PTSD – Agony and Ecstasy

Post-Traumatic Stress Disorder (PTSD) is a mental disorder that can develop after a person is exposed to a traumatic event, such as sexual assault, warfare, traffic collisions, or other threats on a person's life.

In November of 2016, the US Food and Drug Administration (FDA) gave permission for the commencement of large-scale Phase 3 clinical trials into the use of MDMA (Ecstasy) in the treatment of PTSD. If successful, the trials could see an illicit street substance become a potent treatment for PTSD by 2021.

In the typical case, the individual with PTSD persistently avoids trauma-related thoughts and emotions, and discussion of the traumatic event, and may even have amnesia of the event. However, the event is commonly re-lived by the individual through intrusive, recurrent recollections, flashbacks, and nightmares.

Drug abuse and alcohol abuse commonly co-occur with PTSD. Recovery from posttraumatic stress disorder or other anxiety disorders may be hindered, or the condition worsened, by medication or substance use. There is also a high risk of suicide associated with the condition.

Existing pharmacological and psychotherapeutic treatments for PTSD are effective for many, but prove ineffective for 30-40 percent of sufferers. Due to the rate of treatment resistance, research into more effective treatment is necessary.

The Multidisciplinary Association for Psychedelic Studies (MAPS) funded 6 Phase 2 studies treating a total of 130 patients diagnosed with PTSD with the stimulant commonly known as Ecstasy, 3,4-Methylenedioxymethamphetamine (MDMA). It will also fund the Phase 3 research, which will include at least 230 patients.

The first major study was conducted on 20 adult patients who met DSM-IV criteria for crime or war-related PTSD and who had exhibited treatment-resistant symptoms with a minimum score of 50 on the Clinician Administered PTSD Scale (CAPS). Patients had, on average, struggled with their symptoms for 17 years.

The study consisted of two phases: an initial double-blind, placebo-controlled phase in which all patients received psychotherapy accompanied by either MDMA or placebo, followed by an open-label, cross-over phase in which patients assigned to the placebo arm were given the opportunity to receive additional therapy that included MDMA administration.

At 3–5 days following the second of two treatment sessions, the MDMA group showed an average reduction of 49.9 points on their CAPS score. The placebo group showed an average reduction of only 12.8 points on their CAPS score.

Results showed that after three doses of MDMA administered under a psychiatrist’s guidance, the patients reported a 56 percent decrease in severity of symptoms. By the end of the study, two-thirds no longer met the criteria for having PTSD. Follow-up studies found that 17-74 months after therapy, positive improvements were still evident.

Research has shown that the drug causes the brain to release a flood of hormones and neurotransmitters that evoke feelings of trust, love and well-being, while also muting fear and negative emotional memories that can be overpowering in patients with post-traumatic stress disorder.

MDMA is not only a monoamine releaser with particularly prominent effects on serotonin, but it also elevates serum oxytocin, which is a neuropeptide believed to play a role in affiliation and bonding in mammals. Brain imaging studies show there is reduced amygdalar activity after MDMA administration, plus changes in the response to angry and happy facial expressions.

These effects may combine to increase the effectiveness of psychotherapy for PTSD, by increasing self-acceptance, promoting interpersonal trust with therapists and catalyzing the effective processing of emotionally-distressing material. It is believed the treatment acts as a catalyst that speeds-up the natural healing process.

In interviews, study participants said MDMA therapy had not only helped them with painful memories, but also helped them stop abusing alcohol and other drugs and put their lives back together.

These initial findings provide hope that the addition of a few low doses of MDMA (ie, around 2 mg/kg or less) to established psychotherapeutic approaches may be beneficial to patients with chronic treatment-resistant PTSD. Other potential applications of MDMA-assisted therapy include depression and substance abuse.

It is notable that no subjects reported any harm from study participation and all of them reported some degree of benefit.

Research suggests that MDMA can be administered in a clinical setting with minimal risk that the subjects will subsequently seek out and self-administer “street ecstasy,” or become dependent on the drug.

As it is the emotional distress of PTSD that often contributes to the use of intoxicants as an escape or an attempt at self-medication, when that emotional distress is reduced, it follows that the subject’s motivation for drug abuse would be reduced as well.

Even though no major adverse events have thus far been reported in PTSD patients who received MDMA, we cannot rule out the possibility of subtle long-term neurological consequences that might require extensive neuropsychological testing and/or brain imaging to detect.

Virtually all medications involve some degree of risk, and as such, standard medical practice requires that the benefit obtained from a drug significantly outweighs the risk to the patient.

MDMA was first synthesized in 1912 by Merck chemist Anton Köllisch. At the time, Merck was interested in developing substances that stopped abnormal bleeding.

In 1927, Max Oberlin studied the pharmacology of MDMA while searching for substances with effects similar to adrenaline or ephedrine, the latter being structurally similar to MDMA.

The chemist Alexander Shulgin first realized the euphoria-inducing traits of MDMA in the 1970s, and introduced it to psychologists he knew.

Before formal clinical trials could start, “Adam” spread to dance clubs and college campuses under the name “Ecstasy”, and in 1985, the Drug Enforcement Administration made it a Schedule 1 drug, barring all legal use.

The National Center for Biotechnology Information

US National Library of Medicine National Institute of Health

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