-- Small study suggests that careful administration of MDMA in a clinical setting alongside intensive psychotherapy is safe and might be effective, but further research required in phase 3 trial
A new experimental study has tested the safety and effectiveness of MDMA-assisted psychotherapy in 26 service personnel with post-traumatic stress disorder (PTSD). The study, conducted in South Carolina, USA and published in The Lancet Psychiatry journal, suggests that carefully supervised administration of MDMA (3,4-methylenedioxymethamphetamine, the main active drug compound found in ecstasy), delivered in a clinical setting alongside intensive psychotherapy is safe and might enhance the benefits of psychotherapy in the treatment of PTSD.
However, the small experimental study involved only 26 people, and the outcomes of a phase 3 trial will be needed before the potential for the therapy to influence available treatments can be fully assessed. The study did not include an inactive placebo control group, nor did it compare the intervention to current treatments.
Prevalence of PTSD in military personal and veterans (17.1%), and first responders (10-32%) is higher than in the general population (8%). Treatments for PTSD include pharmacotherapy and psychotherapy. Trauma-focused psychotherapies are more effective than pharmacotherapy, but drop-out rates are high (27-40%), and off-label prescriptions of drugs are common, suggesting the need for improved treatments for PTSD.
26 service personnel (22 veterans; 3 firefighters; 1 police officer) took part in the study. All had PTSD for at least 6 months resulting from a traumatic experience during their service. Participants were randomly assigned to receive 30 mg (7 participants), 75mg (7) or 125mg (12) doses of MDMA plus psychotherapy. Neither the participants nor their clinicians were informed of the doses they received.
Six (23%) of the participants had previously taken ecstasy 2-5 times before the study. The majority of participants were self-referred with 22 enrolling through internet advertisements or word of mouth, and 4 enrolled through referral from a mental health professional.
Before the first dose of MDMA, participants took part in three 90-minute psychotherapy sessions to establish a therapeutic alliance with the therapist and prepare for the MDMA experience. MDMA was then administered during 8-hour experimental sessions of specially adapted psychotherapy. These were followed by an overnight stay, seven days of telephone contact, and three 90 minute psychotherapy sessions aimed at integrating the experience. Overall, each course of treatment included 18 hours of non-drug psychotherapy and 16-24 hours (2-3 sessions) of MDMA-assisted psychotherapy.
One month after the second session took place, more participants in high dose groups no longer met diagnostic criteria for PTSD compared with the low-dose group (7/12 [58%] in the 125 mg group; 6/7 [86%] in the 75 mg group; 2/7 [29%] in the 30 mg group). On average, the 75 mg and 125 mg groups experienced greater decreases in PTSD symptom severity (CAPS-IV mean change -58.3 and -44.3) compared to the 30 mg group (-11.4). While the authors found statistically significant differences even though the study was not powered for this, further research from large multi-site phase 3 studies is required to obtain definitive results regarding safety and efficacy.
All groups reported adverse events that emerged after the treatment (8/12 [67%] in the 125 mg group; 6/7 [86%] in the 75 mg group; 6/7 [86%] in the 30 mg group). These included anxiety, headache, fatigue, muscle tension and insomnia. During the treatment transient increases in suicide ideation were observed, including one participant with a history of suicide attempts who was admitted to hospital by their psychiatrist after the session, but who later completed the study.
"Key elements that contribute to the safety and efficacy of MDMA-assisted psychotherapy include careful medical and psychological screening, preparing participants for the MDMA experience and treatment, close support by trained psychotherapists during the sessions as well as professional follow-up support. In this environment, our study suggests that MDMA might help augment the psychotherapeutic experiences and may have a role to play in the future treatment of PTSD. However, we would certainly not recommend that individuals try these drugs for the treatment of psychiatric disorders without the support from trained psychotherapists," says author Dr Allison Feduccia, Multidisciplinary Association for Psychedelic Studies (MAPS) Public Benefit Corporation, Santa Cruz, CA, USA. [1]
At one month, all participants were offered 1-2 additional MDMA sessions at 100 or 125 mg, followed by three 90 minute psychotherapy sessions. At 12 months, 16 participants still did not meet criteria for PTSD diagnosis, but 2 had a renewed diagnosis. 12 participants were also taking other psychiatric medications. This part of the trial was "open-label" meaning participants and clinicians knew what doses they were given. More research is required to fully understand the long-term effect of the therapy.
Participants who had not previously taken ecstasy before the study did not report taking it after having received MDMA as part of the trial.
"This model of treatment is different to most pharmacological interventions, in that its effectiveness appears to be mediated through pharmacological effects augmenting meaningful psychotherapeutic experiences," adds Dr Feduccia. [1] However, the authors note that the study was not designed to explore mechanisms of action.
The study published today builds on two previously published studies led by MAPS Public Benefit Corporation but with different therapists - the first comparing MDMA-assisted psychotherapy with placebo (20 participants), and the other comparing two doses of MDMA (12 participants) [2]. They are among the six phase 2 trials that led to the US FDA designation of MDMA-assisted psychotherapy for PTSD as a "Breakthrough Therapy."
Writing in a linked Comment, Professors Andrea Cipriani and Philip J Cowen, University of Oxford, UK say: "MDMA is legally proscribed and there have been numerous safety concerns attached to its recreational use in the form of ecstasy, which might not contain pure MDMA, including acute fatal toxicity as well as the possibility of long-term cognitive impairment and damage to serotonin neurons. Recreational users can also experience a rebound--ie, lowering of mood a few days after MDMA ingestion--which is a particular concern in individuals vulnerable to depression and suicidal feelings." However, they note "that with rigorous sourcing of MDMA and close medical and psychological supervision, its short-term use in carefully selected patients with PTSD seems safe... This current study describes the therapeutic use of MDMA by committed experts in a specialised setting in a small group of participants, most of whom self-referred for the trial. The unmet need for better PTSD treatment, particularly in veterans and first responders, is undoubted. However, the generalisability of the benefit of MDMA-assisted psychotherapy to more mainstream psychiatry remains to be established."
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NOTES TO EDITORS
The study was funded by the Multidisciplinary Association for Psychedelic Studies.
[1] Quotes direct from author and cannot be found in the text of the Article
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122379/ https://www.ncbi.nlm.nih.gov/pubmed/23118021 https://www.ncbi.nlm.nih.gov/pubmed/23172889
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Journal
The Lancet Psychiatry