Clinical Trial of Cannabis Use Disorder Drug Shows Promise

A first-in-class drug designed to selectively inhibit the cannabinoid receptor signaling pathway shows promise as a safe and effective treatment for cannabis use disorder (CUD), a condition in which a person is unable to control their cannabis use despite the fact that it is causing problems in their lives.

Researchers discovered that the potential medicine, AEFO117, dramatically reduced the effects of cannabis in daily cannabis smokers in a Phase 2a clinical trial led by Columbia University Irving Medical Center and Aelis Farma, a French biopharmaceutical company.

The report, “Signaling-specific inhibition of the CB1 receptor for cannabis use disorder: phase 1 and phase 2a randomized trials,” was published online June 8 by the journal Nature Medicine.

AEF0117 appears to counteract the “high” associated with THC, cannabis’ primary psychoactive component, at type 1 cannabinoid receptors (CB1 receptors), without interfering with the receptors’ physiological and behavioral functions, which include memory and learning, emotional processing, sleep, and eating behavior.

“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,” said Margaret (Meg) Haney, Ph.D., supervisor of the phase I studies and principal investigator of the 2a proof-of-concept study, and a professor of neurobiology in the Department of Psychiatry at Columbia, where she is the director of the Cannabis Research Laboratory.

“Patients seek treatment when they have difficulty controlling their cannabis use despite the problems it is causing at work or in their personal lives. Our findings suggest AEF0117 has great potential for treating problematic cannabis use,” added Dr. Haney, who also co-directs Columbia’s Substance Use Research Center.

Cannabis use disorder is on the rise

With 38 states, three territories, and the District of Columbia legalizing cannabis for medicinal and/or recreational purposes, use is on the rise, as is problematic use, which includes addiction.

Cannabis use disorder is an unrecognized risk of cannabis usage that affects around 14 million people in the United States. Despite the fact that everyday cannabis use among teens and young adults is at an all-time high, many are unaware that cannabis can be addictive.

The Food and Drug Administration (FDA) has yet to approve a pharmaceutical for the treatment of cannabis use disorder, and evidence-based behavioral therapy have demonstrated little results.

Result of a decade of research

AEF0117, produced by Aelis Farma, is the first of a novel pharmacologic class known as CB1-SSi. CB1-SSi is based on a unique mode of action that allows CB1-SSi to suppress only the cellular signals involved in CUD. This innovative technique differs from prior CB1 receptor antagonists, which had severe detrimental effects due to their broad inhibition of all CB1 receptor function, blocking their clinical application.

When he was the head of the Neurocentre Magendie of the French National Institute of Health and Medical Research (INSERM) in Bordeaux, Aelis Farma Chief Executive Officer Pier Vincenzo Piazza, MD, identified this natural brain function.

“The [Nature Medicine] article culminates more than a decade of research, from discovery of this natural brain mechanism to our proof-of-concept clinical trial,” said Dr. Piazza. “We are delighted to contribute to the field of neuropharmacology with a class of drugs never tested in humans before.”

AEF0117 significantly reduced participants’ self-reported ratings of cannabis-related positive mood effects, the primary outcome measure, by a mean of 38% in the Phase 2a crossover trial, which included 29 participants with CUD who received one of two different doses of AEF0117 in one 5-day phase and placebo and another 5-day phase in randomized order. Even for participants who smoked several grams of cannabis per day, these reductions occurred without causing cannabis withdrawal.

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