Studies point to new psychedelic-based depression treatments
New findings on psychedelic-based depression treatments included a UK DMT trial in 34 adults and a mouse study of modified psilocin compounds with fewer hallucinogenic-like effects.
Scientists reported new findings on psychedelic-based treatments for depression, including a UK clinical trial of dimethyltryptamine (DMT) and a preclinical study of modified forms of psilocin. A single dose of DMT, given with psychological support, rapidly reduced depressive symptoms in 34 adults with major depressive disorder, while new psilocin molecules appeared to cause far fewer psychedelic-like effects than pharmaceutical grade psilocybin in mice.
A UK clinical trial, the results of which were published in Nature Medicine, showed that a dose of DMT, given with psychological support, rapidly reduced depressive symptoms in 34 adults with major depressive disorder. In the first stage, participants were divided into groups that received either DMT or a placebo, without knowing which. Two weeks later, all participants received a DMT dose, with therapist support.
After the first fortnight, those who had received a DMT dose showed a greater reduction in depression scores on the Montgomery-Åsberg Depression Rating Scale, and the improvements were also apparent after one week. Twelve weeks after the second phase, the anti-depressant effects lasted for 12 weeks and no difference in depression scores were observed between one-dose and two-dose participants. Side effects were "mild or moderate" and included injection-site pain, nausea, and temporary anxiety.
The report said major depressive disorder is a leading cause of global disability, but many people do not respond to existing treatments, which are also associated with several side effects, including sexual dysfunction, weight gain, and sleep disturbance. It said psychedelic-assisted therapy, including the use of psilocybin, has shown promise, but the effects of psilocybin last for about two hours, which makes therapeutic sessions overly long and difficult to scale up. In contrast, DMT is a fast-acting psychedelic drug that, when given intravenously, causes a brief period of subjective psychedelic effects of around 30 minutes.
In separate research published in the Journal of Medicinal Chemistry, scientists created modified forms of psilocin, the active compound produced when psilocybin is processed in the body. In an early study involving mice, these new molecules maintained their biological activity while triggering fewer hallucinogenic-like effects than pharmaceutical grade psilocybin.
A research team designed five chemical variants of psilocin that were engineered to release the active molecule into the brain more slowly and steadily, potentially reducing hallucinogenic effects while preserving therapeutic activity. Laboratory experiments using human plasma samples and conditions that simulate gastrointestinal absorption identified a candidate known as 4e, which demonstrated strong stability during absorption and produced a gradual release of psilocin. At the same time, 4e continued to activate key serotonin receptors at levels similar to psilocin.
Researchers then compared equivalent doses of 4e and pharmaceutical grade psilocybin in mice over a 48 hour period. In animals treated with 4e, the compound crossed the blood-brain barrier efficiently and produced a lower but longer lasting level of psilocin in the brain compared with psilocybin. Mice receiving 4e showed significantly fewer head twitches, which scientists use as a reliable indicator of psychedelic-like activity in rodents, than mice treated with psilocybin.
The researchers said the findings are consistent with a growing scientific perspective suggesting that psychedelic effects and serotonergic activity may be dissociated, opening the possibility of designing new therapeutics that retain beneficial biological activity while reducing hallucinogenic responses. More research will be needed to understand exactly how these molecules work and to examine their full biological impact before scientists can evaluate their safety and therapeutic potential in people. The DMT researchers said that while larger studies are needed, the results point the way forward for a new method of treating depression, in conjunction with other therapies.