MD-MA: Novel Perspectives

The tiny, amphetamine-like chemical known as MDMA commonly referred to in its unregulated form as “E” or “ecstasy” in Europe and as “molly” in the USA has had a reputation that has gone from being touted as a potential new therapeutic tool to being stigmatized as a brain-damaging recreational drug.

Most of those historical concerns were unfounded, and today MDMA is being reintroduced into medicine thanks to current empirical research, particularly into the treatment of post-traumatic stress disorder (PTSD) and related illnesses. The first phase 3 research of MDMA, which finds considerable benefit and an outstanding safety profile in patients with severe PTSD, is reported by Mitchell et al. in this edition of Nature Medicine. It currently appears plausible that it will be a treatment that is authorized in a few years.

• Merck developed MDMA in 1912 as a starting point for a novel synthesis of hemostatic chemicals; the company tried MDMA in animal models in 1927 and 1959 but came up with nothing of note. Alexander Shulgin revived it later when he self-experimented with a variety of phenylethylamine medications in the 1970s.

Introduction

MDMA is pharmacologically similar to amphetamines, although it affects serotonin more strongly. Additionally, MDMA is a 5-HT2 serotonin receptor agonist. Increased levels of oxytocin, which is known to play a role in social function and which, according to a recent rodent study, may open a crucial window in cortical functioning, allowing the learning of new behavioral responses, may also contribute to the “empathogenic” effects of serotonergic enhancement.

In terms of psychotherapy, MDMA aids exposure therapy. What makes PTSD so distressing is the abrupt, reflexive re-emergence of the feelings that were present during the first trauma. Therefore, contemporary therapies try to revive this emotional memory before erasing it. In accordance with its therapeutic potential, MDMA lessens the impact of unpleasant memories in healthy volunteers, whether they are autobiographical or brought on by unpleasant stimuli experienced during a controlled study.

• A possible explanation for this effect’s mechanism is that MDMA reduces the amygdala’s sensitivity to stressful stimuli, according to human neuroimaging. Additionally, MDMA improves social interactions, which aids in this element of therapy.

In contrast to other similar substances, MDMA distinguished itself because it promoted higher mental clarity and interpersonal empathy. When Shulgin showed it to his psychotherapist wife, she agreed that it had therapeutic promise, especially for couples therapy. Other therapists in the USA were given access to it by the Shulgins, and they discovered that MDMA was effective at reducing the aggressive tensions and frictions that can develop in many relationships.

• The fact that MDMA was legal at the time, in the 1970s, contributed to its demise. Dealers began selling it after realizing that it was a safe alternative to cocaine and amphetamines. They called it “ecstasy” to increase its market value.

It seemed to lack the issues of hostility and violence associated with other drugs such as alcohol or stimulants, making it particularly desirable at large musical gatherings (raves). It also had distinct pro-social benefits that made it particularly attractive there. From a policing perspective, the rave scene was less problematic than typical inebriated parties; yet, politicians were drawn to the usage of MDMA in public settings as US President Reagan and his wife Nancy stepped up the war on drugs.

Summation

Overall, more work needs to be done to persuade the public, regulatory organizations, and the medical community of the benefits and safety of MDMA.

• The numerous lies spread about this drug, together with its current Schedule I classification (used for substances with a high potential for abuse and no recognised medical purpose), only serve to increase people’s concerns about its dangers and addictiveness, which significantly reduces its availability.

The current research confirms that MDMA is safe and effective after only a few encounters at a moderate dose, without showing any signs of tolerance or dependence.

MDMA therapy brings enthusiasm and promise to a profession where results have historically been quite subpar. The World Health Organization and the United Nations should think about rescheduling MDMA to a lower degree of restriction in the UK and the USA since it would significantly speed up research and make it more accessible to individuals who need it.