Opinion – Psychedelic Turn: Largest study with psilocybin for depression comes out

The world’s most influential medical journal, the New England Journal of Medicine (NEJM), on Thursday published the largest clinical trial for depression ever conducted with psilocybin from so-called “magic” mushrooms. psilocybe. There were 233 participants in the phase 2b study, designed to determine effective doses, which had significant but modest results.

The trial was sponsored by the British company Compass Pathways with their stable synthetic formula of psilocybin, patented as COMP360. Three doses were tested, 25 mg, 10 mg and 1 mg (the latter for control), combined with psychotherapy sessions to prepare for the psychedelic trip and to integrate the lived experience with the mind-altering substance.

All patients, from 10 countries in Europe and North America, had treatment-resistant depression, that is, they had been unsuccessfully treated with at least two drugs. Three weeks after taking psilocybin, nearly a third (29.1%) were in remission, but only in the highest dose (25 mg) group.

After 12 weeks of follow-up, 20.3% of the volunteers on the 25 mg team were still doing better. No significant benefit was observed with 10 mg.

Adverse effects occurred in all groups, with a higher incidence in the higher-dose group. In this case, headache (24%), nausea (22%) and dizziness (6%) prevailed.

A total of 7 of 79 participants (8.9%) who took 25 mg had episodes of suicidal ideation or self-harm at 12 weeks. The same occurred with 5 of 75 (6.7%) who ingested 10 mg. But the company noted that they are common manifestations in depression resistant to available therapies.

In 2020, the state of Oregon approved in a referendum the offer of psilocybin services in natura (mushrooms) without a prescription, a measure that takes effect next January. Next Tuesday (8), it will be the turn of Colorado voters to vote on a similar initiative to decriminalize these fungi.

The World Health Organization estimated in 2017 that more than 320 million people in the world suffer from severe forms of depression. A third of them, around 100 million, have the drug-resistant form of the mental disorder, and 30% of this contingent tries to commit suicide at some point in their lives.

“With each new treatment, the chance of response significantly decreases, and patients become even more hopeless,” said Scott Aaronson, leader of the multicenter trial, in a statement from Compass.

“However, in this study, a substantial number of patients in the 25 mg group experienced improvement in their symptoms of depression, with effects lasting for up to three months. I am proud to have been a part of this important study and to see the results recognized today by a respected journal.”

Compass is now preparing to begin phase 3 studies later this year, which could lead to approval of psilocybin-assisted psychotherapy. This is expected to happen around 2025.

The drug licensing process usually takes a decade or more. It moves faster, in this case, because in 2018 the company obtained authorization to follow the fast track from the FDA (US drug agency), as a breakthrough therapy, the same condition granted to a similar investigation by the Usona Institute, in Wisconsin (USA).

“The study is very elegant and well conducted”, says Dráulio de Araújo, a neuroscientist at the Instituto do Cérebro at UFRN whose team in 2018 released a pioneering pilot test for depression with ayahuasca. Currently, the group is testing one of the active ingredients in tea, DMT, in inhaled and injected form, to shorten the effect and make it more suitable for the clinical context, since the trips can last more than four hours.

“Considering that the study is for a single intervention with psilocybin, I find the results very encouraging. In my opinion, we need to move towards understanding the long-term therapeutic effects, not after a single intervention, but after a protocol that would involve multiple interventions. “, proposes Araújo.

The researcher points out that this is not a cure, given that less than a third of the patients were in remission, that is, without a diagnosis of depression three weeks after the intervention. “Of the three doses tested, only the highest dose was observed to have an antidepressant effect,” he notes. “Is this an indication of the need for the subjective experience typically seen at higher doses?”

Araújo refers to a controversy in the field of psychedelic science, the search for drugs developed from classic consciousness alterers (mescaline, LSD, psilocybin, dimethyltryptamine-DMT and 5-MeO-DMT) that exert impacts such as neuroplasticity (formation of connections brain), but dispense with the subjective effect. A more traditional current argues that psychedelics only serve to open floodgates of trauma and contents that need to surface and be elaborated in psychotherapy.

This is just one of the controversies in the so-called psychedelic renaissance for medicine. Another is the business model based on intellectual property, such as Compass’ patent for COMP360, which is basically a drug used for centuries, perhaps millennia, by traditional peoples – for example, the Mazatecs of Mexico. Another is still around the medicalization of ancestral practices.

Marcelo Falchi, a psychiatrist on Araújo’s team at UFRN, draws attention to the fact that almost 9% of the participants had serious adverse events. “A treatment model without ‘wash-out’ (withdrawal of the antidepressant before the beginning of the study) could give greater safety to the alarming suicidal behavior observed, in addition to being more convenient for the office”, he considers.

For Falchi, a model in which the dosage of psilocybin operated in parallel with the use of standard treatment could guarantee greater safety and potentiate the effects of each other. “Our team proposes a psychiatric intervention model with psychedelics associated with standard treatments as adjunctive therapy.”

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To learn more about the history and new developments of science in this area, including in Brazil, look for my book “Psiconautas – Travels with Brazilian Psychedelic Science”.

Be sure to also see the reports from the series “A Resurreição da Jurema”:

https://www1.folha.uol.com.br/ilustrissima/2022/07/reporter-conta-experiencia-de-inalar-dmt-psicodelico-em-teste-contra-depressao.shtml

https://www1.folha.uol.com.br/ilustrissima/2022/07/da-caatinga-ao-laboratorio-cientistas-investigam-efeito-antidepressivo-de-psicodelico.shtml

https://www1.folha.uol.com.br/ilustrissima/2022/07/cultos-com-alucinogeno-da-jurema-florescem-no-nordeste.shtml

It is worth remembering that psychedelics are still experimental therapies and certainly do not constitute a panacea for all mental disorders, nor should they be self-medicated. Talk to your therapist or doctor before venturing into the area.