Serotonin 2A receptors are a stress response system: implications for post-traumatic stress disorder.
Behavioural Pharmacology April 1, 2019 DOI: 10.1097/fbp.0000000000000459 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | PTSD Serotonin |
| Citations | 84 |
| Key findings | The review proposes that stress upregulates 5-HT2A receptors to promote learning and avoidance of danger, and that this system may contribute to PTSD symptoms while also being paradoxically targeted by MDMA for treatment. |
Abstract
Serotonin, one of the first neurotransmitters to be identified, is an evolutionarily old molecule that is highly conserved across the animal kingdom, and widely used throughout the brain. Despite this, ascribing a specific set of functions to brain serotonin and its receptors has been difficult and controversial. The 2A subtype of serotonin receptors (5-HT2A receptor) is the major excitatory serotonin receptor in the brain and has been linked to the effects of drugs that produce profound sensory and cognitive changes. Numerous studies have shown that this receptor is upregulated by a broad variety of stressors, and have related 5-HT2A receptor function to associative learning. This review proposes that stress, particularly stress related to danger and existential threats, increases the expression and function of 5-HT2A receptors. It is argued that this is a neurobiological adaptation to promote learning and avoidance of danger in the future. Upregulation of 5-HT2A receptors during stressful events forms associations that tune the brain to environmental cues that signal danger. It is speculated that life-threatening situations may activate this system and contribute to the symptoms associated with post-traumatic stress disorder (PTSD). 3,4-Methylenedioxymethamphetamine, which activates 5-HT2A receptors, has been successful in the treatment of PTSD and has recently achieved status as a breakthrough therapy. An argument is presented that 3,4-methylenedioxymethamphetamine may paradoxically act through these same 5-HT2A receptors to ameliorate the symptoms of PTSD. The central thematic contention is that a key role of serotonin may be to function as a stress detection and response system.
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 31
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- Understanding the effects of serotonin in the brain through its role in the gastrointestinal tract. Brain September 14, 2022
- Mechanisms and molecular targets surrounding the potential therapeutic effects of psychedelics. Molecular Psychiatry September 1, 2023
- Catalysts for change: the cellular neurobiology of psychedelics Molecular Biology of the Cell May 27, 2021
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Cites 30
- The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. Journal of Psychopharmacology July 19, 2010
- 5-HT2AReceptor-Mediated Regulation of Brain-Derived Neurotrophic Factor mRNA in the Hippocampus and the Neocortex Journal of Neuroscience April 15, 1997
- Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Experimental Brain Research June 1, 2013
- The Background and Chemistry of MDMA Journal of Psychoactive Drugs October 1, 1986
- Neurometabolic Effects of Psilocybin, 3,4-Methylenedioxyethylamphetamine (MDE) and d-Methamphetamine in Healthy Volunteers A Double-Blind, Placebo-Controlled PET Study with [18F]FDG Neuropsychopharmacology June 1, 1999
and 25 more in the library