Psychedelic-Assisted Therapy for Post-Traumatic Stress

As with acceptance and commitment therapy, psychedelic medicines also increase psychological flexibility as we have learned.

Psychedelic medicines also decrease avoidance and, through acceptance, promote learning processes. Below is a proposed model of acceptance-promoting learning processes in the context of psychedelic-assisted therapy for treating PTSD.

Figure 3.1: Psychedelic-therapy-specific factors facilitating the learning process. Adapted from Wolff et al., 2020.

A Spectrum of Self-Perspectives

Psychedelic-assisted therapy supports a spectrum of self-perspectives, as we learned about in the Fundamentals of Psychedelic-Assisted Therapy course when we discussed internal family systems and parts work. The following diagram illustrates, moving from bottom to top, a journey toward the self-as-context in psychedelic-assisted therapy.

When people are fused in self-as-content perspectives (e.g. self-as-trauma, self-as-child, self-as-critic) there is less psychological flexibility and perspective taking and greater risk for psychopathology. Psychedelic-assisted therapy may powerfully promote alternative process and context-based perspective-taking, which may result in more compassionate self-perspectives or self-narratives, direct experience-based perspectives of self (distinct from any narratives), and ultimately unitive perspectives as described in mystical-type experiences.

Figure 3.2: Adapted from Whitfield, 2021.

MDMA-Assisted Therapy for Post-Traumatic Stress

As we learned in Molecular Foundations, MDMA-assisted therapy has been shown to be safe for those with chronic PTSD who have not had success with previous treatments (Bouso et al., 2008; Mithoefer et al., 2013). Additionally, MDMA-assisted therapy has been repeatedly shown to provide significant improvement in persons with PTSD, especially when it is moderate to severe (Jerome et al., 2020; Mithoefer et al., 2019; Mithoefer et al., 2011; Oehen et al., 2013).

A Phase 3 randomized, double blind, placebo-controlled trial of MDMA-assisted therapy with 90 participants suffering from severe PTSD and a range of common comorbidities displayed great efficacy from the treatment (Mitchell et al., 2021).

Long-term follow-up has displayed that benefits from the therapy are enduring, for example, lasting an average of 41 months in one study.

Relapse rate has also been shown to be low, for example, being 12.1% a year after treatment in one study

It was also reported that 67% of participants no longer met diagnostic criteria for PTSD (Jerome et al., 2020; Mithoefer et al., 2013).

A longitudinal pooled analysis of six Phase 2 trials displayed that PTSD symptoms were reduced 1-2 months after MDMA-assisted therapy, with symptoms continuing to improve at least 12 months after the treatment, which supported the expansion into Phase 3 trials and led to the FDA granting Breakthrough Therapy designation to this treatment method (Jerome et al., 2020; Mithoefer et al., 2019). Some research has been conducted specifically examining certain populations, such as service-related PTSD in first responders and veterans, where similar positive outcomes have been observed (Mithoefer et al., 2018).

Ketamine-Assisted Therapy for Post-Traumatic Stress

While less robust than the research literature on depression, there is now a growing body of evidence supporting the efficacy of ketamine for PTSD (Feder et al., 2021; Feder et al., 2014). This has led to a general recognition among clinicians that ketamine is a valid treatment choice for PTSD, particularly treatment-refractory PTSD (Cigognini, 2017; Dougherty et al., 2018; Slomski, 2014). Even more so than with depression, effective pharmacological treatments for PTSD are limited, which makes ketamine an increasingly attractive pharmacological option. This is particularly true given the rapid onset of PTSD symptom reduction with single-session ketamine administration (Dougherty et al., 2018).

References

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Bedi, G., Phan, K. L., Angstadt, M., & de Wit, H. (2009). Effects of MDMA on sociability and neural response to social threat and social reward. Psychopharmacology (Berl), 207(1), 73-83.

Bershad, A. K., Miller, M. A., Baggott, M. J., & de Wit, H. (2016). The effects of MDMA on socioemotional processing: Does MDMA differ from other stimulants? J Psychopharmacol, 30(12), 1248-1258.

Bouso, J. C., Doblin, R., Farré, M., Alcázar, M. A., & Gómez-Jarabo, G. (2008). MDMA-assisted psychotherapy using low doses in a small sample of women with chronic posttraumatic stress disorder. J Psychoactive Drugs, 40(3), 225-236.

Dames, S., Kryskow, P., & Watler, C. (2022). A Cohort-Based Case Report: The Impact of Ketamine-Assisted Therapy Embedded in a Community of Practice Framework for Healthcare Providers With PTSD and Depression. Frontiers in Psychiatry, 12(803279).

Davis, M., & Shi, C. (1999). The extended amygdala: are the central nucleus of the amygdala and the bed nucleus of the stria terminalis differentially involved in fear versus anxiety? Ann N Y Acad Sci, 877, 281-291.

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