The cognitive effects of 5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) are associated with improvements in depression and anxiety conditions

Abstract

5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) is a psychoactive compound found in glandular secretions of Bufo alvarius toads and is synthesized. No human laboratory studies have been conducted, but evidence suggests 5-MeO-DMT may reduce depression and anxiety symptoms among those who use for spiritual or recreational reasons. Probing the effects of 5-MeO-DMT in a naturalistic setting could provide useful information to guide future studies. Therefore, we examined 5-MeO-DMT use among a group in the Unites States with established procedures that guide the type, source, dose, and administration of 5-MeO-DMT, and the preparation of and support during/following sessions, providing a unique opportunity to study the therapeutic effect of 5-MeO-DMT in a naturalistic setting. Using email distribution lists and an anonymous web-based survey, we assessed self-reported rates of, and changes in, the experience of depression and anxiety in this group (n=362; Mage=48, SD=13; Male=55%; White/Caucasian=84%; M5-MeO-DMTUseLifetime=4.3; SD=4.7; MTypicalDose=12.6mg; SD=4.4mg). Next, we examined whether acute subjective experiences (mystical, challenging), and beliefs about persisting effects, were associated with changes in depression and anxiety. Of those reporting a history of being diagnosed with depression (n=149; 41%) or anxiety (n=173; 48%), most reported symptoms were improved (depression=81%; anxiety=79%) following 5-MeO-DMT use and relatively fewer reported symptoms remained the same (depression=17%; anxiety=19%) or worsened (depression=3%; anxiety=2%). Referring to their first session with 5-MeO-DMT, there were no differences in the intensity of acute challenging experiences (e.g., fear, grief, paranoia) between groups (improved vs same/worsened). However, there were differences in the intensity of acute mystical experiences (e.g., transcendence, euphoria, noetic realizations), such that those whose depression or anxiety symptoms improved after 5-MeO-DMT use reported more intense mystical experiences compared to those whose symptoms were the same/worsened. Lastly, those who reported improvements in depression or anxiety rated their first 5-MeO-DMT experience as more spiritually/personally meaningful, and as contributing more to their well-being, compared to those whose depression or anxiety were the same/worsened. Findings suggest that use of 5-MeO-DMT is related to improvements in depression and anxiety, which are associated with acute mystical and persisting beliefs about the effects of 5-MeO-DMT. Future research should examine both the safety, and possible therapeutic efficacy, of 5-MeO-DMT administration in humans using rigorous experimental designs.

Full text

Introduction Results
Method & Data Analysis
The cognitive effects of 5-Methoxy-N,N-Dimethyltrytamine (5-MeO-DMT)
are associated with improvements in depression and anxiety conditions
5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), is a short-acting
(30-90 minutes) tryptamine found in the venom and skin of Bufo
alvarius toads and can also be synthetically produced (1, 2, 3).
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 (4). More
specifically, there have been reports of spontaneous and
unintended symptom improvements in anxiety and depression (4).
Using an email distribution list of people in the US that use 5-MeO-
DMT in a specific group setting, we recruited English-speaking
adults to complete an anonymous web-based survey. The primary
survey used for this study included an extensive series of questions
about the patterns of use, acute subjective effects, and potential
consequences and benefits of using 5-MeO-DMT in this group
setting. Depression and Anxiety measures, the Mystical Experiences
Questionnaire, the Challenging Experiences Questionnaire, and
Persisting Effects Questionnaire was included.
Study Aim
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 the US with procedures that guide the source,
dose, and administration of 5-MeO-DMT, and the preparation of
and support during/following sessions. The second aim of this study
is to examine factors associated with improvement in depression
and anxiety.
Conclusions
1. Araújo AM, Carvalho F, Bastos MD, Pinho PG, Carvalho M. The hallucinogenic world of tryptamines: an updated review. Arch Toxicol. 2015;89(8):1151–73.
2. Ott J. Pharmepéna-Psychonautics: Human Intranasal, Sublingual and Oral Pharmacology of 5-Methoxy-N, N-Dimethyl-Tryptamine. J Psychoactive Drugs. 2001;33(4):403–7.
3. Shulgin AT, Shulgin A. Tihkal: the continuation. Berkeley, CA: Transform Press; 1997.
4. Davis AK, Barsuglia JP, Lancelotta R, Grant R and Renn E. The epidemiology of 5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and
reasons for consumption. J Psychopharmacol. 2018;32(7):779–92.
5. Johnson MW, Griffiths RR. Potential Therapeutic Effects of Psilocybin. Neurotherapeutics. 2017;14(3): 734–40.
6. Carhart-Harris RL, Roseman L, Bolstridge M, Demetriou L, Pannekoek JN, Wall MB, Tanner M, Kaelen M, Mcgonigle J, Nutt DJ. Psilocybin for treatment-resistant depression: FMRI-measured brain
mechanisms. Sci Rep. 2017;7(1).
7. Ross S, Bossis T, Guss J, Agin-Liebes G, Malone T, Cohen B, Mennenga S, Belser A, Kalliontzi K, Babb J, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and
depression in patients with life-threatening cancer: A randomized controlled trial. J Psychopharmacol. 2016;30(12):1165–80.
8. Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, Cosimano MP, Klinedinst MA. Psilocybin produces substantial and sustained decreases in depression and anxiety in
patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. 2016;30(12):1181–9. Griffiths RR, Richards W, Johnson M, McCann U, Jesse R. Mystical-type experiences
occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. J Psychopharmacol. 2008;22(6):621–32.
10. Griffiths RR, Johnson MW, Richards WA, Richards BD, McCann U, Jesse R. Psilocybin occasioned mystical-type experiences: Immediate and persisting dose related effects. Psychopharmacology.
2011;218(4):649–65.
11. Garcia-Romeu A, Griffiths RR, Johnson MW. Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction. Curr Drug Abuse Rev. 2014;7(3):157–64.
Sample Characteristics
Sample
362 respondents completed the survey
The sample was comprised as follows:
•Mean age = 48 (SD=13)
•White/Caucasian = 84%
•Heterosexual = 79%
•College Graduates = 75%
•Females = 45%
Sara So1,2, Rafael Lancelotta3, Joseph P Barsuglia4, Roland R Griffiths2, Alan K. Davis2,
1Johns Hopkins University, Bloomberg School of Public Health, 2 Johns Hopkins University School of Medicine, Psychedelic Research Unit
3University of Wyoming, Counseling Department, 4 New School Research
When administered in a naturalistic group setting, 5-MeO-DMT appears to be associated with spontaneous and unintended
improvements in self-reported depression and anxiety (approximately 80%), which were related to more intense acute mystical effects
and increases in ratings of the personal meaning and spiritual significance of the 5-MeO-DMT session, as well as higher ratings of the
degree to which the session contributed to improved well-being and life satisfaction. These results are consistent with laboratory
studies that found positive psychotherapeutic effects of tryptamines as an adjunct to supportive psychotherapy (5-8) and suggests the
importance of the acute mystical effects of psychedelic substances as one of the mechanisms by which they exert psychotherapeutic
effects (8-11).
References
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Mystical Positive Mood Transcendence Ineffability MEQ Total Score
Cognitive & Emotional Mystical Experiences – Depression Group
Better Not Better
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Mystical Positive Mood Transcendence Ineffability MEQ Total Score
Cognitive & Emotional Mystical Experiences – Anxiety Group
Better
Not Better
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Isolation Fear Grief Physical
Distress
Insanity Death/Dying Paranoia CEQ Total
Score
Challenging Cognitive & Physical Experiences – Depression Group
Better Not Better
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Isolation Fear Grief Physical
Distress
Insanity Death/Dying Paranoia CEQ Total
Score
Challenging Cognitive & Physical Experiences – Anxiety Group
Better Not Better
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Personal Meaning Spiritual Significance Subjective Wellbeing
Attributions of the experience – Depression Group
Better Not Better
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Personal Meaning Spiritual Significance Subjective Wellbeing
Attributions of the experience – Anxiety Group
Better Not Better
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* p<.05; ** p<.01; *** p<.001 ^Small effect; ^^ Medium effect; ^^^ Large effect
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Sample after 5-MeO-DMT use
Rates of Anxiety (n=173)
● Improved: 79%
● Stayed the same/worsened: 21%
Rates of Depression (n=149)
● Improved: 81%
● Stayed the same/worsened: 19%
Funding
AKD was supported by NIDA (DA007209). RL was supported by
Source Research Foundation to provide administrative support on
this study. RL, JPB and AKD are on the board of directors at SRF.
The funding source had no role in study design, data analysis, or
interpretation.
Contact email for corresponding author: adavi157@jhmi.edu