British Journal of Clinical Pharmacology
February 21, 2013
Marieke Niesters, Christian Martini, Albert Dahan
498 citations
The anesthetic ketamine is used to treat chronic pain syndromes, especially those with a neuropathic component. Low-dose ketamine produces strong analgesia, likely by blocking the N-methyl-D-aspartate receptor, though other mechanisms such as enhanced descending inhibition and anti-inflammatory effects may contribute. Short-term infusions provide pain relief only during administration, while prolonged infusions of 4–14 days can yield analgesic effects lasting up to three months. Side effects include psychedelic symptoms, nausea, vomiting, somnolence, cardiovascular stimulation, and occasional hepatotoxicity.
British Journal of Clinical Pharmacology
February 1, 2012
Xiaochen Zhao, Swarajya Lakshmi Vattem Venkata, Ruin Moaddel et al.
136 citations
Ketamine is metabolized into several compounds, and this study shows that norketamine is not the main metabolite circulating in the blood after a single 40-minute infusion of 0.5 mg/kg ketamine in patients with treatment-resistant bipolar depression. Instead, dehydronorketamine was the major metabolite in four out of nine patients, norketamine in three, and hydroxynorketamine in two. Large inter-patient variation in metabolite levels was observed. The findings suggest that future research on ketamine's effects should measure these downstream metabolites.
British Journal of Clinical Pharmacology
June 1, 2002
Jordi Riba, P. Anderer, Adelaida Morte et al.
126 citations
Ayahuasca, a psychoactive tea from South America, produces measurable changes in brain electrical activity that parallel its subjective psychedelic and stimulant effects. In a double-blind crossover trial, 18 volunteers received low and high doses of freeze-dried ayahuasca. Electroencephalography recordings from baseline to eight hours showed dose-dependent decreases in absolute power across all frequency bands, especially theta, and decreases in relative delta and theta power with increases in beta power. Effects began within 15–30 minutes, peaked between 45 and 120 minutes, and returned to baseline by four to six hours. The pattern resembles that of other serotonergic psychedelics and supports the role of 5-HT2 and dopamine D2 receptor activation.
British Journal of Clinical Pharmacology
March 19, 2019
Friederike Holze, Urs Duthaler, Patrick Vizeli et al.
72 citations
After a 100 μg oral dose of LSD, plasma levels peak at about 1.7 hours and decline with a half-life of 3.6 hours. The main metabolite O-H-LSD peaks later, around 5 hours, and has a longer half-life of 5.2 hours. No sex differences in pharmacokinetics were observed. Subjective effects last an average of 8.5 hours, peaking at 2.5 hours. The concentration needed to produce half-maximal effects is 1.0 ng/mL for good effects and 1.9 ng/mL for bad effects, showing that subjective experiences closely track plasma concentrations over time.
British Journal of Clinical Pharmacology
December 11, 2015
Matthias E. Liechti, Boris B. Quednow, Evangelia Liakoni et al.
57 citations
Gamma-hydroxybutyrate (GHB) produced mixed stimulant-sedative effects in healthy men, with higher doses causing more sedation and dizziness but no changes in heart rate or blood pressure. Plasma exposure to GHB rose disproportionately with dose—a 40% greater increase than expected from dose alone—indicating nonlinear pharmacokinetics. The psychotropic effects were closely tied to plasma concentrations, and no acute tolerance developed over time.
British Journal of Clinical Pharmacology
April 1, 1985
Michael Schächter, D.p. Geaney, Dg Grahame‐smith et al.
20 citations
Schizophrenic patients treated with depot thioxanthenes and phenothiazines showed an approximately 30% increase in platelet 5-HT receptor number and a roughly 30% decrease in receptor affinity compared to controls. The decrease in affinity likely resulted from residual neuroleptic in the platelet membrane preparation. A weak positive correlation existed between receptor number and total neuroleptic dosage. The increased receptor number aligns with earlier reports of enhanced 5-HT-induced platelet aggregation in patients on long-term phenothiazines and thioxanthenes, suggesting 5-HT up-regulation in human platelets from depot neuroleptic therapy. Whether parallel changes occur in brain 5-HT receptors remains unknown.
British Journal of Clinical Pharmacology
July 17, 2023
Balázs Szigeti, Lawrence D. Phillips, David Nutt
13 citations
Randomized controlled trials (RCTs) are often considered the gold standard in medical research, but they have limitations including reliance on null hypothesis significance testing and poor generalizability. Bayesian analysis of real-world evidence (RWE) offers a complementary approach. In a case series of 20 children with epilepsy treated with medical cannabis, all experienced reduced seizures; Bayesian analysis with a flat prior gives a 95% probability that the next patient will improve (95% credible interval 87%–100%). For treatment-resistant depression treated with psilocybin, the probability of a favorable response ranges from 62% (QIDS-16) to 82% (MADRS). These analyses require fewer patients than traditional RCTs and provide directly actionable probabilities for clinicians and patients.
British Journal of Clinical Pharmacology
April 22, 2022
Ahmad Shamabadi, Ali Ahmadzade, Alireza Hasanzadeh
11 citations
A systematic review of systematic reviews found preliminary evidence that ketamine may reduce suicidal thoughts in the short term, but long-term effects remain unknown. Most of the 27 reviewed studies reported positive effects, though only four showed mixed or negative results. Among nine reviews of esketamine, only five found significant benefit. Common side effects included a temporary rise in pulse and blood pressure, dissociation, confusion, blurred vision, nausea, and vertigo, mostly mild. Over two-thirds of the included reviews were rated low or critically low quality, highlighting the need for further research.
British Journal of Clinical Pharmacology
February 1, 2000
Rafael de la Torre, Magı́ Farré, Jordi Ortuño et al.
MDMA (ecstasy) shows nonlinear pharmacokinetics in humans: as the dose increases, plasma concentrations rise disproportionately, meaning small dose increases lead to much higher drug levels. In a controlled trial with 14 healthy volunteers given 50–150 mg, urinary recovery of the metabolite HMMA stayed constant while MDMA recovery rose, suggesting saturation or inhibition of the demethylenation metabolic step. Nonrenal clearance was dose-dependent while urinary clearance remained constant. This nonlinearity occurs regardless of CYP2D6 genotype, implying that even moderate dose increases in recreational use can produce unexpectedly high plasma concentrations, raising the risk of acute toxicity for all users, not just the 10% genetically deficient in CYP2D6.