Mushrooms, LSD, ketamine… these amazing treatments for depression

Depression remains a mysterious disease, both in its understanding and in its management. New molecules are emerging, such as ketamine and psychedelics. Decryption.

Dr. Charlotte Tourmente

Written on 08/31/2022

While depression affects 1 in 5 people, antidepressants only work in 55-65% of patients. And they would not improve the long-term quality of life of patients, according to a study published in 2022. Even the mechanisms of depression remain obscure, the theory of a chemical imbalance at the origin of depression having been challenged by a study.

“This article changed our visionexclaims Dr. Guillaume Fond, psychiatrist, specialist at the expert center treating depression that does not respond to antidepressants, researcher, teacher, author and lecturer. There is not one depression but several, with different causes, including serotonin deficiency“.

In this complex context, depression requires new approaches, such as the already prescribed ketamine and psychedelics.

Ketamine, already authorized in spray

Ketamine was authorized at the end of 2020 in depression, in the form of an esketamine spray given in hospital. Initially used in veterinary medicine, it is not its first medical use since it is used as an anesthetic and is already prescribed as a second intention, in refractory pain.

“Ketamine acts much faster than an antidepressant and we know immediately if it works or notconfirms Dr. Guillaume Fond. There is no risk of addiction, side effects are mild and transient.” But the health authorities fear that the use will be diverted to recreational purposes, with a risk of bad trip.

No risk of diversion

“This is not true for the doses administered in psychiatry, which are much lower than those generating risks.categorically reassures Dr. Fond. Its use is highly regulated with 3-hour monitoring, secure prescription and hospital delivery. The administration is done by spray in the hospital. It is therefore impossible for patients to divert ketamine. But the procedures are so cumbersome that this limits the spread of this treatment.”

What the psychiatrist deeply regrets since in February 2022, a study published in the British Medical Journal, showed effectiveness in suicidal thoughts, with and without depression.

Psychedelics: promising effects to be confirmed

Mescaline cactus, iboga plant, ayahuasca and LSD, these psychedelics are also the subject of increased interest in depression resistant to conventional treatments.

“Logically, we turned to substances that we knew had effects on the brain, even if people used them for recreational purposes.explains Dr. Fond. But psychedelics convey a particular imagination with hippies and Woodstock. They are seen as dangerous or transgressive.”

However, studies are multiplying, in particular on psilocybin, a chemical compound present in hallucinogenic mushrooms, and ayahuasca (source: The Lancet).

Focus on psilocybin, ayahuasca and LSD

“Almost all psychiatrists treating depression are waiting for psilocybin! exclaims Dr. Fond. Two randomized trials, published in New England and JAMA, have shown its effectiveness. But in France, we are subject to regulations that are probably too strict, whereas other countries, such as Switzerland, are much more advanced. We therefore await a political decision and the possibility of prescribing it..”

At this time, the Canadian Network for Mood and Anxiety Treatments considers psilocybin an experimental treatment for depression, due to the low level of evidence on its effectiveness. LSD is also being studied. As for mescaline, famous for the changes in perception that it induces, it could improve depression and anxiety, an effect obviously to be confirmed by rigorous studies.

“In general, neither psychiatrists nor patients have any barrier to psychedelics as long as the indication and efficacy are supported by studies.concludes Guillaume Fond. We are expecting larger-scale works but we should already be able to use them given their benefit/risk ratio.”

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