Effects of Ayahuasca and its Alkaloids on Drug Dependence: A Systematic Literature Review of Quantitative Studies in Animals and Humans

This systematic literature review (2016) examined the effects of ayahuasca across animal and human studies which investigated behaviors and symptoms associated with
drug-related disorders. Results suggest that ayahuasca and its alkaloids which include harmine and harmaline may have antiaddictive properties that can alleviate substance dependence by means of modulating dopaminergic neurotransmission. The lack of clinically controlled studies, however, makes it difficult to determine if observed health improvements are related to drug effects, to the religious environment and culture, or the combination of both factors.

Abstract

“Introduction: Recently, the anti-addictive potential of ayahuasca, a dimethyltryptamine(DMT)- and β-carboline-rich hallucinogenic beverage traditionally used by indigenous groups of the Northwest Amazon and currently by syncretic churches worldwide, has received increased attention.

Methods: To better evaluate this topic, we performed a systematic literature review using the PubMed database to find quantitative studies (using statistical analysis) that assessed the effects of ayahuasca or its components in drug-related symptoms or disorders.

Results: We found five animal studies (using harmaline, harmine, or ayahuasca) and five observational studies of regular ayahuasca consumers. All animal studies showed improvement of biochemical or behavioral parameters related to drug-induced disorders. Of the five human studies, four reported significant reductions of dependence symptoms or substance use, while one did not report significant results.

Discussion: The mechanisms responsible for the anti-addictive properties of ayahuasca and its alkaloids are not clarified, apparently involving both peripheral MAO-A inhibition by the β-carbolines and central agonism of DMT at 5-HT2A receptors expressed in brain regions related to the regulation of mood and emotions. Although results are promising, controlled studies are needed to replicate these preliminary findings.”

Authors: Amanda A. Nunes, Rafael G. Dos Santos, Flávia L. Osório, Rafael F. Sanches, José Alexandre S. Crippa & Jaime EC Hallak

Summary

Recently, the anti-addictive potential of ayahuasca has received increased attention. Five animal studies and five observational studies of regular ayahuasca consumers have shown promising results, although controlled studies are needed to replicate these preliminary findings.

Ayahuasca is a hallucinogenic beverage made from the stems of the Banisteriopsis caapi vine and the leaves of the Psychotria viridis bush. It is used by Northwestern Amazonian tribes and is now used in syncretic religions in South and North America, Europe, Asia, and Africa.

The leaves of B. caapi, P. viridis and D. cabrerana contain DMT, a tryptamine hallucinogen with a chemical structure similar to serotonin. The -carbolines in these plants reversibly inhibit the enzyme monoamine oxidase-A (MAO-A), thus enabling DMT to reach the brain.

Ayahuasca’s psychoactive effects start to occur in 30 – 40 minutes after oral intake and reach their maximum intensity around 60 – 80 minutes after ingestion. These subjective effects are associated with dose-dependent changes in brain electrical activity in regions involved in emotion, perception, and memory processing.

Ayahuasca intake is associated with moderate increases in blood pressure, heart rate, body temperature, pupil diameter, prolactin, cortisol, growth hormone, and natural killer cells’ levels, as well as decreases in CD3 T, CD4 T, CD8 T, and CD19 B cells.

Ayahuasca has been shown to have anxiolytic, anti-depressive, and anti-addictive properties. A recent open-label study reported fast-acting and enduring anti-depressive effects associated with administration of a single ayahuasca dose to 17 patients with treatment-resistant major depressive disorder.

A few studies have suggested that ayahuasca may have therapeutic effects in the treatment of drug dependence. A study in Brazil showed that all participants who had tried ayahuasca showed a decrease in the use of drugs and complete alcohol abstinence.

32 Santo Daime members who consumed ayahuasca at least once a week were interviewed about their mental health and drug use. Most reported reductions in drug consumption or complete abstinence after Santo Daime membership.

A study evaluated the pattern of substance use in Brazilian Santo Daime members using an interview based on the diagnostic criteria of the DSM-IV. Nine out of 14 participants reported reduced drug cravings and attenuation of withdrawal symptoms after the use of ayahuasca.

Although some studies suggest beneficial effects of ayahuasca in the treatment of drug dependence, these studies are limited by small sample sizes, heterogeneous methods, and lack of statistical analysis.

Search strategy

Electronic searches were performed using the PubMed database and handsearching of reference lists. All studies published in English up to January 6, 2016, were included.

Data extraction

All studies were screened by two independent reviewers, and discrepancies were resolved by a third reviewer. The sample was divided into (1) animal and (2) human studies for the sake of clarity.

Study selection

The systematic review included eight potentially relevant references, two additional citations were added after handsearching the bibliography, and five animal studies and five human studies (all observational) were included.

Harmaline

A study performed in rats found that harmaline produced significant and dose-dependent acute reductions in morphine and cocaine intake.

Harmine

In rat brain slices, harmine produced a significant increase in dopamine efflux, as did cocaine, and the effects of both drugs combined were additive. However, harmine did not produce significant increases on efflux in the accumbens core or on reuptake in both regions.

A planarian model was used to quantify “C-shape” responses to cocaine, amphetamines, nicotine, and glutamate. Harmine significantly inhibited C-shapes produced by all compounds, with a preferential efficacy against cocaine > amphetamines > nicotine.

Ayahuasca

Oliveira-Lima et al. (2015) investigated the effects of ayahuasca on mice spontaneous locomotor activity and on ethanol-induced acute hyperlocomotion, locomotor sensitization, and reinstatement of ethanol-induced behavioral sensitization.

Ayahuasca

In a retrospective study with adolescents in Brazil, no significant results were found regarding lifetime substance consumption. However, UDV adolescents consumed less alcohol than the control group.

In two studies, regular ayahuasca users in Brazil were compared to rural controls and urban controls. The jungle-based ayahuasca users scored significantly lower in the Medical Status, Alcohol Use, and Psychiatric Status subscales, and significantly higher in the Drug Use subscale.

The ayahuasca group scored lower in the Medical Status and higher in the Drug Use subscales at the follow-up, but showed improvements in the Family/ Social Relationships subscale in the jungle-based ayahuasca group.

Ayahuasca-assisted therapy for problematic substance use and stress was performed in a rural First Nations community in British Columbia, Canada, by Thomas et al. (2013). Participants reported decreases in substance use and improvements in psychological and behavioral factors related to problematic substance use.

Fernández et al. (2014) conducted a non-controlled study in the Brazilian Amazonas State to examine the therapeutic effects of ayahuasca on drug dependence. The results showed that the treatment was associated with significant reductions in personality traits related to drug dependence, as well as increases in self-directedness and responsibility.

Discussion

This systematic review of quantitative animal and human studies suggests that ayahuasca and its alkaloids may have properties that help in the treatment of substance dependence or improvement of related disorders.

The mechanisms of action of harmine and harmaline have not been completely elucidated, but appear to involve MAO inhibition, the glutamatergic, dopaminergic, and serotonergic system, and 5-HT2A/2C receptors. These effects may be related to the decrease of dopamine activity.

Although preclinical evidence suggests that the harmine and harmaline compounds have affinity for 5-HT2A/2C receptors, human studies show that their psychoactive potential is questionable, and that their main mechanism of action seems to be the reversible inhibition of MAO-A.

Although some preclinical studies show that DMT interacts with the dopaminergic system, no human studies have evaluated the effects of pure DMT in dopamine neurotransmission. However, studies using psilocybin, a hallucinogenic tryptamine chemically and pharmacologically related to DMT, have shown increased dopamine levels in the striatum.

These results suggest that ayahuasca and its alkaloids can modulate the dopaminergic system and may have other effects, such as anxiolytic and antidepressive effects, as well as neuroprotective properties.

The observational studies included in this review showed that all reported improvements in drug-related symptoms or disorders, especially regarding alcohol and cocaine use.

Ayahuasca is effective in handling symptoms of drug withdrawal, abuse, or dependence, and may even improve quality of life and well-being, because it is consumed in a ritual context and involves membership in organized religious institutions or groups.

In a study by Fernández et al. (2014), a significant increase in spirituality was observed, and reports from participants suggest that the experiences during the psychedelic effects generated by the beverage appear to help them better understand their problems, in the resolution of traumas, and to make better decisions.

Ayahuasca has therapeutic potential for the recovery from addiction due to its mystical experiences, insights, cognitive and emotional effects, and decreased activity in the cortical areas associated with introspection and self-consciousness.

Although most studies suggest that ayahuasca or its alkaloids have potential use in the treatment of drug abuse and dependence, more clinical and controlled studies are needed to assess whether ayahuasca is actually effective in the treatment of drug dependence.