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Pharmacology student, politics nerd. One time I breathed in a bit of a dead guy.

Agony and Ecstasy

Why MDMA represents the next step in mental healthcare

Posttraumatic Stress Disorder (PTSD) is a recent name for a condition as old as human conflict, its new name reflecting our evolving understanding of a condition which has been variously attributed to traumatic brain injury, psychological fatigue, and most commonly, cowardice.

Baby Steps

Following the First World War, the understanding of PTSD as a medical condition developed incrementally. Funding and interest spiked following the Second World War and the invasion of Vietnam, then reached a steady simmer in our modern climate of incessant combat. We now understand PTSD as a complex illness involving changes in the neurochemistry and neuroanatomy of a patient as well as their psychology, and suspect that it can be predicted in part by their genetics and personality. However, these developments all carry some degree of doubt and controversy. Discussing these conflicts is out of the scope of this article, but we would be remiss not to mention them.

Primarily characterised by regularly reliving the associated trauma (either consciously or through nightmares and dissociative flashbacks), PTSD sufferers will often carefully avoid anything which reminds them of their experience. However, if patients find themselves triggered by something relatively commonplace, this defence mechanism itself is unhealthy, leading to isolation from friends and family or even from the outside world entirely: this is partly why PTSD is often associated with anxiety, depression and dissociative disorders. Combined with several broader symptoms such as hypervigilance, mood swings and cognitive impairments, this produces a complex condition which may present with any number of these symptoms in varying degrees of severity.

For some, PTSD is a simple anxiety disorder; for many it is a disabling condition which drives them from their families, their jobs and ultimately their homes. The image of the homeless, mentally-ill veteran is so well-worn that it’s almost cliché, but for tens of thousands who came home from war, shaken to their core and unable to return to normal life, it is a reality. Additionally, in the US—where two thirds of homeless veterans have PTSD—it’s extremely difficult and expensive to get treatment for the condition.

There is no shortage of medications which can help to manage the symptoms and secondary conditions listed above. PTSD itself is an extremely complex condition and even if a cocktail of drugs were provided to balance out the numerous subtle effects it has on the brain, it would be a sticking plaster covering up a bone-deep wound. Fortunately, psychiatric therapy has developed enormously since our first shaky steps into understanding this illness, and now enjoys record-high success rates of about 55%. While this figure may seem rather underwhelming, it represents a huge leap forward and a strong base from which future treatments can develop: the overwhelming majority of patients experience improvement, if not a cure, and continued treatment will still benefit them. While it would be near-impossible to create a drug to emulate this, one already exists which can radically increase the efficacy of psychotherapy.

Enter MDMA

MDMA (the illegal drug commonly known "ecstasy") was first invented as a useless precursor for methylhydrastinine (best known now as “what they were trying to make when they invented MDMA”) in the late 1960s. For much of the period between this time and the time of its prohibition in 1985, it was used almost exclusively in psychiatric settings. The reasoning was that the effects of MDMA increased trust and bonding between patient and psychiatrist and, while little formal research was carried out in this field for fear of provoking the attention of the US federal government, reports from clinical use and informal study were overwhelmingly positive.

Such a unique compound as MDMA couldn’t evade recreational popularity for long though, and as its use became more widespread it was banned in the US. It was then also added to Schedule I of the 1971 UN Convention on Psychotropic Substances (deemed as worthless and dangerous as psilocybin and LSD, and more so than heroin, cocaine or crystal meth), repudiating any possible medical value it may hold and leading to copycat bans around the world. Shortly afterwards, the Multidisciplinary Association for Psychedelic Science (MAPS) was founded to promote research into banned substances such as cannabis, psychedelics and “atypical psychedelics” like MDMA and ketamine, and to explore their medical value. During this time, however, research into their dangers continued unabated.

The primary risks taken by a recreational MDMA user relate to its criminal nature: adulteration with amphetamines, piperazines and others, as well as the unknown dose contained in a pill or questionably-pure powder have caused a great deal of suffering since MDMA’s criminalisation. Recreational users have thus been hospitalised and killed by hyperthermia, dehydration, or hyponatremia.

It would be irresponsible to discount the harm presented by MDMA itself, such as the danger of valvulopathy in the heart and oxidative stress in the brain which presents itself following heavy, long-term use. It would, however, be equally irresponsible to overstate them, as these risks are manageable and the value of MDMA as a clinical compound arguably outweighs them.

One Small Step for Mandy

It was decades before MAPS were finally able to conduct their first pilot study in 2010, treating PTSD in combat veterans with talk therapy sessions while the patient was on a moderate recreational dose of the drug (125mg). They found that while the therapy alone elicited a strong response in 25% of patients receiving a placebo, adding MDMA increased this effect by more than threefold to 83%, the majority of which was achieved after a single session. The reasoning for this has changed little since the 60s, and the primary change made in modern sessions is solidifying a clear methodology.

Michael Mithoefer (also the primary investigator in the clinical trials) has published an extensive manual on the conduct for trials and, by extension, therapy itself. Detailing everything from dosage to furniture placement, the 73-page document provides a key element in the success of MAPS’s trials which was lacking in pre-prohibition investigation: consistency.

Trials have been conducted across North America and Europe by different investigators, but their results can be easily collated through the use of this single method for treatment and data collection. The distributed nature of the trials mean that, even though they are individually very small, they can be considered replications of an experiment. This earns them a greater deal of evidential significance—enough at least for the FDA to greenlight Phase 3 clinical trials.

Unfortunately, the continued criminality of MDMA and psychedelic drugs leaves them cloaked in danger and taboo, and meaningful discussion of the very real threats presented by their abuse are often lost among sensationalised stories of cannibal bath salts and dead teenagers. However, thanks to the pioneering work of MAPS and universities such as Johns Hopkins, MIT and KCL, real information is filtering into the media and the conversation around the medical value of these compounds is changing for the better.

Riding the wave of this changed dialogue, MAPS plans to achieve FDA approval for PTSD therapy by 2021, and subsequently to open the floodgates for further research. Once MDMA is approved, it will have to be removed from Schedule I, meaning that it will become infinitely cheaper and more expedient to run trials with the drug. In short order, it would likely receive approval for several other conditions it could easily be used in, running the gamut from generalised anxiety disorder to major depression in terminal cancer patients (a condition already being explored with psilocybin). Don’t expect to see it in your local pharmacy though—as MDMA therapy is conducted inside a clinic, its production and supply will remain tightly monitored, regulated more like chemotherapy drugs than any model for medicinal cannabis.

However, the patent for MDMA has lapsed, so it would be impossible to make any significant profit from selling it. MAPS therefore relies entirely on private donations to fund their vital research, which can revolutionise the world of mental healthcare if it succeeds, preventing countless thousands from having to rely on powerful daily medications to mask their symptoms, or losing their entire lives for want of them.

To help support MAPS’s work with MDMA or to learn about their other work with drugs such as LSD, iboga and cannabis, visit them at http://www.maps.org/

References

Bradley, R., Greene, J., Russ, E., Dutra, L. and Westen, D., 2005. A multidimensional meta-analysis of psychotherapy for PTSD. American journal of Psychiatry, 162(2), pp.214-227. DeAngelis, T., 2013. More PTSD Among Homeless Vets. apa.org. Available at: http://www.apa.org/monitor/2013/03/ptsd-vets.aspx (Accessed 5/4/2017) Mithoefer, M., 2013.

MDMA-Assisted Psychotherapy: How Different Is It From Other Psychotherapy?. Mdmaptsd.org. Available at: https://tinyurl.com/MDMAPTSD (Accessed 28/3/2017) Mithoefer, M.C., Wagner, M.T., Mithoefer, A.T., Jerome, L. and Doblin, R., 2011.

The safety and efficacy of±3, 4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. Journal of Psychopharmacology, 25(4), pp.439-452. Shulgin, A. and Shulgin, A., 1991.

PiHKAL: A Chemical Love Story. Berkeley: Transform Press. United Nations Commission on Narcotic Drugs (1986), Inclusion of 3,4-methylenedioxymethamphetamine (MDMA) in Schedule I of the 1971 Convention on Psychotropic Substances. Available at: https://tinyurl.com/UN-MDMA (Accessed 8/2/2017).

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