Mechanisms of Action and Change in Psychedelic-Assisted Therapies: A Holistic Framework for Ethical, Competent Clinical Care
Lynnette A. Averill, Logan Neitzke-Spruill
FOCUS The Journal of Lifelong Learning in Psychiatry July 1, 2026 DOI: 10.1176/appi.focus.20260006 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Topics | Psychedelic-assisted therapy |
| Keywords | Action physics Context archaeology Interpersonal communication Vulnerability computing Experiential learning Mechanism biology Therapeutic relationship Interpersonal relationship Psychotherapist Cognition Engineering ethics |
| Key points | Proposes that therapeutic change in psychedelic-assisted therapies emerges from interactions among neuroplasticity, memory updating, relational processes, contextual factors, and meaning-making, not from neurobiological mechanisms alone. |
Abstract
Psychedelic-assisted therapies (PATs) are emerging as novel combination treatments for selected stress- and trauma-related psychiatric conditions, particularly in cases where existing pharmacologic and psychotherapeutic approaches have provided limited benefit. Although current mechanistic models emphasize neuroplasticity, large-scale network changes, and modulation of neurotransmitter systems, these are insufficient to explain how therapeutic change emerges within the broader context of preparation, altered states of consciousness, interpersonal relationships, meaning-making, and integration. The authors introduce a non-neuroreductionist, multilevel framework that distinguishes mechanisms of action from mechanisms of change, highlighting how neuroplasticity, memory updating, relational processes, contextual factors, and meaning-making may interact to support therapeutic change. They draw on relevant evidence and clinical theory to describe how these treatments may create time-limited windows that support experiential relearning. Ethical considerations; limitations; and implications for practice, including the possibility that vulnerability may be increased when safeguards are inadequate, are discussed. Guidance is provided for clinicians who encounter PATs in practice.