An experimental study has found use of MDMA combined with psychotherapy may help reduce symptoms of PTSD, although there is need for further testing
In a randomised, double-blind, dose-response, phase 2 clinical trial, US researchers have tested the safety and effectiveness of MDMA-assisted psychotherapy in 26 service personnel with post-traumatic stress disorder (PTSD).
Participants included military veterans, firefighters, and police officers who were 18 years or older, with chronic PTSD duration of 6 months or more.
The study, conducted in South Carolina 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.
Participants were randomly assigned to receive 30 mg (active control), 75mg or 125mg 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 two-to-five times before the study. The majority of participants were self-referred with 22 enrolling through internet advertisements or word of mouth, and four 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 (two-to-three 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 compared to the 30 mg group.
While the authors found statistically significant differences, 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,” says author Dr Allison Feduccia, Multidisciplinary Association for Psychedelic Studies (MAPS) Public Benefit Corporation, California, US.
“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.”
At one month, all participants were offered one-to-two 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 two had a renewed diagnosis. Twelve 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. However, the authors note that the study was not designed to explore mechanisms of action.
Writing in a linked Comment, Professors Andrea Cipriani and Philip J Cowen, University of Oxford, UK say: “MDMA is legally prescribed 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—i.e., 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.
“It is worth noting that 22 of the 26 participants were recruited via internet advertisement or word of mouth, which is likely to have enriched the sample with those keen to try the effect of MDMA, perhaps with resultant expectancy effects; this potential bias might limit the external validity of the findings.
“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.”
See the original study here