Imperial College London

Dr Robin Carhart-Harris

Faculty of MedicineDepartment of Brain Sciences

Research Fellow



+44 (0)20 7594 7992r.carhart-harris




Miss Bruna Cunha +44 (0)20 7594 7992




Burlington DanesHammersmith Campus






BibTex format

author = {Carhart-Harris, RL and Nutt, D},
doi = {10.1177/0269881117725915},
journal = {Journal of Psychopharmacology},
pages = {1091--1120},
title = {Serotonin and brain function: a tale of two receptors},
url = {},
volume = {31},
year = {2017}

RIS format (EndNote, RefMan)

AB - 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 5HT1AR 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.
AU - Carhart-Harris,RL
AU - Nutt,D
DO - 10.1177/0269881117725915
EP - 1120
PY - 2017///
SN - 1461-7285
SP - 1091
TI - Serotonin and brain function: a tale of two receptors
T2 - Journal of Psychopharmacology
UR -
UR -
VL - 31
ER -