Abstract

Background/aim:

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a psychoactive compound found in several plants and in high concentrations in Bufo alvarius toad venom. Synthetic, toad, and plant-sourced 5-MeO-DMT are used for spiritual and recreational purposes and may have psychotherapeutic effects. However, the use of 5-MeO-DMT is not well understood. Therefore, we examined patterns of use, motivations for consumption, subjective effects, and potential benefits and consequences associated with 5-MeO-DMT use.

Methods:

Using internet-based advertisements, 515 respondents (Mage=35.4. SD=11.7; male=79%; White/Caucasian=86%; United States resident=42%) completed a web-based survey.

Results:

Most respondents consumed 5-MeO-DMT infrequently (<once/year), for spiritual exploration, and had used less than four times in their lifetime. The majority (average of 90%) reported moderate-to-strong mystical-type experiences (Mintensity=3.64, SD=1.11; range 0–5; e.g., ineffability, timelessness, awe/amazement, experience of pure being/awareness), and relatively fewer (average of 37%) experienced very slight challenging experiences (Mintensity=0.95, SD=0.91; range 0–5; e.g., anxiousness, fear). Less than half (39%) reported repeated consumption during the same session, and very few reported drug craving/desire (8%), or legal (1%), medical (1%), or psychiatric (1%) problems related to use. Furthermore, of those who reported being diagnosed with psychiatric disorders, the majority reported improvements in symptoms following 5-MeO-DMT use, including improvements related to post-traumatic stress disorder (79%), depression (77%), anxiety (69%), and alcoholism (66%) or drug use disorder (60%).

Conclusion:

Findings suggest that 5-MeO-DMT is used infrequently, predominantly for spiritual exploration, has low potential for addiction, and might have psychotherapeutic effects. Future research should examine the safety and pharmacokinetics of 5-MeO-DMT administration in humans using rigorous experimental designs.

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Introduction

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT; also known as ‘5-MeO-DMT,’ ‘Toad,’ or ‘The God Molecule’) is a natural psychoactive indolealkylamine substance (Szabo et al., 2014; Yu, 200. 5-MeO-DMT is the most prominent psychoactive ingredient of Bufo alvarius toad venom (Lyttle et al., 1996; Weil and Davis, 1994) and is also found in a number of plants and shrubs (e.g., virola resin, peregrina seeds, Dictyoloma incanescens) (Agurell et al., 1969; Pachter et al., 1959; Torres and Repke, 2006). 5-MeO-DMT was first synthesized in 1936 (Hoshino et al., 1936), but plant extracts and other botanical 5-MeO-DMT preparations (e.g., Yopo snuff) have reportedly been used among indigenous cultures in the Americas dating back to pre-Columbian times (Ott, 2001b; Weil and Davis 1994). Although some reports also suggest that Bufo alvarius toad venom may have been used historically by indigenous cultures (Weil and Davis, 1994), little evidence supports this claim and it may be that use of toad venom is a more recent development (VICELAND, 2017).

Despite anecdotal reports on the Internet, which describe current spiritual, recreational, and therapeutic use of 5-MeO-DMT in the USA and elsewhere (Erowid, n.d.), prevalence and use characteristics are largely unknown because use of this specific substance is not included in most national epidemiological surveys (Palamar et al., 2015). Nevertheless, recent data from the USA indicate that only 1.2% of adults in the general population reported any ‘psychedelic tryptamine’ use (e.g., N, N-dimethyltryptamine, 5-methoxy-diisopropyltryptamine) between 2009 and 2013 (Palamar et al., 2015). If US adults reported 5-MeO-DMT use within this category of substances, then prevalence appears to be quite low. Additionally, estimates of the global prevalence of 5-MeO-DMT use are limited by lack of inclusion in epidemiological surveys (United Nations Office on Drugs and Crime, 2014). However, when it has been included, 5-MeO-DMT is categorized with other psychoactive tryptamines and synthetic cathinones and cannabinoids as a group of ‘novel psychoactive substances,’ thus limiting ability to estimate global prevalence (Khaled et al., 2016).

In terms of its pharmacological effects, 5-MeO-DMT is a potent, fast-acting, psychedelic substance (Ott, 2001a). In animal models, 5-MeO-DMT acts as a non-selective 5-HT agonist (Shen et al., 2011), active at both the 5-HT1A and 5-HT2A receptors (Jiang et al., 2016). 5-MeO-DMT appears to have a higher affinity for the 5-HT1A receptor subtype (Spencer et al., 1987) and also inhibits the reuptake of 5-HT (Nagai et al., 2007). This pattern of neurotransmitter binding affinity is similar to that of structurally similar psychedelic tryptamines (e.g., N,N-dimethyltryptamine, 5-methoxy-diisopropyltryptamine; Fantegrossi et al., 2006; Rabin et al., 2002; Sadzot et al., 1989; Winter, 2009), and somewhat different from tryptamines with stronger affinity for the 5-HT2 receptor family (e.g., O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine or ‘psilocybin’; McKenna et al., 1990). 5-MeO-DMT is metabolized through oxidative deamination by MAO-A, and its active metabolite, bufotenine, has been shown to be a potent ligand of 5-HT2A receptors (Roth et al., 1997; Shen et al., 2010), although it is unknown whether this metabolite has any discernable psychoactive effect.

Published studies of human self-experiments describe a range of subjective effects of 5-MeO-DMT that vary depending on the dose and route of administration (Ott, 2001a; Shulgin and Shulgin, 1997). Such effects include auditory, visual, and time perception distortions and emotional experiences, as well as memory impairment, with peak effects between 35 and 40 minutes after insufflation or within seconds-to-minutes when smoked (Ott, 2001a; Shulgin and Shulgin, 1997). Furthermore, current unpublished reports of 5-MeO-DMT use describe inhalation (e.g., smoking or vaporizing) as a common means of consumption with initial onset of effects within 60 seconds and peak total duration of effect between 5 and 20 minutes (Erowid, n.d.). Although there is limited evidence about the scope of 5-MeO-DMT use, safety, or its effects, the Drug Enforcement Administration nonetheless placed 5-MeO-DMT in Schedule I of the US Controlled Substances Act in 2011 (Drug Enforcement Administration, Department of Justice, 2010), in large part due to being similar in molecular structure to N,N-dimethyltryptamine and evidence that it was four to five times more potent (Ott, 2001a). Although the legal status of 5-MeO-DMT varies by country, most primarily English-speaking countries have placed restrictions on its use (e.g., Misuse of Drugs Act 1971).

Despite the fact that 5-MeO-DMT use is illegal in the USA and elsewhere, anecdotal reports indicate that consumption continues in a variety of underground ceremonial settings as a form of spiritual exploration (Psychedelic Times, 2016). Additionally, 5-MeO-DMT use continues among individuals who might purchase 5-MeO-DMT sold on the Internet or from other sources, extract 5-MeO-DMT from natural sources, for the purpose of spiritual exploration or recreation (Reddit, 2011). There is also anecdotal and empirical evidence that some people use 5-MeO-DMT for the purpose of treating psychiatric conditions, including symptoms related to depression, anxiety, post-traumatic stress disorder, and problematic substance use, either by self-administration (Psychedelic Times, 2016) or through visiting treatment facilities that provides 5-MeO-DMT in locations where the substance is unregulated (Lancelotta, 2017; Thoricatha, 2015).

Although the basic pharmacology of 5-MeO-DMT has been examined in animal models (e.g., Jiang et al., 2016; Nagai et al., 2007; Shen et al., 2011; Spencer et al., 1987), and the subjective effects have been published in case reports of self-administration (Ott, 2001a; Shulgin and Shulgin, 1997) and provided in anecdotal reports posted on the Internet (Erowid, n.d.), we could find no epidemiological studies examining the patterns of use, subjective effects, motivations for use, or potential medical and psychiatric harms/benefits of consuming 5-MeO-DMT. The relative absence of information about the scope of 5-MeO-DMT use limits understanding of the safety and risk profile of this substance, which is needed to inform the design of future clinical trials. Therefore, the primary aim of this study is to examine the epidemiology of 5-MeO-DMT use among English-speaking adults who have consumed 5-MeO-DMT at least once in their lifetime. As a secondary aim, we examined whether there were changes in medical and psychiatric functioning following 5-MeO-DMT use. Aim 3 involved an examination of differences in the subjective effects and the patterns and motivations for use as a function of the type of 5-MeO-DMT consumed (i.e., synthetic vs toad venom vs plant extracts/yopo snuff).

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Discussion

This study appears to be the first investigation of the epidemiology of 5-MeO-DMT use. Despite some statistically significant differences in the patterns of use and subjective effects as a function of the type of 5-MeO-DMT used (i.e., synthetic, toad venom, plant extract/yopo), these data suggest that most people who consume 5-MeO-DMT use a synthetic source and vaporization/smoking as the route of administration. The majority of the sample used 5-MeO-DMT for the purpose of spiritual exploration, and used infrequently, consuming 5-MeO-DMT less than four times in their lifetime. Similar to other hallucinogens (McCabe et al., 2017), there were also very low rates of addiction-related symptoms including craving/desire or legal consequences following 5-MeO-DMT use, as well as low rates of repeated consumption in the same session and psychiatric or medical complications related to use. Similar to people who use other tryptamines (Barrett et al., 2016; Griffiths et al., 2006; MacLean et al., 2012), most respondents also reported a variety of moderate-to-strong mystical experiences (e.g., awe or awesomeness, amazement, loss of time and space, and difficulty putting experience into words) and relatively fewer experienced very slight challenging experiences (e.g., fear, anxiousness).

Furthermore, large proportions of respondents in this study reported that 5-MeO-DMT use contributed to improvements in symptoms related to several psychiatric conditions, including anxiety, depression, substance use problems, and post-traumatic stress disorder, suggesting that 5-MeO-DMT may have psychotherapeutic effects under optimal conditions. These positive self-reported psychotherapeutic effects across a variety of psychiatric conditions are consistent with anecdotal reports on the Internet (Psychedelic Times, 2016), pharmacological effects in animals (Jiang et al., 2016; Nagai et al., 2007; Shen et al., 2011; Spencer et al., 1987), findings from population-based surveys (Krebs and Johansen, 2013), and findings with related psychoactive tryptamines (e.g., psilocybin) in individuals with problems associated with addiction, anxiety, or depression (for a review see Johnson and Griffiths, 2017).

Such therapeutic potential of tryptamines appears to be due, at least in part, to their ability to occasion mystical experiences, which has been demonstrated to have lasting beneficial effects (Garcia-Romeu et al., 2015). However, this study is cross-sectional, lacked a validated measure of psychiatric symptoms and assessment of prior psychiatric treatment, and included many polysubstance users, which limits any causal inferences in the relation between the use of 5-MeO-DMT and an improvement in symptoms. Thus, the associations of psychiatric benefits remain observational. Nevertheless, that 5-MeO-DMT appears to have a safety/risk profile similar to that of tryptamines, producing moderate-to-strong mystical, and very slight challenging (e.g., anxiety, fear), experiences at a similar intensity as moderate to high-dose psilocybin administered in laboratory settings (Barsuglia et al., 2017; Griffiths et al., 2006), and that the duration of effect is substantially shorter (20-40 minutes compared to 4-6 hours; Erowid, n.d.; Ott, 2001a), suggests that it might be worth examining the possibility of 5-MeO-DMT administration as an adjunct to psychotherapy. These efforts may contribute to the scalability of psychedelic-assisted psychotherapy in that they could substantially reduce the costs associated with treatment if and when psychedelic-assisted psychotherapy is made available to the public.

Limitations of this study include the cross-sectional nature of the data, which precludes any interpretation of causality with regard to the short- or long-term effects of 5-MeO-DMT consumption, and the self-report of 5-MeO-DMT use (e.g., dose, frequency) and related experiences, which are subject to retrospective recall bias and subjective estimates. Additionally, the sample was recruited using Internet advertisements and thus is subject to selection bias. Although there are several practical and methodological advantages to using web-based recruitment (King et al., 2014), and evidence supports the validity and reliability of anonymous reports of substance use and use-related consequences provided via the Internet (Ramo et al., 2012), we cannot rule out the likelihood that people who use 5-MeO-DMT but who did not access the sites from which we recruited respondents, or those who decided not to participate in online research, may have different patterns of use, subjective effects, and other experiences related to their 5-MeO-DMT use.

The study is also limited by the use of a donation to a psychedelic research organization, instead of providing monetary compensation to encourage participation, which may have created unique volunteer biases or otherwise influenced the composition of the sample. Similar to other web-based studies of people who use licit and illicit substances (Ashrafioun et al., 2016; Davis and Rosenberg, 2016), the sample was comprised mostly of white, heterosexual men, which could reflect a limitation in recruitment method, or it could be that the population of people who use 5-MeO-DMT is similarly comprised. Regardless, future studies should attempt to recruit samples comprised of individuals that identify as being from a diverse background, perhaps specifically by recruiting non-English-speaking individuals. This study also lacks validated measures of alcohol and other drug use and medical/psychiatric functioning, thus, more research is needed to determine whether the results from this study are generalizable to the population of people who consume 5-MeO-DMT.

To the extent that these results are generalizable to the international English-speaking population of people who use 5-MeO-DMT, findings highlight the infrequent pattern of use and the moderate-to-strong subjective mystical and very slight challenging effects of 5-MeO-DMT consumption. Similar to other psychedelic tryptamines, 5-MeO-DMT also appears to have a relatively good safety profile of use in spiritual and recreational settings, with little likelihood of producing an addictive or problematic syndrome of consumption in most users. This is especially evident when compared with the prevalence of past-year and lifetime medical, psychiatric, social, and legal problems associated with drugs in other classes (e.g., alcohol, cannabis, cocaine; McCabe et al., 2017). Furthermore, these data suggest that there may be psychotherapeutic effects associated with 5-MeO-DMT consumption, including catalyzing transformative mystical experiences and self-reported reductions in symptoms related to depression, anxiety, substance use problems, and post-traumatic stress disorder. However, there is at least one report of a fatal intoxication associated with ayahuasca containing 5-MeO-DMT and other substances (Sklerov et al., 2005), and there have been no published laboratory studies examining the safety of synthetic 5-MeO-DMT administration in humans, thus limiting understanding of the risk/benefits of consumption. Therefore, we recommend that future research examine the safety and pharmacokinetics of 5-MeO-DMT administration in humans using rigorous experimental designs.