Psychedelics and Ayahuasca: What Modern Science Says

In recent years, modern science has rediscovered the therapeutic potential of psychedelics. Substances that, since the 1970s, had been relegated to cultural contexts or controversial debates about drugs are now being investigated in leading universities and research centers worldwide. Among them, ayahuasca stands out for its unique features: roots in ancestral knowledge, a multi-target pharmacological composition, and promising results in both clinical trials and real-world data.

This article explores how contemporary science has studied ayahuasca, what evidence has already been consolidated, what risks and challenges remain, and how this traditional Amazonian medicine can inspire the future of psychedelic-assisted therapies.

Psychedelics in Contemporary Science

The most well-known psychedelics, such as psilocybin, LSD, and DMT, share the ability to activate serotonergic receptors, mainly 5-HT2A. This interaction produces profound changes in perception, cognition, and emotion, while also generating functional reorganization effects in the brain. Recent models, such as the REBUS theory (Relaxed Beliefs Under Psychedelics), explain how psychedelics reduce rigid mental patterns, allowing greater psychological flexibility.

Clinical studies show that this plasticity can be crucial in conditions such as treatment-resistant depression, anxiety, and substance use disorders. In this scenario, ayahuasca stands out for already having been the subject of controlled human trials, in addition to decades of documented ritual and observational use.

What is Ayahuasca

Ayahuasca is an ancestral medicine, prepared as a brew from two Amazonian plants: the vine Banisteriopsis caapi and the leaves of Psychotria viridis. The vine contains β-carbolines (harmine, harmaline, and tetrahydroharmine), which act as reversible inhibitors of the MAO-A enzyme. This allows dimethyltryptamine (DMT), present in the leaves, to become orally active, reach the brain, and produce its psychedelic effects.

This unique combination makes ayahuasca a singular tool for science. Unlike other psychedelics, which are administered as isolated synthetic doses, the medicine preserves the interaction of multiple compounds, which may enhance therapeutic effects and influence clinical tolerability.

Mechanisms of Action in the Brain

Neuroimaging studies show that ayahuasca reduces the activity of the Default Mode Network, a brain network associated with self-referential thinking and rumination — processes that are often exacerbated in depression. The effect is comparable to what has been observed with psilocybin and LSD.

In addition, studies suggest an increase in neuroplasticity, with greater expression of genes related to neural growth. These findings help explain reports of transformative experiences, a sense of “mental renewal,” and greater emotional openness after using the medicine.

Clinical Evidence with Ayahuasca

One of the most relevant clinical trials, conducted in Brazil, demonstrated that a single dose of ayahuasca significantly and rapidly reduced symptoms of treatment-resistant depression, with effects noticeable within just 24 hours and lasting up to three weeks in some patients.

Observational research also points to improvements in mental health indicators, reduced addictive behaviors, and increased subjective well-being in groups that use the medicine in ritual contexts. While promising, these findings reinforce the need for more controlled, multicenter trials with long-term follow-up.

Comparison with Other Psychedelics

While most large-scale advanced clinical trials focus on psilocybin, ayahuasca has already shown consistent results in smaller and observational studies. The main difference is that, while psilocybin and LSD are isolated compounds, ayahuasca involves multiple alkaloids interacting together.

This feature makes research protocols more complex, but it also opens the door for unique discoveries — especially regarding the impact of β-carbolines on neurotransmitters beyond serotonin.

Safety, Risks, and Contraindications

Although considered safe in controlled environments, ayahuasca can cause nausea, vomiting, and transient changes in blood pressure and heart rate. Because it contains MAO inhibitors, the medicine requires caution for people taking antidepressants (such as SSRIs) or with cardiac conditions.

It is also not recommended for individuals with a history of psychosis or severe personality disorders, as it may trigger acute symptoms. For this reason, medical screening, proper monitoring, and a supportive environment — including preparation, professional guidance, and post-session integration — are essential.

Set, Setting, and Models of Care

The experience with ayahuasca depends not only on the substance but also on the context in which it is administered. Research reinforces the importance of psychological preparation, the presence of trained professionals during the session, and integration afterward.

👉 Integration refers to the therapeutic follow-up that helps process and make sense of the experiences, turning insights into lasting benefits for mental health.

This care increases therapeutic effectiveness, helps consolidate results, and minimizes the risks of challenging experiences. Although hospital and ritual uses differ in many respects, both demonstrate physiological, psychological, and emotional benefits of this medicine.

Regulatory and Ethical Aspects

In Brazil, ayahuasca has been regulated for religious use since the 1980s, but clinical research and pharmaceutical development are still evolving. Ethical issues such as the misappropriation of traditional knowledge, the need for partnerships with Indigenous Peoples, and fair benefit-sharing are central to this debate.

Modern science seeks ways to transform ayahuasca into standardized and regulated formulations without losing sight of its cultural and historical importance. Ayamed is always seeking partnerships with Indigenous entities holding traditional knowledge, to participate in projects and develop a fair and innovative benefit-sharing model.

Standardization and Pharmaceutical Development

One of the greatest scientific challenges is ensuring the standardization of ayahuasca. Variability in the concentration of DMT and β-carbolines between different preparations hinders replicability in clinical research.

Pharmaceutical development must establish parameters of purity, dosage, and chemical stability so that the medicine can be transformed into safe drugs recognized by regulatory agencies. This process is essential for ayahuasca to advance from the realm of tradition into evidence-based medicine.

Future Perspectives

The future of ayahuasca in modern medicine depends on robust clinical trials, integration with mental health models, and ethical collaboration with traditional communities. The trend is that the coming years will bring more evidence about its effectiveness in depression, anxiety, and substance use disorders, as well as greater clarity about biological mechanisms and safety protocols.

Conclusion and Ayamed’s Vision

Ayahuasca represents one of the most fascinating meeting points between ancestral knowledge and modern science. Early studies have already shown real benefits for mental health, while also highlighting the need for methodological rigor, pharmaceutical standardization, and ethical responsibility.

At Ayamed, we believe the future of medicine lies in balancing ancestral roots, modern science, and responsible innovation. That is why we are always seeking partnerships that ensure:- Recognition and respect for Indigenous knowledge- Free, prior, and informed consultation with fair benefit-sharing- Sustainable production in dedicated, protected planting areas, avoiding predatory extraction- Accessibility of the medicine through public health systems, benefiting those most in need - Development of safe, effective formulations with fewer side effects

Our commitment is to transform this potential into safe, regulated, and sustainable natural medicines, while recognizing and rewarding the communities that have safeguarded this wisdom for centuries.

👉 Learn more about how we are developing innovative solutions inspired by ayahuasca: contact Ayamed.