As Scientific Evidence Base for Safety, Efficacy of Ayahuasca Use Grows, a DEA Report Asserts a Position Countering the Data

Following an increase in government seizures of ayahuasca, an Indigenous religious organization requested government records that led to these seizures. The DEA responded by sending a single report condemning use of the drug.

With ongoing legislation granting recreational and medical access to marijuana across the United States and a growing scientific evidence base for the safety and efficacy of drugs such as psilocybin, MDMA, and ayahuasca to treat mental health disorders, psychedelic medicines have captured the attention of the health care field, the US government, and the public at an accelerated rate. However, while psychedelic medicine may be rooting itself further into popular discourse, the US Drug Enforcement Administration (DEA) clarified in a recent report titled “Ayahuasca: Risks to Public Health and Safety” that they remain steadfast in their positioning around the Schedule I status of ayahuasca (1).

Ayahuasca is a traditional Amazonian beverage that is used in several ayahuasca religions that originated in Brazil and have spread globally. It is most commonly prepared by a decoction of two plants from the Amazon region: Psychotria viridis, containing the psychoactive alkaloid N,N-dimethyltryptamine (DMT), and Banisteriopsis caapi, which contains reversible monoamine oxidase inhibitors such as harmine, harmaline, and tetrahydroharmine. More recently, ayahuasca, and DMT in particular, have caught the attention of the pharmaceutical industry in the development of the next wave of clinical therapeutics for mental health and neurological disorders, such as for treatment-resistant depression and addiction. Early-phase trials have shown promising results around the potential of the drug to treat these disorders safely and effectively (2).

The DEA report on ayahuasca’s risks, which was published in July 2020, was sent on February 2023 to the legal team representing the Indigenous religious group the Church of the Eagle and the Condor (CEC). Two years prior, the CEC, in conjunction with Chacruna Institute for Psychedelic Plant Medicines (Chacruna), had submitted two Freedom of Information Act (FOIA) requests to the DEA and the Department of Justice requesting access to all records pertaining to their 2020 seizures of ayahuasca.1-3 Because of the significant increase in ayahuasca border seizures in 2020, lawyers working on behalf of CEC and Chacruna had simultaneously filed the FOIA requests to US Customs Border Patrol (CBP) and the DEA in 2021 (2,3).

In February 2021, the CEC and Chacruna had established the Ayahuasca Religious Freedom Initiative (Initiative) to take steps forward in a two-part process: Firstly, the Initiative sought to open government records disclosures to understand how the CBP and DEA view and handle ayahuasca; and secondly, the Initiative looked to pursue the legal recognition of the CEC as a legitimate ayahuasca church founded in the United States based on Indigenous beliefs, which is a model that has been implemented for ayahuasca churches abroad, such as in Brazil (3).

To better understand whether the government had a specific policy that had led to the increase in ayahuasca seizures in 2020, lawyers working on behalf of the CEC and Chacruna in the first action as a part of the Initiative submitted both FOIA requests asking for the following information (3):

1. The total number of seizures of ayahuasca by CBP or other federal government agencies in 2020
2. All documents that address interceptions, seizures, disposition, or destruction of ayahuasca in 2020
3. All documents that address CBP notification to, or contact with, persons suspected of importing ayahuasca into the United States in 2020
4. All documents that address CBP protocols in 2020 for interception or seizure of ayahuasca
5. All documents, communications, procedures, policies, protocols, matrices, or decision trees relating to whom CBP determines shall receive the agencies’ “official notice” triggering the availability of relief under 19 CFR §171 et seq
6. All communications in 2020 to or from the CBP, US Department of Justice, US Department of Homeland Security, US Postal Service, FDA, DEA, or state or local law enforcement that deal with or address the interception, destruction, or seizure of ayahuasca in 2020

Chacruna’s Response

In June 2023, Chacruna researchers published a response to the DEA report titled “The DEA Report on Ayahuasca Risks: “Science” in Service of Prohibition?” In this article, the authors challenge a number of claims made in the DEA report, highlighting omissions of published pre-clinical and clinical data and misinterpretations of existing scientific data. The authors note that, in their view, the DEA report downplays the existence of data showing the safety profile and therapeutic potential of ayahuasca while overemphasizing the risks (2).

“The impact of the DEA is highly negative, given that the classification of ayahuasca as a controlled substance hinders the possibilities of research regarding its therapeutic potential,” said Chacruna study co-author Henrique Antunes, PhD, ayahuasca community coordinator at Chacruna. “By stating that the use of ayahuasca is a potential risk to public health, the DEA takes the opposite direction of the current research and the available knowledge.”

The first randomized, controlled trial (NCT02914769) investigating the antidepressant effects of ayahuasca was published in 2019. In the parallel-arm, double-blind randomized placebo-controlled trial, investigators enrolled 29 patients with treatment-resistant depression. The investigators assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale and the Hamilton Depression Rating scale at baseline, and at days 1, 2, and 7 after dosing. Overall, the study authors noted that the clinical trial provided new evidence supporting the safety and therapeutic value of ayahuasca to treat depression, when dosed in an appropriate setting (2).

Kelan Thomas, PharmD, MS, an editor at the Chacruna Chronicles, noted that the DEA report makes no mention of these published data from 2019, despite the DEA report being published in 2020.

“The report completely omitted any reference to the first ayahuasca randomized controlled trial that suggested good tolerability and potential efficacy for depression,” said Thomas. “The DEA report evidence review was clearly not systematic and seemed to only use references that reinforced a negative bias.”

Notably, the DEA report cited an animal toxicology extrapolation model that estimated that the LD50 for oral DMT in humans would be 8 mg/kg−1 for its evidence base as to the potential harm cause by consumption of ayahuasca (1). However, the Chacruna authors note the dosage used for this extrapolation model is more than 20 times the dose of oral DMT (approximately 27 mg) that is typical of traditional ayahuasca consumption practices. Further, the investigator who had developed the extrapolation model noted that “simple extrapolation of DMT lethality data from mice to humans is obviously untenable,” and that “the dependence potential of oral DMT and the risk of sustained psychological disturbance are minimal," (2).

In one article cited by the Chacruna authors in their response to the DEA report, study investigators estimated that an extrapolated oral DMT lethal dose in humans would be 2 g, which is close to 75 times greater than the typical 27 mg DMT dose taken in ayahuasca ceremonies. Further, the oral ayahuasca safety ratio between the usual effective dose and the usual lethal dose is around 50, which was substantially higher than the safety ratio of other commonly used legal substances, such as alcohol (10), dextromethorphan (10), and codeine (20) (2).

Additional pre-clinical evidence from rodent and primate studies into ayahuasca's therapeutic potential have indicated the antidepressant and anti-addictive potential of ayahuasca. Further, new evidence has demonstrated that ayahuasca may provide prophylactic action that buffers the experience of depressive symptoms and cortisol changes in a non-human primate animal model of depression. Additionally, there have been data published that indicate that DMT may help to regulate adult neurogenesis, both in vivo and in vitro, as well as help modulate immune response (2).

Indigenous Literature

Notably, the DEA report does not take into consideration the perspective and experience of the Indigenous peoples who have been using ayahuasca for centuries, according to the Chacruna authors. Before the pharmaceutical industry began to assess the drug’s potential benefit, Indigenous peoples were aware of its potential. To this end, Chacruna authors note there is rich anthropological and sociological literature on the use of ayahuasca by and among these peoples. This literature is not cited or considered in the DEA report. Further, the Chacruna authors explain that the DEA report ignores hundreds of accounts of ayahuasca’s benefits present in this literature and instead focuses on negative anecdotal cases for the basis of its positioning (2).

“It is not a matter of opposing traditional healing systems and Western medicine, but of recognizing the uniqueness and importance of the former,” said lead author Bia Labate, PhD, executive director of Chacruna.“ To develop research and policy on ayahuasca, it is crucial to consider the gathered knowledge and the experience of the groups that have been taking ayahuasca for centuries.”

DEA Report on Adverse Events From Ayahuasca

The DEA makes a point to highlight adverse event (AEs) associated with ayahuasca use, such as hallucination and vomiting.

“The clinical effects most reported included hallucinations, agitation, tachycardia, confusion, hypertension, mydriasis, and vomiting,” the DEA report authors write. “The most severe effects … included seizures, respiratory arrest, and cardiac arrest.”

However, Chacruna authors noted that, for Indigenous communities that practice safe ayahuasca consumption, hallucinations and vomiting are not, in fact, adverse. For these individuals, hallucinations have the potential to beget positive emotional breakthroughs and vomiting has the potential to cleanse (or purge) their bodies for beneficial ends, according to the Chacruna authors. Additionally, traditional ayahuasca consumption practices are mediated by shamans and religious leaders in controlled environments. As a part of the ceremony, it is the shaman’s duty to reliably source ayahuasca, screen ceremony participants, and support those who have rare but severe AEs, explain the Chacruna authors (2).

Further, like most drugs, ayahuasca is associated with certain risks in certain contexts. It poses a higher risk to public safety when used among individuals with histories of psychosis and without social support during ayahuasca consumption. It can also be dangerous if taken in an unstructured and unsupervised environment.

But in a controlled setting, ayahuasca has a tolerable safety profile, the Chacruna authors note. Moreover, within a religious context, ayahuasca is taken in a structured and supervised setting as a part of an ayahuasca ceremony.

“It is important to understand that we are dealing with traditions that do not abide by the concepts of Western healing, and that have their own logic and value,” Labate said. “These practices must be recognized on their own terms.”

To broaden the scope of this argument to public health at large, alcohol, for example, is a legalized drug with psychoactive potential; its consumption can be a risk to the user and to public health. However, Chacruna authors note that the difference between alcohol and ayahuasca as a public health risk is an a priori negative bias founded on misconceptions and westernized ideology. One of the primary ways the DEA could combat this would be by assessing all evidence and data published in rigorous clinical studies.

In Brazil, the case for ayahuasca rights started in 1985 with the Federal Council of Narcotics (CONFEN) resolution, explained Chacruna authors. The CONFEN resolution then allowed researchers to study the use of ayahuasca in a religious context, which eventually led to the creation of guidelines in the 2000s that supported ayahuasca use in religious practice.

However, according to Martha Hartney, JD, of the Chacruna Council for the Protection of Sacred Plants, the DEA is not likely to share this open-mindedness with Brazilian legislators anytime soon. Instead, the DEA’s current criminalization of ayahuasca is aligned with an early US prohibitionist paradigm (1,2).

“Criminalizing drug use gives the DEA its raison d’être,” Hartney said. “Ideally, we should have Congress intervene and pass legislation protecting ayahuasca use, which has proven to be able to heal spirituality and psychologically and is an integral part of many legitimate traditions.”

Notably, once the FDA approves a drug for medical use, the DEA will be forced to reschedule the drug. Until that time, the DEA does accept petitions to reschedule, but has never granted one.

“Congress could also legislate the descheduling, but hasn't done so with cannabis, even after 25 years of legalization at the state level,” said Sean McAllister, JD, a Chacruna board member.

According to Labate, until the time when FDA approval is granted and ayahuasca use becomes descheduled from its current Schedule I status, there will exist ongoing limitations and difficulties for medical investigators looking to understand the potential role of the drug in patients facing debilitating mental health disorders.

“There is a lot of stigma [around ayahuasca use],” Labate said. “Unfortunately, these still have influence and resist progress.”

Editor’s Note: To learn more, join Chacruna’s live forum discussing the CEC legal trial set for 2024.

References

1. Ayahuasca: Risks to Public Health and Safety. DEA. July 2020. Accessed Aug 20, 2023. https://chacruna.net/wp-content/uploads/2023/03/2023_3_2_ChacrunaCopy_Ayahuasca-Risks-to-Public-Health-and-Safety-PDF.pdf
2. Labate B, Ermakova A, Sloshower J, et al. The DEA Report on Ayahuasca Risks: “Science” in Service of Prohibition? Journ of Psych Stud. 2023. doi:10.1556/2054.2023.00279
3. McAllister S. Ayahuasca FOIA Requests Reveal Increased Ayahuasca Seizures, Lack of Due Process and Government Secrecy. Chacruna. June 25, 2021. Accessed August 22, 2023. https://chacruna.net/ayahusca_religious_freedom_information_act_church_of_the_eagle_and_condor/

Read the original Pharmacy Times article by Erin Hunter and Alana Hippensteele here.