British journal of pharmacology
November 1, 2025
Yasaman Razavi, Stephen J Kohut, Jack Bergman et al.
1 citation
Adolescent monkeys exposed daily to the cannabis compound Δ9-THC for six months, then tested about a year later as adults on a touchscreen attention task, required higher acute doses of Δ9-THC to impair their performance compared with animals that had not been exposed during adolescence. The impairment itself was dose-related and occurred whether the drug was given by injection or orally, though potency and timing differed. These results suggest that heavy cannabis use during adolescence can produce a lasting tolerance that persists into adulthood, even after a long period of abstinence.
British journal of pharmacology
July 14, 2026
Darta Stalberga, Robert Kronstrand, Bianca Schranz et al.
Synthetic cathinones, a large class of new psychoactive substances, primarily inhibit dopamine, norepinephrine, and serotonin transporters, with high dopamine transporter selectivity linked to abuse potential. In vitro testing of 58 substances showed that N-pyrrolidine cathinones combined with methylenedioxy groups—MDPiHP, MDPEP, and MDPV—had the highest potency at the dopamine transporter. Other N-pyrrolidine cathinones, such as 3F-α-PHP, 3F-α-PiHP, and 4F-α-PiHP, showed the greatest dopamine transporter selectivity relative to the serotonin transporter. Chloromethcathinone and methylmethcathinone compounds, like 3-CMC, displayed an amphetamine-like profile with comparable potency at dopamine and norepinephrine transporters. Some cathinones at high concentrations and phenethylamines at micromolar concentrations also activated the 5-HT2A receptor, while 2C-like arylcyclohexylamines targeted the receptor without transporter inhibition. The majority of compounds, especially N-pyrrolidine cathinones, suggest high abuse potential based on their dopamine transporter selectivity.
British journal of pharmacology
July 1, 2026
Susan Wonnacott, Gary J Stephens, Trevor Sharp
This editorial introduces a themed journal issue on psychedelic and related drugs as potential therapies for a wide range of difficult-to-treat conditions beyond neuropsychiatric disorders. The collection includes reviews and original articles covering the mechanistic basis of how these drugs act, the current status of preclinical research, progress in clinical trials, and insight into regulatory processes for clinical approval. The editorial provides an overview of current controversies and challenges in the field while highlighting the exciting potential these drugs offer.
British journal of pharmacology
July 1, 2019
Panos Zanos, Jaclyn N Highland, Xin Liu et al.
In mice, (R)-ketamine's metabolism to (2R,6R)-hydroxynorketamine (HNK) enhances its antidepressant-relevant actions. A deuterated form of (R)-ketamine that blocks this metabolism had less potency in antidepressant-sensitive behavioral tests, while (2R,6R)-HNK itself produced dose-dependent sustained antidepressant effects. However, (R)-ketamine also caused NMDA receptor-mediated adverse effects—including locomotor stimulation, conditioned-place preference, prepulse inhibition deficits, and motor incoordination—at sub-anaesthetic doses, with about half the potency of racemic ketamine. These findings indicate that while antidepressant-relevant effects occur at lower doses, there is a potential risk for sensory dissociation and abuse liability at higher doses.
British journal of pharmacology
January 1, 2015
B Simonson, A S Morani, A W M Ewald et al.
A synthetic version of salvinorin A, Mesyl Sal B, activates κ opioid receptors and shows potential as an anticocaine agent with fewer adverse effects than classic κ agonists. In rats, Mesyl Sal B had a longer duration of action than salvinorin A, reduced cocaine-seeking behavior, and increased dopamine transporter function in vitro through a κ opioid receptor- and ERK1/2-dependent mechanism. Unlike salvinorin A, Mesyl Sal B raised the maximum rate of dopamine uptake without increasing transporter cell-surface expression. The findings suggest that salvinorin-based compounds like Mesyl Sal B warrant further study as treatments for cocaine addiction, though their side-effect profile requires additional investigation.
British journal of pharmacology
June 1, 2002
Claudio Acuña-Castillo, Claudio Villalobos, Pablo R Moya et al.
A series of phenylisopropylamines and phenylethylamines were tested on rat serotonin 5-HT2A and 5-HT2C receptors expressed in frog eggs. All compounds acted as full agonists at 5-HT2C receptors, while at 5-HT2A receptors they were partial agonists, with relative efficacy ranging from 22% to 58% of serotonin's effect. The phenylethylamines had lower or undetectable efficacy at 5-HT2A receptors. DOI was a full agonist at 5-HT2C, while 2C-N acted as an antagonist at both receptors, competitive at 5-HT2A but non-competitive at 5-HT2C. The alpha-methyl group on the drugs determined their efficacy at both receptor subtypes.
British journal of pharmacology
July 1, 2000
M Bujas-Bobanovic, D C Bird, H A Robertson et al.
In rats, the drug phencyclidine (PCP) produced a complex behavioral syndrome including hyperlocomotion, stereotyped behaviors, and ataxia, and increased expression of the neuronal activity marker c-fos in brain regions, especially the cortex. The nitric oxide donor sodium nitroprusside (SNP) alone had no effect but completely blocked both the behavioral and c-fos responses to PCP in a dose- and time-dependent manner. These findings implicate the nitric oxide system in PCP's mechanism and suggest that drugs targeting the glutamate-nitric oxide system could offer a novel treatment approach for PCP-induced psychosis and schizophrenia.
British journal of pharmacology
August 1, 1990
L I Backus, T Sharp, D G Grahame-Smith
Blocking 5-HT2 receptors with antagonists such as ritanserin, ICI 170,809, or low-dose ketanserin enhances the behavioral syndrome caused by 5-HT1A receptor activation in rats, suggesting that 5-HT2 receptors normally inhibit 5-HT1A-mediated responses. Higher doses of ketanserin reduce the syndrome, likely due to additional alpha1-adrenoceptor blockade. The enhancement is not due to general behavioral activation, as the antagonists do not affect apomorphine-induced stereotypy or hyperactivity. These findings indicate a regulatory interaction between 5-HT2 and 5-HT1A receptor systems.