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The consumption of cannabis is 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 risks, such as cannabis use disorder, or CUD for its acronym in English, which develop up to 19.5% of users of this substance.

This is characterised by persistent impairment, such as lack of attendance at 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 Medicineoffers insights into a new drug that could make it easier to treat cannabis addiction.

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Medical cannabis.

"If you make a very restrictive model in which access is not easy or fast, in the end the patient will continue to resort to the black market"

  • Writing: ROCÍO R. GARCÍA-ABADILLO Madrid

"If you make a very restrictive model in which access is not easy or fast, in the end the patient will continue to resort to the black market"

Forms of administration.

Oils, capsules, vaporization... (none is smoking a joint)

  • Writing: ROCÍO R. GARCÍA-ABADILLO Madrid

Oils, capsules, vaporization... (none is smoking a joint)

A team of researchers led by Pier Vincenzo Piazza of Aelis Farma has tested in various animal models and in phases 1 and 2a with people the safety of AEF0117, 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 had been tested previously, this new drug blocks a specific part of the intracellular cascade, which allows us to maintain the beneficial effects, such as analgesics, and avoid those negative ones that end up causing cannabis use disorder," explains Arnau Busquets-García , from the Hospital del Mar Medical Research Institute (IMIM) and which participated in the most preclinical phase of the development of this new drug, who also points out how other inhibitory drugs that were previously tested ended up being discarded due to their 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 drug development already with humans. Data from preclinical studies showed 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

It also reports the results of two phase 1 clinical trials conducted in 64 healthy volunteers where the drug was found to be safe and well-tolerated.

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% with a dose of 0.06 mg and by 38% with 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 there is the presence of the substance that its activity can be appreciated and above all that it does not have substantial side effects," 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.

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, toxicity, formulation and bioavailability were already taken into account in the in vitro studies of the preclinical phase, which has allowed the dose necessary to achieve therapeutic effects to be well known when reaching the clinical phasesand these can be translated into a faster development compared to the classical approach", explains the IMIM researcher.

Public health implications

Having a treatment that allows treating CUD is one of the main public health concerns considering 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. To this is also added the development of synthetic cannabinoids with very similar mechanisms, which are thought to be harmless, 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.

  • Pharmacology
  • Cannabis

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