Beyond the substance: A systematic review of psychological treatment frameworks in psychedelic-assisted therapy

There’s still no consensus on the most effective way to deliver psychotherapy alongside psychedelic-assisted treatment.

Florineth et al. (2026) conducted a systematic review of 44 clinical trials involving 1,537 participants to examine the psychological frameworks used in psychedelic-assisted therapy. Most trials followed a preparation, dosing and integration model, but psychological support varied substantially, with 0–17 non-dosing sessions and approaches ranging from non-directive support to structured interventions such as Acceptance and Commitment Therapy (ACT), Cognitive Behavioural Therapy (CBT) and motivational enhancement.

Approaches differed by clinical indication: substance-use trials generally incorporated more extensive psychological support, including behavioural and motivational interventions, while some DMT trials provided minimal formal psychotherapy. The authors identified substantial gaps in the reporting and standardisation of therapeutic techniques, therapist training and session content. Importantly, 40 of the 44 trials were rated at high or serious risk of bias.

The review could not establish which psychological framework, or level of support, produces the best outcomes. The authors conclude that comparative trials are needed to clarify the contribution of psychological interventions to treatment efficacy, safety and longer-term outcomes.

Abstract

Background

Classic psychedelics show potential for treating psychiatric disorders, yet the psychological framework of psychedelic-assisted therapy (PAT) remains underspecified. As regulatory approval approaches, defining the contribution of psychological interventions to clinical outcomes is critical for both mechanism inference and implementation.

Objectives

To systematically review the structure, content, and duration of psychological interventions in contemporary clinical trials of serotonergic psychedelics for psychiatric symptoms, and to map the state of current approaches to inform future trial designs.

Design

A systematic review following PRISMA guidelines.

Data Sources and Methods

A systematic literature search was performed across PubMed, PsycINFO, and SCOPUS. Inclusion criteria targeted clinical trials administering serotonergic psychedelics (lysergic acid diethylamide (LSD), psilocybin, or dimethyltryptamine (DMT)) for psychiatric symptoms. Two reviewers independently screened studies and extracted data on dosing frameworks and psychological interventions.

Results

We identified 44 trials (1,537 participants), covering depressive symptoms (n=20), substance use disorders (n=8), life-threatening illness-related distress (n=8), anxiety disorders (n=2), and other indications (n=6). Nearly all trials followed a three-phase preparation–dosing–integration structure, and dosing regimens showed increasing standardization. Psychological support, however, varied substantially: non-dosing sessions ranged from zero to 17, and frameworks spanned minimal/non-directive support to manualized established approaches (e.g., ACT, CBT). These interventions were frequently tailored by clinical indication, such as utilizing motivational enhancement for substance use disorders and addressing existential themes for life-threatening illnesses.

Conclusion

Despite convergence on a shared procedural structure, PAT protocols remain highly heterogeneous in psychological embedding and orientation, reflecting tension between clinical depth and scalability. Because psychedelics are typically administered within a psychological context, this heterogeneity complicates efforts to isolate pharmacological from contextual effects, and existing evidence suggests the therapeutic context may itself moderate safety and efficacy. Advancing the field requires dismantling trials isolating psychological components and applying the same empirical rigor to psychotherapeutic as to pharmacological parameters.

Florineth, G.A., Boeker, A.L., Müller, F., Bracht, T., Denier, N., Jung, A.C., Wopfner, A., Adorjan, K. and Soravia, L.M. (2026). Beyond the substance: A systematic review of psychological treatment frameworks in psychedelic-assisted therapy. Therapeutic Advances in Psychopharmacology, 16. Published online 8 October 2026. Read Paper

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