Hypothesis: The Psychedelic Ayahuasca Heals Traumatic Memories via a Sigma 1 Receptor-Mediated Epigenetic-Mnemonic Process
Frontiers in Pharmacology April 5, 2018 DOI: 10.3389/fphar.2018.00330 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Topics | Ayahuasca |
| Keywords | Memory consolidation Traumatic memories |
| Citations | 91 |
| Key points | Proposes that ayahuasca's DMT-mediated sigma-1 receptor activation and MAOI effects facilitate retrieval and reprocessing of traumatic memories in PTSD through enhanced synaptic plasticity, neurogenesis, and fear extinction mechanisms. |
Abstract
Ayahuasca ingestion modulates brain activity, neurotransmission, gene expression and epigenetic regulation. N,N-Dimethyltryptamine (DMT, one of the alkaloids in Ayahuasca) activates sigma 1 receptor (SIGMAR1) and others. SIGMAR1 is a multi-faceted stress-responsive receptor which promotes cell survival, neuroprotection, neuroplasticity, and neuroimmunomodulation. Simultaneously, monoamine oxidase inhibitors (MAOIs) also present in Ayahuasca prevent the degradation of DMT. One peculiarity of SIGMAR1 activation and MAOI activity is the reversal of mnemonic deficits in pre-clinical models. Since traumatic memories in post-traumatic stress disorder (PTSD) are often characterised by "repression" and PTSD patients ingesting Ayahuasca report the retrieval of such memories, it cannot be excluded that DMT-mediated SIGMAR1 activation and the concomitant MAOIs effects during Ayahuasca ingestion might mediate such "anti-amnesic" process. Here I hypothesise that Ayahuasca, via hyperactivation of trauma and emotional memory-related centres, and via its concomitant SIGMAR1- and MAOIs- induced anti-amnesic effects, facilitates the retrieval of traumatic memories, in turn making them labile (destabilised). As Ayahuasca alkaloids enhance synaptic plasticity, increase neurogenesis and boost dopaminergic neurotransmission, and those processes are involved in memory reconsolidation and fear extinction, the fear response triggered by the memory can be reprogramed and/or extinguished. Subsequently, the memory is stored with this updated significance. To date, it is unclear if new memories replace, co-exist with or bypass old ones. Although the mechanisms involved in memory are still debated, they seem to require the involvement of cellular and molecular events, such as reorganisation of homo and heteroreceptor complexes at the synapse, synaptic plasticity, and epigenetic re-modulation of gene expression. Since SIGMAR1 mobilises synaptic receptor, boosts synaptic plasticity and modulates epigenetic processes, such effects might be involved in the reported healing of traumatic memories in PTSD patients. If this theory proves to be true, Ayahuasca could come to represent the only standing pharmacological treatment which targets traumatic memories in PTSD. Lastly, since SIGMAR1 activation triggers both epigenetic and immunomodulatory programmes, the mechanism here presented could help understanding and treating other conditions in which the cellular memory is dysregulated, such as cancer, diabetes, autoimmune and neurodegenerative pathologies and substance addiction.
Comparable studies
Other theoretical and historical papers on ayahuasca, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The globalization of ayahuasca: Harm reduction or benefit maximization? | 2006 | Theoretical or philosophical paper | |
| Ayahuasca Shamanism in the Amazon and Beyond | 2014 | Theoretical or philosophical paper | |
| The Antipodes of the Mind: Charting the Phenomenology of the Ayahuasca Experience | 2003 | Theoretical or philosophical paper | |
| Towards psychedelic apprenticeship: Developing a gentle touch for the mediation and validation of psychedelic-induced insights and revelations. | 2022 | Theoretical or philosophical paper | |
| Ayahuasca healing beyond the Amazon: the globalization of a traditional indigenous entheogenic practice | 2008 | Theoretical or philosophical paper |
Citations in the library
Cited by 69
- Reviewing the Potential of Psychedelics for the Treatment of PTSD The International Journal of Neuropsychopharmacology March 12, 2020
- Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics Frontiers in Psychiatry September 10, 2021
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- Treatment of Posttraumatic Stress Disorder: A State-of-the-art Review. Current Neuropharmacology 2024
- Modulation of Serum Brain-Derived Neurotrophic Factor by a Single Dose of Ayahuasca: Observation From a Randomized Controlled Trial Frontiers in Psychology June 4, 2019
and 64 more in the library
Cites 26
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- Amphetamine, 3,4-Methylenedioxymethamphetamine, Lysergic Acid Diethylamide, and Metabolites of the Catecholamine Neurotransmitters Are Agonists of a Rat Trace Amine Receptor Molecular Pharmacology December 1, 2001
- The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Science February 13, 2009
- Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression Journal of Clinical Psychopharmacology December 11, 2015
- The Psychedelic State Induced by Ayahuasca Modulates the Activity and Connectivity of the Default Mode Network PLoS One February 18, 2015
and 21 more in the library