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A Dose of Psilocybin Can Fight Depression For Two Weeks, Study Finds

By Alexander Beadle

Published: Jan 12, 2023   
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A single, moderate dose of psilocybin combined with psychological support counseling can rapidly and significantly reduce symptoms of depression, a new study has found.

Published in eClinicalMedicine, the study saw a clinically-significant improvement in depressive symptoms among individuals with major depressive disorder (MDD) who were given psilocybin, compared with those who were given a placebo.

The antidepressant effect of the psilocybin continued to last for at least 14 days after the psychedelic-assisted therapy session. However, the researchers do say that additional studies with longer observation periods are still needed before psilocybin is considered as a complement to routine mental health care.

A moderate psilocybin dose can fight depression

A total of 52 participants with MDD took part in this new double-blind, placebo-controlled study. At the beginning of the experiment, all participants were screened to ensure that they had stopped other medication and/or substance use. Of these 52 participants, only 16 reported having had a previous experience with psychedelic drugs.

After the medical screening and two preparatory visits, participants were randomly assigned to receive either an oral capsule of psilocybin or an oral placebo pill. Each participant was instructed to “immerse themselves in the experience” and was accompanied at all times by a trained therapist who could provide them with support when needed.

Additionally, every participant was asked to attend three integration visits held two days, eight days, and 14 days after the psychedelic session. At these visits, participants received additional psychological counseling, where a therapist would help them to work through any challenging emotions they might be experiencing and to facilitate “the creation of a meaningful narrative” related to the experience.

Participants were assessed using two scales that are commonly used to rate depression symptoms: the Montgomery-Åsberg Depression Rating Scale (MADRS), which is administered by a clinician, and the Beck’s Depression Inventory (BDI), which is a self-assessment questionnaire. MADRS and BDI assessments were conducted at both preparatory visits, on the day of administration and at each integration visit thereafter.

The researchers found that the absolute scores on both scales fell by around 13 points for the group given psilocybin, compared to baseline. This was a clinically significant improvement, and a significantly larger improvement in scores compared to those who only received a placebo. This improvement in symptom severity also persisted until the final assessment on day 14.

“The main takeaway from this publication is that a single, moderate dose of psilocybin administered in conjunction with psychological support in patients with major depressive disorder is capable of producing rapid alleviation of depressive symptoms,” study author Robin von Rotz, who conducted the trial as part of his PhD at the University of Zurich, told PsyPost.

More than half of those given psilocybin reached remission

After 14 days, 58% of the psilocybin group responded to treatment according to the MADRS scale, which defines “response” as either a 50% reduction in total score or a decrease below the remission threshold of 10 points overall. In the placebo group, just 15% of participants met these conditions. Additionally, the remission rate among the psilocybin group was 54% by the 14-day mark.

While this does point toward the effectiveness of psychedelics as a complement to psychological counseling, the researchers also highlight the number of participants who were not significantly affected by the psychedelic-assisted therapy approach.

“Noteworthy, not all patients responded equally well, which points to the fact that this therapeutic approach should not be treated as a ‘magic bullet’ and considerable research into mode(s) of treatment action is still required to draw a more definite conclusion,” von Rotz told PsyPost.

Over the course of this study, the moderate dose of psilocybin was well tolerated by the group, with no major adverse events being reported. The most common side effect experienced by the participants were headaches, followed by two cases of dizziness. Data gathered from monitoring the participants’ heart rate, systolic and diastolic blood pressure, and rate pressure product (RPP) also indicated no major cardiovascular safety concerns; only a moderate increase in blood pressure was recorded in the hours shortly after taking psilocybin.

Psychedelics and mental health

At the time of this study’s conception and writing, it was the first to examine the effects of a single, moderate dose of psilocybin compared with a placebo in this way. Yet its finding – that psilocybin can be a well-tolerated and effective treatment for depressive symptoms – is consistent with other research in the area.

Earlier this year, researchers from Johns Hopkins University found that two doses of psilocybin with supportive psychotherapy, given two weeks apart, produced anti-depressant effects that could last for up to a year.

Another recent double-blind clinical trial, looking at the effects of a single low, moderate, or high dose of psilocybin in individuals with treatment-resistant depression (TRD), also found significant improvements in the individuals’ MADRS scores, which lasted up to 12 weeks.

Von Rotz is very firm in saying that, while the results of this latest study are encouraging, there is still a long way to go before psychedelic therapy can become an accepted part of routine treatments for mental health conditions.

“Most of the results obtained from this study point towards the necessity of future studies utilizing multimodal measurement approaches and long observation periods to foster a deeper understanding of this novel treatment paradigm,” Von Rotz said. “Despite the promising findings that were published to date, there is still a considerable scientific journey to undertake, before psychedelic therapy is well enough understood to complement existing mental health care.”


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