This review examines the role of trauma in psychiatric morbidity and analogous psychoneurobiological changes. Trauma is a necessary criterion for Post-Traumatic Stress Disorder (PTSD), however, trauma history is highly correlated with a variety of psychiatric conditions. Some evidence suggests that Major Depressive Disorder (MDD) is the most common psychiatric condition that arises following trauma. Approximately 50% of PTSD cases present with co-morbid MDD. Overlapping symptomatology and neurobiology between these conditions underlie the debate over whether these phenomena result from problematic nosology or whether comorbid MDD þ PTSD is a distinct phenotype of trauma-related psychopathology. Regardless, similar treatment approaches have been employed historically, with varying success. The drug-assisted psychotherapy treatment model, which combines pharmacological and psychotherapeutic approaches, is currently being trialled as a novel treatment approach in psychiatry. Both psilocybin-and 3,4-Methylenedioxymethamphetamine (MDMA)-assisted psychotherapy have received Food and Drug Administration 'breakthrough therapy' designation for the treatment of resistant MDD and PTSD, respectively. This paper reviews the therapeutic rationale of both psilocybin and MDMA for treating both trauma-related MDD and PTSD.
IntroductionPsilocybin-assisted therapy may be a new treatment for major depressive disorder (MDD), with encouraging data from pilot trials. In this trial (short name: PsiDeR) we aimed to test the feasibility of a parallel-group, randomised, placebo-controlled design. The primary outcomes in this trial are measures of feasibility: recruitment rates, dropout rates and the variance of the primary outcome measure of depression.Methods and analysisWe are recruiting up to 60 participants at a single centre in London, UK who are unresponsive to, or intolerant of, at least two evidence-based treatments for MDD. Participants are randomised to receive a single dosing session of 25 mg psilocybin or a placebo. All participants receive a package of psychological therapy. The primary outcome measure for depression is the Montgomery Asberg Depression Rating Scale collected by blinded, independent raters. The primary endpoint is at 3 weeks, and the total follow-up is 6 weeks. With further informed consent, this study collects neuroimaging and omics data for mechanism and biomarker analyses and offers participants an open label extension consisting of a further, open label dose of 25 mg of psilocybin.Ethics and disseminationAll participants will be required to provide written informed consent. The trial has been authorised by the National Research Ethics Committee (20-LO/0206), Health Research Authority (252750) and Medicine’s and Healthcare Products Regulatory Agency (CTA 14523/0284/001-0001) in the UK. Dissemination of results will occur via a peer-reviewed publication and other relevant media.Trial registration numbersEUDRACT2018-003573-97; NCT04959253.
The psychedelic state can be thought about as an interdependent intrapsychic, somatic, interpersonal and spiritual happening which encourages, perhaps both to the relief and dismay of those participating in the experience, the shocking and impressive emergence of one's unconscious desires and traumata's; a state which may be experienced as cathartic or healing, and as anxiety-provoking and confusing. Often, in clinical trials investigating psychedelics in mental health conditions, these go hand in hand. Amid a renewed, at times hyperbolic, interest in psychedelics as a potential treatment for mental ill health, significant gaps of knowledge remain. Additional studies exploring the impact of the extra-pharmacological factors and adjunct therapeutic models on treatment outcomes are needed. Drawing from psychoanalytic perspectives, this paper explores points of intersectionality between psychedelic therapy under investigation and psychoanalysis in the context of traumatic stress. To that end, the psychedelic state will be considered an attempt to make the unconscious conscious by immersing self in a bewildering waking-dream to better tolerate reality; immersing self in a wilful state of vulnerability, to develop trust in one's agency and capacity to trust others; immersing self in an indescribable experience to learn how to redescribe, to self and to others the traumatic past.
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