Special Report: Psychedelics in Medicine Part 2: Psychedelics for depression & trauma-related disorders

Section 2: Psychedelics for depression & trauma-related disorders

Posttraumatic Stress Disorder (PTSD) and other trauma-related conditions are common across the globe and particularly pernicious among combat veterans. For patients who have not responded well to traditional first line pharmacotherapy or counselling, psychedelics may be considered as an alternative or adjunct treatment in the future. In some studies, the effects of psychedelics, such as lysergic diethylamide (LSD), psilocybin, and methylenedioxymethamphetamine (MDMA) suggest an ability to improve mood and help people recover from traumatic events.[1] For example, racial minority groups are generally underrepresented in psychedelic drugs research, but it has been discovered that therapeutic doses of LSD, psilocybin, and MDMA reduced mental health and traumatic stress symptoms, even after controlling for level of racial discrimination.[2]  One study investigated the psychological effects of ibogaine, a psychoactive indole alkaloid, among Special Operations Forces personnel. Substantial reductions in suicidal ideation, depression, anxiety, PTSD symptoms, and cognitive impairment were found. Regarding the psychedelic experiences themselves, 84% of the sample reported them as one of the top five personally meaningful experiences of their lives.[3] An increase in psychological flexibility is noted in numerous studies as mediating the relationship between acute psychedelic effects and reductions in depression and anxiety, including international samples,[3,4] suggesting that psychedelics may be of even greater value when used to enhance psychotherapy. For example, MDMA-assisted psychotherapy trial has completed Phase 3 with positive results for individuals with PTSD, with approximately 67% of participants no longer meeting criteria for PTSD two months after treatment.[5,6]

In addition to PTSD, substantial research has recently been done investigating the potential usage of psychedelic drugs for anxiety and depression. A psychedelic drug less common in research is 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), is known for recreational use to achieve spiritual enlightenment and other subjective effects. In recent literature, there is evidence that up to 80% of participants with depression and anxiety experience significant reductions following use of 5-MeO-DMT. These improvements were not associated with the intensity of negative drug effects, though they were associated with positive, mystical drug effects.[7] Users often associate these mystical outcomes to benefit enhancement strategies to reduce risk of negative drug experiences.[8] These same mystical experiences, in the context of psilocybin, mediate positive effects on personal meaning up to 14 months after drug administration.[9,10] These results extend to individuals with comorbid medical conditions such as terminal cancers, with depression and anxiety being common experiences. Psilocybin is one drug that showed improved mood and anxiety symptoms at five weeks, with approximately 80% of patients experiencing sustained improvements at six-month follow-up, with a dose-dependent effect.[11,12] However, even a single dose of psilocybin has demonstrated ability to reduce negative affect and amygdalar responses, as well as increase positive affect and pre- and orbitofrontal cortices responses, when confronted with emotionally-conflicting stimuli.[13]

In summation, there is a substantial and strong body of evidence supporting psychedelic drugs to benefit patients with mood disorders and trauma-related symptoms.

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