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5-HT2A receptor
Also known as: 5-HT2A receptors, 5-HT2A receptor subtype, 5-HT2A serotonin receptors, 5-HT2A serotonin receptor, 5-HT2A receptor, serotonin 5HT2a receptor, 5-HT2a receptor system
Facts (38)
Sources
Neuroimaging in psychedelic drug development: past, present, and ... nature.com Sep 27, 2023 14 facts
claimThe pharmacological mode of action of classical psychedelics as 5-HT2 receptor agonists was confirmed using the 5-HT2 antagonist ketanserin and the development of 5-HT2A receptor (5-HT2AR) knockout mice.
measurementA single dose of psilocybin increases synaptic density and decreases 5-HT2A receptor density in the pig brain, according to a 2020 study.
claimClassic serotonergic psychedelics, such as psilocybin and lysergic acid diethylamide (LSD), primarily act on the 5-HT2A receptor.
claimAnimal models in psychedelic research have limitations due to structural differences in the 5-HT2AR receptor, binding differences between rodents and humans, and species differences in brain penetrance.
claimGenetic polymorphisms in the 5-HT2AR receptor are known to influence personality factors, cognitive factors, clinical conditions, and responses to psychiatric medications.
referenceFinnema et al. (2014) published a study in NeuroImage characterizing [11C]Cimbi-36 as an agonist PET radioligand for the 5-HT2A and 5-HT2C receptors in the nonhuman primate brain.
claimResearchers are currently developing novel 5-HT2A active compounds, including attempts to discover non-hallucinogenic analogues.
claimThe 5-HT2AR agonist PET ligand [11C]Cimbi-36 has higher sensitivity to serotonin receptor agonists and has been used to demonstrate that the acute subjective effects of psilocybin (specifically its active metabolite psilocin) are related to its binding at 5-HT2A receptors.
claimFuture research in psychedelic therapy aims to address the relationship between acute drug effects and longer-term clinical effects, the characterization of 5-HT2A receptor effects, and the impact of these compounds on neuroplasticity.
claimClinical studies in psychedelic therapy aim to establish a 'molecular-functional-clinical bridge' by characterizing the relationship between acute and longer-term clinically-relevant effects, investigating the 5-HT2A receptor's association with functional and clinical effects, and focusing on neuroplasticity.
referenceQin B, Sun Z, Liang Y, Yang Z, Zhong R authored 'The Association of 5-HT2A, 5-HTT, and LEPR Polymorphisms with Obstructive Sleep Apnea Syndrome: A Systematic Review and Meta-Analysis', published in PLOS ONE in 2014, volume 9, page e95856.
referenceEttrup et al. (2013) published a preclinical safety assessment of the 5-HT2A receptor agonist PET radioligand [11C]Cimbi-36 in Molecular Imaging and Biology.
referenceK.H. Preller, J.B. Burt, J.L. Ji, C.H. Schleifer, B.D. Adkinson, P. Stämpfli, et al. published 'Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor' in the journal eLife in 2018.
claimGenotyping polymorphisms in the 5-HT2AR receptor or other relevant molecular targets in the psychedelic response pathway may help reduce variability in outcome parameters, identify underlying biological substrates, or stratify patients in future studies.
Psychedelics, Sociality, and Human Evolution frontiersin.org 9 facts
claimThe brain displays two different serotonin-mediated responses to adversity: a default response involving a passive coping strategy mediated by 5-HT1A receptor signaling, and an active coping strategy that provides an enhanced capacity for change mediated by 5-HT2A receptor signaling.
claimSerotonergic psychedelics preferentially engage and functionally modulate the 5-HT2A receptor signaling pathway.
claimPsychedelics elevate synaptic efficacy and neuroplasticity through their agonist action at 5-HT2A receptors, as reported by Ly et al. in 2018.
claimDe Gregorio et al. (2021b) demonstrated that repeated administration of low doses of LSD in mice enhances social interaction by potentiating 5-HT2A and AMPA receptor neurotransmission in the medial prefrontal cortex via increased phosphorylation of the mTORC1 protein.
claimPsychedelic stimulation of 5-HT2A receptors increases the excitability of neocortical pyramidal neurons and augments extracellular glutamate release in the prefrontal cortex, which disrupts cortical rhythmicity and large-scale brain networks.
claimPsychedelics function as serotonin analogs that preferentially activate the 5-HT2A receptor subtype, according to Nichols (2016).
claimPsychedelic substances generate their effects primarily by interacting with the serotonin (5-hydroxytryptamine; 5-HT) system, binding to the 5-HT2A receptor as partial agonists.
referencePsilocybin may have been harnessed to increase adaptability and fitness through its capacity to modulate the 5-HT2A receptor-mediated active coping strategy, which provides elevated cortical plasticity, an enhanced rate of associative learning, and an elevated capacity to mediate psychological transformation, according to Carhart-Harris and Nutt (2017) and Brouwer and Carhart-Harris (2021).
claimPsychedelics can facilitate adaptive stress coping by upregulating 5-HT2A receptor functioning, as described by Carhart-Harris and Nutt (2017).
Effects of psychedelics on neurogenesis and broader neuroplasticity link.springer.com Dec 19, 2024 9 facts
claimPsychedelics are believed to primarily activate 5-HT2A serotonin receptors, which are G protein-coupled receptors abundant in the cerebral cortex responsible for characteristic hallucinogenic effects.
claimActivation of 5-HT2A and 5-HT2B serotonin receptors can alter serotonin release and elicit specific behavioral responses, according to behavioral and electrophysiological studies.
claim5-HT2C receptors contribute to the effects of psychedelics by influencing mood and anxiety regulation, though to a lesser extent than 5-HT2A receptors.
claimActivation of 5-HT2A receptors by substances such as LSD and psilocybin results in altered sensory perception and cognition.
claim5-HT2A receptors play a physiological role in working memory, as described by Williams, Rao, and Goldman-Rakic in a 2002 study.
claimPsychedelics may act as partial agonists at 5-HT1A receptors, affecting anxiolytic and antidepressant responses, but this role is minor compared to the activation of 5-HT2A receptors.
claimThe 5-HT2A serotonin receptor rapidly modulates spine morphology through kalirin-7 signaling.
claimThe serotonergic hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) disrupts cortical activity in a regionally-selective manner via 5-HT1A and 5-HT2A receptors, as reported by Riga et al. in Neuropharmacology (2016).
claimThe neural plasticity effects of DOI and 25I-NBOMe are primarily mediated through serotonin receptors, specifically 5-HT2A and 5-HT2B.
The Mechanisms of Psychedelic Visionary Experiences - Frontiers frontiersin.org Sep 27, 2017 3 facts
claimWhile the 5-HT2a receptor system is considered the primary system affected by psychedelics, research has established that psychedelics also act on other serotonin receptors and receptor systems.
claimHallucinations can be induced by various pharmacological mechanisms, including dopamine receptor hyperactivation (e.g., psychostimulants), serotonin 5HT2a receptor stimulation (e.g., psychedelics), and glutamate NMDA receptor blockage (e.g., dissociative anesthetics).
claimLSD's hallucinogenic effect via 5-HT2A receptor binding requires dimerization with the mGlu2 receptor, meaning 5HT2A receptor agonism is a necessary but not sufficient condition for psychedelic effects.
Psychedelic Drugs News - ScienceDaily sciencedaily.com 1 fact
claimThe 5-HT2A receptor modulates brain signals, influencing mood, perception, and behavior.
Ancient Roots of Today's Emerging Renaissance in ... link.springer.com 1 fact
claimLSD-induced altered states of consciousness are attributable to the 5-HT2A receptor, according to a 2018 study by Katrin Preller et al.
Published Studies — Johns Hopkins Center for Psychedelic and ... hopkinspsychedelic.org 1 fact
referenceL., Magsamen, M., Sandu, C. C., Roebuck, G. M., Shi, K. M., & Barrett, F. S. published 'Dream to Explore: 5-HT2a as Adaptive Temperature Parameter for Sophisticated Affective Inference' in the journal 'Machine Learning and Principles and Practice of Knowledge Discovery in Databases' in 2022.