Response

The recent article titled ‘Transdiagnostic use of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy to treat obsessive–compulsive disorder (OCD)’ by Saade and Keuroghlian, and published in the British Journal of Psychiatry, ^{Reference Saade and Keuroghlian1} is noteworthy because it explores the potential mechanisms by which psychedelic-assisted therapy may be useful for the often treatment-resistant and disabling symptoms of OCD. Individuals with OCD have heard of psychedelic-assisted therapy and can occasionally ask about it in their desperate search for symptomatic relief. Because studies using psychedelic-assisted therapy are rapidly evolving, it is important that psychiatrists have an awareness of research in the field, including an understanding of both efficacy and safety features. Considering that exposure and response prevention therapy is regarded as the most effective and most evidence-based psychological therapy for OCD, it is fitting that the article attempts to understand how MDMA may assist this therapy.

The article highlights three potential mechanisms that might explain how psychedelics could augment the effect of exposure and response prevention therapy to alleviate symptoms of OCD. The first is to facilitate fear extinction during exposure and response prevention therapy, the second to promote metaplasticity and the reopening of social reward learning critical periods to facilitate psychological flexibility and generalizable learning; and the third is the promotion of self-compassion, healing from the ego dystonic experience of OCD and the interpersonal mediation of family accommodation via the empathogenic effect of MDMA-assisted psychotherapy.

The comparisons drawn between post-traumatic stress disorder (PTSD) and OCD are important, because exposure-based psychological therapy is central to treating both disorders and is met by resistance from individuals with OCD. This results in high drop-out rates due to the distress associated with exposing themselves to anxiety-provoking situations. ^{Reference Ong, Clyde, Bluett, Levin and Twohig2} There have been several published case reports and one small, published study, by Moreno et al, of the therapeutic effects of psilocybin for OCD. ^{Reference Moreno, Wiegand, Taitano and Delgado3} This study indicated an acute transient reduction in OCD symptoms, but there were only nine participants and no control group. The study faced additional shortcomings including lack of multiple therapeutic sessions both before and after treatment, and no long-term follow-up; it may thus be assumed that there was limited opportunity to use exposure and response prevention therapy, or to explore psychological flexibility or self-compassion in any meaningful way.

Clinical trials of psilocybin and MDMA are currently being conducted in Australia and the USA for people with OCD. ^{Reference Fitzgerald, Bailey, Fitzgibbon and Perera4–Reference Ehrmann, Allen and Moreno7} It should be noted that there are a number of design issues that have made psychedelics research difficult, including the potential difficulty in adequate blinding of studies due to the obvious effects of psychedelics and participant anticipation. An ongoing study by Ehrmann et al uses lorazepam as a control in an attempt to improve blinding. ^{Reference Ehrmann, Allen and Moreno7} Trials are also using biomarkers such as neuroimaging ^{Reference Yaden6} and longer follow-up periods, as well as assessing participant expectations and past experiences. The issue of high comorbidity rates in OCD also needs to be considered, because 90% of people with OCD are reported to have a further comorbid psychiatric disorder and 50% to have had a traumatic life experience. ^{Reference Ruscio, Stein, Chiu and Kessler8}

The paper concludes with some words of caution in relation to the potential for worsening of psychotic symptoms in people with comorbid schizophrenia whose diagnosis may have been missed, and the potential for serotonin syndrome. In addition, future research should consider the potential for hallucinogens to lead to a traumatic experience with worsening or emergent PTSD, suicidal ideation and ethical issues relating to the boundaries between the recreational and therapeutic use of psychedelics. ^{Reference Sisti9} Careful screening is paramount for the safety of all psychedelics work; ensuring that clinicians have a full understanding of previous symptoms and life experiences is critical to successfully guiding patients through their journey in a meaningful and careful way.

In conclusion, it is hoped that the results of future clinical trials will demonstrate the effectiveness of psychedelics in the treatment of OCD and give those who experience OCD more effective treatment options. However, there are important factors, such as the mechanisms of action and biomarkers, that need to be considered and assessed in future trials. The paper by Saade and Keuroghlian ^{Reference Saade and Keuroghlian1} is to be commended for exploring potential psychological mechanisms; improving our understanding of neurobiological mechanisms is also encouraged.