A study now published in the journal Nature Medicine provides data on a new drug that could make it easier to treat cannabis addiction. Beyond its therapeutic uses, among which its analgesic capacity stands out, excessive consumption is not without risks, such as cannabis use disorder (CUD) developed by consumers of this substance.
Symptoms of persistent impairment are characterized by a lack of concentration and the inability to reduce drug use. For this reason, a team of researchers led by Pier Vincenzo Piazza, by Aelis Farmahas tested in various animal models and, in different phases, with people the medication AEF0117.
The article, which has just been published, includes both the data obtained with various animal models and the first results in the early stages of drug development 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.
In previous investigations they had shown that the activation of this receptor by the tetrahydrocannabinol (THC)), the main psychoactive component of cannabis, is responsible for its behavioral effects. “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.” , explained Arnau Busquets-García, from the Hospital del Mar Institute for Medical Research (IMIM) of Spain.
Results were also reported from two phase 1 clinical trials conducted in 64 healthy volunteers, in which the drug was found to be safe and well tolerated. In addition, in a phase 2a trial, involving 29 participants with CUD, the drug was found 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 effects substantial side effects,” said Arnau Busquets-Garcia and added: “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. Typically, drug candidates are 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 can translate into faster development compared to the classical approach,” explained the IMIM researcher.
“In some of the states where it has been legalized in USA there has been a significant increase in psychotic breakdowns. 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,” concluded Busquets-García. In 2020, according to medical records, 14.2 million people were diagnosed with CUD only in the United States.
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