Cannabis use has been increasing steadily in recent years, both due to increasingly permissive legislation and its potential therapeutic uses, among which its analgesic capacity stands out.. However, it is not without its risks, such as cannabis use disorder, or CUD, which develops in up to 19.5% of cannabis users.
This is characterized by persistent impairment, such as failure to attend work or personal obligations, and the inability to reduce cannabis use. There is no treatment for this disorder, despite growing public health concerns.
A study now published in the journal Nature Medicine offers data on a new drug that could facilitate the treatment of cannabis addiction.
“If a very restrictive model is made in which access is not easy or fast, in the end the patient will continue to resort to the black market”
Oils, capsules, vaporization…. (none is smoking a joint)
A team of researchers led by Pier Vincenzo Piazza, from Aelis Farma, has tested the safety of AEF0117 in various animal models and in phases 1 and 2a with people, a drug that targets a mechanism that inhibits a subset of the molecular pathways activated by the cannabinoid receptor 1 (CB1).
Previous research had shown that activation of this receptor by tetrahydrocannabinol (THC), the main psychoactive component of cannabis, is responsible for the behavioral effects of cannabis.
“Unlike other antagonists that have been tested before, this new drug blocks a specific part of the intracellular cascade, allowing beneficial effects, such as pain relievers, to be maintained and negative ones that end up causing cannabis use disorder to be avoided.” , explains Arnau Busquets-García, from the Hospital del Mar Medical Research Institute (IMIM) and who participated in the most preclinical phase of the development of this new drug, who also points out how other inhibitor drugs that were previously tested ended up being discarded due to its adverse effects.
The article that has just been published includes both the data that have been obtained with various animal models and the first results in the initial phases of development of the drug, already with humans.. Thus, data from preclinical studies demonstrated that the drug was able to inhibit the behavioral effects of THC without altering normal behavior or physiological activities in mice and primates.
Two clinical trials
Results of two phase 1 clinical trials conducted in 64 healthy volunteers where the drug was found to be safe and well tolerated are also reported.
And in a phase 2a trial, involving 29 participants with CUD, the drug was seen to reduce the positive subjective effects of cannabis by 19% at a dose of 0.06 mg and by 38% at a dose of 1 mg compared to placebo, further reducing self-administration of cannabis.
“It was also possible to see with all these studies that in a basal population, without cannabis consumption, the drug has no effect and that it is when the substance is present that its activity can be appreciated and above all that it has no side effects. substantial”, adds Arnau Busquets-García. “Now the next step will be to do trials with a much larger population, but there already seem to be positive effects that will make it easier to get funding to continue the research.”
The development of this new drug has also followed a different process than usual in what may mean a paradigm shift.
Drug candidates are typically selected for their potency and efficacy. Toxicity, formulation, and bioavailability are studied only later in development, resulting in only about 4% of developed compounds gaining approval.
“In this case, the toxicity, formulation and bioavailability were already taken into account in the in vitro studies of the preclinical phase, which has allowed the necessary dose to achieve therapeutic effects to be well known upon reaching the clinical phases, and these were can translate into faster development compared to the classical approach”, explains the IMIM researcher.
Public health implications
Having a treatment that makes it possible to treat CUD is one of the main public health concerns, taking into account the growing use of cannabis among the general population.
“In some of the states where it has been legalized in the United States, there has been a significant increase in psychotic crises.. Added to this is the development of synthetic cannabinoids with very similar mechanisms, which are thought to be innocuous, but this is not the case,” adds Busquets-García.. It should not be forgotten that in 2020, 14.2 million people were diagnosed with CUD in the United States alone.