5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety, Alan K. Davis et al., 2018

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety

Alan K. Davis PhD, Sara So MS, Rafael Lancelotta MS, Joseph P. Barsuglia PhD, Roland R. Griffiths PhD

The American Journal of Drug and Alcohol Abuse, 2018

DOI: 10.1080/00952990.2018.1545024


Background : A recent epidemiological study suggested that 5-methoxy-N,Ndimethyltryptamine (5-MeO-DMT) used for spiritual and recreational reasons is associated with subjective improvement in depression and anxiety. Further exploration of the potential psychotherapeutic effects of 5-MeO-DMT could inform future clinical trials.

Objectives : We examined self-reported improvement in depression and anxiety among people who use 5-MeODMT in a group setting with structured procedures guiding dose and administration of 5-MeODMT. Such procedures also include activities for the preparation of, and support during/following sessions, which are similar to procedures used in clinical trials of hallucinogen administration. Next, we examined whether depression or anxiety were improved following use, and whether the acute subjective effects (mystical/challenging) or beliefs about the 5-MeO-DMT experience were associated with improvements in these conditions.

Methods : Respondents (n=362; Mage=47.7; Male=55%; White/Caucasian=84%) completed an anonymous web-based survey. Results: Of those reporting having been diagnosed with depression (41%) or anxiety (48%), most reported these conditions were improved (depression=80%; anxiety=79%) following 5-MeO-DMT use, and fewer reported they were unchanged (depression=17%; anxiety=19%) or worsened (depression=3%; anxiety=2%). Improvement in depression/anxiety conditions were associated with greater intensity of mystical experiences and higher ratings of the spiritual significance and personal meaning of the 5-MeO-DMT experience. There were no associations between depression or anxiety improvement and the intensity of acute challenging physical/psychological experience during the 5-MeO-DMT experience.

Conclusions : Future prospective controlled clinical pharmacology studies should examine the safety and efficacy of 5-MeO-DMT administration for relieving depression and anxiety.

Keywords : 5-MeO-DMT; psychedelic; tryptamine; depression; anxiety



Anxiety and depression are common mental health conditions (1), with global lifetime prevalence of approximately 13% and 10%, respectively (1, 2). In the United States (US), past year prevalence of any mood disorder is 10% and is 19% for any anxiety disorder (3-5). Additionally, the public health burden of depression and anxiety contributes to occupational impairment, such as reduced workforce participation and lost productivity (6), and increases the risk for chronic physical conditions (e.g., cardiovascular disease) (7, 8). Given high prevalence rates and the public health and personal burden, several interventions have been developed to address these conditions, which include a combination of psychotherapy and pharmacotherapy (9, 10). Despite supportive evidence for these interventions, many people do not have access to such services (11), and many people who have access continue to experience symptoms despite intervention (12-16), highlighting the need for more research.

One emerging area of research has examined the possible psychotherapeutic action of classic psychedelics as an adjunct to psychotherapy (17, 18). Classic psychedelics are a class of hallucinogens, which act primarily as agonists of the 5-HT2A receptor and are capable of producing profound changes in sensory perceptions, mood, and cognitions (19-22). Recent studies examining psilocybin administered as an adjunct to structured supportive psychotherapy have demonstrated efficacy in decreasing symptoms of depression and anxiety (18, 22-24). For example, two placebo-controlled studies showed that psilocybin-assisted supportive psychotherapy was efficacious in decreasing depression and anxiety in the context of cancerrelated psychiatric distress following a single administration, with the suggestion of sustained effects for at least 6 months (23, 24). Moreover, a recent open label study in patients with treatment-resistant depression showed that psilocybin contributed to reductions in depression and anxiety symptoms at 1 week and was sustained in the 3-month follow-up (17). Although more work is needed to fully understand the neurological and psychological mechanisms of action, efficacy appears to be associated with the intensity of acute mystical-type phenomena experienced during psilocybin sessions (23-27).

If future trials with larger samples continue to show positive therapeutic effects and a favorable safety profile (for a review see 18), psilocybin could potentially garner regulatory approval for use as an adjunct to psychotherapy in the US and elsewhere. However, despite these advances, the widespread dissemination of psilocybin-assisted psychotherapy is potentially challenging, given that drug administration sessions consist of a 7- to 10-hour day with two therapist guides and a medical monitor, which may be difficult to implement in traditional outpatient mental health settings. Therefore, short-acting psychedelics may warrant examination as potential therapeutics in order to overcome these barriers. One possible substance is 5- methoxy-N,N-dimethyltryptamine (5-MeO-DMT), which is a short-acting (30-90 minutes) tryptamine found in the venom and skin of Bufo alvarius toads and can also be synthetically produced (19, 28, 29). According to a recent epidemiological survey study, 5-MeO-DMT is used infrequently, primarily for spiritual exploration, has a safe profile of use and low potential for psychiatric or biomedical consequences, and might have psychotherapeutic effects (30). For
example, most respondents reported having anxiety (63%) or depression (61%), with over twothirds (69% to 77%) claiming improvement in symptoms following 5-MeO-DMT use (30).

Although epidemiological findings regarding the association of 5-MeO-DMT use and improvements in anxiety and depression are encouraging, no laboratory studies administering 5- MeO-DMT to humans have been conducted. However, some people use 5-MeO-DMT in a group setting in the US, with established procedures that stipulate the dose and administration of 5-MeO-DMT, and provide guidelines for the preparation of, and support during/following sessions similar to those procedures used in clinical trials (31). Such a group provides a unique opportunity to examine the possible therapeutic effects of 5-MeO-DMT in a naturalistic group setting. Therefore, using data from a survey study of people who use 5-MeO-DMT in this group, the primary aim of this current analysis is to examine whether use of 5-MeO-DMT is associated with spontaneous and unintended improvements in depression and anxiety among people who have used 5-MeO-DMT in this specific structured setting. The second aim of this study is to examine whether acute subjective effects (i.e., mystical or challenging), or beliefs about the 5- MeO-DMT experience are associated with improvement in depression and anxiety.