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
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 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.