful development was the selection process, which used toxicity, formulation and bioavailability as the first criteria.

Because of this, “we were able to reduce the impact of two of the three primary causes of attrition early on and could then dedicate considerable resources for an extensive pharmacodynamic characterization of a small number of compounds that had a higher chance of achieving and succeeding in phase 2 studies than by using the classic approach,” they wrote.

The researchers noted that further research is needed to identify the drug’s full mechanism of action and how it could potentially affect other CB₁-activated signaling pathways.

“Our findings suggest AEF0117 has great potential for treating problematic cannabis use,” Haney said in the release.

References:

• Addiction (marijuana or cannabis use disorder). https://www.cdc.gov/marijuana/health-effects/addiction.html. Accessed June 13, 2023.
• Drug to treat cannabis use disorder shows promise in clinical trial. https://www.columbiapsychiatry.org/news/new-pharmacological-treatment-cannabis-use-disorder-shows-promise. Published June 7, 2023. Accessed June 12, 2023.
• Haney M, et al. Nat Med. 2023;doi:10.1038/s41591-023-02381-w.