Ayahuasca is a traditional brew originating from the Amazonian region, renowned for its potent psychoactive properties. Ayahuasca is a brew prepared from the vine Banisteriopsis caapi, which contains monoamine oxidase inhibitors (MAOIs), and the leaves of Psychotria viridis, which provide the hallucinogenic compound N,N-dimethyltryptamine (DMT). Used for centuries by indigenous populations for ritualistic and therapeutic purposes, ayahuasca has recently attracted the attention of the scientific community due to its potential therapeutic benefits, particularly in the treatment of substance use disorders (SUDs).

Pharmacology and Mechanism of Action

Ayahuasca's pharmacological effects are attributable to its distinctive combination of compounds. DMT is a potent agonist of the 5-HT2A receptor, similar to other psychedelic compounds such as LSD and psilocybin. When orally ingested, DMT is typically broken down by monoamine oxidase (MAO) enzymes in the gut and liver. However, the β-carboline alkaloids present in Banisteriopsis caapi inhibit these enzymes, thereby allowing DMT to remain active and reach the brain (Domínguez-Clavé et al., 2016).

The anti-inflammatory properties of ayahuasca, particularly those mediated through sigma-1 receptors, are of significant importance in understanding its therapeutic effects. These receptors play a role in regulating neuroinflammation, which is a contributing factor in many psychiatric and neurological disorders. The activation of 5-HT2A receptors and the inhibition of MAO result in a cascade of neurochemical changes that promote neuroplasticity and may facilitate the treatment of substance use disorders (SUDs) (Silva et al., 2020).

Therapeutic Potential for Substance Use Disorders

Recent studies indicate that ayahuasca may prove an efficacious agent in the treatment of substance use disorders (SUDs). One of the principal mechanisms through which ayahuasca exerts its therapeutic effects is by enhancing mindfulness-related capacities. This encompasses augmented acceptance and the capacity to observe one's thoughts and emotions without judgement, which are pivotal elements in the process of overcoming addiction. A study demonstrated that ayahuasca intake significantly improved mindfulness scores, indicating its potential to assist in addiction treatment by fostering greater self-awareness and emotional regulation (Soler et al., 2016).

Qualitative research involving both indigenous healers and Western therapists has demonstrated that ayahuasca-assisted therapy can assist individuals in confronting and processing deep-seated psychological issues that contribute to their addictive behaviours. Those who participated in these therapies reported a reduction in substance use and cravings, attributing their success to the introspective and emotionally cathartic experiences facilitated by ayahuasca (Loizaga-Velder & Verres, 2014).

A systematic review of studies conducted between 2016 and 2020 provided evidence to support the therapeutic effects of ayahuasca and its alkaloids in the treatment of substance use disorders (SUDs). These studies, which employed both preclinical and observational research methods, reported a reduction in drug use, anxiety, and depression among participants. Furthermore, improvements in quality of life and well-being were observed, which provides additional evidence that ayahuasca has the potential to support long-term recovery and prevent relapse (Rodrigues et al., 2021).

Furthermore, observational studies have indicated that regular use of ayahuasca in ceremonial settings can result in sustained reductions in substance use. For example, an observational study conducted among an indigenous community in Canada revealed that participants reported a notable reduction in problematic cocaine use following ayahuasca ceremonies. These findings emphasise the significance of contextual factors and the setting in optimising the therapeutic benefits of ayahuasca (Argento et al., 2019).

Despite the encouraging outcomes observed thus far, the clinical investigation of ayahuasca is confronted with a number of significant challenges. The regulatory obstacles presented by the legal status and the complexity of its chemical composition make the approval and standardisation of clinical trials a challenging process. Furthermore, the variability in the botanical and chemical composition of ayahuasca preparations introduces an additional layer of complexity in ensuring consistent and reproducible results (Mckenna, 2004).

Another significant issue is that of safety. Ayahuasca's monoamine oxidase inhibitor (MAOI) properties have the potential to precipitate serious interactions with other medications, necessitating meticulous screening and monitoring of participants in clinical settings. Notwithstanding these challenges, no serious adverse events have been reported in controlled studies, indicating a relatively safe profile when used appropriately (Malcolm & Lee, 2017).

In conclusion, ayahuasca represents a promising avenue for the treatment of substance use disorders. Its distinctive pharmacological profile, encompassing serotonergic and anti-inflammatory pathways, offers a multifaceted approach to addressing the complex nature of addiction. While existing evidence supports its potential, further rigorous clinical trials are necessary to fully elucidate its efficacy and safety. Addressing regulatory and methodological challenges will be critical in advancing ayahuasca from traditional use to a recognised treatment modality in modern medicine.

Ref:

Domínguez-Clavé, E., Soler, J., Elices, M., Pascual, J., Álvarez, E., Revenga, M. D. L. F., Friedlander, P., Feilding, A., & Riba, J. (2016). Ayahuasca: Pharmacology, neuroscience and therapeutic potential. Brain Research Bulletin, 126, 89-101.

Silva, M. G., Daros, G. C., & Bitencourt, R. M. (2020). Anti-inflammatory activity of ayahuasca: therapeutical implications in neurological and psychiatric diseases. Behavioural Brain Research, 400.

Soler, J., Elices, M., Franquesa, A., Barker, S., Friedlander, P., Feilding, A., Pascual, J., & Riba, J. (2016). Exploring the therapeutic potential of Ayahuasca: acute intake increases mindfulness-related capacities. Psychopharmacology, 233, 823-829.

Loizaga-Velder, A., & Verres, R. (2014). Therapeutic Effects of Ritual Ayahuasca Use in the Treatment of Substance Dependence—Qualitative Results. Journal of Psychoactive Drugs, 46, 63-72.

Rodrigues, L. S., Rossi, G. N., Rocha, J. M., Osório, F. L., Bouso, J. C., Hallak, J. E. C., & Santos, R. G. (2021). Effects of ayahuasca and its alkaloids on substance use disorders: an updated (2016–2020) systematic review of preclinical and human studies. European Archives of Psychiatry and Clinical Neuroscience, 1-16.

Argento, E., Capler, R., Thomas, G., Lucas, P., & Tupper, K. W. (2019). Exploring ayahuasca-assisted therapy for addiction: A qualitative analysis of preliminary findings among an Indigenous community in Canada. Drug and Alcohol Review.

Mckenna, D. (2004). Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges. Pharmacology & Therapeutics, 102(2), 111-129.

Malcolm, B., & Lee, K. C. (2017). Ayahuasca: An ancient sacrament for treatment of contemporary psychiatric illness? The Mental Health Clinician, 7(1), 39-45.

I believe there could be some potential pending further research, yet the usage of Ayahuasca in such contexts would need to be regulated and supervised by people that know what they are doing and with enough first aid knowledge.