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Trevor Sharp

17 papers in the library · 172 citations · publishing 1990-2026

Papers

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Emerging therapeutic opportunities for psychedelic and related drugs.

British Journal of Pharmacology July 1, 2026 Susan Wonnacott, Gary J. Stephens, Trevor Sharp

Increasing interest in psychedelic and related drugs as potential therapies for a wide spectrum of difficult-to-treat conditions, that extend beyond neuropsychiatric disorders, provided the impetus for this themed issue. This collection of reviews and original articles includes the mechanistic basis of how these drugs act, the current status of preclinical research and progress in clinical...

Editorial Emerging therapeutic opportunities for psychedelic and related drugs

April 1, 2026 Susan Wonnacott, Gary J. Stephens, Trevor Sharp

Increasing interest in psychedelic and related drugs as potential therapies for a wide spectrum of difficult to treat conditions that extend beyond neuropsychiatric disorders provided the impetus for this Themed Issue. This collection of reviews and original articles includes the mechanistic basis of how these drugs act, the current status of preclinical research and progress in clinical...

Vigilance state dissociation induced by 5-MeO-DMT in mice.

Commun Biol January 5, 2026 Benjamin J. B. Bréant, José Prius-Mengual, Alexander Andrews et al. 1 citation

Psychedelics lead to profound changes in subjective experience and behaviour, which are typically conceptualised in psychological terms rather than corresponding to an altered brain state or a distinct state of vigilance. Here, we performed chronic electrophysiological recordings from the neocortex concomitant with pupillometry in freely moving adult male mice following an injection of a...

Evidence that 5-HT2A receptor signalling efficacy and not biased agonism differentiates serotonergic psychedelic from non-psychedelic drugs.

British Journal of Pharmacology June 22, 2025 Aurelija Ippolito, Sridhar Vasudevan, Shaun Hurley et al. 9 citations

Serotonergic psychedelic drugs are under investigation as therapies for various psychiatric disorders, including major depression. Although serotonergic psychedelic drugs are 5-HT2A receptor agonists, some such agonists are not psychedelic, potentially due to differences in 5-HT2A receptor ligand bias or signalling efficacy. Here, we investigated 5-HT2A receptor signalling properties of...

Neuropsychopharmacology of hallucinogenic and non-hallucinogenic 5-HT2A receptor agonists.

British Journal of Pharmacology May 23, 2025 Trevor Sharp, Aurelija Ippolito 8 citations

Psychedelic drugs such as LSD and psilocin were once relegated to the fringes of medical research because of their association with counterculture movements and a perceived concern about harm through recreational use, and their consequent legal prohibition in the early 1970s. However, these drugs are now experiencing a renaissance in the field of psychiatry based on increasing evidence that...

Vigilance state dissociation induced by 5-MeO DMT in mice

Research Square May 6, 2025 Benjamin J. B. Bréant, José Prius-Mengual, Alexander Andrews et al.

Abstract Psychedelics lead to profound changes in subjective experience and behaviour, which are typically conceptualised in psychological terms rather than corresponding to an altered brain state or a distinct state of arousal. Here, we performed chronic electrophysiological recordings from the neocortex concomitant with pupillometry in freely moving adult male mice following an injection of a...

Increased 5-HT 2A receptor signalling efficacy differentiates serotonergic psychedelics from non-psychedelics

bioRxiv (Cold Spring Harbor Laboratory) June 16, 2024 Aurelija Ippolito, Sridhar Vasudevan, Shaun Hurley et al. 1 citation preprint

ABSTRACT Background and Purpose Serotonergic psychedelic drugs are under renewed investigation for the potential treatment of several psychiatric disorders. While all serotonergic psychedelics have 5-HT 2A receptor activity, the explanation for why some 5-HT 2A receptor agonists are not psychedelic is unknown. To address this question, we investigated the 5-HT 2A receptor signalling bias and...

Increased 5-HT 2A receptor signalling efficacy differentiates serotonergic psychedelics from non-psychedelics

bioRxiv (Cold Spring Harbor Laboratory) June 16, 2024 Aurelija Ippolito, Sridhar Vasudevan, Shaun Hurley et al. 1 citation preprint

ABSTRACT Background and Purpose Serotonergic psychedelic drugs are under renewed investigation for the potential treatment of several psychiatric disorders. While all serotonergic psychedelics have 5-HT 2A receptor activity, the explanation for why some 5-HT 2A receptor agonists are not psychedelic is unknown. To address this question, we investigated the 5-HT 2A receptor signalling bias and...

Mechanisms of SSRI Therapy and Discontinuation.

Current Topics in Behavioral Neurosciences 2024 Trevor Sharp, Helen M Collins 40 citations

SSRIs are one of the most widely used drug therapies in primary care and psychiatry, and central to the management of the most common mental health problems in today's society. Despite this, SSRIs suffer from a slow onset of therapeutic effect and relatively poor efficacy as well as adverse effects, with recent concerns being focused on a disabling SSRI discontinuation syndrome. The mechanism...

Sleep-like state during wakefulness induced by psychedelic 5-MeO-DMT in mice

bioRxiv (Cold Spring Harbor Laboratory) December 11, 2022 Benjamin J. B. Bréant, José Prius-Mengual, David M. Bannerman et al. 5 citations preprint

Abstract Psychedelics lead to profound changes in subjective experience and behaviour, which are typically conceptualised in psychological terms rather than corresponding to an altered brain state or a distinct state of arousal. Here, we performed chronic electrophysiological recordings from the cortex concomitant with pupillometry in freely moving adult male mice following an injection of a...

Sleep-like state during wakefulness induced by psychedelic 5-MeO-DMT in mice

bioRxiv (Cold Spring Harbor Laboratory) December 11, 2022 Benjamin J. B. Bréant, José Prius-Mengual, David M. Bannerman et al. 5 citations preprint

Abstract Psychedelics lead to profound changes in subjective experience and behaviour, which are typically conceptualised in psychological terms rather than corresponding to an altered brain state or a distinct state of arousal. Here, we performed chronic electrophysiological recordings from the cortex concomitant with pupillometry in freely moving adult male mice following an injection of a...

Psilocin acutely alters sleep-wake architecture and cortical brain activity in laboratory mice

Translational Psychiatry February 23, 2022 Trevor Sharp, Christopher W. Thomas, Cristina Blanco-Duque et al. 40 citations

Abstract Serotonergic psychedelic drugs, such as psilocin (4-hydroxy-N,N-dimethyltryptamine), profoundly alter the quality of consciousness through mechanisms which are incompletely understood. Growing evidence suggests that a single psychedelic experience can positively impact long-term psychological well-being, with relevance for the treatment of psychiatric disorders, including depression. A...

Psilocin acutely disrupts sleep and affects local but not global sleep homeostasis in laboratory mice

bioRxiv Preprint Server February 16, 2021 Christopher W. Thomas, Cristina Blanco-Duque, Benjamin J. B. Bréant et al. 4 citations preprint

Serotonergic psychedelic drugs, such as psilocin (4-hydroxy-N,N-dimethyltryptamine), profoundly alter the quality of consciousness through mechanisms which are incompletely understood. Growing evidence suggests that a single psychedelic experience can positively impact long-term psychological well-being, with relevance for the treatment of psychiatric disorders, including depression. A...

Neurovascular and neuroimaging effects of the hallucinogenic serotonin receptor agonist psilocin in the rat brain

Neuropharmacology July 18, 2015 Aisling Spain, Clare Howarth, Alexandre A. Khrapitchev et al. 45 citations

The development of pharmacological magnetic resonance imaging (phMRI) has presented the opportunity for investigation of the neurophysiological effects of drugs in vivo. Psilocin, a hallucinogen metabolised from psilocybin, was recently reported to evoke brain region-specific, phMRI signal changes in humans. The present study investigated the effects of psilocin in a rat model using phMRI and...

Behavioural and neuroendocrine responses to D-fenfluramine in rats treated with neurotoxic amphetamines

Journal of Psychopharmacology May 1, 1995 Hugh Series, Marisa Le Masurier, Sarah E. Gartside et al. 13 citations

The amphetamine derivatives p-chloroamphetamine (pCA), 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') and D-fenfluramine can, if given repeatedly in high doses to rats, produce a degeneration of serotonergic nerve terminals which we have previously shown to result in a reduction in D-fenfluramine-evoked release of 5-HT in vivo. It is therefore possible that fenfluramine-evoked responses...

p-Chloroamphetamine (PCA), 3,4-methylenedioxy-methamphetamine (MDMA) and d-fenfluramine pretreatment attenuates d-fenfluramine-evoked release of 5-HT in vivo.

Psychopharmacology December 1994 Hugh Series, P J Cowen, Trevor Sharp

Previous work has suggested that repeated treatment with substituted amphetamines including PCA, MDMA and d-fenfluramine produces a persistent neurodegeneration which is relatively selective for the fine serotoninergic terminals arising from the dorsal raphe nucleus. The aim of the present study was to investigate whether the acute releasing effect of d-fenfluramine might also be sensitive to...

Behavioural evidence for a functional interaction between central 5-HT2 and 5-HT1A receptors.

British Journal of Pharmacology August 1, 1990 L I Backus, T Sharp, D G Grahame-Smith

1. The possibility of 5-HT2 receptor modulation of central 5-HT1A receptor function has been examined using the 5-hydroxytryptamine (5-HT) behavioural syndrome induced by 5-HT1A receptor active drugs in rats. 2. The 5-HT2/5-HTIC antagonist ritanserin (0.1-2 mg kg-1) increased the 5-HT behavioural syndrome induced by submaximally effective doses of 8-hydroxy-2-(di-n-propylamino)tetralin...