Hypotheses regarding the mechanisms of ayahuasca in the treatment of addictions

This hypothesis paper (2012) proposes four unique but interrelated mechanisms in the domains of biochemical, physiological, and psychological pathways and transcendent experiences, through which ayahuasca may exert anti-addictive effects.

Abstract

“Ayahuasca is a medicinal plant mixture utilized by indigenous peoples throughout the Amazon River basin for healing purposes. The “vine of the soul” or “vine of death,” as it is known in South America, contains a combination of monoamine oxidase inhibitors and N,N-dimethyltryptamine (DMT). When ingested together, these medicines produce profound alterations in consciousness. Increasingly, ayahuasca is being utilized to treat addictions. However, the mechanism of action by which ayahuasca treats addictions remains unclear. We offer four hypotheses to explain possible biochemical, physiological, psychological, and transcendent mechanisms by which ayahuasca may exert its anti-addiction effects.”

Authors: Mitchell B. Liester & James I. Prickett

Summary

Hypotheses Regarding the Mechanisms of Ayahuasca in the Treatment of Addictions

Indigenous peoples of South America have used ayahuasca for healing and spiritual purposes for at least four thousand years. Recently, it has been used to treat addictions.

Ayahuasca is a plant that is used by 72 different indigenous groups in South America. It is known to transport individuals who ingest this medicine beyond time and space.

Ayahuasca has been touted as a treatment for addictions in newsletters, books, and the esteemed medical journal, The Lancet.

History of Atahuasca Use

Europeans first became aware of ayahuasca in the sixteenth century, when Spanish and Portuguese explorers encountered indigenous people who ingested a plant mixture that caused hallucinations. The Holy Inquisition condemned ayahuasca and other plant medicines, leading to horrible tortures and death.

The first written documentation of ayahuasca use occurred in 1851 when the British botanist Richard Spruce encountered indigenous Tukanos in Brazil drinking ayahuasca.

Three Brazilian churches use ayahuasca as their primary sacrament, and are found in 23 different countries including Germany, Spain, Holland, Canada, Mexico, and the USA.

Due to the difficulty of obtaining ayahuasca’s active ingredients, medicines similar to ayahuasca are now being synthesized via nontraditional methods.

Biochemistry of Ayahuasca

Ayahuasca is prepared by boiling the bark or vine of Banisteriopsis caapi with up to 75 different plants, including Psychotria viridis and Brugmansia species.

Banisteriopsis caapi is a South American jungle vine that contains beta-carboline alkaloids that are potent monoamine oxidase inhibitors (MAOIs). MAOIs are used to treat Parkinson’s disease and major depressive disorder.

Monoamines are chemically similar molecules that serve as neurotransmitters and neuromodulators. When ingested orally, they are degraded by monoamine oxidase enzymes found in the gastrointestinal tract.

DMT is a naturally occurring tryptamine alkaloid found in many plant and animal species. It is also a short acting, potent medicine that induces a rapidly altered state of consciousness when smoked or snorted.

DMT is a small molecule with 188 molecular units, and is easily synthesized from indole or tryptamine in vitro and in vivo. It has agonist actions at the 5-HT2a and 5-HT2c sites.

DMT is broken down by the enzyme monoamine oxidase into indoleacetic acid, but remains active when ingested in the presence of MAOIs.

The Ayahuasca Experience

Ayahuasca produces vivid visual imagery, dizziness, nausea, and vomiting. The second phase involves contact with the spirit world and the third phase involves a fading of visions, a decrease in nausea, and a state of physical lassitude.

Biochemical Effects

Ayahuasca’s biochemical effects relate to DMT’s action on the serotonin system, including an increased number of serotonin receptors on platelets.

Physiologic Effects

Ayahuasca’s physiologic effects include nausea, vomiting, diarrhea, tremors, dizziness, mydriasis, synesthesia, and tingling sensations. It can also cause changes in perception of body temperature and skin sensitivity.

Psychological Effects

Ayahuasca’s psychological effects include alterations in perception, emotions, and thinking. Perceptual alterations frequently include visual imagery, such as snakes and jaguars, while the individual is awake but the eyes are closed.

Ayahuasca may cause intense emotional reactions, including happiness, sadness, awe, amazement, anxiety, and fear. Thoughts may center on personal psychological content and provide new insight into personal concerns.

Transcendent Effects

Ayahuasca users often report experiencing visions of a spiritual reality, an altered sense of space and time, ineffability, intuitive insights, out of body experiences, and feelings of oneness with the universe.

Individuals who have ingested ayahuasca frequently report experiencing their consciousness being separate from their body and traveling through space.

Biochemical Theory

Various theories of addictions exist, but the release of dopamine in the mesolimbic system by various drugs of abuse reinforces the use of these drugs. Excessive or repetitive dopamine release is associated with positive symptoms of psychosis.

Ayahuasca reduces dopamine in the mesolimbic pathway via two mechanisms: direct stimulation of 5HT2A receptors on dopamine neurons and indirect stimulation of 5HT2A receptors on dopamine neurons via GABA interneurons.

Imaging of dopamine receptors in the nigrostriatal pathway shows that typical antipsychotic drugs block dopamine receptors almost completely. Atypical antipsychotic drugs, however, slightly increase dopamine levels, which may explain the reduced appearance of extra pyramidal side effects.

The theory that ayahuasca reduces brain dopamine levels is supported by the finding that ayahuasca users have increased prolactin levels, which are indicative of decreased dopamine levels, likely due to 5HT2A receptor agonism.

Ayahuasca is hypothesized to reduce activity in the reward center of the brain by inhibiting dopamine release. Antipsychotic drugs may cause a phenomenon known as mesolimbic dopaminergic supersensitivity, which may explain why typical antipsychotics do not show significant efficacy as anti-addictive medicines.

Atypical antipsychotics have been shown to have anti-addictive properties and do not show a proclivity towards MDS development. They also help people with nicotine addiction to quit smoking more easily.

Dopamine effects on postsynaptic neurons may be influenced by three variables: amount of dopamine released, number of dopamine receptors, and availability of dopamine receptors.

DMT is an agonist at 5HT2A receptors and atypical antipsychotics act as antagonists at 5HT2A receptors, causing an increase in dopamine release. Atypical antipsychotics do not bind to D2 receptors.

A third variable modulating dopamine’s effect is the number of dopamine receptors on the postsynaptic neuron. Atypical antipsychotics do not show a proclivity towards MDS development, and may be due to their lower affinity for the D2 receptor.

Although both typical and atypical antipsychotics reduce dopaminergic activity in the mesolimbic pathway, atypical antipsychotics have been shown to possess anti-addictive properties.

The frequency of dosing may play a role in the antiaddictive effects of antipsychotics and ayahuasca. The less frequent dosing of ayahuasca may contribute to its different effects.

Physiological Theory

Dopamine exerts varying effects in the brain depending on the location, the specific types of dopamine receptors activated, and the level of dopamine.

Dopamine is the primary neurotransmitter involved in the mesolimbic pathway, which involves the ventral tegmental area (VTA), the nucleus accumbens, and the prefrontal cortex.

Dopamine release in the mesolimbic pathway has been associated with synaptic plasticity, which is thought to reorganize neuronal circuits, leading to addictive behaviors. This process is thought to be primarily related to changes in the amygdala, which is implicated in learning having to do with reward, fear, and other emotional responses to stimuli. Using pharmaco-neuroimaging, structural remodeling of dopaminergic pathways has been shown to occur in the striatal pathway within hours of acute blockade of D2 receptors.

Psychological Theory

Ayahuasca has been found to affect perceptions, emotions, ideation, and behavior. Some individuals who ingested hallucinogenic substances reported experiences that were very different from mental illnesses, such as depression, increased one’s sense of well-being, reduced compulsions, and reduced anxiety.

In 1957, Humphrey Osmond suggested the term “psychedelics” be used to replace the older term “hallucinogens” based upon these drugs’ ability to produce life-changing visions and a “mind manifesting” state.

Osmond and Hoffer initially studied LSD with the intention of using it to create a model of delirium tremens to study psychosis. However, they later conjectured that LSD could be used to treat alcoholism.

Hoffer and Osmond (1967) found that the environment and attitude of the people around the person had a profound influence upon the individual’s reaction to LSD.

Researchers began to use LSD as an aid to psychotherapy, and used a psychodynamic therapy approach to understand the phenomena resulting from the LSD sessions.

LSD and peyote are used to treat alcoholism, and ayahuasca is used to treat addictions. Ayahuasca allows individuals to access unconscious emotional issues and heal traumas, which improves decision-making.

Transcendent Theory

Ayahuasca may exert anti-addictive properties via a fourth mechanism, which is a transcendent experience. Transcendent experiences have previously been reported to help individuals overcome addictions, such as Bill W., the founder of Alcoholics Anonymous, who gave up alcohol after having a transcendent experience.

Studies performed in the 1960s reported that 50% of individuals treated with LSD utilizing this model were able to remain sober or significantly reduce their use of alcohol.