5-MeO-DMT for post-traumatic stress disorder: a real-world longitudinal case study

Abstract

Psychedelic therapy is, arguably, the next frontier in psychiatry. It offers a radical alternative to longstanding, mainstays of treatment, while exciting a paradigm shift in translational science and drug discovery. There is particular interest in 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)-a serotonergic psychedelic-as a novel, fast-acting therapeutic. Yet, few studies have directly examined 5-MeO-DMT for trauma- or stress-related psychopathology, including post-traumatic stress disorder (PTSD). Herein, we present the first longitudinal case study on 5-MeO-DMT for chronic refractory PTSD, in a 23-year-old female. A single dose of vaporized bufotoxin of the Sonoran Desert Toad (Incilius alvarius), containing an estimated 10-15 mg of 5-MeO-DMT, led to clinically significant improvements in PTSD, with next-day effects. This was accompanied by marked reductions in hopelessness and related suicide risk. Improvements, across all constructs, were sustained at 1-, 3-, 6-, and 12-months follow-up, as monitored by a supporting clinician. The subject further endorsed a complete mystical experience, hypothesized to underly 5-MeO-DMT's therapeutic activity. No drug-related, serious adverse events occurred. Together, results showed that 5-MeO-DMT was generally tolerable, safe to administer, and effective for PTSD; however, this was not without risk. The subject reported acute nausea, overwhelming subjective effects, and late onset of night terrors. Further research is warranted to replicate and extend these findings, which are inherently limited, non-generalizable, and rely on methods not clinically accepted.

Keywords: 5-MeO-DMT; 5-methoxy-N; N-dimethyltryptamine; PTSD; case report; post-traumatic stress disorder; psychedelic therapy; trauma.

Figure 1

Timeline of historical and clinical events. 5-MeO-DMT, 5-methoxy-N,N-dimethyltryptamine (experimental treatment); COVID-19, coronavirus disease pandemic; CPT, cognitive processing therapy (cognitive behavioral therapy); PE, prolonged exposure (cognitive behavioral therapy); SARI, serotonin antagonist and reuptake inhibitor (trazadone); SCID-5, Structured Clinical Interview for DSM-5 (diagnostic assessment); SIT, stress inoculation therapy (cognitive behavioral therapy); SSRI, selective serotonin reuptake inhibitor (sertraline); T0, baseline; T1, 24 h follow-up; T2, 1 month follow-up; T3, 3 months follow-up; T4, 6 months follow-up; T5, 12 months follow-up.

Figure 2

Vital signs taken before and after 5-MeO-DMT dosing. 5-MeO-DMT, 5-methoxy-N,N-dimethyltryptamine; DBP, diastolic blood pressure (mmHg); HR, heart rate (bmp); SBP, systolic blood pressure (mmHg); SpO₂, peripheral blood oxygenation (%).

Figure 3

Mystical effects of 5-MeO-DMT. Blue dotted line indicates the cut-off point for a complete mystical experience (≥60% of total scores across factors). 5-MeO-DMT, 5-methoxy-N,N-dimethyltryptamine; MEQ-30, Mystical Experience Questionnaire.

Figure 4

Change in PTSD symptoms by time point [(A), line graph]. Change in PTSD symptoms across time [(B), bar chart]. Change in hopelessness symptoms by time point [(C) line graph]. Change in hopelessness symptoms across time [(D), bar chart]. BHS, Beck Hopelessness Scale; CB, cluster B (thought intrusion); CC, cluster C (stimuli avoidance); CD, cluster D (negative mood and cognitions); CE, cluster E (altered reactivity); EF, expectations about the future (hopelessness); FF, feelings about the future (hopelessness); LM, loss of motivation (hopelessness); PCL-5, PTSD Checklist for DSM-5; PTSD, post-traumatic stress disorder; SS, symptom severity; T0, baseline; T1, 24 h follow-up; T2, 1 month follow-up; T3, 3 months follow-up; T4, 6 months follow-up; T5, 12 months follow-up.