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

This relatively early study (2006) combined a literature review with interviews of ceremony participants to establish the effects and toxicity of ayahuasca. The author concludes that risks are relatively low (transient psychological effects, low toxicity, low abuse/addiction potential).

Abstract

“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.”

Author: Robert S. Gable

Summary

A systematic literature search was conducted to assess the acute toxicity and psychological hazards of ayahuasca, a brew of dimethyltryptamine and harmala alkaloids used in religious ceremonies. The results indicated that ayahuasca has a safety margin comparable to codeine, mescaline or methadone.

INTRODUCTION

DMT has received relatively little attention, but in 2006 the US Supreme Court decided that ayahuasca/hoasca was safe for ceremonial use by members of a small spiritualist Christian church.

The concept of risk refers to the quantified probability of a future harm. There is limited scientific data regarding the effects of oral DMT, so a probabilistic estimate of risk is often an intrinsic aspect of the research process.

Ayahuasca is a mixture of tryptamine and a monoamine oxidase inhibitor. DMT alone has psychological activity, but ayahuasca becomes psychoactive when combined with an MAOI.

Ayahuasca/hoasca is prepared by boiling Psychotria viridis leaves and Banisteriopsis caapi vine bark for several hours and then decanting the resulting thick, brown, oily liquid.

The most commonly recognized sacramental use of ayahuasca occurs among members of two churches in Brazil: the O Centro Espirita Beneficiente Uniao Do Vegetal (UDV) and the Santo Daime. Both churches use a decoction of plant DMT and harmala alkaloids called hoasca.

The UDV cultivates the plants used in their hoasca ‘tea’ on land that the church owns and maintains for that purpose.

METHOD

The present paper extends previous reviews of the acute lethal toxicity and abuse potential of various psychoactive substances by searching six databases for English-language serial publications, from 1969 to 2005, and consulting the most relevant books, reference works and special journal issues.

The literature search was limited to articles that met at least two of four criteria: quantification, health status, and possible concomitant substances.

RESULTS

Fewer than 100 scholarly articles were located in English-language serial publications that focused specifically on ayahuasca/hoasca. The majority of these articles involved inapplicable topics such as neurological experiments, ethnographic descriptions or potential medical uses.

Description of ayahuasca/hoasca brew

DMT concentrations in P. viridis leaves range from 0.1% to 0.66% dry weight, while b-carboline concentrations in B. caapi leaves range from 0.05% to 1.95% dry weight.

Ayahuasca brews can have a fivefold variation in DMT concentrations and proportions due to the varying chemical composition of the source plants and different methods of preparation.

UDV members ingest hoasca in a ritual structure that provides some control over dosage and subsequent psychological effects.

Injected, smoked or insufflated DMT is noted for its rapid activity, while oral DMT preparations consisting of DMT and MAOI have slower onset of effects and peak at 120 minutes.

Acute lethality

Traditional toxicity tests use the lethal dose of a substance to cause death in 50% of experimental animals. More humane tests are being implemented, but many regulatory agencies still use the lethal dose.

The criterion of single-dose acute lethality is an extremely limited estimate of human toxicity, but the LD50 is a clearly defined, replicable and important benchmark of toxicity.

DMT has an LD50 of 47 mg/kg intraperitoneally and 32 mg/kg intravenously in mice. Five compounds with structural resemblance to DMT have LD50s similar to or substantially less toxic than DMT.

The principal b-carboline alkaloids added to DMT in ayahuasca mixtures are harmine, harmaline and tetrahydroharmine. These alkaloids are found in the Peganum harmala shrub, a desert plant native to Central Asia.

To extrapolate DMT lethality data from mice to humans, we have to make some intrepid, but not original assumptions. This results in a human LD50 of 1.6 mg/kg for DMT administered intravenously. To calculate the potential toxicity of oral DMT in ayahuasca, we must convert the estimated intravenous LD50 dose of 1.6 mg/kg DMT to an oral equivalent of 8 mg/kg DMT. This is a very high dose, and half of potential DMT fatalities would occur at an oral dose less than 560 mg.

Cardiac stress

Ayahuasca increases heart rate and blood pressure, but at a lower rate than intravenous DMT or b-carbolines. A typical dose of ayahuasca appears to be less potentially hazardous than many commonly used psychoactive substances.

Ayahuasca may cause acute hemodynamic changes, including heart rate elevation. Individual differences in metabolism and health status may result in a wide range of reactions to psychoactive substances, including heart rate elevation.

The heart rate increases with ayahuasca are minimal, and may be the result of unrelated physical activity of the participants. In comparison, a beverage containing 230 mg doseof caffeine resulted in only negligible increases in heart rate and blood pressure.

Ayahuasca inhibits MAO, which allows more serotonin to accumulate in nerve terminals, causing a variety of adverse physiological symptoms. Individuals who have recently used ginseng, St John’s wort, dextromethorphan or MDMA should be cautious about using ayahuasca.

Six instances of severe toxic reactions to psychoactive tryptamines and/or b-carbolines were reported, including the death of a 25-year-old male caused by amine intoxication. 5-MeO-DMT is more potent than DMT when smoked or taken orally with harmaline, but should not be casually interchanged in ayahuasca-like preparations.

A 71-year-old diabetic female died after ingesting an unorthodox nicotine/b-carboline brew, which exceeded the average post-mortem nicotine concentration by at least 20 times.

Two individuals consumed 15 – 50 times more b-carboline alkaloids than is needed to maintain the oral activity of DMT in an ayahuasca preparation. The caffeine used by one of the decedents probably intensified the effect.

A meditation session named “releasing autohypnosis of forest medicine men” involved more than 30 individuals between the ages of 20 and 50 years who consumed 100 – 200 ml of herbal tea. Several participants required mechanical ventilation due to severe reactions to the combination of harmine, atropine and scopolamine.

To this author’s knowledge, there have been no deaths caused by hoasca or any other traditional DMT/b-carboline ayahuasca brews. People with an abnormal metabolism or a compromised health status should avoid using ayahuasca preparations.

Psychological dysfunction

Ayahuasca users experience a visionary state, where objects in the environment appear to vibrate and increase in brightness, and rapid-moving patterns and scenes emerge that are visible with eyes either open or closed.

Riba and colleagues [20] reported that six volunteers experienced emotions of happiness, sadness, awe and amazement after receiving doses of 0.05, 0.75 and 01.0 mg/kg of ayahuasca. They also reported that the sense of self and the passing of time were deeply affected.

In interviews with 150 informants, Shannon reported that ayahuasca use prompted users to reflect seriously on life, nature and human consciousness. A pilot study by Grob and colleagues revealed that ayahuasca users showed more rigidity, regimentation, reflection and word-recall on various tests than nonmembers.

Certain perceptual characteristics of the ayahuasca experience overlap those of schizophrenia, and some researchers have suggested that increased DMT levels in schizophrenic individuals may serve as a homeostatic response to calm or suppress psychotic activity.

Ayahuasca, 5-MeO-DIPT, psilocybin and LSD can all cause hallucinations and psychotic episodes, but 5-MeO-DIPT is more potent and more commonly used outside of ceremonial practices.

The medical studies section of the UDV documented 13 to 24 cases of psychosis in people who consumed 25 000 servings of hoasca tea. The psychotic episodes were transient in nature and resolved spontaneously.

Dependence and abuse potential

The extent to which ayahuasca might lead to physiological dependence or compulsive drug-seeking remains to be documented convincingly. However, non-human animal studies have shown varying degrees of tolerance to behavioral and physiological responses over a period of 3 or 4 weeks.

Ayahuasca might function as a positive reinforcer leading to significant abuse potential, if individuals who try it once or twice fall into a pattern of chronic use that they then find difficult to quit.

Ayahuasca has a low frequency of use in the general population and lacks the abuse potential of amphetamines, cocaine, opiates or other widely abused substances.

DISCUSSION

The limited number of relevant scientific studies of DMT and b-carboline decoctions hampered any attempt to characterize the possible acute adverse health effects of ayahuasca. However, the acute systemic toxicity of ayahuasca is substantially less than alcohol.

Many public safety hazards are accepted grudgingly because they perceive a potential benefit, but some risks are actively sought. The internet is a popular source of information for individuals seeking drug-related experiences, but it also contains descriptions of intoxicated misadventures that might serve as a cautionary tale.

Ayahuasca has a low abuse potential in social settings, as it causes unpredictable frightening images and thoughts, plus predictable nausea and diarrhea. Its beneficial effects are outside the realm of toxicology, but not necessarily beyond the scientific requirement of falsifiability.