Stay up to date on the latest research in psychedelic medicine

Every month, around 100 new studies on psychedelics are published, adding to what we know about these substances. To help clinicians and practitioners stay up-to-date with the most important findings, the Psychedelic Provider Network has teamed up with Blossom to review the latest studies.

October 2024 Research Summary

To help clinicians and practitioners stay up-to-date with the most important findings, the Psychedelic Provider Network has teamed up with Blossom to review the latest studies from October 2024.

This month, we'll focus on key findings that could be useful for people working with psychedelics. We'll look at the impact of antidepressant discontinuation on the efficacy of psilocybin treatment. We'll also review research examining the correlation between subjective effects and therapeutic outcomes for psilocybin and ketamine. Finally, we'll cover a study exploring the impact of MDMA on personality traits and affect states.

Antidepressant Discontinuation and Psilocybin Treatment

When using classical psychedelics such as psilocybin, the general recommendation for clinicians is to have patients discontinue the use of antidepressants before treatment. This guidance arises from concerns about potential interaction effects, as antidepressants primarily target the serotonin system, which is also modulated by psychedelics. There are concerns that ongoing antidepressant use might dampen the subjective effects of the psychedelic experience, potentially impacting therapeutic outcomes.

However, for ketamine, this is less of a concern, as multiple studies have demonstrated the feasibility and potential benefits of combining ketamine treatment with ongoing antidepressant use. In contrast, MDMA studies have shown that individuals who discontinued antidepressants may experience a less pronounced effect on PTSD symptom reduction.

A recent study has addressed these concerns by analyzing data from the largest Phase II randomized controlled trial of psilocybin for treatment-resistant depression (TRD). This post hoc analysis investigated whether discontinuing antidepressants before psilocybin treatment impacted outcomes. The study compared 233 participants who received either 25 mg, 10 mg, or 1 mg of psilocybin (COMP360) with psychological support. The researchers examined various factors, including changes in depression severity during the antidepressant discontinuation period, baseline suicidality, acute subjective psychedelic effects, and the primary endpoint of the study - the change in depression symptom severity between baseline and week 3.

The findings revealed that antidepressant discontinuation was not associated with worsening depression severity before the baseline assessment. Additionally, suicidality levels were comparable between the groups at baseline. Most importantly, psilocybin's efficacy and the intensity of the subjective psychedelic experience did not appear to be negatively affected by recent antidepressant use and discontinuation. This suggests that for those seeking treatment with psilocybin, prior antidepressant use may not be a significant barrier to experiencing therapeutic benefits.

Examining Subjective Effects and Therapeutic Outcomes

The role of subjective experiences in the therapeutic effects of psychedelics like ketamine and psilocybin remains a critical question in psychedelic research. Clinicians are increasingly interested in whether improvements in conditions such as depression and substance use disorders (SUD) are primarily influenced by these drugs' perceptual and emotional effects or by their biological action on the brain.

A recent meta-analysis covering 31 studies directly explores this relationship. This research synthesized data from 23 ketamine studies (471 patients) and eight psilocybin studies (183 patients), focusing on whether the subjective experiences patients report—such as mystical or dissociative states—correlate with clinical improvement.

Key findings include a modest but meaningful correlation between subjective experiences and therapeutic outcomes for both ketamine and psilocybin. Ketamine showed a weaker link, with subjective effects accounting for 5-10% of the therapeutic variance, while psilocybin’s effects were stronger, explaining up to 24% of treatment outcomes. This suggests that, especially for psilocybin, the subjective experience might play a more integral role in fostering mental health improvement, particularly in depression treatment.

Moreover, this effect was more significant in treating SUD, with subjective effects accounting for a larger portion of positive outcomes than in depression. This distinction hints at the possibility that certain conditions might be more responsive to the experiential aspects of psychedelic therapy, an insight valuable for tailoring clinical approaches.

The Effect of MDMA on Personality

Emerging research continues to probe the interplay between psychedelics and personality, specifically how psychedelic compounds may influence personality traits and how personality traits can, in turn, shape psychedelic experiences. Studies using the Five-Factor Model (FFM/OCEAN) of personality (Openness, Conscientiousness, Extraversion, Agreeableness, and Neuroticism) have shown that classical psychedelics, such as psilocybin and LSD, often enhance Openness—a trait associated with curiosity, creativity, and willingness to explore new ideas.

A recent study investigates this dynamic with MDMA. In a controlled trial with 34 healthy adults, participants were administered either a 100 mg dose of MDMA or a placebo. Their FFM personality traits and affective states were measured before and 48 hours after dosing. While none of the initial hypotheses reached statistical significance, MDMA showed medium effect sizes for increasing Openness and Positive Affect, suggesting a trend toward enhanced openness and emotional positivity in the MDMA group compared to placebo. This aligns with other psychedelic research indicating that psychedelic-induced shifts in Openness are linked to positive well-being outcomes.

For clinicians, this study offers insights beyond MDMA’s recognized therapeutic potential in treating PTSD. By enhancing Openness and Positive Affect, MDMA may foster self-exploration, emotional resilience, and a more open mindset—qualities that may be valuable across various therapeutic settings. 

However, as this study involved healthy adults without therapeutic support, clinicians should consider the distinct influences of therapeutic context and patient populations in practice. Further studies will be key to understanding how MDMA’s personality effects manifest in clinical populations and with therapeutic support.

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October 2024 in Psychedelic Research

This month’s research brings fresh insights for clinicians integrating psychedelics into practice. First, findings from the largest psilocybin trial for treatment-resistant depression suggest that patients discontinuing antidepressants receive the same benefits from psilocybin, potentially expanding access to this therapy. A meta-analysis on subjective effects in psychedelic therapy also underscores the therapeutic significance of the psychedelic experience itself, especially for psilocybin, highlighting the interplay between psychological and biological mechanisms in treatment.

Additionally, a study on MDMA reveals that a single dose may increase Openness and Positive Affect, suggesting potential uses beyond PTSD therapy to support emotional well-being and openness. As the field of psychedelic medicine evolves, staying updated on these insights will support clinicians in applying these treatments effectively.