May 1, 2018

expert reaction to study looking at MDMA-assisted psychotherapy for PTSD

Reporters present a study that tests MDMA in a clinical setting, alongside intensive psychotherapy, for veterans with post-traumatic stress disorder, as published in The Lancet Psychiatry.

Dr James Stone, Clinical Senior Lecturer, Institute of Psychiatry Psychology & Neuroscience, King’s College London (IoPPN), said:

“I think the press release is a good reflection of the science. This is a high quality double blind dose-response study and as such is the highest level of evidence for drug treatment studies. The conclusions are appropriate.

“In terms of limitations, as mentioned in the press release, this is a relatively small study. It was funded by the MAPS Public Benefit Corporation, which is a US based charity set up in order to investigate the clinical benefits of MDMA and other drugs. This study was one of 6 Phase II studies that led the FDA to give approval for the further Phase III investigation of MDMA assisted psychotherapy as a treatment for PTSD. The Phase III studies are currently in the planning stage, with funds currently being raised for this by MAPS (see https://www.maps.org/research/mdma/ptsd/phase3/timeline) and only after the results of that are known will we know whether MDMA assisted psychotherapy is likely to be approved as a treatment for PTSD. The fact that the researchers used a low dose of MDMA as the control is a strength of the study – it is hard to blind participants to whether they are getting a placebo or active compound when the active drug has strong physical or psychological effects. The use of lower dose MDMA and the finding that the lower dose was not as effective gives support to the idea that this is a drug-related effect rather than an epiphenomenon or placebo response.

“PTSD is a hard condition to treat because the most effective psychological treatment is very unpleasant for patients, and many people are not able to complete it. This study provides some of the first evidence that MDMA may allow more people to engage with effective psychological treatment for PTSD. It is exciting because this would be the first time in decades that such an approach has been used for the treatment of mental illness. However, this study was of a relatively small number of patients and it is too soon to tell whether MDMA assisted psychotherapy will be a useful treatment for PTSD. The results of Phase III studies (predicted to be due in 2021) will determine whether MDMA assisted psychotherapy might be used more widely in the treatment of PTSD.”

Prof. Neil Greenberg, Professor of Defence Mental Health, King’s College London and Royal College of Psychiatrists Lead for Military and Veterans’ Health, said:

“This looks like an interesting way of trying to help people suffering from chronic PTSD who have not responded well to previous treatment. However, it is not clear that all participants had received all available evidence based treatment before enrolling in the trial.

“As yet there is also an exclusion criteria which we do not know but will be revealed after a phase 3 trial

“22/26 people in the trial came from self-referral from the internet and one has to assume they were interested in taking a psychedelic drug. This would be an unusual attribute within veterans/emergency services personnel who were the focus of the trial. Indeed almost 1/4 of the subjects had taken MDMA before.

“Some of the prior talking treatments that subjects had received were not ones that are known to be evidence based (e.g. psychodynamic therapy or CBT which was not trauma-focused) and some had received medication which is not known to be effective with PTSD (e.g. stimulant medication).

“The 75mgs dose seemed to have a good positive effect on symptoms including at follow up.

“Also of note is that whilst serious side-effects were rare – suicidal ideation and cardiac problems happening in 5% of the sample with the understanding that people with chronic PTSD may well be not in ideal physical health in the first place.

“Overall, I would say this is an interesting pilot study but does not fundamentally change what service providers should be doing at present. Given the controversial nature of the medication, the risk of serious side effects and the small and biased sample mean that this should lead to a watch with interest comment rather than anything stronger.”

Prof. David Nutt, The Edmond J Safra Chair and Head of the Centre for Neuropsychopharmacology, Imperial College London, and founder of DrugScience, Independent Scientific Committee on Drugs, said:

Does the press release accurately reflect the science?

“Yes.”

Is this good quality research?  Are the conclusions backed up by solid data?

“Yes and it’s a necessary replication of a previous study in a different population of PTSD sufferers.”

How does this work fit with the existing evidence?

“This is a major extension of current, limited data sets – pooling these now gives a very significant effect size in the use of MDMA in treating PTSD.”

What are the implications for treating PTSD?

“This is the biggest breakthrough in medicinal PTSD treatment for two decades. The evidence is now sufficient to warrant the wider use of MDMA in treating PTSD.”

“Also there is good neuroscience evidence for how this might work – our research shows MDMA reduces negative memories and supresses amygdala activity and connectivity in healthy volunteers^{1, 2}”

“This is a very sophisticated combination of MDMA with intensive psychotherapy sessions with two skilled PTSD therapists – not something to be tried at home”

Carhart-Harris et al. (2014) The effect of acutely administered MDMA on subjective and BOLD fMRI responses to favourite and worst autobiographical memories, International Journal of Neuropsychopharmacology (https://doi.org/10.1017/S1461145713001405)

Carhart-Harris et al. (2015) The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level-Dependent Resting State Functional Connectivity, Biological Psychiatry (https://doi.org/10.1016/j.biopsych.2013.12.015)

Dr Michael Bloomfield, Clinical Lecturer in General Psychiatry, UCL, said:

“PTSD can be a potentially devastating condition.  Whilst many people benefit from existing treatments, there are some people who remain unwell despite current treatments.  This new, well conducted study adds to fascinating research which suggests that MDMA may be a candidate drug in a future era of medicine-assisted psychotherapy.

“However, larger research studies are needed which include a placebo group and can tease out which specific parts of the psychotherapy the MDMA may be helping with.  This research was conducted in a highly supervised setting using “medical grade” MDMA and so survivors of trauma who are experiencing PTSD should not try this on themselves because of the risks associated with street ecstasy and the need for good quality psychiatric care including psychotherapy in recovering from PTSD.”

* ‘3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial’ by Michael C Mithoefer, et al. published in Lancet Psychiatry on Tuesday 1 May 2018.

All our previous output on this subject can be seen at this weblink: http://www.sciencemediacentre.org/tag/ptsd/

Declared interests

Dr James Stone: I am employed by King’s College London. I have taken part in advisory board work for Janssen Pharmaceuticals in the last year.

Prof. David Nutt: Prof Nutt is about to conduct a study of MDMA in alcoholics who’s drinking is an attempt to deal with prior trauma

None received.