Gianluca Florineth, MSc, from the Translational Research Center, University Hospital of Psychiatry and Psychotherapy at the University of Bern in Switzerland.

Gianluca Florineth, MSc

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 

, 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.

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 (

 =.04), whereas integration therapy hours (

=.86) were not significantly associated with short-term outcomes. Longer follow-up periods were linked to smaller effect sizes (

 =.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 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. 

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

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Meta-analysis links longer preparation therapy and follow-up duration to depressive symptom change in psilocybin- and LSD-assisted treatment. 

Preparation Before Psychedelics Tied to Better MDD, With Gianluca Florineth, MSc

, the timing of psychotherapy may be as important as its delivery, with new evidence highlighting preparation sessions as a key driver in symptom improvement.

A recent systematic review and meta-analysis suggests that greater exposure to preparation therapy before psychedelic dosing is associated with larger reductions in depressive symptoms, whereas post-dosing integration therapy and total therapy duration show no clear relationship with short-term outcomes.

“We were also quite surprised, but there are some ways that we can explain this non-significant association,” said investigator Gianluca Florineth, MSc, from the Translational Research Center, University Hospital of Psychiatry and Psychotherapy at the University of Bern in Switzerland, in an interview with 

. “We definitely do not want to encourage people to stop doing integration sessions because we also believe that it's very important. However, the role may not be as much in reducing the depressive symptoms, but in, for example, maintaining them long-term, or in helping participants reduce potential follow-up effects from the substances.”

The analysis pooled data from 12 controlled clinical trials involving 733 adults (49.8% females; mean age, 42.1 years) who received psilocybin- or LSD-assisted therapy for depressive symptoms. Across studies, investigators examined associations between depressive symptom change and several therapy-related variables, including hours of preparation therapy, integration therapy, total psychotherapy exposure, and overall treatment duration.

Each additional hour of preparation therapy correlated with greater symptom reduction (

 = .86) were not significantly associated with outcomes. Florineth suggested that integration therapy may address functions not captured by short-term depression scales, such as helping patients process challenging material, consolidate insights, and sustain benefits over time.

The study also found that longer follow-up periods were associated with smaller effect sizes, consistent with an attenuation of treatment effects over time (

 = .003). Most studies (75%) had a high risk of bias, often due to ineffective blinding.

Additionally, Florineth emphasized that preparation therapy may play a critical role in shaping the acute psychedelic experience by establishing psychological safety, aligning expectations, and strengthening the therapeutic alliance before dosing. These factors may reduce the risk of distressing or destabilizing experiences during psychedelic sessions and support more favorable clinical outcomes.

When asked which element of preparation therapy most strongly drives symptom reduction, Florineth cited a combination of factors.

“The most important is that participants or patients have a sense of safety, because if you have very short preparation periods before the substance sessions, you may not really feel comfortable with the facilitators that are present,” Florineth said. “This general therapeutic alliance building is probably most important.”

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

Greater exposure to preparation therapy before psychedelic dosing was linked to larger reductions in depressive symptoms, a new study found.

Gianluca Florineth, MSc

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