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Effects of a single dose of psilocybin on behaviour, brain 5-HT2A receptor occupancy and gene expression in the pig

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@article{075ce95ebf0743d0992c1e253ca4db22,
title = "Effects of a single dose of psilocybin on behaviour, brain 5-HT2A receptor occupancy and gene expression in the pig",
abstract = "Psilocybin has in some studies shown promise as treatment of major depressive disorder and psilocybin therapy was in 2019 twice designated as breakthrough therapy by the U.S. Food and Drug Administration (FDA). A very particular feature is that ingestion of just a single dose of psilocybin is associated with lasting changes in personality and mood. The underlying molecular mechanism behind its effect is, however, unknown. In a translational pig model, we here present the effects of a single dose of psilocybin on pig behaviour, receptor occupancy and gene expression in the brain. An acute i.v. injection of 0.08 mg/kg psilocybin to awake female pigs induced characteristic behavioural changes in terms of headshakes, scratching and rubbing, lasting around 20 min. A similar dose was associated with a cerebral 5-HT2A receptor occupancy of 67%, as determined by positron emission tomography, and plasma psilocin levels were comparable to what in humans is associated with an intense psychedelic experience. We found that 19 genes were differentially expressed in prefrontal cortex one day after psilocybin injection, and 3 genes after 1 week. Gene Set Enrichment Analysis demonstrated that multiple immunological pathways were regulated 1 week after psilocybin exposure. This provides a framework for future investigations of the lasting molecular mechanisms induced by a single dose of psilocybin. In the light of an ongoing debate as to whether psilocybin is a safe treatment for depression and other mental illnesses, it is reassuring that our data suggest that any effects on gene expression are very modest.",
keywords = "5-HT receptor, Behaviour, Brain, Gene expression, Immune response, Psychedelic",
author = "Donovan, {Lene Lundgaard} and Johansen, {Jens Vilstrup} and Ros, {N{\'i}dia Fernandez} and Elham Jaberi and Kristian Linnet and Johansen, {Sys Stybe} and Brice Ozenne and Shohreh Issazadeh-Navikas and Hansen, {Hanne Demant} and Knudsen, {Gitte Moos}",
note = "Copyright {\textcopyright} 2020. Published by Elsevier B.V.",
year = "2021",
month = jan,
doi = "10.1016/j.euroneuro.2020.11.013",
language = "English",
volume = "42",
pages = "1--11",
journal = "European Neuropsychopharmacology",
issn = "0924-977X",
publisher = "Elsevier BV",

}

RIS

TY - JOUR

T1 - Effects of a single dose of psilocybin on behaviour, brain 5-HT2A receptor occupancy and gene expression in the pig

AU - Donovan, Lene Lundgaard

AU - Johansen, Jens Vilstrup

AU - Ros, Nídia Fernandez

AU - Jaberi, Elham

AU - Linnet, Kristian

AU - Johansen, Sys Stybe

AU - Ozenne, Brice

AU - Issazadeh-Navikas, Shohreh

AU - Hansen, Hanne Demant

AU - Knudsen, Gitte Moos

N1 - Copyright © 2020. Published by Elsevier B.V.

PY - 2021/1

Y1 - 2021/1

N2 - Psilocybin has in some studies shown promise as treatment of major depressive disorder and psilocybin therapy was in 2019 twice designated as breakthrough therapy by the U.S. Food and Drug Administration (FDA). A very particular feature is that ingestion of just a single dose of psilocybin is associated with lasting changes in personality and mood. The underlying molecular mechanism behind its effect is, however, unknown. In a translational pig model, we here present the effects of a single dose of psilocybin on pig behaviour, receptor occupancy and gene expression in the brain. An acute i.v. injection of 0.08 mg/kg psilocybin to awake female pigs induced characteristic behavioural changes in terms of headshakes, scratching and rubbing, lasting around 20 min. A similar dose was associated with a cerebral 5-HT2A receptor occupancy of 67%, as determined by positron emission tomography, and plasma psilocin levels were comparable to what in humans is associated with an intense psychedelic experience. We found that 19 genes were differentially expressed in prefrontal cortex one day after psilocybin injection, and 3 genes after 1 week. Gene Set Enrichment Analysis demonstrated that multiple immunological pathways were regulated 1 week after psilocybin exposure. This provides a framework for future investigations of the lasting molecular mechanisms induced by a single dose of psilocybin. In the light of an ongoing debate as to whether psilocybin is a safe treatment for depression and other mental illnesses, it is reassuring that our data suggest that any effects on gene expression are very modest.

AB - Psilocybin has in some studies shown promise as treatment of major depressive disorder and psilocybin therapy was in 2019 twice designated as breakthrough therapy by the U.S. Food and Drug Administration (FDA). A very particular feature is that ingestion of just a single dose of psilocybin is associated with lasting changes in personality and mood. The underlying molecular mechanism behind its effect is, however, unknown. In a translational pig model, we here present the effects of a single dose of psilocybin on pig behaviour, receptor occupancy and gene expression in the brain. An acute i.v. injection of 0.08 mg/kg psilocybin to awake female pigs induced characteristic behavioural changes in terms of headshakes, scratching and rubbing, lasting around 20 min. A similar dose was associated with a cerebral 5-HT2A receptor occupancy of 67%, as determined by positron emission tomography, and plasma psilocin levels were comparable to what in humans is associated with an intense psychedelic experience. We found that 19 genes were differentially expressed in prefrontal cortex one day after psilocybin injection, and 3 genes after 1 week. Gene Set Enrichment Analysis demonstrated that multiple immunological pathways were regulated 1 week after psilocybin exposure. This provides a framework for future investigations of the lasting molecular mechanisms induced by a single dose of psilocybin. In the light of an ongoing debate as to whether psilocybin is a safe treatment for depression and other mental illnesses, it is reassuring that our data suggest that any effects on gene expression are very modest.

KW - 5-HT receptor

KW - Behaviour

KW - Brain

KW - Gene expression

KW - Immune response

KW - Psychedelic

UR - http://www.scopus.com/inward/record.url?scp=85097476326&partnerID=8YFLogxK

U2 - 10.1016/j.euroneuro.2020.11.013

DO - 10.1016/j.euroneuro.2020.11.013

M3 - Journal article

C2 - 33288378

VL - 42

SP - 1

EP - 11

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

SN - 0924-977X

ER -

ID: 62236746