The incidence of post-traumatic stress disorder (PTSD) is rising globally, impacting approximately 6-7% of all adults. PTSD presents a complex clinical picture, often complicated by resistance to conventional therapies which typically comprise medications or therapy-based approaches.
The rising burden of PTSD is further compounded by our mental health capacity constraints. Patients struggle to obtain out-patient appointments, and there is increasingly limited access to inpatient care and support among specialists. Against this backdrop, MDMA-assisted therapy (MDMA-AT) is emerging as a novel and promising approach, particularly in Australia, where a legal access pathway was established on July 1, 2023.
This update provides an overview of MDMA-AT and its real-world potential.
Current PTSD treatments
The current clinical guidelines for PTSD recommend psychological treatments such as Cognitive Behaviour Therapy (CBT) and Eye Movement Desensitisation and Reprocessing (EMDR), as well as SSRIs (e.g., sertraline, paroxetine) and SNRIs (e.g., venlafaxine).
Typical pharmacotherapy, while effective for some, is associated with variable efficacy, acceptability challenges, and adverse effects increasing the risk of discontinuation. Notably, there have been no new drug approvals for PTSD treatment in over 20 years. Psychological interventions, although effective, require significant time, engagement, and access to trained professionals, which can be a barrier given the strained mental health resources.
MDMA-assisted therapy (MDMA-AT)
MDMA-AT represents a new paradigm in the treatment of PTSD. This approach involves the careful co-administration of
3,4-methylenedioxymetham-
phetamine (MDMA or ‘ecstasy’).
The unique pharmacological action of MDMA facilitates the release of serotonin, dopamine and noradrenaline by reversing membrane-bound transporter proteins and inhibiting reuptake as well as stimulating neurohormonal signalling of oxytocin. The dynamic interaction of these neurotransmitters and hormones produces a range of subjective effects that are believed to enhance the therapeutic process by reducing fear responses, increasing emotional engagement and increasing feelings of trust. These experiences allow patients to process traumatic memories with greater ease.
In practice, a typical MDMA-AT program will involve 2–3 administrations of MDMA in a controlled and supervised setting 2-4 weeks apart, in conjunction with several non-drug therapy sessions before and after by two therapists. Recent phase 3 clinical trials demonstrated that MDMA-AT significantly reduced PTSD symptoms and functional impairment in a diverse population with moderate to severe PTSD, with a higher effect size compared to placebo with therapy.
More than 80% of participants in the active arm achieved a clinically significant improvement in PTSD symptoms and over two thirds achieved a remission as measured by the CAPS-5. Importantly, MDMA-AT was well tolerated, with most adverse events being mild and transient.
Australia’s role in MDMA-AT
On July 1, 2023, Australia became one of the first countries to establish a legal access pathway for MDMA-AT, creating an unprecedented opportunity to explore this therapy in a real-world setting. This regulatory progress reflects an urgent need to address the limitations of existing treatments and the broader capacity challenges within the mental health system.
However, the delivery of MDMA-AT presents several complexities, including the requirement for specialised training, comprehensive patient screening, and robust clinical protocols to ensure safety and efficacy. Today, MDMA can only be prescribed by TGA-endorsed Authorised Prescriber psychiatrists who must also present a care model that has been endorsed by an NHMRC-accredited ethics committee.
A multidisciplinary and personalised approach
MDMA-AT represents a necessarily multidisciplinary approach, integrating elements of pharmacology, psychology, and holistic patient care. This therapy offers a more personalised treatment pathway, potentially redefining how we tackle PTSD and other complex mental health conditions with input from psychologists, psychiatrists and other mental health specialists.
Conclusion
As the incidence of PTSD continues to rise and the capacity of traditional mental health systems remains strained, by advancing our understanding and refining the delivery of MDMA-AT, we aim to contribute to a broader reorganisation of mental health care, emphasising multidisciplinary, thorough, and personalised approaches that can meet the growing demand for effective PTSD treatment.
– References available on request
Author competing interests –
Dr Michael Winlo is the CEO of Emyria Ltd which partners with Pax Centre for MDMA-assisted therapy for patients with complex PTSD. Dr Laugharne is
a co-founder of the Pax Centre