AEF0117, a first-in-class drug, shows potential in the treatment of cannabis use disorder (CUD) by blocking specific signals at cannabinoid receptors. The drug suppresses the euphoria caused by THC, the key psychoactive component of cannabis, without affecting physiology, thereby reducing cannabis use without causing withdrawal symptoms.
There are currently no FDA-approved treatments available for cannabis disorders or addictions.
First-in-class agents designed to selectively inhibit cannabinoid receptor signaling pathways have potential as safe and effective treatments for cannabis use disorders (CUD). CUD is a condition in which individuals struggle to regulate cannabis consumption even though it causes problems in their lives.
In a phase 2a clinical trial conducted by Columbia University Irving Medical Center and French biopharmaceutical company Ellis Farma, researchers found that drug candidate AEFO117 significantly reduced the effects of cannabis in daily cannabis smokers. .
This report was recently published in a magazine natural medicine.
AEF0117 is a type 1 cannabinoid receptor, the CB1 receptor, which stimulates the “high feeling” associated with THC, the main psychoactive component of cannabis, through the physiological and It appears to suppress without interfering with behavioral function. , and eating behavior.
“While we have tested over a dozen potential therapeutic agents in our cannabis lab, this is the first drug to reduce both the positive mood effects of cannabis and the decision to use cannabis in everyday smokers. ‘ said Dr. Margaret (Meg) Haney. D. is the supervisor of the Phase 1 study, principal investigator of the Phase 2a proof-of-concept study, Professor of Neurobiology in the Department of Psychiatry, Columbia University, and Director of the Cannabis Research Institute.
“Patients seek treatment when cannabis use is difficult to control, even though cannabis causes problems in their work and personal lives. It suggests that it has great therapeutic potential,” added Dr. Haney, who is also co-director of Columbia’s Center for Substance Use Research.
Cannabis use disorders are on the rise
With cannabis use becoming increasingly mainstream, with 38 states, three territories, and the District of Columbia legalizing its use for medical and/or recreational purposes, consumption is on the rise, leading to addiction. Problematic uses, including , are also on the rise.
Cannabis use disorders are an underestimated risk of cannabis use, affecting approximately 14 million people in the United States. Despite record high levels of daily cannabis use among adolescents and young adults, many are unaware that cannabis is addictive.
To date, there are no Food and Drug Administration (FDA)-approved drugs to treat cannabis use disorders, and evidence-based behavioral therapy has limited efficacy.
A culmination of 10 years of research
Developed by Aelis Farma, AEF0117 is the first of a new pharmacological class, CB1-SSi, based on a unique mechanism of action that allows CB1-SSi to inhibit only cellular signals involved in CUD. I’m here. This breakthrough approach broadly blocks all his CB1 receptor activity, unlike his previous CB1 receptor antagonists, which caused significant side effects that precluded clinical use.
This natural brain mechanism was discovered by the research group of Pierre Vincenzo Piazza, M.D., CEO of Ellis Pharma, where he was Director of the Neural Center Magendie at the French National Institute of Health and Medical Research (INSERM) in Bordeaux. was sometimes discovered.
” [Nature Medicine] This paper is the culmination of more than a decade of research, from the discovery of this natural brain mechanism to proof-of-concept clinical trials,” said Dr. Piazza. “We are pleased to contribute to the field of neuropharmacology with a class of drugs that has never been tested in humans.”
In a phase 2a crossover study involving 29 patients with CUD, two different doses of AEF0117 were administered in one 5-day phase plus placebo and in another 5-day phase in randomized order. I was. AEF0117 significantly reduced participants’ self-reported ratings. The primary endpoint, cannabis-related positive mood effects, was reduced by an average of 38%, along with a reduction in cannabis use. These reductions occurred without promoting cannabis withdrawal, even in volunteers who smoked several grams of cannabis per day.
Aelis Farma is currently sponsoring a multicenter, placebo-controlled Phase 2b trial in collaboration with Columbia Medical Center. Francis R. Levin, M.D., Kennedy Levy Professor of Psychiatry and director of the Division of Substance Use Disorders at Columbia University, conducted a two-year study in which 330 participants were enrolled in CUD and three AEF0117 We plan to evaluate dose levels. In the treatment of cannabis addiction.
“We are very grateful to the team at the Columbia Psychiatric Cannabis Lab for their contributions in conducting these studies with AEF0117,” said Dr. Haney. We also appreciate the support of the National Institute on Drug Abuse. “
Reference: “Specific inhibition of CB1 receptor signaling for cannabis use disorders: Phase 1 and Phase 2a randomized trials.” Margaret Haney, Monique Vallée, Sandy Fabre, Stephanie Collins Reed, Marion Zanese, Ghislaine Campistron, Caroline A Arout, Richard W. Fortin, Ziva D. Cooper, Tonysha Carney-Ramos, Matilde Metna, Zuzana Justinova, Charles Schindler, Etienne Hébert-Chatran, Luigi Bellocchio, Adeline Catala, Andrea Barry, Romain Serato, David B. Finlay, Filippo Karachi, Bastian Redon, Elena Martin-Garcia, Arnau Busquets-Garcia, Isabel Matias, Francis R. Levin, François-Xavier Felpin, Nicola Simon, Daniela Cota, Humberto Spapinato, Rafael Maldonado, Yavin Shaham, Michel Glas, Lars Lucke Thomsen, Helle Mengel, Giovanni Marsicano, Stephanie Monruzun, Jean-Michel Levesto, Pierre Vincenzo Piazza, June 8, 2023, natural medicine.
DOI: 10.1038/s41591-023-02381-w
