British journal of clinical pharmacology
January 1, 2024
Friederike Holze, Livio Erne, Urs Duthaler et al.
12 citations
After oral doses of 85 and 170 μg, LSD reaches peak blood concentrations of 1.8 and 3.4 ng/mL at about 1.7 hours, with elimination half-lives of 3.7 and 4.0 hours. Only 1% of the dose is excreted unchanged in urine within 24 hours, while 16% is eliminated as the metabolite 2-oxo-3-hydroxy-LSD. Subjective drug effects last 9.3 to 11 hours, with maximal intensity reaching 77% to 87%. LSD shows dose-proportional pharmacokinetics and first-order elimination, and its effects are dose-dependent. The findings confirm earlier work on LSD's metabolism and time course.
British journal of clinical pharmacology
December 1, 2024
Jeremy Weleff, Julio C Nunes, Gabriel P A Costa et al.
8 citations
Chronic pain and opioid use disorder (OUD) are two interconnected public health crises that lack effective treatments. This review examines whether psychedelics could serve as novel therapeutics by acting on shared brain mechanisms underlying both conditions. Preclinical and human evidence suggests psychedelics may reverse pain- and opioid-induced neuroadaptations like central sensitization. The authors map how psychedelics could modulate overlapping dimensions of pain (sensory, affective, cognitive) and opioid-related phenomena (craving, withdrawal). They note a scarcity of controlled studies but propose mechanistic insights and methodological guidelines for future clinical trials. The goal is to accelerate development of alternatives to opioids amid the escalating crisis.
British journal of clinical pharmacology
November 25, 2024
Aaron Klaiber, Mélusine Humbert-Droz, Laura Ley et al.
6 citations
Mescaline doses up to 800 mg appear safe in controlled clinical settings for healthy individuals. In two double-blind, placebo-controlled studies with 48 participants and 96 administrations, positive subjective effects increased with dose and consistently outweighed negative effects. Autonomic effects rose moderately: systolic blood pressure exceeded 180 mmHg in 6% of administrations, heart rate above 100 beats/min occurred in 3%, and body temperature above 38 °C in 5%. Nausea limited higher doses. Kidney and liver function and blood cell counts remained normal. Flashbacks followed 2% of administrations. Adverse effects totaled 51 at 100 mg and 180 at 800 mg.
British journal of clinical pharmacology
August 1, 2024
Kaizheng Chen, Yaming Xie, Songyuan Chi et al.
6 citations
Low-dose esketamine given during surgery for vestibular schwannoma did not reduce pain at rest or with movement in the first 24 hours after the operation. The trial randomly assigned 90 adults to receive either 0.2 mg/kg of esketamine or a placebo after dural closure. Esketamine moderately increased brain activity as measured by the bispectral index for at least 30 minutes after administration, prolonged the time to removal of the breathing tube, and lowered the required dose of remifentanil at that point, but did not affect heart rate, blood pressure, or the time to regain spatial orientation. Rates of nausea and vomiting were similar between groups, and no hallucinations or excessive sedation occurred.
British journal of clinical pharmacology
December 1, 2024
Gisela Lima, Carla Soares, Marta Teixeira et al.
4 citations
Psychedelics are being explored for physical and mental health applications beyond psychiatry, including chronic pain, palliative care, and neuroprotection in ischemia. This article reviews dimethyltryptamine (DMT) and ayahuasca pharmacology, effects, safety, and toxicity, and details the anaesthetist's role in clinical and experimental research—covering participant screening, dosing sessions, adverse effect management, and toxicity treatment. It draws on a current neuroimaging study protocol. The authors argue that anaesthetists are uniquely positioned to manage psychedelic therapy in medically complex, polymedicated patients, but note that non-mental medical applications remain underexplored.
British journal of clinical pharmacology
June 16, 2025
Wellenberg K Simon, Tanja M Gampfer, Wagmann Lea et al.
1 citation
A workflow using zebrafish embryos (ZEs) followed by human microdosing (HMD) can identify human urine biomarkers for drugs of abuse and new psychoactive substances. Metabolites of amphetamine, cocaine, LSD, MDMA, methamphetamine, THC, MDMB-CHMICA, and MDPPP were first identified in ZEs exposed via immersion or injection, then compared with known human metabolites and confirmed by HMD. Both methods identified main human urine metabolites, except for LSD (due to low dose) and cannabinoids (due to low oral bioavailability). ZEs produced more metabolites, including conjugates, than HMD. The approach provides quick, reliable data for urinary drug screening, though challenges remain with HMD, including different administration routes and low-dose detectability.
British journal of clinical pharmacology
July 1, 2026
Marije E Otto, Gabriël E Jacobs, Joost C Van Mechelen et al.
Oral (S)-ketamine for treatment-resistant depression undergoes extensive first-pass metabolism, yielding low parent drug but high levels of active metabolites like (S)-norketamine. Using data from 17 healthy participants in a crossover trial, researchers developed a population PK model linking (S)-ketamine and (S)-norketamine concentrations to subjective 'Feeling High' scores. A significant relationship was found for (S)-norketamine alongside (S)-ketamine, though model variance was high. The analysis suggests that (S)-norketamine, not (S)-ketamine itself, primarily drives subjective effects after oral administration and may contribute to antidepressant effects in patients.
British journal of clinical pharmacology
June 24, 2026
Catherine M K E De Cuba, Annika A De Goede, Joost C Van Mechelen et al.
A single intravenous dose of S-ketamine produced acute and delayed effects on brain activity and motor cortex excitability that lasted up to seven days in 16 healthy adults. Intravenous S-ketamine reduced motor-evoked potential amplitude acutely and caused a sustained weakening of long-interval intracortical inhibition, which followed a linear relationship with drug concentration. Transcranial magnetic stimulation combined with electroencephalography showed acute changes in brain electrical activity across all treatments, but delayed changes only after intravenous and high-dose oral S-ketamine. Electroencephalography revealed acute decreases in alpha, beta, and delta power with eyes closed, and sustained increases in delta power with eyes open, the latter also showing a linear concentration-effect relationship. These delayed pharmacodynamic effects are distinct from acute effects and may help explain S-ketamine's antidepressant action.
British journal of clinical pharmacology
May 8, 2026
Ioanna Artemis Vamvakopoulou, Dasha Nicholls, David J Nutt et al.
Rates of mental illness among young people are rising, but few new treatments have emerged. Psychedelic-assisted therapy with psilocybin and MDMA has shown promise for adults with depression, anxiety, and PTSD, and interest is growing in its use for adolescents. A comprehensive review of all research on children and young people—from 1950s experiments to recent observational and retrospective studies of traditional and non-medical use—finds that psychedelics appear safe overall and may improve mental wellbeing in this age group. However, young people may face greater risks of anxiety, challenging experiences, and ego dissolution, warranting more thorough clinical research. The authors recommend a rigorous ethical framework with family involvement and consideration of lower doses to reduce potential harms.