With more and more states and countries embracing cannabis whether for medical or recreational purposes, it could be assumed that the number of people dependent on it would also increase. Even now, the Centers for Disease Control and Prevention warns that estimates show every 3 in 10 people who consume it has cannabis use disorder. Thankfully, a new study shows promise for the treatment of this condition. 

What is cannabis use disorder (CUD) exactly? It is a condition often described as the continued use of cannabis despite its negative impact on one's life and health. It also causes withdrawal symptoms that come from the development of dependency, which are often compared to nicotine withdrawal. The most common cannabis withdrawal symptoms include anxiety, poor mood, agitation and sleep problems.

Despite the need, there are no FDA-approved medications to treat CUD and behavioral treatments have shown limited benefit.

A clinical-stage biopharmaceutical company focused on treatments for brain disease Aelis Farma AELIS announced Thursday the publication of several studies describing a new pharmacological class, cannabinoid receptor 1 signaling-specific inhibitors (CB1-SSi) and its first drug candidate, AEF0117 for the treatment of CUD. 

What Happened

The report Signaling-specific inhibition of the CB1 receptor for cannabis use disorder: phase 1 and phase 2a randomized trials, was published in the journal Nature Medicine. It describes AEFO117 as the first compound that selectively inhibits the CB1 receptor signaling pathway responsible for the addictive effects of cannabis, without interfering with the receptor's fundamental physiological and behavioral functions.

Why It Matters

AEF0117 is the first of the new pharmacologic class, CB1-SSi based on a natural brain mechanism that combats CB1 receptor hyperactivity. It differs from previous CB1 receptor antagonists that caused significant adverse effects, making them unsuitable for clinical use. This unique mechanism of action enables CB1-SSi to inhibit only the cellular signals involved in CUD – without disrupting the receptor’s physiological activity. 

The report states that the CB1-SSi class and AEF0117 represent a breakthrough in CB1 pharmacology.

It was discovered by the research group of Aelis Farma chief executive officer Pier Vincenzo Piazza, MD, Ph.D. when he was the director of the Neurocentre Magendie of the French National Institute of Health and Medical Research (INSERM) in Bordeaux.

“This landmark article culminates more than a decade of research, from discovery of this natural brain mechanism to our proof-of-concept clinical trial,” stated  Piazza. “We are delighted to contribute to the field of neuropharmacology with a class of drugs never tested in humans before. Now, we at Aelis are sponsoring a large, placebo-controlled phase 2b study in collaboration with Columbia University Irving Medical Center, enrolling 330 participants with CUD to evaluate three dose levels of AEF0117 in treating cannabis addiction. Results should be available by mid-2024.”

AEF0117 produced no treatment-related serious adverse events or treatment-emergent adverse events. What’s more, it helped with the reduction in cannabis effect without precipitating withdrawal, even in volunteers who consumed several grams of cannabis daily.

“No other medication has been shown to safely reduce the direct effects of smoked cannabis in daily cannabis smokers,” said Margaret (Meg) Haney, Ph.D., supervisor of the phase 1 studies and principal investigator of the 2a proof-of-concept study. She is a professor of Neurobiology in the Department of Psychiatry at Columbia University Irving Medical Center, where she is the director of the Cannabis Research Laboratory and co-director of the Substance Use Research Center. “These novel findings clearly suggest that AEF0117 may be an effective approach for patients seeking treatment for CUD.”

What’s Next? 

Development of AEF0117 as a treatment for cannabis addiction is currently ongoing.

A phase 2b U.S. multi-center study, sponsored by Aelis Farma and coordinated by Professor Frances Levin of Columbia University, which will include 330 participants with CUD, is comparing the efficacy of three AEF0117 doses with placebo. Initial results are expected in mid-2024. 

Photo: Courtesy of Elsa Olofsson on Unsplash.