The Key Role of Intracellular 5-HT2A Receptors: A Turning Point in Psychedelic Research?
J. Sapienza
Psychoactives October 13, 2023 DOI: 10.3390/psychoactives2040018 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Serotonin |
| Key findings | Psychedelics induce neuroplasticity by stimulating intracellular 5-HT2A receptors, which serotonin cannot reach because it cannot cross the lipophilic neuronal membrane. |
Abstract
Psychedelics could have revolutionary potential in psychiatry, although, until recently, the pharmacodynamic properties of such compounds have not seemed to differ much from those of serotonin, whose levels are raised by Serotonin Reuptake Inhibitors (SSRI). The cardinal point is that serotonergic compounds, such as antidepressive drugs, do not have the potential to induce long-lasting neuroplasticity as psychedelics do. Therefore, the biological underpinnings of the peculiar effect of such compounds had not been fully understood until new astonishing molecular findings came out this year to shed new light on them. Specifically, the phenomena of neuroplasticity are triggered by the stimulation of a peculiar type of receptors: the intracellular 5-HT2A receptors. Interestingly, psychedelics can reach this pool of intracellular receptors due to their lipophilic properties, as they can cross the lipophilic neuronal membrane while serotonin cannot. The importance of such a discovery should not be underestimated as the specific mechanisms involved have not yet been elucidated and a better understanding of them could pave the way to the development of new drugs (and/or new tailored therapeutic strategies) able to sustain neuroplasticity while minimizing side effects.
Comparable studies
Other narrative reviews on serotonin, most cited first.
Citations in the library
Cited by 5
- Psychedelics and schizophrenia: a double-edged sword. Molecular Psychiatry February 1, 2025
- An overview of psilocybin, LSD, MDMA, and ketamine in revitalizing psychedelic-assisted therapy: Insights, limitations and future directions. Progress in Neuro-Psychopharmacology and Biological Psychiatry July 25, 2025
- Psychedelic Drugs in Mental Disorders: Current Clinical Scope and Deep Learning‐Based Advanced Perspectives Advanced Science March 20, 2025
- N, N-dimethyltryptamine (DMT) in rodent brain: Concentrations, distribution, and recent pharmacological data. Progress in Neuro-Psychopharmacology and Biological Psychiatry March 20, 2025
- Microdosing Psychedelics to Restore Synaptic Density in Schizophrenia. International Journal of Molecular Sciences September 14, 2025
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