Completed Trials

• Tolerabllity:
  A) DMT was tolerated by both HC (n=3) and MDD participants (n=7) studied; there were no dropouts.
• Safety:
  A) DMT increased blood pressure, heart rate, which resolved within 20–30 min of injection.
• Adverse Events:
  A) Adverse events were mostly mild with one self-limited serious event. (patient with hisory of reflex syncope)
  B) DMT increased anxiety which resolved within 20–30 min of injection.
• Subjective Effects:
  A) DMT increased psychedelic effects, and psychotomimetic effects, which resolved within 20–30 min of injection.
• Abuse Liability and Drug reinforcement:
  There were no dose-related differences in measures of drug reinforcement and abuse liability.
• Efficacy:
  A) HAMD-17 scores decreased significantly by - 4.5 (mean difference) compared to baseline in MDD participants the day after receiving 0.3 mg/kg DMT.
  B) Reductions in depression were observed the day after DMT dosing, In contrast to other psychedelic treatment models.
  C) Persistent effect - reduction in HAMD17 scores -1 week later (data not captured in completed open label trial, data expected in trial underway).

In an exploratory double-blind, placebo-controlled, cross-over study, adults with migraine received oral placebo and psilocybin (0.143 mg/kg) in 2 test sessions spaced 2 weeks apart. Subjects maintained headache diaries starting 2 weeks before the first session until 2 weeks after the second session. Physiological and psychological drug effects were monitored during sessions and several follow-up contacts with subjects were carried out to assure safety of study procedures. Ten subjects were included in the final analysis. Over the 2-week period measured after single administration, the reduction in weekly migraine days from baseline was significantly greater after psilocybin (mean, - 1.65 (95% CI: - 2.53 to - 0.77) days/week) than after placebo (- 0.15 (- 1.13 to 0.83) days/week; p = 0.003, t(9) = 4.11). Changes in migraine frequency in the 2 weeks after psilocybin were not correlated with the intensity of acute psychotropic effects during drug administration.

Psilocybin was well-tolerated; there were no unexpected or serious adverse events or withdrawals due to adverse events. This exploratory study suggests there is an enduring therapeutic effect in migraine headache after a single administration of psilocybin.

The separation of acute psychotropic effects and lasting therapeutic effects is an important finding, urging further investigation into the mechanism underlying the clinical effects of select 5-HT2A receptor compounds in migraine, as well as other neuropsychiatric conditions.