The epidemiology of 5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and reasons for consumption
Alan K. Davis, Joseph P. Barsuglia, Rafael Lancelotta, Robert M. Grant, and Elise Renn
Journal of Psychopharmacology, 2018, 32, (7), 779–792.
doi : 10.1177/0269881118769063
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.
Method : 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.
Keywords : Epidemiology; tryptamines; 5-MeO-DMT; 5-Methoxy-N; N-Dimethyltryptamine
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 (Yu, 2008; Szabo et al., 2014). 5-MeO-DMT is the most prominent psychoactive ingredient of Bufo alvarius toad venom (Weil and Davis 1994; Lyttle et al., 1996) 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 (Weil and Davis 1994; Ott, 2001). 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 United States (US) and elsewhere (Erowid, 2017), 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 US indicates 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 (UNODC, 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, 1999). 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; Winter; 2009; Sadzot et al., 1989; Fantegrossi et al., 2006; Rabin et al., 2002), 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, Repke, & Peroutka, 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 (Shen et al., 2010; Roth et al., 1997), 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, 2001; Shulgin & Shulgin, 1997). Such effects include auditory, visual, and time perception distortions, emotional experiences, as well as memory impairment, with peak effects between 35–40 minutes after insufflation or within seconds-to-minutes when smoked (Ott, 2001; Shulgin & 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, 2017). 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 (Federal Register, 2010), in large part due to being similar in molecular structure to N,N-dimethyltryptamine and evidence that it was 4 to 5 times more potent (Ott, 1999). 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 US 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., Shen et al., 2011; Jiang et al., 2016; Spencer et al., 1987; Nagai et al., 2007), and the subjective effects have been published in a case report of self-administration (Ott, 1999; Shulgin & Shulgin, 1997) and provided in anecdotal reports posted on the Internet (Erowid, 2017), 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).