Psycholytic Therapy Using LSD: a Realist Review.

PURPOSE

Psycholytic therapy, utilizing psychoactive compounds such as d-lysergic acid diethylamide (LSD) to enhance psychoanalytically oriented therapy, was once the most common form of psychedelic-assisted psychotherapy. Despite its historical prominence, little attention has been given to the reasons behind its decline, and there is a lack of standardized guidance for new clinical trials. This review addresses the diversity of psycholytic methods and their association with effectiveness and safety.

METHOD

A realist review was conducted in which studies were identified via a comprehensive bibliography of publications on psycholytic therapy with entheogens from 1948 to 1995. Intervention variables were examined in relation to rates of adverse events and diagnosis-adjusted improvement, allowing for an analysis of risk factors and practices associated with positive outcomes.

FINDINGS

Analysis of studies published from 1954 to 1965 revealed several features conducive to successful therapy: using a flexible, intuitive therapeutic approach; promptly correcting transference issues; maintaining therapist presence throughout; providing more than ten treatment sessions and extensive preparatory work; incorporating creative activities during integration; using maximal tolerated doses; and avoiding abrupt pharmacological termination.

CONCLUSIONS

Psycholytic therapy has shown potential to significantly improve severe mental health conditions, especially when trust in the therapist is fostered. Developing a strong therapeutic relationship helps address trauma-based responses resistant to psychotherapy alone, while rapid resolution of internal conflicts may ease the subsequent integration process.

© 2026 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.