British Journal of Pharmacology
June 2, 2008
Andrew R. Green
30 citations
Serotonin (5-hydroxytryptamine or 5-HT) was identified as a vasoconstrictor substance by Maurice Rapport in 1949. Gaddum and colleagues soon detected 5-HT in brain and discovered that lysergic acid diethylamide (LSD) antagonized its action in peripheral tissues, leading Gaddum to propose that 5-HT might regulate mood. This review covers the first 20 years of UK scientists' contributions, including developing assays for brain 5-HT, identifying its synthesis and metabolism enzymes, and studying drug effects on brain 5-HT. It describes human LSD experiments, including Gaddum's self-administration, and investigations into 5-HT's role in psychiatric disorders and antidepressant drug effects on 5-HT levels in rodent and human brain.
British Journal of Pharmacology
June 1, 1974
M J Berridge, William Prince
26 citations
LSD mimics serotonin (5-HT) in stimulating fluid secretion, changing electrical potentials, and increasing cyclic AMP in isolated salivary glands of the blowfly Calliphora. Unlike serotonin, LSD disengages slowly from the receptor, causing continued secretion even after repeated washing. Both serotonin and tryptamine prevent LSD from acting, and bound LSD is slowly displaced by agonists like tryptamine or antagonists like gramine. The ability of LSD to remain tightly bound while still functioning as an agonist may explain its profound effects in the central nervous system.
British Journal of Pharmacology
June 2, 2024
Oscar Sandoval, Quynh Nguyen, Ryan J. Rakoczy et al.
23 citations
Several tryptamines found in psilocybin-containing mushrooms—baeocystin, norbaeocystin, and aeruginascin—were compared with psilocybin to assess their pharmacological and behavioral effects. All compounds showed nearly identical rates of dephosphorylation and metabolism by monoamine oxidase. Only dephosphorylated baeocystin and norbaeocystin crossed a blood–brain barrier mimetic as effectively as psilocin. Norbaeocystin's dephosphorylated form activated the 5-HT2A receptor with similar efficacy to psilocin and norpsilocin. While only psilocybin induced head twitch responses in rats (a marker of hallucinogenic potential), norbaeocystin, like psilocybin, improved outcomes in the forced swim test. All compounds showed minimal changes to renal and hepatic health markers, suggesting safe profiles. Norbaeocystin may share therapeutic potential with psilocybin without causing hallucinations.
British Journal of Pharmacology
September 4, 2012
Kim P. C. Kuypers, Rafael de la Torre, Magı́ Farré et al.
23 citations
MDMA acutely impairs memory, but this effect is not caused by the rise in cortisol that MDMA also triggers. In a placebo-controlled, within-subject experiment with 17 polydrug MDMA users, blocking the cortisol increase with metyrapone (a cortisol synthesis inhibitor) did not prevent the memory deficit produced by a 75 mg dose of MDMA. Memory was tested at peak drug concentrations. The finding suggests that the neuropharmacological mechanism behind MDMA-induced memory impairment is independent of cortisol.
British Journal of Pharmacology
November 1, 1980
V. P. Poshivalov
23 citations
Mice living in small groups form a rigid, despotic social hierarchy that resists change even when psychotropic drugs are administered, making rapid pharmacological shifts in social rank impossible. Maintaining territory and social interaction are key to this inertia. Drugs such as diazepam, droperidol, and mescaline alter these factors to different degrees and vary in their ability to preserve hierarchy stability. Lowering aggression in a subordinate mouse does not change its social position. However, chronic administration of these drugs can eventually invert the hierarchy when a competitive rival is present, with the speed of inversion depending on the existing hierarchy type. The drugs' capacity to maintain hierarchy inertia may serve as an index of their effect on species-specific behaviors, particularly aggression.
British Journal of Pharmacology
December 19, 2024
David J Nutt, Peter Hunt, Anne Katrin Schlag et al.
21 citations
In 2023, the Australian Therapeutic Goods Administration (TGA) approved psilocybin for treatment-resistant depression and MDMA for PTSD, effective from 1 July 2023. The approval followed a campaign led by Mind Medicine Australia, Professor David Nutt, Drug Science, and Monash University professors, supported by clinical, academic, and patient groups. Prescribing rights are limited to psychiatrists authorized under the TGA's Authorised Prescriber Scheme. This paper reviews the background of the decision, its implications for approvals in other jurisdictions, and development pathways for other psychedelic drugs.
British Journal of Pharmacology
December 1, 1971
C. M. Bradshaw, M.h.t. Roberts, E. Szabadi
16 citations
Mescaline applied directly to single neurons in the cerebral cortex produces excitatory or depressant effects similar to those of noradrenaline and serotonin. The direction of the response to mescaline usually matches that of noradrenaline, but the correlation with serotonin is less consistent. The beta-adrenoceptor blocker MJ-1999 and the serotonin antagonist methysergide both block mescaline's effects, suggesting mescaline acts through multiple receptor mechanisms.
British Journal of Pharmacology
November 29, 2024
Tate Askey, Reena Lasrado, Maria Maiarù et al.
13 citations
Psychedelic drugs are being considered for clinical use, particularly as anti-nociceptive treatments for chronic pain and co-morbid depression. This review examines preclinical animal models used to study psilocybin's potential as an anti-nociceptive agent. Initial studies in animal models of neuropathic and inflammatory pain are summarized, highlighting areas needing further research. Potential mechanisms include activation of 5-HT2A receptors in serotonergic pathways at spinal and central levels, and neuroplastic actions that improve functional connectivity in brain regions involved in chronic pain. Current clinical aspects and the translational potential of psilocybin from animal models to chronic pain patients are reviewed. Psilocybin is discussed as an ideal anti-nociceptive agent with broad effects against chronic pain and its inflammatory or emotional components.
British Journal of Pharmacology
September 1, 1975
Ian E. Lush
13 citations
In male mice from seven genetically diverse laboratory strains, mescaline (35 mg/kg) inhibited emotional defecation and stimulated open field activity in five strains (A2G, C3H/He, C57BR/cd, CBA/Cam, F/St) but not in two others (ICFW, Schneider). The degree of emotional defecation under saline control correlated positively with mescaline's inhibitory effect. Pre-treatment with tranylcypromine did not alter emotional defecation or mescaline's inhibition of it.
British Journal of Pharmacology
September 8, 2023
Maleesha Ubhayarathna, Christopher J. Langmead, Natalie Diepenhorst et al.
10 citations
Substance use disorder (SUD) is a chronic condition marked by maintained substance abuse leading to physiological and psychological changes, often altering cognitive and social behaviors. Current therapies combining psychotherapy and medication have high relapse rates, revealing their limitations. The serotonin 2C receptor (5-HT2C receptor) is a candidate for SUD treatment due to its signaling, expression profile, and neurological function. Recent interest in psychedelics, which broadly act at 5-HT2 receptors, has rekindled studies on the 5-HT2C receptor, especially structural analyses. This review examines the structural, molecular, and cellular mechanisms governing 5-HT2C receptor function in SUD, summarizing preclinical and clinical evidence and highlighting future research potential.
British Journal of Pharmacology
June 15, 2025
Daniël Hoyer
9 citations
Psychedelics like psilocybin, LSD, and ayahuasca, along with non-hallucinogenic entactogens such as MDMA, are being investigated as rapidly acting treatments for major depressive disorder, treatment-resistant depression, PTSD, and generalized anxiety disorder. Late-stage clinical trials support their use in assisted psychotherapy. These drugs primarily target serotonin and monoamine systems, with classical psychedelics acting as 5-HT2A receptor agonists. Advanced imaging shows that depression involves reduced brain serotonin levels and impaired neural networks, which psychedelics and entactogens can correct. They promote neuroplasticity and synaptogenesis through monoamine or glutamate receptors and pathways like BDNF and mTORC1, supporting a biological basis for these disorders.
British Journal of Pharmacology
September 6, 2013
Cédric M. Hysek, Yasmin Schmid, Anna Rickli et al.
7 citations
A 125 mg dose of MDMA, a common recreational amount, produces only a moderate increase in body temperature in controlled clinical settings where risk factors like high ambient temperature, physical exertion, and dehydration are avoided. Severe hyperthermia, a rare but life-threatening complication of recreational MDMA use, typically requires additional permissive factors such as repeated or high doses, crowded conditions, or hyperthyroidism. The drug carvedilol, which blocks both α- and β-adrenoceptors, reduced MDMA-induced thermogenesis in humans and reversed established hyperthermia in rats, but its utility for treating severe MDMA toxicity in emergency settings remains unknown and requires further evaluation in case reports or series.
British Journal of Pharmacology
May 1, 1976
Paul Bevan, C. M. Bradshaw, E. Szabadi
4 citations
Desipramine both potentiates and antagonizes the responses of single cortical neurones to mescaline. The antagonism may stem from desipramine's α-adrenolytic action, while the potentiation is unlikely due to uptake blocking because desipramine does not block mescaline uptake in the cerebral cortex. The potentiation may instead result from a post-synaptic action of desipramine.
British Journal of Pharmacology
October 21, 2025
Austen B. Casey, Boris D. Heifets
3 citations
MDMA, known as the illicit drug ecstasy, shows promise when used alongside psychotherapy for posttraumatic stress disorder (PTSD), though how it works remains unclear. This review traces MDMA's path from military interrogation aid to prohibited substance and now to clinical use. The authors identify three core subjective effects—prosocial behavior, reduced threat perception, and euphoria—and examine how each may contribute to both therapeutic benefits and abuse potential. They emphasize serotonin's central role in MDMA's effects while noting gaps in understanding its mechanism. The review also critiques preclinical models, highlights limitations like sex biases and assumptions about therapeutic alliance, and calls for clarifying mechanisms to develop safer, more effective MDMA-like treatments.
British Journal of Pharmacology
September 2, 2025
Lucas M Wittenkeller, Gary A. Gudelsky, Theresa Winhusen et al.
3 citations
Psychedelics are being studied as treatments for substance use disorders (SUDs), not just depression. A scoping review identified 34 clinical trials targeting alcohol, cannabis, cocaine, methamphetamine, nicotine, and opioid use disorders, mostly open-label without placebo controls. Alcohol use disorder was the most common target. From animal studies, four publications measured dopamine in the nucleus accumbens after psilocybin or MDMA. High-dose psilocybin caused a sustained mild increase in dopamine, suggesting it may help restore tonic dopamine levels, which could be relevant for treating addiction.
British Journal of Pharmacology
May 5, 2026
Giorgia Corli, Deborah Rudin, Dino Luethi et al.
Some new synthetic cannabinoid receptor agonists (SCRAs) also directly activate the serotonin 5-HT₂A receptor, which may contribute to unexpected psychiatric side effects. Many SCRAs with a valinamide or tert-leucinamide head moiety showed in vitro activity at the 5-HT₂A receptor at high concentrations. In mice, the compound AB-5′F-BUTINACA caused neurological changes, sensorimotor alteration, antinociception, hypothermia, reduced breath rate, and hypolocomotion. These effects were mediated by both CB₁ and 5-HT₂A receptors, as they were prevented by selective antagonists. The findings indicate potential risks of SCRA consumption that could exacerbate unexpected psychiatric conditions.
British Journal of Pharmacology
May 26, 2011
Ján Kehr, Fumio Ichinose, Shimako Yoshitake et al.
The designer drug mephedrone, compared with MDMA (ecstasy) and amphetamine in rats, rapidly increased dopamine levels in the nucleus accumbens by 496% and serotonin levels by 941%, closely matching MDMA's serotonin release but also producing an amphetamine-like fast dopamine surge and elimination. Amphetamine raised dopamine by 412% and serotonin by only 165%. Mephedrone's dopamine levels cleared within 25 minutes, versus 303 minutes for MDMA, suggesting its brief but potent effect on the brain's reward system may underlie strong addictive potential. Locomotor activity increased most with amphetamine; mephedrone and MDMA had weaker, shorter effects.
British Journal of Pharmacology
August 1, 2022
Michael Tagen, Linda E. Klumpers
Delta-8-THC, an intoxicating cannabinoid, has rapidly grown in use. This review summarizes decades of pharmacological studies on delta-8-THC, including receptor binding, cell signaling, animal and human activity, and pharmacokinetics, with special focus on comparisons to delta-9-THC. The pharmacokinetics and pharmacodynamics of the two isomers are very similar. Delta-8-THC is a partial agonist of the CB1 receptor and has cannabimimetic activity in both animals and humans. Its reduced potency in clinical studies compared to delta-9-THC can be explained by weaker CB1 receptor affinity, though other mechanisms may contribute. Gaps in knowledge, particularly in human studies, are highlighted.