Preparation Improves Psychedelic Therapy for MDD, With Gianluca Florineth, MSc

Longer follow-up periods and therapy design choices may influence outcomes in psychedelic-assisted therapy (PAT) for depression, a recent meta-analysis found. The study highlights preparation therapy as a key factor in symptom reduction, while post-dosing integration sessions and total therapy duration showed no significant association with short-term outcomes.

HCPLive spoke with investigator Gianluca Florineth, MSc, from the Translational Research Center at the University Hospital of Psychiatry and Psychotherapy, University of Bern, on this research. Despite many studies in the analysis having a high risk of bias due to ineffective blinding, Florineth has confidence in the strength of the association between preparation therapy and positive outcomes.

“It's a limitation that is very difficult to control in psychedelic research because the blinding is one of the most significant challenges that are faced in randomized trials using psychedelics, because the effects are so noticeable that participants can distinguish them if you assess it most of the time, over 95% probability,” Florineth said. “In my opinion, this doesn't really influence our findings that much because we look at this treatment as a combination of psychological and pharmacological therapy.”

He believes that the therapeutic processes occurring during preparations are not affected by this risk of bias. While these biases may influence the overall treatment effect, the relationship between therapeutic factors and symptom reduction is likely less affected.

Florineth’s team pooled data from 12 controlled trials, including 733 adults (49.8% female; mean age 42.1) receiving psilocybin- or LSD-assisted therapy. They examined associations between depressive symptom change and therapy-related variables, including preparation hours, integration hours, total therapy exposure, and overall treatment duration.

Each additional hour of preparation therapy correlated with greater depressive symptom reduction (P =.04), whereas integration therapy hours (P =.53) and total therapy duration (P =.86) were not significantly associated with short-term outcomes. Longer follow-up periods were linked to smaller effect sizes (P =.003), consistent with the natural attenuation of therapeutic benefits over time. Most studies (75%) carried a high risk of bias, primarily due to ineffective blinding.

The findings suggest that preparation therapy may directly influence symptom reduction, while integration sessions and total therapy time likely serve other roles, such as consolidating therapeutic insights and maintaining gains, which are not captured by short-term depression measures. Factors such as therapeutic alliance, therapist experience, and patient readiness may critically shape outcomes, potentially outweighing the quantity of sessions.

From a trial design perspective, the study highlights the importance of reporting and evaluating psychological therapy components, including comparisons of high- versus low-support conditions and therapy intensity. For clinical implementation, the results underscore the need to consider psychedelics within a framework that integrates psychotherapy, regulatory guidance, therapist training, and minimum support standards to achieve and sustain clinical benefit.

“We hope that the role of psychological therapy will not just be dismissed,” Florineth said. “We see somewhat of a trend currently because of the FDA rejection of MDMA-assisted therapy, which was in some parts due to this unclear role of psychological therapy or this combination approach. Now, as a solution, some have started to prohibit the use of psychotherapy in their trial designs so that they can say it's a purely pharmacological intervention, but we think that this is a bit dangerous if you haven't really assessed the psychological therapy itself or its potential role or benefits. We hope that this gives at least some ideas that the role of psychological therapy should be explored further before we draw preliminary conclusions without really assessing it.”

Florineth has no relevant disclosures.

References

1. Florineth GA, Klima I, Boeker AL, et al. Psychological Therapy Quantity and Depressive Symptom Reduction in Psychedelic-Assisted Therapy: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2026;9(1):e2554843. Published 2026 Jan 2. doi:10.1001/jamanetworkopen.2025.54843

2. Derman C. Preparation Before Psychedelics Tied to Better MDD, With Gianluca Florineth, MSc. HCPLive. Published on January 26, 2026. Accessed on January 30, 2026. https://www.hcplive.com/view/preparation-before-psychedelics-tied-better-mdd-gianluca-florineth-msc