The psychoactive substance psilocybin, which comes from Psilocybe mushrooms, has shown good antidepressant potential. The origin of this effect is still poorly understood, but a study at Johns Hopkins University (JHU) in the USA showed that positive emotions last for a week and that 30 days later the pattern of brain connections was still enriched.
After 7 or 30 days, the first and second data collection points in the study, there are no more traces of psilocybin in the body, as the compound is metabolized quickly. A trip with Psilocybe cubensis lasts about 6 hours.
The fact that psychic changes persist for up to a month helps explain the positive effects on mental disorders experimentally verified after a single dose. Psilocybin is in preliminary trials to treat not only depression and anxiety, by Roland Griffiths’ group at the JHU, but also alcohol and tobacco addiction.
It is a banned substance, but authorized studies have elevated it to the status of the second controlled drug closest to becoming a psychiatric drug (the first is MDMA, the basis of ecstasy). Until the FDA and its counterparts like Anvisa approve them, which could happen in less than two years, no one will be able to get legal treatment with them outside of research institutions.
Despite the ban, Psilocybe cubensis mushrooms have been used religiously for centuries, for example in Mexico; for decades by hippies; and, more recently, by geeks in Silicon Valley and traders in the capital market. It’s not difficult to find these fungi on the internet or in a cattle pasture after the rain, but identifying them is not trivial.
Psilocybin research continues
Griffiths and his pioneering group in psychedelic research used a high dose of psilocybin in this study, 25 mg per 70 kg of weight of the 12 healthy people without mental disorders. A small sample, to be sure, but it yielded noteworthy results.
The volunteers were subjected to various batteries of tests (standardized questionnaires) to quantitatively assess their mental state, such as positive and negative emotions. Contrary to what happens with chronically depressed people, they found an increase in the former and a reduction in the latter.
This benign pattern, however, only manifested itself within a week. In the questionnaires answered after 30 days, the participants returned to the scores measured before the psilocybin dose.
The promising effects after one month were observed using functional magnetic resonance imaging (fMRI). Dynamic images of brain activity measured the volunteers’ reactions to emotional stimuli, as well as recording which areas of the brain were interacting with which others.
The JHU team observed the emergence of new communication patterns between brain regions, which presupposes new connections between neurons. This increase in neuroplasticity would explain the benefit for those suffering from mental disorders characterized by rigidity and rumination of negative ideas or feelings.
In metaphorical terms, it would be like comparing a depressed mind, for example, to a computer that repeats the same faults when running very old programs. The person is trapped in a vicious cycle of bad thoughts.
Psilocybin would then act as a reset. In this analogy, the drug would allow new neuronal circuits to come online and, with luck, open a psychic window to glimpse new ways of processing the pains and ills of the soul.
Maybe a new horizon for antidepressants
Imagine an antidepressant capable of resolving 70% of serious cases in just two doses of medication, accompanied by therapy sessions?
For anyone who has experienced an episode of depression or knows someone in this situation, it sounds like a fictional story. This is because the drugs currently available on the market are not always effective for everyone. Traditional antidepressants usually take two to six weeks to take effect. And when they do. Several studies have shown that up to half of all users of common antidepressants develop treatment-resistant conditions, as well as causing various adverse effects.
But now a new alternative for this psychiatric disorder, which the WHO considers one of the most worrying diseases of the 21st century, is emerging as a promising bet: psilocybin, a substance found in so-called “magic mushrooms” of the genus Psilocybe.
A new randomized study (in which participants were randomly assigned to start treatment immediately or within eight weeks), carried out at Johns Hopkins University and published in the prestigious journal JAMA Psychiatry, showed resounding success rates in treating severe cases of depression with psilocybin-assisted psychotherapy.
The 24 patients received just two capsules of psilocybin, with a one-week interval between them. During the marked psychoactive effects of the substance – which is also one of the safest known psychotropic drugs – the patients underwent 11 hours of psychotherapy, listening to music, accompanied constantly by two therapists.
The results, evaluated statistically, are impressive: more than two thirds of the patients showed almost immediate and persistent improvements for up to 8 weeks. The psilocybin studies are already in Phase 2, in which safety and efficacy are tested, and the method could be approved for clinical use in the next few years.
Treatment for resistant depression
Compass Pathways has announced positive results from its study of experimental psilocybin therapy COMP360 for Treatment Resistant Depression (TRD), depression that does not improve after two or more adequate antidepressant treatments. Compass is a mental health company dedicated to accelerating patient access to evidence-based innovation in mental health.
This is the largest randomized, controlled, double-blind study of psilocybin therapy ever completed. It shows rapid and sustained response for patients receiving a single dose of psilocybin COMP360 with psychological support. The aim of the study was to find the appropriate dose for a larger phase III lead program, which Compass hopes to start in 2022.
Compass announced on November 9, 2021 that the groundbreaking phase IIb clinical trial of COMP360 psilocybin therapy for TRD met the primary endpoint for the highest dose of 25 mg, demonstrating a statistically significant and clinically relevant reduction in the severity of depressive symptoms after three weeks, with an adequate response.
