Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids.

AIM: To extend previous reviews by assessing the acute systemic toxicity and psychological hazards of a dimethyltryptamine and beta-carboline brew (ayahuasca/hoasca) used in religious ceremonies. METHOD: A systematic literature search, supplemented by interviews with ceremony participants. RESULTS: No laboratory animal models were located that tested the acute toxicity or the abuse potential of ayahuasca. Separate animal studies of the median lethal dose of dimethyltryptamine (DMT) and of several harmala alkaloids indicated that a lethal dose of these substances in humans is probably greater than 20 times the typical ceremonial dose. Adverse health effects may occur from casual use of ayahuasca, particularly when serotonergic substances are used in conjunction. DMT is capable of inducing aversive psychological reactions or transient psychotic episodes that resolve spontaneously in a few hours. There was no evidence that ayahuasca has substantial or persistent abuse potential. Long-term psychological benefits have been documented when ayahuasca is used in a well-established social context. CONCLUSION: A decoction of DMT and harmala alkaloids used in religious ceremonies has a safety margin comparable to codeine, mescaline or methadone. The dependence potential of oral DMT and the risk of sustained psychological disturbance are minimal.

Acute toxic effects of club drugs.

This article summarizes the short-term physiological toxicity and the adverse behavioral effects of four substances (GHB, ketamine, MDMA, and Rohypnol) that have been used at latenight dance clubs. The two primary data sources were case studies of human fatalities and experimental studies with laboratory animals. A safety ratio was calculated for each substance based on its estimated lethal dose and its customary recreational dose. GHB (gamma-hydroxybutyrate) appears to be the most physiologically toxic; Rohypnol (flunitrazepam) appears to be the least physiologically toxic. The single most risk-producing behavior of club drug users is combining psychoactive substances, usually involving alcohol. Hazardous drug-use sequelae such as accidents, aggressive behavior, and addiction were not factored into the safety ratio estimates.

Comparison of acute lethal toxicity of commonly abused psychoactive substances.

AIMS: To determine the acute lethal toxicity of a range of psychoactive substances in terms of the dose customarily used as a single substance for non-medical purposes. DESIGN AND METHOD: A structured English-language literature search was conducted to identify experimental studies and clinical reports that documented human and non-human lethal doses of 20 abused substances that are distributed widely in Europe and North America. Four inclusion criteria were specified for the reports, and approximately 3000 relevant records were retrieved from search engines at Biosis, Science Citation Index, Google and the National Library of Medicine's Gateway. In order to account for different drug potencies, a 'safety ratio' was computed for each substance by comparing its reported acute lethal dose with the dose most commonly used for non-medical purposes. FINDINGS: The majority of published reports of acute lethal toxicity indicate that the decedent used a co-intoxicant (most often alcohol). The calculated safety ratios varied between substances by more than a factor of 100. Intravenous heroin appeared to have the greatest direct physiological toxicity; several hallucinogens appeared to have the least direct physiological toxicity. CONCLUSIONS: Despite residual uncertainties, the substantial difference in safety ratios suggests that abused substances can be rank-ordered on the basis of their potential acute lethality.