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).

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 ).

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 ).

We began by conducting frequency counts and descriptive analyses of demographic characteristics, patterns of using 5-MeO-DMT, motivations for consumption, subjective mystical and challenging effects, and medical/psychiatric harms/benefits variables. Next, using a series of chi-square and oneway ANOVAs, we examined differences in demographic characteristics, subjective mystical and challenging effects, patterns of use, and motives for consumption as a function of the type of 5-MeO-DMT that respondents reported they had the most experience with (i.e., synthetic vs toad venom vs plant extract/yopo). Because of the limitations of using a Bonferroni-corrected alpha (e.g., testing of an irrelevant null hypothesis (study-wide error rate) and increasing the likelihood of Type II error in a large sample; Perneger, 1998 ), an alpha of 0.05 was used to determine the significance of statistical tests. All analyses were conducted using SPSS v.24 (IBM Corp, New York, NY, USA).

We included the Challenging Experiences Questionnaire (CEQ), a 26-item self-report measure developed to assess the intensity of challenging experiences one might have after taking a hallucinogen ( Barrett et al., 2016 ). Respondents were asked to reflect on the first experience they had with 5-MeO-DMT and to describe the intensity with which they experienced each challenging psychological or physical experience using a 6-point scale from ‘None; not at all’ to ‘Extreme.’ Previous research ( Barrett et al., 2016 ) has found that the measure produces seven subscales: (1) Fear; (2) Grief; (3) Physical distress; (4) Insanity; (5) Isolation; (6) Death; and (7) Paranoia. We also calculated a CEQ total scale score to rate the overall intensity of challenging experiences. Internal consistency of the total scale and each subscale in the current sample was: Total Scale (Cronbach’s alpha = 0.94), Fear (Cronbach’s alpha = 0.93), Grief (Cronbach’s alpha = 0.85), Physical distress (Cronbach’s alpha = 0.79), Insanity (Cronbach’s alpha = 0.78), Isolation (Cronbach’s alpha = 0.87), Insanity (Cronbach’s alpha = 0.78), Death (Cronbach’s alpha = 0.88), and Paranoia (Cronbach’s alpha = 0.63).

We included the Mystical Experiences Questionnaire (MEQ30), a 30-item self-report measure developed to assess the subjective mystical experiences one might have after taking a hallucinogen ( Maclean et al., 2012 ). Respondents were asked to reflect on the first experience they had with 5-MeO-DMT and to describe the intensity with which they experienced each mystical effect using a 6-point scale from ‘None; not at all’ to ‘Extreme.’ Previous research ( Maclean et al., 2012 ) has found that the measure produces four subscales: (1) Mystical; (2) Positive mood; (3) Transcendence of time/space; and (4) Ineffability. The MEQ also yields an MEQ total scale score which can be used to rate the overall intensity of mystical experiences. Furthermore, similar to Griffiths et al. (2006) , we also calculated the proportion of the sample who experienced a ‘complete mystical experience’ (i.e., the proportion of the sample whose mean score for each of the four MEQ subscales was at least three-fifths of the total possible score = 60%). Internal consistency of the total scale and each subscale in the current sample was: Total scale (Cronbach’s alpha = 0.97), Mystical (Cronbach’s alpha = 0.96), Positive Mood (Cronbach’s alpha = 0.90), Transcendence (Cronbach’s alpha = 0.93), and Ineffability (Cronbach’s alpha = 0.91).

We also asked respondents questions about the typical location of 5-MeO-DMT use (e.g., own home/apartment, friend’s home/apartment) and who (if anyone) has administered the 5-MeO-DMT to them (versus self-administration). In addition, we included variables assessing several aspects of addiction potential, such as the frequency of repeated consumption in the same session, craving/desire, possible consequences they may have experienced related to 5-MeO-DMT use (e.g., psychiatric problems, medical treatment, or legal problems associated with use), and whether they ever attempted to quit, reduce, or increase their consumption. Moreover, we asked from where or from whom they obtained their 5-MeO-DMT, the potential clinical or spiritual applications of 5-MeO-DMT, and we asked them to compare the intensity of 5-MeO-DMT to other psychedelic substances with which they were familiar (e.g., LSD, psilocybin). Finally, we included a series of questions about respondents’ history of being diagnosed with several medical (e.g., asthma, coronary artery disease) or psychiatric (e.g., depression, anxiety) conditions and whether their symptoms associated with each condition had improved, stayed the same, or worsened following 5-MeO-DMT use. The full survey is available from the corresponding author.

We began the survey by describing the various types of 5-MeO-DMT (i.e., chemical/synthetic, toad venom, plant extract, yopo, other). We also asked respondents to report which of these types of 5-MeO-DMT they had ever used and with which type of 5-MeO-DMT they had the most experience. The survey also included items that asked about frequency of use, typical dose, and motives for using 5-MeO-DMT (e.g., recreation, spiritual exploration, healing from trauma, treatment for addiction, treatment for depression, because my friends tried it). Additionally, the survey included questions examining the most common routes of administration (e.g., smoking/vaporizing, insufflation, injecting), age at first use, stability of recent consumption (e.g., use in the past 12 months increased, stayed the same, or decreased), and whether there were other people present when they consumed 5-MeO-DMT, and if so, how many people were also using 5-MeO-DMT and how many were not also using.

From April 2017 to August 2017 we posted written recruitment advertisements on the Internet (e.g., at 5meodmt.org , reddit.com, bluelight.org), created a Facebook group for the study (i.e., 5-MeO-DMT Research Project) and posted several advertisements in this Facebook group page and on other pages on Facebook related to 5-MeO-DMT use. All recruitment advertisements contained information regarding the purpose of the study, the estimated amount of time required to complete the survey (approximately 20 minutes), and the anonymity of completing the survey. Additionally, we informed potential respondents that we would donate US$2 per person, up to US$250, to the Multidisciplinary Association for Psychedelic Studies as a way to ‘pay it forward’ for their time. We also created website banner advertisements that were shown to visitors at erowid.com and bluelight.org. Upon clicking any of our advertisments, potential respondents were sent to the secure survey site (hosted by surveygizmo.com), where they viewed the informed consent document which repeated the purpose of the study and described eligibility criteria, including being at least 18 years old, able to read and understand English, and having used 5-MeO-DMT at least once in their lifetime. No personal identifying information was collected in the survey. All study procedures were approved by the human subject’s review board at Bowling Green State University.

Similarly, Table 5 shows the most common statistical differences in the proportions of each group reporting challenging experiences were between the Synthetic and Toad groups, but the direction of effect was opposite to that found in reporting of mystical experiences. Specifically, when statistically significant differences were found it was typically those in the Synthetic group who endorsed slightly more intense challenging experiences compared with the Toad group. Despite these statistically significant differences, the overall mean scores on the challenging experiences subscales indicate that most respondents experienced these challenging subjective effects to only a very slight degree.

As Table 3 also reveals, although most respondents in each group reported spiritual exploration as their top reason for using 5-MeO-DMT, significantly larger proportions of those in the Synthetic and Plant Extract/Yopo groups reported recreation as a top motivation compared with those in the Toad group. Conversely, significantly larger proportions of those in the Toad group reported their top motivation for use was spiritual exploration or psychological healing/treatment compared with those in the Synthetic group. Regarding mystical experiences reported in this sample, Table 4 reveals that most of the statistically significant differences in the proportion of those who experienced mystical effects were between the Synthetic and Toad groups, with people in the Toad group endorsing more intense mystical effects. Despite these statistically significant differences, the overall mean scores on the mystical experiences subscales indicate that most respondents experienced these subjective effects at a strong intensity.

As Table 1 reveals, the Synthetic 5-MeO-DMT group was similar in age and gender distribution to the Plant Extract/Yopo group, both groups being significantly younger and comprised of fewer females compared with the Toad group. Additionally, as shown in Table 2 , there were few differences in the number of days (in the past 3 months) that respondents used other substances, regardless of the subtype of 5-MeO-DMT consumed. When significant differences were found, it was typically those in the Synthetic group who used other substances more frequently (e.g., marijuana/cannabis, benzos, psychedelic research chemicals, other psychedelics) compared with those in the Toad group. As Table 3 reveals, almost all of the Toad group smoked/vaporized 5-MeO-DMT and significantly larger (but still small) proportions in the Synthetic and Plant Extract/Yopo groups consumed by other means (i.e., swallowed or snorted). Additionally, those respondents in the Synthetic and Plant Extract/Yopo groups had higher numbers of total lifetime use of 5-MeO-DMT compared with the Toad group, but the Synthetic group consumed less frequently than the Toad or Plant Extract/Yopo groups. Frequency of re-dosing immediately after consumption was also different between groups, wherein more people in the Toad group reported never re-dosing compared with the Synthetic and Plant Extract/Yopo groups. Moreover, there were no significant group differences in addiction potential or safety variables including no differences in the proportion experiencing craving/desire, legal trouble, medical treatment, or psychiatric treatment associated with 5-MeO-DMT use, and notably small and statistically equivalent proportions in each group reported ever attempting to reduce or quit using 5-MeO-DMT.

Very few respondents reported being diagnosed with medical conditions (see Table 6 ), including asthma (12%), high blood pressure (9%), or chronic fatigue syndrome (8%), but almost all of these respondents (73–78%) reported that there were no changes in medical functioning following 5-MeO-DMT use. Interestingly, small proportions (15–24%) reported that symptoms associated with these medical conditions were better after 5-MeO-DMT use, and notably small proportions (4–7%) reported that their symptoms had worsened. The incidence of self-reported lifetime psychiatric disorders in this sample included anxiety (63%), depression (61%), drug use disorder (33%), alcoholism or hazardous drinking (22%), attention deficit hyperactivity disorder (22%), post-traumatic stress disorder (21%), eating disorder (10%), obsessive compulsive disorder (11%), and bipolar disorder (8%). Similar to those with medical conditions, psychiatric symptoms were rarely reported as worsened following 5-MeO-DMT use (average of 4% reporting worsening of symptoms across all psychiatric conditions), but comparatively larger proportions reported that their psychiatric conditions were improved following 5-MeO-DMT use, including those experiencing improvements in depression (77%), post-traumatic stress disorder (79%), anxiety (69%), substance use problems (~63%), and obsessive compulsive disorder (53%). Moreover, smaller proportions, but often more than one-third of the sample (35–50%), reported improvements in symptoms related to attention deficit hyperactivity disorder, autism, bipolar disorder, and eating disorder.

Although relatively less common compared with mystical effects, some respondents (average of 37%) reported experiencing challenging psychological and somatic experiences ( M intensity =0.95, SD=0.91; range 0–5; see Table 5 ). For example, between 40% and 66% of respondents reported experiences of feeling their heart beat, fear, frightened, their body shake/tremble, anxious, as if they were dead or dying, shaky inside, that something horrible would happen, like crying, pressure or weight in their chest or abdomen, and panic, and having the profound experience of their own death. Despite endorsement of these challenging experiences, the overall intensity of these experiences was rated as ‘very slight’ (1) on a scale from ‘None; not at all’ (0) to ‘Extreme’ (5).

As Table 4 reveals, large proportions of respondents (average of 90%) reported experiencing moderate-to-strong mystical-type experiences after consuming 5-MeO-DMT ( M intensity =3.64, SD=1.11; range 0–5). For example, more than 90% reported on individual items of the MEQ that they experienced freedom from the limitations of their personal self and feeling a unity or bond with what was felt to be greater than their personal self, experience of pure being or awareness, experience of oneness in relation to an inner world within, and gained insightful knowledge experienced at an intuitive level. Large proportions (84–96%) also experienced a variety of moderate-to-strong euphoric and positive mood experiences, including amazement, tenderness and gentleness, peace and tranquility, ecstasy, awe or awesomeness, and joy. Transcendent experiences (e.g., loss of sense of time, sense of space, awareness of location) were also very common (87–97% of sample), as were the endorsement of ineffable qualities of their experience such as a sense that the experience could not adequately be described in words. Approximately one-half (57%) of the sample had a ‘complete mystical experience’ characterized by endorsement of ≥ 60% of the total possible score across all four subscales of the MEQ30.

Regarding addiction potential, most respondents (61%) reported that they never re-dosed immediately after taking 5-MeO-DMT, although approximately one-quarter (28%) reported sometimes re-dosing, and a notably small proportion (11%) reporting that they frequently or always re-dosed. Additionally, very few respondents reported craving/desire for 5-MeO-DMT (8%), ever being arrested or in legal trouble due to 5-MeO-DMT use (1%), ever being in therapy or psychiatric treatment (1%), or seeking medical attention (1%) as a result of 5-MeO-DMT use. Moreover, most respondents (86%) reported that their use in the past year had decreased or stayed the same, and almost all (~95%) reported that they never attempted to reduce or quit their use of 5-MeO-DMT, suggesting that use is moderated in large part without a need for personal or medical/psychiatric interventions, and is not associated with behaviors requiring law enforcement.

Overall, respondents reported having the most experience with synthetic 5-MeO-DMT (55%; n =284), and almost one-third (29%; n =148) reported having the most experience with toad venom. The remainder of the sample (16%; n =83) reported that they had the most experience with plant extracts or other botanical preparations containing 5-MeO-DMT (e.g., yopo snuff). As Table 3 reveals, most respondents (60%) had consumed 5-MeO-DMT in the past year, had consumed 5-MeO-DMT through a smoking/vaporizing route of administration (81%), had consumed 5-MeO-DMT less than four times in their lifetime (59% 1–4 times total), with less than one-quarter (21%) reporting lifetime use of more than 10 occasions. Of those who had used 5-MeO-DMT more than one time, most (54%) used 5-MeO-DMT at a frequency of about once per year or less. Of all respondents, most used in the setting of their own or a friend’s apartment/home (64%), and had obtained the substance from a guide/session leader (30%), a friend (29%), or the Internet (26%). Regarding their motivations for consumption, the majority of the sample (68%) reported spiritual exploration as their top reason, with small proportions reporting that recreation (18%) or healing/psychological treatment (14%) as the primary reason for use.

As examination of Table 1 reveals, the majority of respondents were Caucasian (86%), heterosexual (82%), and male (79%), with a mean age of 35.4 years (SD = 11.7), and resided outside the USA (58%). See Table 1 for further demographic characteristics of the sample. Respondents also reported consuming a variety of substances in the 3 months prior to the survey, with marijuana/cannabis ( M days =34.22; SD=37.43), tobacco ( M days =25.12; SD=36.99), and alcohol ( M days =16.22; SD=23.59) being consumed the most frequently. See Table 2 for more details about frequency of other substance use.

During recruitment, 2207 people clicked one of the recruitment ads and were presented with information about the study. Of these individuals, 569 consented to participate, began filling out the survey, and completed all of the main study questionnaires related to 5-MeO-DMT consumption. Of these respondents, we excluded 46 because they did not know or were unable to identify what form of 5-MeO-DMT they had used (i.e., synthetic, toad venom, plant extract/yopo) and thus would have been eliminated in analyses of subgroup differences. Of the remaining 523, we excluded 4 because of duplicate IP addresses, 1 for careless responding, 2 for reporting that they were under age 18 at the time of survey, and 1 for reporting that they had never used 5-MeO-DMT. The final sample was comprised of 515 respondents.

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.