First-in-class drug for treating cannabis use disorders shows promise in clinical trials

A first-in-class drug designed to selectively block the signaling pathway of the cannabinoid receptor CB1 has promise as a safe and effective treatment for cannabis use disorder (CUD). Studies in animal models and newly reported phase I and IIa clinical trials showed that the drug reduced the effects of cannabis without causing withdrawal symptoms. New Drug Candidate AEFO117 Significantly Reduces the Effects of Cannabis in Daily Cannabis Smokers, Data from a Phase IIa Clinical Trial Led by a Team at Columbia University Irving Medical Center and French Biopharmaceutical Company Ellis Pharma bottom.

“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 Haney, the study’s supervisor. Principal Investigator of Phase I and Phase IIa Empirical Studies. Haney is Professor of Neurobiology in the Department of Psychiatry at Columbia University and Director of the Cannabis Research Institute. Haney is also co-director of Columbia’s Center for Substance Use Research.

“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,” continued Haney, lead author of a paper the team published in 2016. natural medicinetitled “Specific Inhibition of CB1 Receptor Signaling for Cannabis Use Disorders: A Phase 1 and 2a Randomized Trial”

Cannabis is the most widely used illicit drug in the world, and 19.5% of people who use cannabis develop a cannabis use disorder (CUD), the authors noted. CUD is characterized by persistent impairments such as neglecting work or personal obligations, continued cannabis use despite problems, or an inability to reduce its use. “In the United States, 14.2 million people will be diagnosed with CUD in 2020, and 14% of those being treated for substance use disorders reported cannabis as the primary drug of abuse,” the research team continued. And as cannabis use becomes more mainstream, with 38 states, three territories and the District of Columbia legalizing cannabis for medical and/or recreational purposes, consumption along with problematic uses, including addiction, has increased. is also increasing. But despite record high levels of daily cannabis use among adolescents and young adults, many are unaware that cannabis is addictive. And to date, there are no FDA-approved drugs to treat cannabis use disorders. Evidence-based behavioral therapy has also shown limited efficacy. “…Despite the growing need, there are no drugs that facilitate CUD treatment,” the researchers continued.

AEF0117, developed by Aelis Farma, is the first of a new pharmacological class known as signaling-specific inhibitors of CB1 (CB1-SSi), and is capable of inhibiting only cellular signals mediated by CB1-SSi. Based on a unique mechanism of action that in CUD. AEF0117 appears to counteract the ‘high’ associated with THC, the main psychoactive component of cannabis, at the type 1 cannabinoid receptors, but the physiological effects of these receptors on memory and learning, emotional processing, sleep, and eating. and does not interfere with behavioral function. action. 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. “CB1-SSi appears to be one of the few classes of compounds that can block the effects of receptor agonists without having psychoactive effects per se. , and represents a major advance in the pharmacology of inhibitors,” the researchers noted.

This natural brain mechanism was discovered by the research group of Ellis Farma CEO Pierre Vincenzo Piazza, MD. That was when he was director of Magendie, the neurological center of the French National Institute of Health and Medical Research (INSERM) in Bordeaux. Piazza is the senior and corresponding author of the newly published paper. natural medicine, he commented: “…from the discovery of this natural brain mechanism to a proof-of-concept clinical trial is the culmination of more than a decade of research…we are in the field of neuropharmacology with a class of drugs that has never been tested in humans. I am delighted to be able to contribute to the ”previous. “

A phase IIa, randomized, double-blind, placebo-controlled, crossover study enrolled 29 treatment-unseeking cannabis smokers of both sexes (patients with CUD aged 29-44 years). Participants were given 5 days so that in one phase he received 1 of his 2 different doses of AEF0117 and another he received a placebo in a 5 day phase. assigned randomly. “The primary objective of the study was to assess the effects of AEF0117 on cannabis ‘beneficial effects’ and self-administration, a recognized measure of abuse liability. An additional aim was to determine whether AEF0117 reversed the effects of cannabis on cognitive performance, pain thresholds and heart rate,” the authors explained.

Results showed that AEF0117 significantly reduced participants’ self-reported ratings of the primary endpoint, cannabis-related positive mood effects, by an average of 38%, while reducing cannabis use. These reductions did not promote cannabis withdrawal or disrupt normal functioning (mood, sleep, food intake, etc.) over five days, even in volunteers who smoked several grams of cannabis per day. Occurred. “Overall, the lack of effects of AEF0117 on food intake or sleep (reliable measures of cannabis withdrawal), and the small amplitude changes observed in certain mood assessments, suggest that AEF0117 promotes cannabis withdrawal or does not promote cannabis-smoking volunteers. It does not suggest that it will cause clinically relevant changes in mood in people,” investigative sources said.

Aelis Farma is currently sponsoring a multicenter, placebo-controlled Phase IIb 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,” Haney said. He also appreciates the support of the National Institute on Drug Abuse. ”

In conclusion, the authors stated: “AEF0117 is the first of a new pharmacological class of inhibitors, CB1-SSi, that modulate the activity of target receptors in a signaling-specific manner. Therefore, these compounds can inhibit the effects of THC without altering the basal activity of CB1, thus mitigating the effects of cannabis abuse-associated and reinforcing effects while maintaining normal behavior. and physiological activity, resulting in a well-tolerated and potentially effective treatment for CUD.”