Introduction

Research in neuroscience and pharmaceutical sciences continues to divulge the unique and expansive nature of traditionally used entheogens as replacements or adjuvants for Western medical practices (Dong, 2013; Zhang & Li, 2011). An entheogen is a psychoactive compound, typically from natural sources such as plants or fungi, that can be used to alter consciousness for spiritual purposes (Johnstad, 2018). Thousands of years of knowledge from traditional medicine practices outlined the dose, efficacy, and preparation of many natural medicines and have demonstrated that entheogens are a powerful tool for healing various conditions (Yuan, Ma, Ye, & Piao, 2016). There is early evidence that these substances can provide unique interventions for patients with mental health conditions that do not respond well to standard psychopharmaceuticals (Agin-Liebes et al., 2021; Bogenschutz et al., 2022).

Entheogens are most often complex biological organisms with diverse bioactive compounds. It has been argued that, if used responsibly and legally, entheogens have incredible potential to assuage human suffering and constructively contribute to the quality of life on our planet (Richards, 2015).

The complex pharmacological nature of many chronic conditions including post-traumatic stress disorder (PTSD) and other mental health disorders that involve multiple body systems requires complex therapeutic options, in which single-agent pharmaceuticals continue to fall short (DePierro, Lepow, Feder, & Yehuda, 2019; King, 2012; Krediet et al., 2020; Letheby, 2016). Altering the signaling of single neurotransmitters with pharmaceutical drugs has limitations and complex conditions may require complex natural products to pharmacologically induce changes such as those that can occur during psychotherapy (DePierro et al., 2019; Krediet et al., 2020).

Humans have used entheogens for thousands of years and their safety profile is well characterized (King, 2012). The substances' molecular complexity present unique challenges to their investigation in randomized clinical trial environments, however, human clinical studies are medically necessary to evaluate treatment patterns and response outcomes across various demographics cohorts.

More real-world data must be collected to design and evaluate these practices in clinical trial settings to help connect traditional and modern medical practices. This is a necessary step in informing United States policymakers, clinicians, and patients to explore the efficacy of entheogens for conditions most often treated with pharmaceutical medications. There has been a growing resurgence of entheogen use for therapeutic and medicinal purposes in the United States that is shifting patient and providers' perceptions in how to address health issues ranging from mental health problems to chronic pain (Agin-Liebes et al., 2021; Carhart-Harris et al., 2018, 2021; Erritzoe et al., 2018; Tupper, Wood, Yensen, & Johnson, 2015). There are estimated to be over 30 million entheogen therapy participants in the United States alone (Krebs & Johansen, 2013). However, significant barriers to access create a skewed demographic of patients who are able to utilize this therapy. Increased access through the decriminalization of substances traditionally used as entheogens at the local and state level is underway, but hindered by the vast misunderstanding and general lack of knowledge of health care practitioners when it comes to the proper usage, dosage, indications, and contraindications for the use of these plants (Winkelman, 2019). Due to the increasing availability and acceptance of these substances, regulators and treatment providers may also be called to explore safe, real-world approaches to the oversight and administration of these powerful substances. As such, it is imperative to build on the progress in leveraging real-world evidence to support the regulatory decision-making process to evaluate the safety and efficacy of medical treatments, as demonstrated by the passing of the 21st Century Cures Act (Beaulieu-Jones et al., 2020). Naturalistic use of entheogens with control over set and setting can add extrapharmacological factors not available in typical research settings that may improve the efficacy of its therapeutic use. This study describes demographic characteristics of a patient population accessing substances traditionally used as entheogens and their willingness to participate in future research.

Methods

Results

The age range of respondents was 24–73 years old, with a mean age of 45 years old. When asked to identify their “racial or ethnic background” and “gender”, 84% of our sample identified as White and 66% identified as female, respectively. Fifty-four percent of participants reported receiving “insurance from my employer or through a private company,” and 58% reported “full-time employment”. 71.6% reported educational attainment of a “4-year degree” or higher. Regarding the “average yearly household income before taxes” 52% reported $60,000 or higher with 38.3% reporting $80,000 or higher. Before proceeding, we would like to highlight that our survey population does not closely reflect the socioeconomic breakdown of the current US population, which will be addressed further in the discussion section.

The sociodemographic characteristics of the population surveyed are summarized in Table 2. The majority of participants were white (84%), female (66%), and had a 4-year degree or more education.

The majority of respondents answered that they definitely (70/84, 83.3%) or probably (10/84, 11.9%) thought this research should be done, Table 1. Most respondents were willing to participate in research that lasted longer than one year (73/84, 86.9%): 55.9% in studies lasting up to 5 years (47/84), 14.3% of respondents were willing to participate for a maximum of 2 years, and 16.1% of people willing to participate up to 1 year.

Being financially compensated for participating in the research was noted to be important for a significant portion of respondents (39%): very important for 6% (5/84); somewhat important for 33% (28/84), not very important for 33% (28/84), not important at all for 21.4% (18/84), and 6% (5/84) said would not take financial compensation for partaking in research.

When study participants were asked what level of involvement they would be willing to participate in for a more comprehensive study about entheogen use 39.8% (66/84) of respondents were willing to participate in in-person interviews, 89.3% (75/84) in remote interviews, 84.5% (71/84) in online or app-based research, 44% (37/84) allowing the research staff access to medical or pharmacy records, 63.1% (53/84) laboratory tests (blood tests, urine samples, etc.), and 9.5% of respondents noted none of the above or other.

Discussion

The study aimed to evaluate the willingness to participate in entheogen research of people who have used entheogens in the past to inform researchers on feasible designs for future studies. The anonymous online survey's results indicated that 97.9% of participants who have recently used entheogens would be willing to participate in a similar entheogen experience in the future and that 95.5% of these survey participants think that this research should be done (Table 1). A fundamental factor in designing successful future research studies is the degree of study participant involvement required for data collection. Respondents preferred participating in online or app-based surveys (69.6%) and participating in surveys that lasted longer than one year (86.9%). A greater proportion of respondents preferred remote interviews (73.5%) rather than in-person interviews (64.7%), however, there are many confounding factors that may play a role in this decision. One factor is the pay or compensation for study participants, in which 72.6% of respondents found some degree of importance to financial compensation for participating in research regarding entheogen use in naturalistic settings.

Compensating study participants for their time and effort in a research study would likely lessen the barrier to entry, as many people might be interested in participating in future research do not fit the demographic profile of the cohort surveyed in this study. The majority of respondents were white (84%), middle-aged (mean age of 45), women (66%) who were educated with at least a 4-year college degree (71.6%), employed full-time (58%), and over 90% (90.8%) of participants were making over $60,000 annually (Table 2). These data are significant because there is a confirmed positive association between income and health (Cui & Chang, 2021); employed individuals have access to various healthcare options, and formally educated individuals will have more resources to explore before experimenting with entheogen use. These demographics also do not accurately represent the United States population as a whole. For example, the national average of people with a four-year degree was almost double in this study at 71.6% of participants compared to the national average of 37.9% (Irwin et al., 2021).

Although participants were overwhelmingly open to future entheogen studies in various iterations, many indicated they were unwilling to participate where 1.) access to medical or pharmacy records and 2.) laboratory tests, including blood and urine samples, would be necessary. A consideration to minimize the potential for exclusion and increase data specificity for future research would be to create a two-item assessment for biological sex at birth and gender-identity at time of data collection.

Entheogen use for psychiatric conditions has significantly different applications and outcomes compared to pharmaceutical medications. Antidepressants and anxiolytics are prescribed and used daily for extended periods, which accumulate significant costs and burdens to the healthcare system and to the individual over time. These medications can take weeks to reach the desired therapeutic effects, and often have significant adverse effects associated with use (Saha, Torous, Kiciman, & De Choudhury, 2021). Traditionally used entheogens offer a new paradigm as they can offer patients both pharmacologically and psychologically focused treatments. If entheogen use is executed correctly for the patients, single doses can have lasting benefits of weeks to months (Dos Santos, Bouso, Rocha, Rossi, & Hallak, 2021). In addition, the use of traditional entheogenic substances should not be limited to treating illnesses, but explored in other ways that might facilitate human health, from lifestyle modification to increased interpersonal and community connection.

One component of using traditional entheogen compounds that results in unique endpoints is experiencing awe and mysticism (Barrett & Griffiths, 2018). This complex emotion can allow the users to experience spiritual growth and facilitate positive effects towards community growth, compassion, and well-being (Van Elk et al., 2022). The desire to meet these unique growth endpoints is consistent with one of the most common reasons that research participants reported willingness to participate in similar entheogen experiences in the future, which was continued spiritual growth (26.3%). The ritual nature of plant medicine in many cultures involves a component of intention associated with the ceremony of ingestion (Lowe et al., 2021; Rondilla et al, 2021). Setting intentions prior to entheogen use may help facilitate making meaning of the altered state and setting goals rather than avoiding impending issues. 68.6% of survey participants reported that with their recent entheogen use they appreciated “the degree to which you feel your intentions were met during and after your experience” noting that conservation of traditional practices and rituals is likely important for users to achieve the maximal benefits of this medicine.

Further research is needed to evaluate the traditional ceremony use involving entheogens as an acceptable practice in western societies, likely informing these practices' legality, stigmatization, and accessibility. Our data suggest that willingness to participate in research involving traditionally used entheogens is not the limiting factor for expanding the evidence base for naturalistic use. Participants in this study demonstrated an overwhelming willingness to participate in this research, belief in its importance and necessity, and that they should be compensated to participate in future studies. Further exploratory studies are needed to examine a larger and demographically diverse patient population.

Conclusion

We found that participants who have previously experienced entheogens are willing to participate in future entheogenic research, and find research involving entheogen use necessary for expanding clinical data and encouraging policy reform. Participants were willing to participate in future longitudinal studies, and felt they should be financially compensated for their involvement in the research. Future studies should be designed to include more diverse and inclusive cohorts of study participants to generate a generalizable patient population. While access to entheogens and experts in entheogenic practices are still limited, future studies investigating the efficacy of these formulations will help inform policy reform and accessibility to these traditional medicines.