Psychedelics for the Treatment of PTSD

 

    Post-Traumatic Stress Disorder (PTSD) is a disorder that affects millions of people that have witnessed/experienced traumatic events, the effects of which alter the futures of those affected. There are no defining parameters that identify people who will experience PTSD symptoms, however, certain factors such as length, intensity, and reaction to the trauma all play a role, it is thought that 1 in 10 men and 2 in 10 women that experience traumatic events will experience PTSD symptoms.¹

   The behaviors that accompany PTSD are thought to be incurred from stress induced structural changes in the amygdala, hippocampus, and the prefrontal cortex, as well as neurochemical changes (cortisol and norepinephrine) altering the long term circuitry that is involved in the stress response (Figure 1 and 2.).³ Each of these areas can be seen to play a role in the symptoms that accompany PTSD. The amygdala becomes hyperactive and amplifies both the flight or fight response and feelings of anxiety/fear. The hippocampus becomes underactive/down regulated showing decreases in hippocampal volume along with deficits in memory. The prefrontal cortex acts on logical thinking and also becomes down regulated, impairing executive cognitive function.²

                                     Figure 1. Effects of stress on the cortisol/norepinephrine neurochemical response.

                                               Figure 2. Overview of regulation in the main areas affected by PTSD.

    To date, the current treatment plans are time intensive and geared more towards cognitive reframing and mitigation of symptoms.¹ Trauma-focused therapy is the most common approach used for treating PTSD and commonly lasts 3-4 months.¹  Antidepressants continue to be the first line of defense against PTSD. Both SSRI (selective serotonin reuptake inhibitor) and SNRI (serotonin-norepinephrine reuptake inhibitor) have shown to be effective in treating PTSD symptoms because of their ability to increase neurogenesis within the hippocampus. However, the common themes in literature suggests that this approach is modest at best and new therapies must be introduced. The unique world of psychedelics has shown promise in the area of treating not only PTSD but also anxiety, depression, even addiction disorders. The Multidisciplinary Association for Psychedelic Studies (MAPS) has entered into phase 3 clinical trials for the use of 3,4-methylenedioxymethamphetamine (MDMA/Ecstasy) in the treatment of PTSD.

     The usage of MDMA as a treatment differs from other psychedelics as it acts as an enactogen rather than a hallucinogen. This enhancement in feelings of openness highlights the difference between the psychoactivity between the two, and this is precisely the lens that allows the patient to process and eventually accept traumatic memories.⁴ The first controlled study was completed in 2010 and showed significant results in psychoactive assisted therapy using MDMA. The study used 20 patients with treatment-resistant PTSD, with patients either receiving a placebo or MDMA at the regular treatment intervals (Figure 3.) At follow up appointments of 2 and 12 months, 83% of participants in the experimental group no longer met the criteria to be diagnosed with PTSD.⁴

Figure 3. Treatment outline.

    MDMA exerts its effect as a release of serotonin, noradrenaline and even dopamine. As an activator of the 5-HT system that enhances activity at the 5-HT1a and 5-HT1b; MDMA reduces the fear response elicited by the amygdala.^4,5 In addition to dampening of the fear response, MDMA aids in the release of oxytocin, yielding a feeling of bonding and closeness which facilitates the effect of psychotherapy and causes a decrease in the overall stress response.⁴

     While the advent of this research still lies ahead of us, the initial breach has shown promising results. Even though we may feel like we are viewing an event horizon, there is a promise of better days ahead and in all cases it can’t come quite soon enough. Yet, as the light starts to edge its way over the horizon,quickly approaching we can forget how fast progress moves.  MDMA is currently in Phase 3 clinical trials and may potentially be approved by the FDA in 2021.

Joseph Devine, Master’s Medical Sciences Student, University of Kentucky 

 References

 1.  Https://www.ptsd.va.gov/publications/print/understandingptsd_booklet.pdf. (n.d.). Retrieved November 17, 2020, from https://www.ptsd.va.gov/

2.  Oehen, P., Traber, R., Widmer, V., & Schnyder, U. (2012). A randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD). Journal of Psychopharmacology, 27(1), 40-52. doi:10.1177/0269881112464827

3.  Bremner, J. D., MD. (2006). Traumatic stress: Effects on the brain. Dialogues Clinical Neuroscience, 8(4), 445-461.

4.  Sessa, B., Higbed, L., & Nutt, D. (2019). A Review of 3,4-methylenedioxymethamphetamine (MDMA)-Assisted Psychotherapy. Frontiers in Psychiatry, 10. doi:10.3389/fpsyt.2019.00138

5.  Sessa, B. (2011). Could MDMA be useful in the treatment of post-traumatic stress disorder? Progress in Neurology and Psychology, 15(6).

6.  Devine, W. (2019). Crowd’s at 23rd. New York, NY: www.billydevine.com..