Psychedelics, a hope for psychiatry?

“Psychedelic. The word alone conveys a whole imagination made up of kaleidoscopic figures, tortuous guitar solos and swirls of acid colors. We do not expect to find it in black characters in the very serious pages of Nature or Lancet… And yet, for the past twenty years, scientific journals have been teeming with publications on psychedelic substances. LSD, psilocybin, ayahuasca, mescaline… These psychotropic products with strong hallucinogenic power, classified since 1971 as narcotics, could help treat certain mental disorders.

“These molecules have promising effects in various psychiatric indications: anxiety associated with the end of life, resistant depression and addictions, in particular to alcohol and tobacco”, explains Lucie Berkovitch, psychiatrist, researcher at Yale University (United States) and author of a review on the subject. However, these pathologies remain poorly treated today: according to Inserm, almost a third of depressive patients show resistance to treatment, and around half of alcohol dependent people who follow withdrawal treatment relapse within six month.

In this context, psychedelic molecules “have a particularly interesting efficacy profile, continues the psychiatrist. They have an almost immediate effect, in a few hours, compared to several weeks for the usual antidepressants. And these effects will, in a single dose, last over time, several months or even years..

“Associating the taking of these substances with psychotherapy”

A study published in 2020 thus shows the interest of psilocybin, the active substance derived from hallucinogenic mushrooms, in moderate to severe depression. 71% of the 27 participants saw a significant reduction in their symptoms one month after taking it. Half were in remission. An even more recent publication, from February 2022, shows similar results, but one year after taking.

By activating serotonin receptors – involved in particular in mood regulation – psychedelics allow the release of glutamate, an excitatory neurotransmitter that will profoundly modify communication between the different brain areas, and ultimately induce a phenomenon of neuroplasticity.

In brain imaging, “we observe a deactivation of certain regions, in particular those involved in ruminations and self-centered thoughts”, describes Valérie Bonnelle, neuroscientist research fellow at the Beckley Foundation, UK. “Conversely, there is greater connectivity between brain areas that usually do not really communicate with each other, especially at the level of sensory areas. »

In short, taking psychedelics will allow a sort of mental “reset”: by focusing less on themselves and more on the outside, subjects will perceive their problems differently. But it is far from being a miracle product. “What is very important is to associate the taking of these substances with psychotherapy, insists the neuroscientist. Their effectiveness depends enormously on the context and the state of mind at the time of taking. »

A favorable risk-benefit balance

All these studies are indeed carried out in a very controlled medical framework, on selected populations, and with psychological support before, during and after taking the substance. Because consumed recreationally, these products entail real risks for mental health, recalls Public Health France: anxieties, sensory disturbances, delirious puffs, even the occurrence of a psychotic disorder (such as schizophrenia) in predisposed people.

In medical research, psychedelics have only been shown “to date no serious long-term side effects”, explains Lucie Berkovitch. Nausea, headache or temporary anxiety have been reported. A risk-benefit balance that therefore seems favorable. However, “We need to be able to generalize these results, with larger studies, on samples of several hundred participants, and which compare these molecules to reference treatments”, tempers the psychiatrist.

The British group Compass Pathways is developing large-scale clinical trials of psilocybin for resistant depression. In France, a first large-scale research program was launched at the end of 2021. “AdelyLSD aims to evaluate the interest of LSD as a possible treatment for alcohol dependence”, explains the project coordinator, Luc Mallet, professor of psychiatry at the University of Paris-Est Créteil and researcher at the Brain Institute. A project that combines studies on rodents and a controlled clinical trial that will involve 210 patients. The first results are not expected before 2025.

“Addiction treatment”

This program is a continuation of the promising work on LSD published in the 1950s and interrupted at the end of the 1960s, when it was banned in several Western countries.. “It is now commonly accepted by the entire scientific community that psychedelics are not addictive, and could even be a treatment for addiction. There is therefore a discrepancy between the legal status of these molecules, which are still considered narcotics, and the state of scientific knowledge,” notes the specialist.

However, the latter warns of the recent media and societal craze around these substances: “Across the Atlantic, there is a real hype around unsupervised alternative therapies using these products, and many people have completely unreasonable expectations. But there is a real danger in wanting to self-medicate. »

Hence the increased need for “structuring this field of research”. At the origin of a section of psychedelic medicine created this year within the French Association of Biological Psychiatry, Luc Mallet thus hopes “to offer a place conducive to giving rise to rigorous scientific reflection around the supervised and secure therapeutic use of these substances”. A vast area still to be cleared.

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A resurgent field of research

End of the 19th centurye century. The Western scholarly world is interested in mescaline, derived from the hallucinogenic peyote cactus used in ancestral rites by Native Americans.

1950-1960. Therapeutic research on LSD (lysergic acid diethylamide) is in full swing. At the same time, recreational use is spreading.

1971. Psychedelics are classified as narcotics under the UN Convention on Psychotropic Substances. Medical research stops.

2000s. Gradual resumption of work on psychedelics in the United States, the United Kingdom, Switzerland, then in France.

Psychedelics, a hope for psychiatry?