A single dose of the psychedelic drug psilocybin combined with supportive counseling leads to significant reductions in depressive symptoms, according to a new double-blind, placebo-controlled study. The findings have recently been published in eClinicalMedicine.
Psilocybin is a psychoactive compound found in certain types of “magic” mushrooms. It has been used for hundreds of years in spiritual and religious rituals for its ability to alter one’s state of consciousness. Psilocybin produces powerful effects on the brain, mediated through its activation of serotonin 5-HT2A receptors.
In recent years, psilocybin has undergone clinical studies to explore its potential therapeutic benefits, with promising results in areas including depression and anxiety. However, further research is needed to understand the efficacy of psilocybin-assisted therapy.
“I developed a scientific passion for the topic when investigating the neuro-behavioral and subjective effects of 5-HT2A agonists in my earlier academic career. That passion was further fueled with the current shortcomings in several psychiatric standard of care treatment options and the therapeutic potential of psychedelic molecules like psilocybin,” said study author Robin von Rotz, who conducted the trial as part of his PhD at the University of Zurich.
In the study, 52 participants diagnosed with major depressive disorder were randomly assigned to receive either a single dose of psilocybin or placebo combined with psychological support. Five participants in the psilocybin treatment group and 11 participants in the control group reported having previous experience with psychedelic drugs. The study utilized a double-blind procedure, meaning neither the researchers or the participants knew who was in the psilocybin group and who was in the control group.
The participants first completed a medical screening at the Psychiatric University Hospital in Zürich. They then underwent two preparatory visits prior to psilocybin/placebo administration. On their next visit, those in the psilocybin treatment group received a pill containing 0.215 mg/kg body weight of psilocybin, while those in the control group received received a pill that was identical in size, weight, shape and color and contained pure mannitol (a common sweetener with no psychoactive properties).
The “participants were instructed to immerse themselves in the experience with an introspective focus,” the researchers explained. “A standardised playlist with music was played via headphones or speakers. One trained therapist was present in the room throughout the administration day to respond to the participants’ needs. All visits were conducted in a living-room like environment.”
The participants then completed three integration visits two days, eight days, and 14 days after the intervention in which therapists helped them to work through challenging emotions and create a meaningful narrative of their experience. Throughout the study, depression symptom severity was assessed via the Montgomery-Åsberg Depression Rating Scale and Beck’s Depression Inventory.
The researchers found evidence that psilocybin-assisted therapy was efficacious in reducing depressive symptoms. Immediately after the intervention, those in the psilocybin condition showed an decrease in symptom severity of −13.0 points compared to baseline, which was a significantly larger reduction compared to those in the placebo condition. This statistically significant decrease in symptom severity persisted until at least 14 days after the intervention.
“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,” von Rotz told PsyPost. “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.”
As part of the study, the participants completed the Altered States of Consciousness questionnaire, which assesses subjective psychedelic experiences related to oceanic boundlessness, ego dissolution, visual restructuralization, auditory alterations, and vigilance reduction. Contrary to previous findings, the researchers found no evidence that these subjective experiences were associated with treatment response.
“I was probably most surprised by the lack of an empirically salient relationship between the phenomenology of subjective experiences and clinical response,” von Rotz said. “This stands in contrast to the practical clinical observations during the conductance of the study pointing towards a sensible relationship.”
However, he noted that “when designing the study, the primary focus was set on detecting clinically relevant amelioration of symptoms and only secondarily on the sensitivity to explain underlying the mechanisms. Therefore, the not confirmed relationship between treatment outcomes and subjective experiences in this publication needs to be taken with a grain of salt.”
The researchers also found that psilocybin had to a relatively mild adverse event profile. Psilocybin increased systolic and diastolic blood pressure, but not heart rate. The most frequently reported adverse event was mild headache.
“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. 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.”
The study, “Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial00538-7/fulltext)“, was authored by Robin von Rotz, Eva M. Schindowski, Johannes Jungwirth, Anna Schuldt, Nathalie M. Rieser, Katharina Zahoranszky, Erich Seifritz, Albina Nowak, Peter Nowak, Lutz Jäncke, Katrin H. Preller, and Franz X. Vollenweider.
