OPEN Foundation

Z. Walsh

MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials.

Abstract

BACKGROUND:
Posttraumatic stress disorder is a prevalent mental health condition with substantial impact on daily functioning that lacks sufficient treatment options. Here we evaluate six phase 2 trials in a pooled analysis to determine the study design for phase 3 trials of MDMA-assisted psychotherapy for PTSD.
METHODS:
Six randomized, double-blind, controlled clinical trials at five study sites were conducted from April 2004 to February 2017. Active doses of MDMA (75-125 mg, n = 72) or placebo/control doses (0-40 mg, n = 31) were administered to individuals with PTSD during manualized psychotherapy sessions in two or three 8-h sessions spaced a month apart. Three non-drug 90-min therapy sessions preceded the first MDMA exposure, and three to four followed each experimental session.
RESULTS:
After two blinded experimental sessions, the active group had significantly greater reductions in CAPS-IV total scores from baseline than the control group [MMRM estimated mean difference (SE) between groups - 22.0 (5.17), P < 0.001]. The between-group Cohen’s d effect size was 0.8, indicating a large treatment effect. After two experimental sessions, more participants in the active group (54.2%) did not meet CAPS-IV PTSD diagnostic criteria than the control group (22.6%). Depression symptom improvement on the BDI-II was greatest for the active group compared to the control group, although only trended towards significant group differences [MMRM, estimated mean difference (SE) between groups - 6.0 (3.03), P = 0.053]. All doses of MDMA were well tolerated, with some expected reactions occurring at greater frequency for the active MDMA group during experimental sessions and the 7 days following.
CONCLUSIONS:
MDMA-assisted psychotherapy was efficacious and well tolerated in a large sample of adults with PTSD. These studies supported expansion into phase 3 trials and led to FDA granting Breakthrough Therapy designation for this promising treatment.
Mithoefer, M. C., Feduccia, A. A., Jerome, L., Mithoefer, A., Wagner, M., Walsh, Z., … & Doblin, R. (2019). MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology, 1-11., https://doi.org/10.1007/s00213-019-05249-5
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Psychedelics and the new behaviourism: considering the integration of third-wave behaviour therapies with psychedelic-assisted therapy

This narrative review examines evidence related to the potential for third wave behaviour therapies to serve as adjuncts to psychedelic-assisted therapy. It identifies shared theoretical foundations for both approaches, and notes enhanced mindfulness, decentering, emotion regulation, and distress tolerance as common mechanisms of action. It also identifies potential targets for which both approaches have demonstrated therapeutic potential, including problematic substance use, self-directed and other-directed violence, and mood disorders. Based on these commonalities, there is a call for research on the potential integration of psychedelic-assisted therapy and third wave behaviour therapies including Dialectical Behaviour Therapy, Acceptance and Commitment Therapy, and Mindfulness Based Cognitive Therapy.

Walsh, Z., & Thiessen, M. S. (2018). Psychedelics and the new behaviourism: considering the integration of third-wave behaviour therapies with psychedelic-assisted therapy. International Review of Psychiatry30(4), 343-349., 10.1080/09540261.2018.1474088
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Psychedelic use and intimate partner violence

Abstract

Background:

Recent evidence suggests that psychedelic use predicts reduced perpetration of intimate partner violence among men involved in the criminal justice system. However, the extent to which this association generalizes to community samples has not been examined, and potential mechanisms underlying this association have not been directly explored.

Aims:

The present study examined the association between lifetime psychedelic use and intimate partner violence among a community sample of men and women. The study also tested the extent to which the associations were mediated by improved emotion regulation.

Methods:

We surveyed 1266 community members aged 16–70 (mean age=22.78, standard deviation=7.71) using an online questionnaire that queried substance use, emotional regulation, and intimate partner violence. Respondents were coded as psychedelic users if they reported one or more instance of using lysergic acid diethylamide and/or psilocybin mushrooms in their lifetime.

Results/outcomes:

Males reporting any experience using lysergic acid diethylamide and/or psilocybin mushrooms had decreased odds of perpetrating physical violence against their current partner (odds ratio=0.42, p<0.05). Furthermore, our analyses revealed that male psychedelic users reported better emotion regulation when compared to males with no history of psychedelic use. Better emotion regulation mediated the relationship between psychedelic use and lower perpetration of intimate partner violence. This relationship did not extend to females within our sample.

Conclusions/interpretation:

These findings extend prior research showing a negative relationship between psychedelic use and intimate partner violence, and highlight the potential role of emotion regulation in this association.

Thiessen, M. S., Walsh, Z., Bird, B. M., & Lafrance, A. (2018). Psychedelic use and intimate partner violence: The role of emotion regulation. Journal of psychopharmacology, 0269881118771782.
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The relationships of classic psychedelic use with criminal behavior in the United States adult population

Abstract

Criminal behavior exacts a large toll on society and is resistant to intervention. Some evidence suggests classic psychedelics may inhibit criminal behavior, but the extent of these effects has not been comprehensively explored. In this study, we tested the relationships of classic psychedelic use and psilocybin use per se with criminal behavior among over 480,000 United States adult respondents pooled from the last 13 available years of the National Survey on Drug Use and Health (2002 through 2014) while controlling for numerous covariates. Lifetime classic psychedelic use was associated with a reduced odds of past year larceny/theft (aOR = 0.73 (0.65-0.83)), past year assault (aOR = 0.88 (0.80-0.97)), past year arrest for a property crime (aOR = 0.78 (0.65-0.95)), and past year arrest for a violent crime (aOR = 0.82 (0.70-0.97)). In contrast, lifetime illicit use of other drugs was, by and large, associated with an increased odds of these outcomes. Lifetime classic psychedelic use, like lifetime illicit use of almost all other substances, was associated with an increased odds of past year drug distribution. Results were consistent with a protective effect of psilocybin for antisocial criminal behavior. These findings contribute to a compelling rationale for the initiation of clinical research with classic psychedelics, including psilocybin, in forensic settings.
Hendricks, P. S., Crawford, M. S., Cropsey, K. L., Copes, H., Sweat, N. W., Walsh, Z., & Pavela, G. (2017). The relationships of classic psychedelic use with criminal behavior in the United States adult population. Journal of Psychopharmacology, 0269881117735685.
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Hallucinogen use and intimate partner violence: Prospective evidence consistent with protective effects among men with histories of problematic substance use

Abstract

Evidence suggests that hallucinogens may have therapeutic potential for addressing a variety of problem behaviors related to the externalizing spectrum of psychopathology, such as substance misuse and criminality. Intimate partner violence (IPV) is a prevalent form of criminal violence that is related to externalizing pathology. However, the association between hallucinogen use and IPV has not been comprehensively examined. In this prospective study, we examined the association between IPV and naturalistic hallucinogen use among 302 inmates at a US county jail. Cox regression analyses indicated that hallucinogen use predicted reduced arrest for IPV independently (β=−0.54, SE=0.20, χ2=7.19, exp(B)=0.58, p<0.01) and after accounting for covariates (β=−0.48, SE=0.23, χ2=4.44, exp(B)=0.62, p<0.05). These results add to a growing literature suggesting distinct therapeutic potential for hallucinogens to assist in the attenuation of problematic behavior.

Walsh, Z., Hendricks, P. S., Smith, S., Kosson, D. S., Thiessen, M. S., Lucas, P., & Swogger, M. T. (2016). Hallucinogen use and intimate partner violence: Prospective evidence consistent with protective effects among men with histories of problematic substance use. Journal of psychopharmacology (Oxford, England). http://dx.doi.org/10.1177/0269881116642538
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22 May - Delivering Effective Psychedelic Clinical Trials

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