Overcoming epistemic injustices in the biomedical study of ayahuasca: Towards ethical and sustainable regulation

Ayahuasca refers both to the Amazonian vine Banisteriopsis caapi and to a family of traditional brews prepared across the upper Amazon; preparations often include psychotria species or Diplopterys cabrerana and may involve dozens of other plant additives. Schenberg and colleagues describe considerable biocultural diversity in plant varieties, ritual diets, songs, and cosmologies among groups such as the Huni Kuin, emphasising that different vine and admixture varieties, ritual practices and songs shape the phenomenology of ayahuasca experiences and the meanings ascribed to them. The introduction frames ayahuasca as a complex ethnobotanical and ritual phenomenon rather than a single molecular product. Against that background, the paper interrogates how contemporary biomedical research and regulation have approached ayahuasca, raising the question of whether scientific epistemic authority has been accorded in ways that marginalise indigenous knowledges and practices. The authors set out to document regulatory and scientific developments, to identify forms and consequences of epistemic injustice, and to propose pathways for ethically and ecologically sustainable regulation that respect indigenous rights and knowledge systems.

Schenberg and colleagues review the regulatory landscape and biomedical literature concerning ayahuasca and outline several interrelated empirical and legal findings. On regulation, they report that international conventions since 1971 placed DMT under control but exempted traditional brews; national approaches differ. The United States Supreme Court permitted religious ayahuasca use for one church in 2006. Colombia and Peru have enacted policies recognising cultural aspects of yagé/ayahuasca—Peru declared traditional uses and íkaros as national cultural heritage—while Brazil formalised responsible religious use after a 1985 prohibition and by a 2010 National Drug Policy Council resolution, which nonetheless postponed therapeutic authorisation pending biomedical proof and did not incorporate prior indigenous consent obligations under ILO Convention 169. Regarding biomedical research, the authors trace a programme that began in the late 1990s and progressed from small open-label trials to at least one double-blind clinical trial for depression. They note three early studies for depression: two open-label trials (n=6 and n=17) and a randomized double-blind study (n=29). Biomedical investigators pursued standardisation (freeze-drying and encapsulation) and quantified key alkaloids (DMT and beta-carbolines) to align ayahuasca with pharmacological research norms. Schenberg and colleagues identify several substantive problems emerging from the biomedical approach. First, attempts to standardise have been incomplete: concentrations of principal compounds vary markedly across preparations, and safe dose ranges (for example for DMT) have not been established. Second, reductionist focus on single molecules has produced inconsistent molecular explanations across trials (MAO-A inhibition, 5-HT receptor agonism, BDNF and other targets), while largely excluding patients' qualitative reports. Third, double-blind designs are problematic for psychoactive brews: subjective effects and emesis can unblind participants and staff. In one double-blind trial the authors report that about 72% of the placebo group correctly guessed they had placebo; comparable unblinding rates are cited from psilocybin (therapists' correct guesses 97%) and MDMA (reported estimates around 59% to 100%). Fourth, emesis—which occurs in roughly 50% or more of participants in biomedical studies—is variably treated as an adverse event, sometimes excluded from analysis, although indigenous traditions regard vomiting as a meaningful cleansing process. Biomedical responses (e.g. consideration of antiemetics) raise pharmacological safety questions and may ignore potential adaptive functions of emesis. The review also documents legal and commercial pressures: historical patent disputes over B. caapi in the USA, ongoing start-up activity and early clinical development of DMT-based therapies, and concerns about bioprospecting without adequate benefit-sharing. The authors highlight ecological and social risks: large-scale medicalisation without indigenous consent or sustainable management could threaten plant resources and Amazonian ecological resilience.

Schenberg and colleagues interpret these findings as evidence of epistemic injustice: biomedical epistemic authority has displaced indigenous testimony and interpretive frameworks, with practical consequences for culture, law, safety, and resource stewardship. They characterise testimonial injustice where indigenous knowledge was devalued and hermeneutical injustice where indigenous interpretations (for example that emesis is therapeutic) were not taken seriously, and they argue these injustices also undermine the epistemic completeness and practical safety of biomedical research. To address these problems, the authors propose a shift in research strategy and regulation. Research should move beyond the clinic into community contexts in partnership with indigenous groups, combining ethnographic and qualitative methods with modern, minimally invasive biomedical measures (dried-blood-spot pharmacokinetics, mobile EEG, wearable vital-sign monitoring, environmental sampling and omics). Such mixed-data approaches would allow correlational and dose–response analyses linking plasma alkaloid profiles, physiological measures, brain signals and richly recorded subjective reports. The authors also recommend formally assessing blinding integrity in psychedelic trials (asking participants and staff about treatment guesses and confidence), broadening outcomes beyond self-report to include less placebo-sensitive measures, and respecting ritual and dietary contexts that may affect outcomes via microbiome or other pathways. On policy and ethical governance, the review emphasises legal tools and community-led mechanisms to protect indigenous rights and biocultural heritage. Options discussed include national cultural heritage designations (already used in Peru), communal protocols and prior, free, and informed consent procedures for access to genetic resources and traditional knowledge, benefit-sharing agreements under national biodiversity statutes and the UN Convention on Biological Diversity, creation of Indigenous Ethical Councils on Traditional Medicine, ethnobotanical centres to co-produce knowledge, and integration of traditional medicine in indigenous health services. The authors caution that simple monetary compensation or researcher-approved projects cannot redress epistemic harms and stress the importance of indigenous self-determination in crafting rules for cultivation, circulation and knowledge transmission. Finally, the authors situate ayahuasca within a broader pattern affecting other psychedelics (for example psilocybin) and warn of ecological risks if medical demand leads to extractive practices or unsustainable cultivation. They acknowledge that proposals to take biomedical science into the forest can be framed as medicalising shamanism, but present such engagement as a possible intercultural dialogue rather than unilateral appropriation.

Schenberg and colleagues conclude that ethical and sustainable regulation of ayahuasca requires centring indigenous rights, customary rules and co-designed research. They recommend legal recognition of biocultural heritage, mandatory prior, free, and informed consent and benefit-sharing for research and commercial development, community governance mechanisms (such as Indigenous Ethical Councils and communal protocols), and research programmes that combine indigenous knowledge with multidimensional biomedical methods conducted in partnership with source communities. Properly implemented, these measures could protect indigenous cultures and local ecologies while enabling responsible investigation of ayahuasca's therapeutic potential.