Hallucinogenic mushrooms: a first experiment carried out in France with psilocybin

“I never imagined experiencing such a revolution! » Amandine Luquiens, addiction psychiatrist at Nîmes University Hospital, is enthusiastic: she has just taken care of the very first patient* in a pioneering study in France on psychotherapy assisted by psilocybin, the active substance in hallucinogenic mushrooms.

Carried out at the Grau-du-Roi Rehabilitation, Rehabilitation and Addictology Hospital (Gard) on 30 patients suffering from alcohol use disorders associated with depression, this will firstly to study the “feasibility and acceptability” of the treatment before it is eventually evaluated in a larger cohort. “We include patients whose addiction is severe and in whom signs of depression remain present after withdrawal, which is a major risk factor for relapse,” specifies Dr. Luquiens. On average, almost half of alcohol-dependent patients relapse within 6 months following withdrawal, and a third of depressed patients are resistant to current treatments.

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Psychedelics have several advantages over antidepressant medications, which justify the renewed interest of doctors in them. These products which modify the state of consciousness seem effective in one or two doses, immediately and persistently. They act on serotonin receptors, a neurotransmitter notably involved in the management of moods and anxiety, and induce a profound alteration of perceptions and consciousness, indicates Inserm. In a study recently published in Scientific Reports, New York researchers performed MRI scans on 11 alcohol-dependent patients three days before receiving psilocybin-assisted psychotherapy, then two days later. After. They show changes in brain activity that “suggest better goal-directed action, better emotional regulation, and reduced cravings.”

In November 2023, a large American study carried out on 233 patients resistant to antidepressants and published in the New England Journal of Medicine showed a significant and lasting improvement in those who received 25 mg of psilocybin combined with psychotherapy, i.e. 79 participants (the others having received 10 or 1 mg). However, the authors reported that “adverse events occurred in 179 of 233 participants (77%), including headache, nausea and dizziness. Suicidal ideation or behavior or acts of self-harm were observed in all dose groups. »

The handling of psychedelics therefore requires close supervision from the medical team. Each session must take place in a warm and reassuring environment, with support from caregivers who must remain with the patient throughout the experience. “It is time-consuming for caregivers, but if this strategy proves effective, it could be efficient because in just two doses the patient could enter remission,” underlines Amandine Luquiens. Patients who have been weaned from alcohol for at least two weeks will receive psilocybin twice, three weeks apart. “They will remain hospitalized for 4 weeks,” adds the doctor. Our patients may have withdrawal-related complications and are psychologically vulnerable. »

This is why taking psilocybin is associated with psychotherapeutic support before, during and after the session. “The day before, we explain to them in detail what is going to happen, and we work with them on their intentions,” explains Dr. Luquiens. They are also prepared to deal with emotional difficulties that may arise during the session, so that they feel safe. » Between the two sessions, “an entire intensive care program to prevent alcohol relapse is carried out during hospitalization”. However, patients will be able to leave the day after the second dose of psilocybin.

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On the day of the session, the patient's room is transformed into a welcoming cocoon with, for example, the presence of green plants and the playing of music specially designed for this type of experience. “We are lucky to have a very nice hospital. All the rooms have a sea view, so we don’t have to do much decorating effort! », recognizes the doctor. Psilocybin acts around forty minutes after taking it and its effect lasts six hours, during which the patient, lying on his bed, with his eyes covered, must be solicited as little as possible: the psychedelic experience is an inner journey that nothing must come and disturb. “We even try not to move from our chair,” slips the doctor. On the other hand, we are present at all times with the patient: he or she may feel things more or less intense, sometimes with reliving difficult moments or anxiety. It is important to be supported throughout the experience and to feel psychologically safe. »

The patients are divided into two groups, by random draw and double-blind: two thirds will take 25 mg of the product, the others a microdose of 1 mg, all in addition to their usual treatment. The two dosages tested constitute “the regimens which have been most documented in studies on resistant depression”, explains Amandine Luquiens. The molecule received special authorization from the Medicines Agency as part of this study, and is packaged in capsules in the hospital pharmacy.

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The doctor, however, warns against using psilocybin without support, outside of a medical setting: “On the one hand, it is a product banned in France, so it is difficult to know exactly what we are consuming. In addition, medical complications may appear that must be managed, such as hypertension. Finally, without psychotherapeutic support, negative emotions are likely to persist and worsen depression. In certain American states, where the consumption of hallucinogenic mushrooms has exploded, the number of visits to emergency rooms for major anxiety among people who have taken these products recreationally has more than doubled! »

In France, other trials of the same type are planned by other teams, with psilocybin and another molecule from ergot: the famous LSD. They mark the great return of psychedelic medicine. Before being diverted for recreational purposes, these substances had in fact been developed as medications against depression, anxiety or alcohol dependence. Work carried out in the United States had notably shown benefits from the medical use of these products, and France was also among the first countries to study the effects of psilocybin. But the appearance of antidepressants, the lack of enthusiasm of French psychiatrists to use them as part of real psychotherapeutic support, as well as a “moral panic” born in the 1960s had sounded the death knell for their use in medical purposes in France, historian Zoë Dubus explained to Le Figaro in 2022.

The tide therefore seems to be turning. Last March, members of the European Medicines Agency (EMA), the EMA central nervous system working group and the European College of Neuropsychopharmacology (ECNP) even launched a call in The Lancet to conduct “additional research into the therapeutic potential of psychedelics for mental disorders.” Will psychedelics ever be a routine psychiatric treatment?

*The Nîmes University Hospital is looking for patient volunteers for the PAD study. If you wish to participate and advance the research, you can contact by email the clinical research associate, Julie Hemart (julie.hemart@chu-nimes.fr), or the investigating doctor, Amandine Luquiens (amandine.luquiens@chu -nimes.fr).