The Journal of Nervous and Mental Disease
March 4, 2014
Peter Gasser, Dominique Holstein, Yvonne Michel et al.
752 citations
In a small pilot study, 12 patients with anxiety related to life-threatening diseases underwent two sessions of LSD-assisted psychotherapy, receiving either a full 200-microgram dose or a low 20-microgram active placebo, with the placebo group later crossing over to the full dose. At a 2-month follow-up, trait anxiety decreased with a large effect size, and state anxiety also dropped significantly. These anxiety reductions persisted for 12 months. No serious adverse effects occurred beyond one day after treatment. The findings suggest that, under careful medical supervision, LSD can reduce anxiety, supporting the need for larger controlled trials.
Journal of Psychopharmacology
October 5, 2012
Amir Englund, Paul D. Morrison, Judith Nottage et al.
463 citations
Pre-treatment with 600 mg of cannabidiol (CBD) reduced the likelihood of clinically significant psychotic symptoms and paranoia caused by intravenous delta-9-tetrahydrocannabinol (THC, 1.5 mg) in healthy volunteers. Participants who received CBD before THC had lower scores on the State Social Paranoia Scale and smaller declines in episodic memory compared with those who received placebo before THC. The odds of experiencing a clinically significant increase in positive psychotic symptoms were about 78% lower in the CBD group. These results support the view that cannabis products high in THC and low in CBD pose greater mental health risks.
Biological Psychiatry
November 29, 2014
Yasmin Schmid, Florian Enzler, Peter Gasser et al.
425 citations
In a double-blind, placebo-controlled crossover study, 200 μg of lysergic acid diethylamide (LSD) given to 16 healthy subjects produced pronounced alterations in consciousness lasting 12 hours, including visual hallucinations, audiovisual synesthesia, and positively experienced derealization and depersonalization. LSD increased subjective well-being, happiness, closeness to others, openness, and trust, and decreased prepulse inhibition (PPI) of the acoustic startle response, a measure of sensorimotor gating. It also significantly increased blood pressure, heart rate, body temperature, pupil size, and plasma levels of cortisol, prolactin, oxytocin, and epinephrine. All adverse effects subsided within 72 hours, with no severe acute adverse effects observed. LSD produces empathogenic mood effects similar to methylenedioxymethamphetamine and alters sensorimotor gating in a human model of psychosis, supporting its potential use in psychotherapy and translational psychiatric research.
Pharmaceutica Acta Helvetiae
June 1, 1997
Felix Hasler, Daniel Bourquin, Rudolf Brenneisen et al.
231 citations
After oral ingestion of psilocybin, the main psychoactive compound in Psilocybe mushrooms, peak plasma levels of its metabolite psilocin occur around 105 minutes, averaging 8.2 ng/ml. Another metabolite, 4HIAA, peaks at about 113 minutes at 150 ng/ml. Intravenous administration produces psilocin peaks within roughly 2 minutes at 12.9 ng/ml, indicating rapid dephosphorylation of psilocybin. 4HIAA was not detected after intravenous dosing. The absolute oral bioavailability of psilocin from psilocybin is estimated at about 53%.
Journal of Analytical Toxicology
October 1, 1996
H. J. Helmlin, K. Bracher, Daniel Bourquin et al.
160 citations
MDMA (Ecstasy) is a widely abused illicit drug at European all-night dance parties. Analytical methods were established to detect MDMA and its metabolites (HMMA, HHMA, MDA, HMA, HHA) in plasma and urine. Plasma and urine samples from two participants in a controlled clinical study were analyzed using high-performance liquid chromatography and gas chromatography-mass spectrometry. After a single oral dose of 1.5 mg/kg MDMA, peak plasma levels of 331 ng/mL MDMA occurred at 2 hours, and 15 ng/mL MDA at 6.3 hours. Peak urine MDMA concentration was 28.1 micrograms/mL at 21.5 hours. Conjugated HMMA and HHMA are the main urinary metabolites.
Clinical Pharmacology & Therapeutics
June 15, 2011
C.m. Hysek, Linda D. Simmler, M. Ineichen et al.
153 citations
Blocking the norepinephrine transporter with reboxetine reduces the cardiovascular and subjective stimulant effects of MDMA (ecstasy) in humans, even though MDMA and its active metabolite reach higher concentrations in the blood. In a double-blind, placebo-controlled crossover study with 16 healthy adults, reboxetine lowered MDMA-induced increases in plasma norepinephrine, blood pressure, heart rate, drug high, stimulation, and emotional excitement. The findings indicate that transporter-mediated norepinephrine release is essential for MDMA's cardiovascular and stimulant-like effects.
Journal of Pharmaceutical and Biomedical Analysis
August 26, 2002
Felix Hasler, Daniel Bourquin, Rudolf Brenneisen et al.
100 citations
After oral doses of psilocybin (212 ± 25 µg/kg body weight), the metabolite psilocin appears in urine, peaking at 870 µg/L between 2 and 4 hours. Within 24 hours, 3.4 ± 0.9% of the dose is excreted as free psilocin. Adding beta-glucuronidase doubles measured psilocin levels, indicating partial excretion as psilocin-O-glucuronide, though 18 ± 7% of unconjugated psilocin decomposes during incubation. Enzymatic hydrolysis extends detectability in urine.
Electrophoresis
January 1, 1997
Matthias Lanz, Rudolf Brenneisen, Wolfgang Thormann
70 citations
A capillary electrophoresis method using a phosphate buffer with a chiral selector separates the enantiomers of MDMA (Ecstasy) and its metabolites HMMA and MDA in human urine. After enzymatic hydrolysis and solid-phase extraction, detection at 195 nm achieves detection limits of 20–50 ng/mL with 5 mL samples. Analysis of two patients' urine shows enantioselective metabolism: one patient excreted 42.28% of the racemic MDMA dose as R-(−)-MDMA and 10.16% as S-(+)-MDMA; the other excreted 28.63% and 9.34%, respectively. Metabolite enantiomer excretion varied between individuals, demonstrating interindividual differences in MDMA metabolism.
Zeitschrift für Naturforschung C
August 1, 1988
Rudolf Brenneisen, Stefan Borner
10 citations
The hallucinogenic mushroom Psilocybe semilanceata contains psilocybin and baeocystin at varying levels, with psilocybin ranging from 0.21 to 2.02% and baeocystin from 0.05 to 0.77%, while psilocin appears only in trace amounts. Analysis of 52 samples collected across multiple sites in Switzerland over one to five years showed that alkaloid content varies with the mushroom's origin, year of collection, size, and the part of the mushroom tested. These findings describe the chemical variability of tryptamine derivatives in this species.
Archiv der Pharmazie
January 1, 1988
Rudolf Brenneisen, Stefan Borner, Nelly Peter‐oesch et al.
8 citations
Baeocystin, a naturally occurring psilocybin-related alkaloid, was synthesized from 2-methyl-3-nitrophenol. The synthetic product's spectral data (UV, IR, NMR, and mass spectrometry) matched those of baeocystin isolated from the mushroom Psilocybe semilanceata, confirming the compound's identity.
Mycologist
November 1, 1999
Béatrice Senn-Irlet, Adolf Nyffenegger, Rudolf Brenneisen
6 citations
No Summary
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.