MDMA-assisted Therapy a “Promising New Treatment” for PTSD, Finds Review
MDMA-assisted psychotherapy holds significant potential as a novel treatment for severe post-traumatic stress disorder (PTSD), say scientists.
In a new literature review published in the European Journal of Psychotraumatology, the researchers from the University of Cardiff sifted through 21 randomized controlled trials that tested the effectiveness of drug-assisted psychotherapy in treating PTSD.
They found MDMA-assisted psychotherapy (MDMA-AP) to have a particularly “impressive effect size” in reducing PTSD symptoms, concluding that MDMA-AP is “the most promising novel treatment for chronic and often treatment-resistant PTSD”. However, the researchers say that larger-scale phase three trials are still needed before MDMA-AP can be fully recommended as safe and effective for clinical practice.
Pharmacological-assisted psychotherapy, explained
PTSD is ordinarily treated through a trauma-focused therapy technique, whether that is prolonged exposure (PE), cognitive processing therapy (CPT), cognitive therapy for PTSD (CT-PTSD), or eye movement desensitization and reprocessing (EMDR).
But crucially, for any of these techniques to work, the person with PTSD must remain emotionally engaged with the traumatic memory during the course of the therapy session – something which can be extremely difficult for many given distress and emotional numbing that can come with PTSD.
By using drugs that affect the brain’s fear extinction mechanism in combination with therapy – an approach called pharmacological-assisted psychotherapy – people with PTSD could potentially go into their therapy sessions with an already reduced symptom load, allowing for more emotional engagement. There are also hopes that pharmacological-assisted psychotherapy could lessen the effects of hypervigilance and social detachment in PTSD patients, and so create a better relationship between the patient and their therapist.
MDMA outperforms antidepressants in drug-assisted therapy trials
In an earlier systematic review of randomized controlled trials, the University of Cardiff team found only small improvements in therapy reducing PTSD symptom severity when combined with antidepressants. Given the relatively disappointing effects seen in these studies, researchers in the field are now beginning to investigate the effects of more unconventional agents – including psychedelic drugs – on trauma when combined with psychotherapy.
In this new review, the scientists screened over ten thousand studies on the topic, finally narrowing the search to 115 studies dealing with pharmacological approaches to PTSD. Twenty-one of these studies dealt directly with pharmacological-assisted psychotherapy and were chosen to form the basis of this review.
The majority of the studies focused on the use of selective serotonin reuptake inhibitor (SSRI) and serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressants or beta blockers in pharmacological-assisted psychotherapy. However, four employed the use of the psychedelic MDMA (3,4-methylenedioxymethamphetamine) as an unconventional drug-assisted intervention.
Reviewing the results of the studies, the researchers found that only MDMA-AP was statistically superior to using a placebo in reducing PTSD symptom severity. When considered collectively there was a very small positive effect seen in the other pharmacologically assisted therapies. But individually there was no evidence to suggest greater effectiveness than the placebo, and certainly not a greater effectiveness on PTSD symptomatology than MDMA.
Three out of the four MDMA-AP studies reported zero adverse events related to using MDMA, with the fourth having one “possibly related” to the study drug. In addition to being well-tolerated, there is also evidence that MDMA-AP might be useful for patients who did not find success with therapy alone or with SSRI treatment, as two of the MDMA studies included patients with chronic drug-resistant PTSD.
However, the University of Cardiff researchers caution that more research is needed before MDMA-AP can be confidently recommended for clinical use. The four MDMA-AP studies focused on only 85 patients and a larger sample size is needed to conclusively prove the drug’s safety and efficacy. Also, as MDMA can cause hallucinations, it is difficult to create a properly blinded study because participants should realize if they have taken the drug or not. Three of the four studies employed low-dose MDMA to act as a placebo to assist with the blinding.
Furthermore, all four studies were managed and funded by a single sponsor, the non-profit Multidisciplinary Association for Psychedelic Studies (MAPS), which could increase the risk of bias.
But now that the US Food and Drug Administration (FDA) has granted MDMA a Breakthrough Therapy Designation, and the substance is currently being tested in phase two trials in the USA, Israel, and Canada, the researchers expect this evidence base to widen appropriately in the near-future.
The emergence of psychedelics in medicine
The use of psychedelic drugs in therapy sessions might seem like some outlandish new idea, but psychedelic medicine is a movement that has been around for decades.
Synthesis of the psychedelic LSD in the 1930s led to new breakthroughs in understanding how serotonin works in the human body. Two decades later, scientists discovered ketamine, a psychedelic drug that is still in common clinical use as an anesthetic. But the use of psychedelics extends even further back than the 1900s. For many centuries plant-derived psychedelics have been used and revered by indigenous cultures as an important part of spiritual ceremonies and indigenous medicine.
Burdensome government regulation suppressed psychedelics research for most of the past 50 years. But now, psychedelics such as psilocybin (the active component in magic mushrooms) are re-emerging in mainstream scientific research as a novel treatment for addiction, mood disorders, and other mental health problems.
“In our lab, we're mainly focusing right now on psilocybin for therapeutic studies, but we have done work here with lots of different types of drugs, including dextromethorphan and Salvinorin A [a dissociative hallucinogen],” Albert Garcia-Romeu, an assistant professor at the Center for Psychedelic and Consciousness Research at Johns Hopkins University, recently told Analytical Cannabis. Earlier this year the team at Johns Hopkins University authored a paper detailing the history and resurgence of this clinical interest in psychedelics.
“With psilocybin, the main areas that are being studied are mood disorders and depression. There's been work looking at a treatment of addiction, like tobacco or nicotine addiction, alcohol dependence, and cocaine. We're working on studies for opioid dependence as well. Those have been some of the main areas that were kind carryovers from the 1960s, where they showed promise and we’ve picked that back up more recently,” Garcia-Romeu explained.
“The other big areas were more in the palliative care side, for patients with terminal illnesses who also have mental health challenges like anxiety, depression, and usually don't tend to respond very well to the normal course of antidepressant medications.”
Researchers in the field are keen to avoid another episode of prohibition befalling the current interest in psychedelics research. The best avenue for doing so, the Johns Hopkins University researchers conclude in their paper, is to solidify the compounds’ legitimacy with a focus on creating more ethical and high-quality randomized controlled trials – like those being conducted on MDMA.
