A single inhalation of vapor from dried toad secretion containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting is related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptoms

M V Uthaug, R Lancelotta, K van Oorsouw, K P C Kuypers, N Mason, J Rak, A Šuláková, R Jurok, M Maryška, M Kuchař, T Páleníček, J Riba, J G Ramaekers, M V Uthaug, R Lancelotta, K van Oorsouw, K P C Kuypers, N Mason, J Rak, A Šuláková, R Jurok, M Maryška, M Kuchař, T Páleníček, J Riba, J G Ramaekers

Abstract

Background: 5-methoxy-N,N-dimethyltryptamine (hereinafter referred to as 5-MeO-DMT) is a psychedelic substance found in the secretion from the parotoid glands of the Bufo alvarius toad. Inhalation of vapor from toad secretion containing 5-MeO-DMT has become popular in naturalistic settings as a treatment of mental health problems or as a means for spiritual exploration. However, knowledge of the effects of 5-MeO-DMT in humans is limited.

Aims: The first objective of this study was to assess sub-acute and long-term effects of inhaling vapor from dried toad secretion containing 5-MeO-DMT on affect and cognition. The second objective was to assess whether any changes were associated with the psychedelic experience.

Methods: Assessments at baseline, within 24 h and 4 weeks following intake, were made in 42 individuals who inhaled vapor from dried toad secretion at several European locations.

Results: Relative to baseline, ratings of satisfaction with life and convergent thinking significantly increased right after intake and were maintained at follow-up 4 weeks later. Ratings of mindfulness also increased over time and reached statistical significance at 4 weeks. Ratings of depression, anxiety, and stress decreased after the session, and reached significance at 4 weeks. Participants that experienced high levels of ego dissolution or oceanic boundlessness during the session displayed higher ratings of satisfaction with life and lower ratings of depression and stress.

Conclusion: A single inhalation of vapor from dried toad secretion containing 5-MeO-DMT produces sub-acute and long-term changes in affect and cognition in volunteers. These results warrant exploratory research into therapeutic applications of 5-MeO-DMT.

Keywords: 5-MeO-DMT; Affect; Altered states of consciousness; Bufo alvarius; Cognition; Field study; Psychedelic; Satisfaction with life.

Conflict of interest statement

The authors declare that they have no competing interests. None of the authors of this paper were directly involved in any way with the organization of the sessions where vapor from dried toad secretion was inhaled.

Figures

Fig. 1
Fig. 1
Mean ratings (range 0–100%) of the psychedelic experience as assessed with the 5D-ASC subscales after inhalation of vapor from dried toad secretion containing 5-MeO-DMT as well as frequency distributions of ego dissolution and oceanic boundlessness ratings (lower panels)
Fig. 2
Fig. 2
Mean (SE) satisfaction with life before and after inhalation of vapor from dried toad secretion containing 5-MeO-DMT (* = p < 0.05)
Fig. 3
Fig. 3
Mean (SE) correct responses (PCT), subjective ratings of mindfulness (FFMQ-15) depression, anxiety (DASS-21 and BSI-18), stress (DASS-21), and somatization (BSI-18) as a function of time after inhalation of vapor from dried toad secretion containing 5-MeO-DMT (* = p < 0.05)
Fig. 4
Fig. 4
Pearson correlations between satisfaction with life and ego dissolution/oceanic boundlessness (upper panel), between correct responses in the PCT and ego dissolution/oceanic boundlessness (middle panel), and between ego dissolution and stress and depression ratings (lower panel) on the day after inhalation of vapor from dried toad secretion containing 5-MeO-DMT)

References

    1. Abdallah CG, Salas R, Jackowski A, Baldwin P, Sato JR, Mathew SJ. Hippocampal volume and the rapid antidepressant effect of ketamine. J Psychopharmacol. 2015;29:591–595. doi: 10.1177/0269881114544776.
    1. Baer RA, Smith GT, Hopkins J, Krietemeyer J, Toney L. Using self-report assessment methods to explore facets of mindfulness. Assessment. 2006;13:27–45. doi: 10.1177/1073191105283504.
    1. Barsuglia J, Davis A, Palmer R (2017) Characterization of mystical experiences occasioned by 5-MeO-DMT-containing toad bufotoxin and comparison with prior psilocybin studies. Psychedelic Sci 23
    1. Barsuglia JP, Davis AK, Palmer R, Lancelotta R, Windham-Herman AM, Peterson K, Polanco M, Grant RM, Griffiths RR. Intensity of mystical experiences occasioned by 5-MeO-DMT and comparison with a prior psilocybin study. Front Psychol. 2018;9:2459. doi: 10.3389/fpsyg.2018.02459.
    1. Beuningen J. The satisfaction with life scale examining construct validity. Stat Neth. 2012;201209:3–23.
    1. Bogenschutz MP, Forcehimes AA, Pommy JA, Wilcox CE, Barbosa PCR, Strassman RJ. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. J Psychopharmacol. 2015;29:289–299. doi: 10.1177/0269881114565144.
    1. Catlow BJ, Song S, Paredes DA, Kirstein CL, Sanchez-Ramos J. Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning. Exp Brain Res. 2013;228:481–491. doi: 10.1007/s00221-013-3579-0.
    1. Chen K, Kovaříková A. Pharmacology and toxicology of toad venom. J Pharm Sci. 1967;56:1535–1541. doi: 10.1002/jps.2600561202.
    1. Dakic V, Minardi Nascimento J, Costa Sartore R, Maciel RM, de Araujo DB, Ribeiro S, Martins-de-Souza D, Rehen SK. Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT. Sci Rep. 2017;7:12863. doi: 10.1038/s41598-017-12779-5.
    1. Davis AK, Barsuglia JP, Lancelotta R, Grant RM, 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):779–792. doi: 10.1177/0269881118769063.
    1. Davis AK, So S, Lancelotta R, Barsuglia JP, Griffiths RR (2019) 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic setting is associated with unintended improvements in depression and anxiety. Am J Drug Alcohol Abuse. 10.1080/00952990.2018.1545024
    1. Daza P, Novy DM, Stanley MA, Averill P. The depression anxiety stress scale-21: Spanish translation and validation with a Hispanic sample. J Psychopathol Behav Assess. 2002;24:195–205. doi: 10.1023/A:1016014818163.
    1. De Lima Osório F, De Macedo LRH, De Sousa JPM, Pinto JP, Quevedo J, de Souza Crippa JA, Hallak JEC (2011) The therapeutic potential of harmine and ayahuasca in depression: evidence from exploratory animal and human studies. Ethnopharmacol Ayahuasca 75–86
    1. Derogatis LR (2001) Brief symptom inventory 18. Johns Hopkins University, Johns Hopkins University
    1. Diener E, Emmons RA, Larsen RJ, Griffin S. The satisfaction with life scale. J Pers Assess. 1985;49:71–75. doi: 10.1207/s15327752jpa4901_13.
    1. Dittrich A. The standardized psychometric assessment of altered states of consciousness (ASCs) in humans. Pharmacopsychiatry. 1998;31:80–84. doi: 10.1055/s-2007-979351.
    1. Duman RS, Aghajanian GK. Synaptic dysfunction in depression: potential therapeutic targets. Science. 2012;338:68–72. doi: 10.1126/science.1222939.
    1. Erspamer V, Vitali T, Roseghini M, Cei JM. 5-Methoxy-and 5-hydroxyindoles in the skin of Bufo alvarius. Biochem Pharmacol. 1967;16:1149–1164. doi: 10.1016/0006-2952(67)90147-5.
    1. Evans WE, Relling MV. Pharmacogenomics: translating functional genomics into rational therapeutics. Science. 1999;286:487–491. doi: 10.1126/science.286.5439.487.
    1. Franke GH, Jaeger S, Glaesmer H, Barkmann C, Petrowski K, Braehler E. Psychometric analysis of the brief symptom inventory 18 (BSI-18) in a representative German sample. BMC Med Res Methodol. 2017;17:14. doi: 10.1186/s12874-016-0283-3.
    1. Garcia-Romeu A, Griffiths RR, Johnson MW. Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction. Curr Drug Abuse Rev. 2014;7:157–164. doi: 10.2174/1874473708666150107121331.
    1. 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;30:1181–1197. doi: 10.1177/0269881116675513.
    1. Gu J, Strauss C, Crane C, Barnhofer T, Karl A, Cavanagh K, Kuyken W. Examining the factor structure of the 39-item and 15-item versions of the Five Facet Mindfulness Questionnaire before and after mindfulness-based cognitive therapy for people with recurrent depression. Psychol Assess. 2016;28:791–802. doi: 10.1037/pas0000263.
    1. Hadidi H, Güzey C, Idle J. Pharmacogenetics and toxicological consequences of human drug oxidation and reduction. Macmillan Reference: General and Applied Toxicology. Basingstoke; 1999. pp. 215–250.
    1. Hammerson G, Georgina S-B (2004) Incilius alvarius. The IUCN Red List of Threatened Species 2004. IUCN
    1. Henry JD, Crawford JR. The short-form version of the Depression Anxiety Stress Scales (DASS-21): construct validity and normative data in a large non-clinical sample. Br J Clin Psychol. 2005;44:227–239. doi: 10.1348/014466505X29657.
    1. Idell RD, Florova G, Komissarov AA, Shetty S, Girard RB, Idell S. The fibrinolytic system: a new target for treatment of depression with psychedelics. Med Hypotheses. 2017;100:46–53. doi: 10.1016/j.mehy.2017.01.013.
    1. Johnson MW, Richards WA, Griffiths RR. Human hallucinogen research: guidelines for safety. J Psychopharmacol. 2008;22:603–620. doi: 10.1177/0269881108093587.
    1. Krebs-Thomson K, Ruiz EM, Masten V, Buell M, Geyer MA. The roles of 5-HT 1A and 5-HT 2 receptors in the effects of 5-MeO-DMT on locomotor activity and prepulse inhibition in rats. Psychopharmacology. 2006;189:319–329. doi: 10.1007/s00213-006-0566-1.
    1. Kučera D, Havigerová J, Haviger J, Cvrček V, Urbánek T, Jelínek T, Lukeš D, Komrsková Z (2018) Výzkum CPACT: Komputační psycholingvistická analýza českého textu (CPACT research: computational psycholinguistic analysis of Czech Text. České Budějovice, PF JU. (in press)
    1. Kuypers KP, Riba J, de la Fuente RM, Barker S, Theunissen EL, Ramaekers JG. Ayahuasca enhances creative divergent thinking while decreasing conventional convergent thinking. Psychopharmacology. 2016;233:3395–3403. doi: 10.1007/s00213-016-4377-8.
    1. Lebudaa IZ, Zabelina D, Karwowski M. Mind full of ideas: a meta-analysis of the mindfulness–creativity link. Personal Individ Differ. 2015;93:22–26. doi: 10.1016/j.paid.2015.09.040.
    1. Ma Z, Zang T, Birnbaum SG, Wang Z, Johnson JE, Zhang CL, Parada LF. TrkB dependent adult hippocampal progenitor differentiation mediates sustained ketamine antidepressant response. Nat Commun. 2017;8:1668. doi: 10.1038/s41467-017-01709-8.
    1. Nour MM, Evans L, Nutt D, Carhart-Harris RL. Ego-dissolution and psychedelics: validation of the Ego-dissolution inventory (EDI) Front Hum Neurosci. 2016;10:269. doi: 10.3389/fnhum.2016.00269.
    1. Ott J. Pharmepena-psychonautics: human intranasal, sublingual and oral pharmacology of 5-methoxy-N, N-dimethyl-tryptamine. J Psychoactive Drugs. 2001;33:403–407. doi: 10.1080/02791072.2001.10399925.
    1. Pachter IJZ, Ribeiro DE, Ribeiro O. Indole alkaloids of acer saccharinum (the silver maple), Dictyoloma incanescens, Piptadenia colubrina, and Mimosa hostilis. J Org Chem. 1959;24:1285–1287. doi: 10.1021/jo01091a032.
    1. Palhano-Fontes F, Barreto D, Onias H, Andrade KC, Novaes MM, Pessoa JA, Mota-Rolim SA, Osório FL, Sanches R, dos Santos RG (2018) Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychol Med 1–9
    1. PsychedelicsToday (2018) Psychedelic today’s - 5-MeO-DMT course (unpublished). Psychedelic Today . Accessed 12 December 2018
    1. Ray TS. Psychedelics and the human receptorome. PLoS One. 2010;5:e9019. doi: 10.1371/journal.pone.0009019.
    1. Roseman L, Nutt DJ, Carhart-Harris RL. Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression. Front Pharmacol. 2017;8:974. doi: 10.3389/fphar.2017.00974.
    1. Ross S, Bossis A, Guss J, Agin-Liebes G, Malone T, Cohen B, Mennenga SE, Belser A, Kalliontzi K, Babb J. 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;30:1165–1180. doi: 10.1177/0269881116675512.
    1. Sampedro F, de la Fuente RM, Valle M, Roberto N, Dominguez-Clave E, Elices M, Luna LE, Crippa JAS, Hallak JEC, de Araujo DB, Friedlander P, Barker SA, Alvarez E, Soler J, Pascual JC, Feilding A, Riba J. Assessing the psychedelic “after-glow” in ayahuasca users: post-acute neurometabolic and functional connectivity changes are associated with enhanced mindfulness capacities. Int J Neuropsychopharmacol. 2017;20:698–711. doi: 10.1093/ijnp/pyx036.
    1. Sanches RF, de Lima OF, Dos Santos RG, Macedo LR, Maia-de-Oliveira JP, Wichert-Ana L, de Araujo DB, Riba J, Crippa JA, Hallak JE. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a SPECT study. J Clin Psychopharmacol. 2016;36:77–81. doi: 10.1097/JCP.0000000000000436.
    1. Sandoval GR (2006) The god molecule: 5-MeO-DMT and the spiritual path to the divine Light, Divine Arts
    1. Shen HW, Jiang XL, Winter JC, Yu AM. Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions. Curr Drug Metab. 2010;11:659–666. doi: 10.2174/138920010794233495.
    1. Soler J, Elices M, Franquesa A, Barker S, Friedlander P, Feilding A, Pascual JC, Riba J. Exploring the therapeutic potential of ayahuasca: acute intake increases mindfulness-related capacities. Psychopharmacology. 2016;233:823–829. doi: 10.1007/s00213-015-4162-0.
    1. Studerus E, Gamma A, Vollenweider FX. Psychometric evaluation of the altered states of consciousness rating scale (OAV) PLoS One. 2010;5:e12412. doi: 10.1371/journal.pone.0012412.
    1. Szabo A, Kovacs A, Frecska E, Rajnavolgyi E. Psychedelic N, N-dimethyltryptamine and 5-methoxy-N, N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. PLoS One. 2014;9:e106533. doi: 10.1371/journal.pone.0106533.
    1. Uthaug M, van Oorsouw K, Kuypers K, van Boxtel M, Broers N, Mason N, Toennes S, Riba J, Ramaekers J (2018) Sub-acute and long-term effects of ayahuasca on affect and cognitive thinking style and their association with ego dissolution. Psychopharmacology 1–11
    1. Vazquez C, Duque A, Hervas G. Satisfaction with life scale in a representative sample of Spanish adults: validation and normative data. Span J Psychol. 2013;16:E82. doi: 10.1017/sjp.2013.82.
    1. Wardenaar KJ, Wanders RBK, Jeronimus BF, al e (2017) The psychometric properties of an internet-administered version of the Depression Anxiety and Stress Scales (DASS) in a Sample of Dutch Adults. J Psychopathol Behav Assess 1–16
    1. Weil AT, Davis W. Bufo alvarius: a potent hallucinogen of animal origin. J Ethnopharmacol. 1994;41:1–8. doi: 10.1016/0378-8741(94)90051-5.
    1. Yu A-M, Idle JR, Byrd LG, Krausz KW, Küpfer A, Gonzalez FJ. Regeneration of serotonin from 5-methoxytryptamine by polymorphic human CYP2D6. Pharmacogenet Genomics. 2003;13:173–181. doi: 10.1097/00008571-200303000-00007.

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