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The molecular structure of Ayahuasca
  • Ayahuasca is a psychedelic tea originating from the Upper Amazon in South America.  It is typically prepared from two plants– Psycotra viridis, containing the psychedelic compound DMT (N,N-Dimethyltryptamine), and Banisteriopis Caapi (the ayahuasca vine) which contains monoamine oxidase inhibitors (MAOIs) that prevent DMT from being broken down in the gut and liver. This combination allows DMT to have psychoactive effects when taken orally, and prolongs the intense psychedelic experience.

    Ayahuasca has a long history of ceremonial consumption among various indigenous populations throughout the region, in countries such as Bolivia, Ecuador, and Peru. Ayahuasca is considered in its traditional context as an important element of shamanic tradition and as a medicine. As such, it is consumed within a ceremony or ritual under the guidance of a Shaman; a person of significant social standing who is sought for the healing of physical, emotional and psychological issues.  More recently, its psychedelic properties and therapeutic potential have attracted significant attention in the global West, with a rapidly-emerging tourism sector centred around offering the ayahuasca ceremony to international visitors at ayahuasca retreats.

    As a psychedelic drug, ayahuasca is increasingly consumed outside of traditional retreats and ceremonies due to the online availability of the plants used in ayahuasca preparation. New trends in consumption have led to controversy around the impact on the traditional communities where its plant components grow, and the potential risks of unsupervised use. For a deeper exploration of these debates, please find here the Drug Science podcast episode with Dr Simon Ruffell on ayahuasca.

  • Ayahuasca is a reddish-brown tea. Traditionally, ayahuasca contains the Banisteriopis Caapi vine and psycotra viridis as its base. However, there may be regional variations in the preparation and it is common for other plants to be included in the admixture. Some additions may have psychoactive properties of their own, and these may also be potentiated by the β-carbolines of the MAOI. Substitutions are also possible; plants such as Mimosa, Acacia, Syrian Rue containing the same active compounds sometimes replace their original counterparts.

  • DMT is an indole alkaloid, acting as an agonist upon the 5-HT2A receptors (along with all other classic psychedelics such as LSD, psilocybin, 5-meo-dmt, etc). It is capable of producing strong visionary effects and other indicators of altered state of consciousness. Under normal circumstances, DMT is inactive when consumed orally, as it is denatured by an enzyme found in the stomach before it can take effect.  Therefore, it is more commonly vaporised, or, as has been the case in some clinical trials, administered intravenously. In ayahuasca preparations however, the addition of a MAOI (β-carboline compounds such as harmine, and harmaline) slows this process of enzyme oxidation, allowing oral preparations to produce a profound psychedelic experience, sometimes referred to as an ‘ayahuasca trip’.

    To find out how DMT works in the brain, click here.

  • As with other 5-HT2A agonists (such as LSDpsilocybin5-meo-dmt etc), a serotonergic response is observed. The subjective effects – which last approximately four hours – are highly variable and often difficult to describe, but can include:

    1. Intense closed and open eye visuals

    2. Re-experiencing of memorable events

    3. Distortions in sense of time, place, and sometimes sense of self

    4. Possible auditory and sensory hallucinations

    5. A deep state of introspection

    6. Profound spiritual experiences

    7. Perceived contact and interaction with other entities

    8. Temporary alterations in mood and emotion that can range from terror to euphoria.

    ‘Autobiographical’ elements of content are often reported by those experiencing ayahuasca-induced visuals. The resurgence of memories, and a ‘third person’ perspective on life events have frequently been reported.

    The psychedelic effects may be preceded by nausea, vomiting, and sometimes diarrhoea. This emetic action is perceived of as a cathartic expulsion in traditional settings, and is welcomed as part of the overall experience.

  • Emerging research into ayahuasca on brain function and potential clinical applications attest to some positive effects on mental wellbeing.

    In clinical settings, preliminary observations indicate anxiolytic and antidepressant effects, along with reductions in suicidality in people with treatment-resistant depression. It may have a role in supporting people through addiction rehabilitation; clinical trials have demonstrated improvements in hopefulness, empowerment, mindfulness, and quality of life and outlook have been observed in those with dependency on other substances, as well as reductions in self-reported use of tobaccoalcohol and cocaine.

    The therapeutic potential of ayahuasca has been reported after use in religious and ritual practices. It is consumed as a religious sacrament in a number of Brazilian syncretic churches. Studies have consistently reported higher wellbeing scores in churchgoers who are regular ayahuasca consumers (usually twice per month), when compared with members of non-ayahuasca churches.

  • Ayahuasca has a long history of use, with very few reported incidents of harm. Clinical studies (both animal and human) indicate it to be extremely safe when appropriate dosage, setting and supervision is applied. There is very little risk of toxicity, as is the case with most of the classical psychedelic drugs. The most frequently reported adverse event is an intense, challenging experience that can be emotionally difficult. For some, prior traumas can be revisited, and sometimes painful emotions require processing. Usually, this is temporarily unpleasant and causes no lasting harm.

    As with all substances, there is risk around the composition of the preparation. Toxicological studies of ayahuasca ‘brews’ have revealed that concentrations of both DMT and the β-carboline MAOIs vary substantially across preparations. Many different types of additional plant matter  have been reported, some of which may pose risk of interaction or potentiation. Storage duration and transport conditions have also been shown to affect composition, with significant changes observed to the harmala alkaloids (present in the MAOI).

    Caution is also advised in any setting where usual decision-making and awareness may be compromised. The risk of sexual assault and accidental injury or death is higher where psychoactive substances are used.

  • Although ayahuasca is pharmacologically safe at usual doses, there are some pre-existing conditions and medications that may preclude the use of ayahuasca. Common prescription drugs with interaction risks include:

    1. Other MAOIs (sometimes prescribed as antidepressants)

    2. Antipsychotics

    3. Antihypertensives

    4. Selective Serotonin reuptake inhibitors (SSRIs)

    SSRIs, commonly prescribed for depression, present a hypothetical risk of Serotonin Syndrome when combined with MAOIs. Some medications may also limit the efficacy of ayahuasca, especially if they bind on the same receptors. Prescribed medications should not be suspended without consulting your doctor first.

    Diagnoses of some types of mental illness (such as schizophrenia, history of psychosis, and bipolar disorder) are considered an exclusionary criteria in many settings.

    Typically, full or partial fasting or is recommended prior to an ayahuasca experience. This not only reduces the chances of vomiting, it also promotes maximum absorption of the ayahuasca, and prevents potentially dangerous drug-food interactions. For example it is believed that foods high in tyramine (such as many cheeses and meats) may interact with β-carboline alkaloids present in ayahuasca.

  • Ayahuasca should not be consumed together with alcohol or other drugs. In particular, amphetamines should be avoided, due to their hypertensive action which when combined with a MAOI could prove fatal. Although, this particular drug interaction does not appear to be documented with ayahuasca. Detailed information on drug interactions can be found here.

    Ayahuasca is commonly used in traditional settings with other ethnobotanical or otherwise naturally derived psychoactive substances. These include:

    1. Tobacco (rapé; mapacho)

    2. Kambo (from the Kambo frog)

    3. 5-MeO-DMT (from the Bufo Alvarus toad)

    4. Peyote (mescaline cactus)

    5. Psilocybin (from certain types of mushroom)

    6. Yopo (N,N-DMT, 5-MeO-DMT and Bufotenine containing seeds).

    Caution should be exercised even if these options are presented as a usual part of the programme. Although there is little anecdotal evidence of adverse effect, few studies have looked at the clinical implications of taking these substances in close proximity.

  • Ayahuasca, like the other classical psychedelic drugs, is not addictive. Despite the documented (and further anecdotal) benefits, the trip process can be unpleasant and difficult, and therefore does not lend itself to regular use. Psychedelics in general also demonstrate a pharmacological mechanism of short-term reduced efficacy (tolerance) which inhibits their prolonged or frequent use. In fact, ayahuasca is valued for its anti-addictive properties and its potential role in supporting those with dependency on other substances is being explored.

  • If you have already made the decision to consume ayahuasca there are a number of precautions you can take to reduce the risk of harm. Adequate supervision is strongly advised; a person who is both sober and experienced with the psychedelic state can support any challenging aspects of the trip experience. If this is in a retreat setting attention should be paid to screening processes, preparation, supervision arrangements and integration, as well as the independent reviews by previous participants where available. The setting should be as comfortable and secure as possible and free of interruptions. As mentioned, any pre-existing conditions or medications should be discussed with a physician wherever possible.

  • Ayahuasca is hailed by some proponents as an all-round panacea for physical and mental health. While there are many interesting research avenues being/to be explored, it is dangerous to assume that any one substance can ‘cure’ ailments for which we do not (yet) have an evidence base for. This particularly applies to any choices one may make about rejecting or discontinuing mainstream medical accompaniment. Prescription medication should not be suspended to take part in, or as a result of, an ayahuasca experience without medical guidance.

    It would be a harmful misconception for ayahuasca to be viewed as a recreational drug, or for ceremonies and other organised settings to be viewed as ‘drug-fuelled’ gatherings. On the contrary, the taking of ayahuasca is often referred to as trabajo (‘work’) in traditional contexts; from the nausea and vomiting, to the solitary introspection and the potentially challenging emotional experiences, it is not considered an easy or reliably pleasant activity. It is not therefore used as a recreational substance and is rarely taken at parties, festivals and nightclubs.

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