Evidence map›Paper›PMID 28858536›Full record

ReviewJournal of psychopharmacology (Oxford, England)2017

Serotonin and brain function: a tale of two receptors.

R L Carhart-Harris, D J Nutt

Open access · bronzeAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Journal of psychopharmacology (Oxford, England), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 322 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
322citing papers in PubMed, 7 pooled it
56.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

322 citing papers in PubMed, 7 syntheses or guidelines pooled it, 713 citations in OpenAlex.

  1. Cortical 5-HTMolecular psychiatry · 2025
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  3. Effects of ayahuasca in preclinical studies with animals: a systematic review.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2025
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  7. Toxic Effects of Glyphosate on the Nervous System: A Systematic Review.International journal of molecular sciences · 2022
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  18. Low doses of lysergic acid diethylamide (LSD) increase reward-related brain activity.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023
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262 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

R L Carhart-HarrisPsychedelic Research Group, Neuropsychopharmacology Unit, Centre for Psychiatry, Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
D J NuttPsychedelic Research Group, Neuropsychopharmacology Unit, Centre for Psychiatry, Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
Imperial College London · GB

Funding

Medical Research Council MR/J00460X/1
6 · The paper itself

Abstract

Previous attempts to identify a unified theory of brain serotonin function have largely failed to achieve consensus. In this present synthesis, we integrate previous perspectives with new and older data to create a novel bipartite model centred on the view that serotonin neurotransmission enhances two distinct adaptive responses to adversity, mediated in large part by its two most prevalent and researched brain receptors: the 5-HT1A and 5-HT2A receptors. We propose that passive coping (i.e. tolerating a source of stress) is mediated by postsynaptic 5-HT1AR signalling and characterised by stress moderation. Conversely, we argue that active coping (i.e. actively addressing a source of stress) is mediated by 5-HT2AR signalling and characterised by enhanced plasticity (defined as capacity for change). We propose that 5-HT1AR-mediated stress moderation may be the brain's default response to adversity but that an improved ability to change one's situation and/or relationship to it via 5-HT2AR-mediated plasticity may also be important - and increasingly so as the level of adversity reaches a critical point. We propose that the 5-HT1AR pathway is enhanced by conventional 5-HT reuptake blocking antidepressants such as the selective serotonin reuptake inhibitors (SSRIs), whereas the 5-HT2AR pathway is enhanced by 5-HT2AR-agonist psychedelics. This bipartite model purports to explain how different drugs (SSRIs and psychedelics) that modulate the serotonergic system in different ways, can achieve complementary adaptive and potentially therapeutic outcomes.

Indexed as

AnimalsAntidepressive AgentsBrainHallucinogensHumansReceptor, Serotonin, 5-HT1AReceptor, Serotonin, 5-HT2ASelective Serotonin Reuptake InhibitorsSerotoninSynaptic TransmissionAntidepressive AgentsHallucinogensReceptor, Serotonin, 5-HT1AReceptor, Serotonin, 5-HT2ASelective Serotonin Reuptake InhibitorsSerotoninDepressionpsychedelicsserotonin

Identifiers

PMID28858536
PMCPMC5606297
OpenAlexW2753654430

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.