Psychedelics: A review of their effects on recalled aversive memories and fear/anxiety expression in rodents
Isabel Werle, Leandro J Bertoglio
Neuroscience & Biobehavioral Reviews September 20, 2024 DOI: 10.1016/j.neubiorev.2024.105899 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Population | Rodents |
| Interventions | psilocybin/psilocin lysergic acid diethylamide (LSD) N N-dimethyltryptamine (DMT) mescaline 5-methoxy-N N-dimethyltryptamine (5-MeO-DMT) DOI) 3 4-methylenedioxymethamphetamine (MDMA) |
| Topics | Ayahuasca Ibogaine Ketamine MDMA Neuroplasticity PTSD Anxiety |
| Keywords | Bdnf Fear conditioning Nbomes Psychedelics/hallucinogens/entheogens PTSD/Trauma/Post-Traumatic Stress Disorder Neuroscience/neuroplasticity/brain plasticity Mental health/psychiatry/psychological treatment |
| Citations | 17 |
| Key findings | Psychedelics often show biphasic effects on locomotion at doses that enhance extinction learning, impair memory reconsolidation, or reduce learned fear and anxiety in rodents. |
Abstract
Threatening events and stressful experiences can lead to maladaptive memories and related behaviors. Existing treatments often fail to address these issues linked to anxiety/stress-related disorders effectively. This review identifies dose ranges associated with specific actions across various psychedelics. We examined psilocybin/psilocin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), mescaline, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), serotonin 2 A/2 C agonists (e.g., DOI) and 3,4-methylenedioxymethamphetamine (MDMA) on aversive memory extinction and reconsolidation, learned fear, anxiety, and locomotion in rodents. Nearly 400 studies published since 1957 were reviewed. Psychedelics often show biphasic effects on locomotion at doses that enhance extinction learning/retention, impair memory reconsolidation, or reduce learned fear and anxiety. Emerging evidence suggests a dissociation between their prospective benefits and locomotor effects. Under-explored aspects include sex differences, susceptibility to interference as memories age and generalize, repeated treatments, and immediate vs. delayed changes. Validating findings in traumatic-like memory and maladaptive fear/anxiety models is essential. Understanding how psychedelics modulate threat responses and post-retrieval memory processes in rodents may inform drug development and human studies, improving therapeutic approaches for related psychiatric conditions.
Comparable studies
Other preclinical and animal studies on ayahuasca for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Behavioral Changes Over Time Following Ayahuasca Exposure in Zebrafish Adult zebrafish | 2017 | Experimental study | n = 70 |
| Effects of Long-Term Ayahuasca Administration on Memory and Anxiety in Rats Rats | 2015 | Animal study | |
| Antidepressant and anxiolytic-like effects of ayahuasca in rats subjected to LPS-induced neuroinflammation Male rats, about 90 days old | 2022 | Randomized controlled trial | n = 80 |
| An ontogenic study of the behavioral effects of chronic intermittent exposure to ayahuasca in mice C57BL/6 mice | 2017 | Animal study | |
| Ayahuasca Pretreatment Prevents Sepsis-Induced Anxiety-Like Behavior, Neuroinflammation, and Oxidative Stress, and Increases Brain-Derived Neurotrophic Factor. Rats | 2025 | Animal study |
Citations in the library
Cited by 17
- Evaluation of behavioural and neurochemical effects of psilocybin in mice subjected to chronic unpredictable mild stress Translational Psychiatry June 14, 2025
- Psychedelics and autobiographical memory - six open questions. Psychopharmacology March 17, 2025
- Psychedelics as pharmacotherapeutics for substance use disorders: A scoping review on clinical trials and perspectives on underlying neurobiology British Journal of Pharmacology September 2, 2025
- The psychedelic-peptide paradox: a hormetic hypothesis. Comprehensive Psychoneuroendocrinology June 2, 2025
- The effect of psychedelic microdosing on animal behavior: A review with recommendations for the field Neuroscience & Biobehavioral Reviews May 9, 2025
and 12 more in the library
Cites 185
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Science February 13, 2009
- A non-hallucinogenic psychedelic analogue with therapeutic potential. Nature 2021
and 180 more in the library