How Psychedelics Modulate Multiple Memory Mechanisms in Posttraumatic Stress Disorder.
Manoj K. Doss, Annamarie Demarco, Joseph E Dunsmoor, Josh M. Cisler, Gregory A. Fonzo, Charles B. Nemeroff
Drugs November 1, 2024 DOI: 10.1007/s40265-024-02106-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | PTSD |
| Citations | 14 |
| Key findings | The acute effects of psychedelics can enhance extinction learning, which is impaired in PTSD, but may also enhance fear conditioning; post-acute effects may also enhance extinction learning. |
Abstract
Posttraumatic stress disorder (PTSD) is a psychiatric disorder with defining abnormalities in memory, and psychedelics may be promising candidates for the treatment of PTSD given their effects on multiple memory systems. Most PTSD and psychedelic research has investigated memory with fear conditioning and extinction. While fruitful, conditioning and extinction provide a limited model of the complexity of PTSD and phenomenology of psychedelics, thereby limiting the refinement of therapies. In this review, we discuss abnormalities in fear conditioning and extinction in PTSD and review 25 studies testing psychedelics on these forms of memory. Perhaps the most reliable effect is that the acute effects of psychedelics can enhance extinction learning, which is impaired in PTSD. However, the post-acute effects may also enhance extinction learning, and the acute effects can also enhance fear conditioning. We then discuss abnormalities in episodic and semantic memory in PTSD and review current knowledge on how psychedelics impact these memory systems. Although PTSD and psychedelics acutely impair the formation of hippocampal-dependent episodic memories, psychedelics may acutely enhance cortical-dependent learning of semantic memories that could facilitate the integration of trauma memories and disrupt maladaptive beliefs. More research is needed on the acute effects of psychedelics on episodic memory consolidation, retrieval, and reconsolidation and post-acute effects of psychedelics on all phases of episodic memory. We conclude by discussing how targeting multiple memory mechanisms could improve upon the current psychedelic therapy paradigm for PTSD, thereby necessitating a greater emphasis on assessing diverse measures of memory in translational PTSD and psychedelic research.
Comparable studies
Other narrative reviews on PTSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelic Psychiatry's Brave New World. | 2020 | Review | |
| Reviewing the Potential of Psychedelics for the Treatment of PTSD | 2020 | Review | |
| Novel psychopharmacological therapies for psychiatric disorders: psilocybin and MDMA. | 2016 | Review | |
| MDMA-assisted psychotherapy for PTSD: Are memory reconsolidation and fear extinction underlying mechanisms? | 2018 | Review | |
| Clinical applications of hallucinogens: A review. | 2016 | Review |
Citations in the library
Cited by 14
- Key competencies for psychedelic treatment in real-world mental health care settings. General Hospital Psychiatry 2025
- Is there a place for psychedelics in sports practice? Acta Neuropsychiatrica 2025
- A critical review of brain entropy as a biomarker of the psychedelic state. Neuroscience & Biobehavioral Reviews July 1, 2026
- Psychedelics do not always enhance cognitive flexibility: The potential role of time-varying effects on reward learning processes Neuroscience & Biobehavioral Reviews May 30, 2026
- Questioning the recovery of dissociated traumatic memories under psilocybin: comment on “Therapeutic emergence of dissociated traumatic memories during psilocybin treatment for anorexia nervosa” Journal of Eating Disorders December 4, 2025
and 9 more in the library
Cites 83
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
- MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine June 1, 2021
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
and 78 more in the library