Scientists develop a novel therapy for cannabis addiction

This drug is unique as it doesn't trigger withdrawal symptoms.
Tejasri Gururaj
a bag of weed and a rolled joint sit on a table
New therapy offers support for marijuana addiction


Cannabis, also known as marijuana, is one of the most widely used illicit drugs. According to the Centers for Disease Control and Prevention, 3 in 10 people who use marijuana have cannabis addiction or cannabis use disorder (CUD). 

CUD manifests in many ways, such as compulsive use of cannabis, loss of control, continued use despite problems, and neglected responsibilities. Despite its prevalence and the severity of symptoms, no treatments are available. 

However, there is a promising new treatment. Scientists have reported a new drug that could potentially facilitate the treatment of CUD. The team led by Pier Vincenzo Piazza from Aelis Farma, a biotechnology company based in Bordeaux, France, has developed a new drug that acts as an inhibitor of the cannabinoid receptor 1 (CB1) that reduces the effects of cannabis without triggering withdrawal symptoms.

The findings are based on data from animal models and phase 1 and 2a clinical trials.

Cannabis and addiction

Cannabis is a psychoactive drug derived from the cannabis sativa plant. Its consumption leads to changes in perception, mood, and cognition which can cause relaxation and stress relief. 

The main psychoactive compound in cannabis is Δ9-tetrahydrocannabinol, more commonly known as THC. THC binds to cannabinoid receptors in the brain, primarily the CB1, resulting in various psychological and physiological effects.

Traditional interventions for CUD treatments have focused on counseling, support groups, and therapy in the form of cognitive behavioral therapy (CBT). However, the limited success rates of these interventions have highlighted the need for pharmacological treatments that can more effectively address CUD.

The team led by Piazza now reports AEF0117, a new drug targeting a mechanism that inhibits some of the biochemical pathways activated by the CB1 receptor.

AEF0117: A drug with no withdrawal symptoms

The AEF0117 is the first compound of a new pharmacological class called CB1-SSi (signaling-specific inhibitors of the cannabinoid receptor 1). These compounds work by inhibiting specific intracellular effects, due to THC binding to the CB1 receptor, without directly modifying behavior.

Selective inhibition allows for a more focused approach to modulating the effects of THC without affecting overall behavior.

In animal studies, authors noted that AEF0117 reduced self-administration of cannabis and related behavioral impairment without significant adverse effects.

The team also tested the drugs on volunteers in two human trials. Phase 1 trials are initial studies assessing a drug's dosage and safety in a small group of healthy volunteers. Phase 2a trials are larger studies to evaluate the safety and effectiveness of the drug in individuals with targeted conditions or diseases, in this case, CUD.

In phase 1 trials involving healthy volunteers, AEF0117 was well-tolerated and safe. 

Compared to the placebo, AEF0117 dramatically reduced cannabis' favorable subjective effects and cannabis self-administration in the phase 2a trials involving volunteers with CUD. Additionally, AEF0117 did not lead to cannabis withdrawal and was well-tolerated in volunteers with CUD. 

Due to its ability to inhibit the effects of THC without producing psychoactive effects, AEF0117 has a unique advantage over traditional CB1 antagonists and agonists. Furthermore, the long half-life of AEF0117 may be beneficial for treatment compliance. 

The innovative selection process used in developing AEF0117 focused on early assessment of toxicity, formulation, and bioavailability, potentially reducing the chances of failure.

AEF0117 represents a promising new class of drugs for CUD that can selectively modify CB1 receptor activity in a signaling-specific manner, offering a potentially well-tolerated and effective therapy for CUD.

The findings were published in Nature Medicine.

Study abstract:

Cannabis use disorder (CUD) is widespread, and there is no pharmacotherapy to facilitate its treatment. AEF0117, the first of a new pharmacological class, is a signaling-specific inhibitor of the cannabinoid receptor 1 (CB1-SSi). AEF0117 selectively inhibits a subset of intracellular effects resulting from Δ9-tetrahydrocannabinol (THC) binding without modifying behavior per se. In mice and non-human primates, AEF0117 decreased cannabinoid self-administration and THC-related behavioral impairment without producing significant adverse effects. In single-ascending-dose (0.2 mg, 0.6 mg, 2 mg and 6 mg; n = 40) and multiple-ascending-dose (0.6 mg, 2 mg and 6 mg; n = 24) phase 1 trials, healthy volunteers were randomized to ascending-dose cohorts (n = 8 per cohort; 6:2 AEF0117 to placebo randomization). In both studies, AEF0117 was safe and well tolerated (primary outcome measurements). In a double-blind, placebo-controlled, crossover phase 2a trial, volunteers with CUD were randomized to two ascending-dose cohorts (0.06 mg, n = 14; 1 mg, n = 15). AEF0117 significantly reduced cannabis’ positive subjective effects (primary outcome measurement, assessed by visual analog scales) by 19% (0.06 mg) and 38% (1 mg) compared to placebo (P < 0.04). AEF0117 (1 mg) also reduced cannabis self-administration (P < 0.05). In volunteers with CUD, AEF0117 was well tolerated and did not precipitate cannabis withdrawal. These data suggest that AEF0117 is a safe and potentially efficacious treatment for CUD. identifiers: NCT03325595, NCT03443895 and NCT03717272.

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