Major depression is a debilitating mental health condition that affects millions of individuals worldwide. Despite available treatment options, a significant number of patients do not achieve satisfactory improvement. In recent years, there has been growing interest in exploring alternative therapeutic approaches, such as psilocybin-assisted therapy, for the treatment of depression. Psilocybin, a psychedelic compound found in certain mushrooms, has shown promising results in alleviating symptoms of depression and facilitating meaningful therapeutic experiences. This article presents a detailed summary of a research study conducted to evaluate the efficacy of psilocybin-assisted therapy in patients with major depression.
Study Design and Approval
The study received ethical approval from the National Research Ethics Service London—West London and was sponsored and approved by Imperial College London's Joint Research and Compliance Office. It was also adopted by the National Institute for Health Research Clinical Research Network. The Medicines and Healthcare products Regulatory Agency (MHRA) reviewed and approved the study, and a Home Office Schedule One license was obtained for drug storage and administration. Prior to participation, all individuals provided written informed consent after receiving a comprehensive description of the study.
The study enrolled a total of 29 patients with major depression of moderate to severe degree. The inclusion criteria included a score of 16 or higher on the 21-item Hamilton Depression Rating scale (HAM-D) and a lack of improvement despite undergoing two adequate courses of antidepressant treatment. Participants were required to be free from antidepressant medication for at least two weeks before the study. The mean age of the participants was 44.7 ± 10.9, and there were six females and 23 males.
Each participant underwent two psilocybin-assisted therapy sessions, which were scheduled one week apart. During the first session, a low dose of psilocybin (10 mg, p.o.) was administered orally, while the second session involved a higher dose (25 mg, p.o.). After ingesting the psilocybin capsules, participants reclined with their eyes closed and listened to pre-selected music. The therapy sessions followed a non-directive, supportive approach, allowing participants to experience introspection without interference. A preparation session occurred one week before the low-dose session, and an integration session was held one day and one week after the high-dose session.
The primary clinical outcome measure for this analysis was the self-rated 16-item Quick Inventory of Depressive Symptoms (QIDS-SR16). Post-treatment ratings of depressive symptomatology were compared against baseline measurements collected before therapy. The response rate, defined as a ≥50% reduction in QIDS-SR scores, was assessed at the five-week mark after the high-dose session. Secondary clinical outcomes included additional depression rating scales, measures of anxiety, pessimism, optimism, and anhedonia, collected at various time points ranging from one day to six months after the therapy sessions.
Measures of Acute Psilocybin Session
The altered state of consciousness questionnaire (ASC) was employed to measure the acute subjective experience during the psilocybin sessions. The ASC assesses various dimensions of altered states of consciousness, such as visionary restructuralization, auditory alterations, and vigilance reduction. Of particular interest were the dimensions of oceanic boundlessness (OBN) and dread of ego-dissolution (DED), which were hypothesized to predict clinical outcomes.
The repeated measures ANOVA revealed significant interactions between Time and OBN, as well as between Time and DED, confirming the study's primary hypothesis. Regression analysis indicated that OBN and DED together accounted for 54% of the variance in the reduction of depressive symptoms at the five-week follow-up. Specifically, a higher OBN score and a lower DED score were associated with greater improvements in depressive symptoms. The correlation analysis between the dimensions of the ASC and clinical outcomes revealed that OBN showed a stronger correlation with depression changes compared to other perceptual factors, such as visionary restructuralization and auditory alterations. Furthermore, participants who had a "complete" OBN experience, defined by a threshold of OBN > 0.6, tended to have better clinical outcomes.
Descriptive exploratory analyses were conducted using the in-house psychedelic questionnaire (PQ) and the full ASC to further examine the relationship between subjective experiences and clinical outcomes. Correlations between PQ items and clinical outcomes at the five-week mark were calculated, revealing potential associations between specific aspects of the psychedelic experience and symptom reduction.
The findings of this study provide compelling evidence for the therapeutic potential of psilocybin-assisted therapy in patients with major depression who have not responded to conventional treatments. The significant interactions between OBN and DED with the passage of time suggest that the nature of the acute subjective experience during the psilocybin sessions is linked to the lasting effects on depressive symptoms. The mystical-type experience, characterized by a sense of unity, spiritual experience, and insightfulness, appears to be particularly relevant in predicting positive clinical outcomes.
The study's results align with previous research highlighting the importance of the mystical-type experience in therapeutic outcomes with psychedelics. The present study expands on these findings by specifically examining the role of OBN and DED in predicting treatment response and demonstrating their association with depressive symptom reduction.
Limitations of the study include a relatively small sample size and the absence of a control group. Future research with larger samples and rigorous control conditions is necessary to further validate these findings. Additionally, the study primarily focused on the five-week follow-up as the primary endpoint, and longer-term follow-up data would provide a more comprehensive understanding of the sustained effects of psilocybin-assisted therapy.
In conclusion, this study provides evidence supporting the effectiveness of psilocybin-assisted therapy as a potential treatment for major depression. The findings suggest that the acute subjective experience, particularly the sense of oceanic boundlessness and the absence of ego-dissolution dread, is associated with improved depressive symptoms. These results contribute to the growing body of research on the therapeutic applications of psychedelics and highlight the need for further investigation into the mechanisms underlying their effects. Psilocybin-assisted therapy shows promise as a novel approach for individuals with treatment-resistant depression, offering hope for improved mental health outcomes.
Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression (Imperial College London)