Instant Gratification: Weighing the Psychological Benefits and Costs of MDMA Use

Posted by Christian Cazares on January 25, 2018 in Creativity, Culture, Drugs, Emotions, Mood, Neurological Disorders, Neuroscience, Pharmacology | Leave a comment

 

“Remember one cubic centimetre cures ten gloomy sentiments.” – Lenina

Brave New World (Huxley, 1932)

 

For citizens of the World State, Soma is what they would take when hard times opened their eyes. Aldous Huxley’s famous science-fiction dystopia sets up an Earth where privileged citizens abiding to a caste system have the luxury of rejecting their negative feelings with the gulp of a pill. While Brave New World can be interpreted as a warning to society about depending on such a substance, it begs the question whether its existence is even possible. Can a pill exist that brings instant happiness without any negative side effects?

A Brief Trip Through Time

 

MDMA (3,4-Methylenedioxymethamphetamine), commonly referred to as ecstasy, was first synthesized in 1912 for reasons unrelated to its psychoactive side-effects. Contrary to popular belief, it was a precursor compound in pharmaceutical research looking to develop a substance to stop abnormal bleeding. Decades later, recreational MDMA use skyrocketed in popularity throughout the early 1980s and was met by conservative push-back, with Nancy Reagan’s “Just Say No” campaign being a notable contributor. What shortly followed was Schedule I classification for MDMA, effectively making the drug illegal, which resulted in a decline of production and distribution within the United States.This initial decision to classify MDMA as a drug that offered no therapeutic effects (i.e. Schedule I) was met with backlash from academic experts who testified to the substance’s medical use in their own research, and surprisingly, a federal court sided with them. 

However Drug Enforcement Agency (DEA) administrator John C. Lawn, who was appointed by Reagan, overruled this decision, making MDMA a criminalized drug. In retrospect, the reasoning is clear: the “War on Drugs” had been kicked into high gear. Even now, the drug’s illegality continues to be a struggle for U.S. researchers looking to study its therapeutic benefits, yet some laboratories have been leading the way in re-opening the conversation regarding MDMA’s safety when used in controlled, clinical settings.

 

 

On a Roll Towards MDMA Treatment of Post-Traumatic Stress Disorder

 

A break in the drug’s controversial use has been found by researchers looking to improve PTSD treatment. PTSD affects up to 9% of the general population over their lifetime, with women being at risk at twice the rate as men [1]. Symptoms include nightmares, persistent negative mood, avoidance and dissociation, in some cases accompanied with the inability to function in daily life. With the backdrop of a large patient population in need of therapy, researchers recruited psychiatric patients (some with previous history of MDMA use) and orally administered initial doses of 125 mg coupled with psychotherapy [2]. This was the first randomized controlled pilot study in the U.S., which was published in 2011, and its results were interpreted in favor of its use as an alternative PTSD therapeutic. 85% of patients in the MDMA group reported improvements in PTSD symptoms after three months of MDMA-guided psychotherapy, compared to 15% in the placebo group. Interestingly, these results held up alongside a lack of adverse cognitive effects, and lasted through follow-up evaluation performed 3.5 years later. These patients were virtually cured and reported a significant decrease or cessation of other psychiatric medications intended to treat PTSD symptoms [3]. However, careful consideration must be taken when interpreting these results, as only 20 patients participated in this study. Since then, further research on using MDMA alongside psychotherapy to treat PTSD have been conducted. A recent review of the literature regarding randomized controlled trials concluded that MDMA, in conjunction with psychotherapy, reduced symptoms associated with PTSD in patients that had not responded to other conventional drug therapies [1].

Yet, alongside increasing evidence of the clinical benefits of MDMA, recreational use has seen a recent surge in parallel to the rise of giant electronic dance music (EDM) festivals, known as “massives”. A 2016 survey conducted in New York City around music festivals found that out of the 679 young adults (age 18-25) queried, 42.8% reported a lifetime use [4]. What makes its recreational use so alluring? Was Huxley’s vision of a Brave New World prophetic?

 

What Makes the Good Times Roll

 

The psychoactive effects of MDMA have long been hypothesized to manifest via the continuous presynaptic release of brain serotonin followed by a perceived increase in empathy and euphoria for up to 6 hours after its ingestion [5]. However, the drug’s mechanism of action, or the process which directly leads to making someone feel this way, is more complex. For example, the “happy” effects of the drug are also thought to bias neurons towards increased oxytocin release and binding. A Swiss study found that a single 125 mg dose led to similar, yet sex-specific altered recognition of emotions, emotional empathy, and prosociality [6]. While the drug’s pro-social outcomes have long been reported by users, another Swiss study confirmed this by using assays sensitive to ideas like “closeness to others”, “openness”, and “trust” [7].  If these effects were reported in the lab setting, it seems reasonable to believe that these effects are accentuated in the context of a music festival. Indeed, MDMA’s current affiliation with EDM culture, and the scene’s infatuation with the drug, trace back to the original raves of the 1980’s. Large crowds and good music, coupled with copious recreational drug use, led to the million dollar massive event industry known today. It seems so simple: people use MDMA because it makes them feel good. But what’s the catch?

 

Every High has a Low

 

When you bombard your brain with a surplus of chemicals, it’s intuitive to suspect that something could go wrong. In popular culture, MDMA has been grouped with other substances into the stereotype of a drug that “fries” your brain. How much of that is true? Can cells in your brain literally die as a result of MDMA use?

A line of research aiming to elucidate why chronic MDMA users experience memory difficulties investigated the effects of MDMA on the mouse hippocampus, a key region involved in learning and memory. In particular, they assessed caspase-3 activity because of this enzyme’s role in the apoptotic (cell death) process. MDMA administration was found to increase caspase-3 in the hippocampus, however careful consideration must be taken regarding this study’s methodology. Their dosing paradigm used 3 separate injections, spaced two hours apart, of MDMA at levels not typical in human recreational use [8].

Given the potential neurotoxicity of MDMA at elevated and frequent doses, clinicians may have reasonable concern for patient safety if the compound is to be used as a therapeutic. Fortunately, a group of researchers have begun to modify the compound into one that may isolate the pro-social, mood-elevating from possible neurotoxicity [9].

While the results of this study did not confirm this possibility, it’s encouraging to know efforts are being made to pinpoint what aspect of the compound’s structure leads to its harmful effects. While the debate on MDMA neurotoxicity remains open, recreational users should nonetheless ask themselves if they’re willing to risk brain cell death in exchange for transient bursts of intense happiness. Some find that risk worth taking, and different lines of work have assessed whether the possible harmful effects of MDMA can be avoided by “preparing your brain” for the chemical imbalances of recreational use.

 

 

 

Mollifying the Harm

 

History has shown that the illegality of a substance does not cease its use. Websites like RollSafe have come to terms with the idea that despite potential dangers, people will use MDMA in social settings. RollSafe provides users with guides on what to expect both mentally and physically, citing various research literature in the search for a protective supplement regimen to be taken before and after the high. In a rodent study, alpha-lipoic acid has been reported to reduce MDMA-induced neurotoxicity if administered beforehand [10]. However, be aware that this curated list of protective supplements is biased by the fact that there is money to be made by selling them.

So what’s the hold up?

 

Summarizing the pros and cons of MDMA use is tricky. On one hand, the data should speak for itself, but when you consider how the majority of the funding in the United States comes from federal agencies, one should be mindful of any potential agendas at play. At the end of it, however, the answer is relatively simple: in order to draw a conclusion, more research on the effects of MDMA in the brain is needed. Maybe a day will come when the federal government catches up to the will of the people and revisits drug legality in the context of the Controlled Substances Act. Access to legal, tested MDMA pills could avoid the implicit dangers of buying from dealers far removed from the synthesis of the drug. Until then, refusal to reschedule MDMA denies a vast patient population a potential treatment they desperately need.

 

References:

1. White CM. 3,4-Methylenedioxymethamphetamine’s (MDMA’s) Impact on Posttraumatic Stress Disorder. Ann Pharmacother. 2014 Jul;48(7):908-915. Epub 2014 Apr 16.
2. Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, Doblin R. 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. J Psychopharmacol 2010; 25: 439–52.
3. Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, Martin SF, Yazar-Klosinski B, et al. Durability of improvement in PTSD symptoms and absence of harmful effects or drug dependency after MDM-assisted psychotherapy: a prospective long-term follow-up study. J Psychopharmacol 2013; 27: 28–39.
4. Palamar JJ Acosta P, Ompad DC, Cleland CM. Self-Reported Ecstasy/MDMA/”Molly” Use in a Sample of Nightclub and Dance Festival Attendees in New York City. Subst Use Misuse. 2017 Jan 2;52(1):82-91. Epub 2016 Sep 23.
5. https://en.wikipedia.org/wiki/MDMA#Pharmacodynamics
6. Hysek CM, Schmid Y, Simmler LD, Domes G, Heinrichs M, Eisenegger C, Preller KH, Quednow BB, Liechti ME. MDMA enhances emotional empathy and prosocial behavior. Soc Cogn Affect Neurosci. 2014 Nov;9(11):1645-52. doi: 10.1093/scan/nst161. Epub 2013 Oct 4.
7. Schmid Y, Hysek CM, Simmler LD, Crockett MJ, Quednow BB, Liechti ME. Differential effects of MDMA and methylphenidate on social cognition. J Psychopharmacol. 2014 Sep;28(9):847-56. doi: 10.1177/0269881114542454. Epub 2014 Jul 22.
8. Tamburini, F. Blandini, M. Gesi, G. Frenzilli, M. Nigro, M. Giusiani, et al. MDMA induces caspase-3 activation in the limbic system but not in striatum Ann N Y Acad Sci, 1074 (2006), pp. 377-381
9. Karuppagounder SS, Bhattacharya D, Ahuja M, Suppiramaniam V, Deruiter J, Clark R, Dhanasekaran M. Elucidating the neurotoxic effects of MDMA and its analogs. Life Sci. 2014 Apr 17;101(1-2):37-42. doi: 10.1016/j.lfs.2014.02.010. Epub 2014 Feb 19.
10. Aguirre N, Barrionuevo M, Ramírez MJ, Del Río J, Lasheras B. Alpha-lipoic acid prevents 3,4-methylenedioxy-methamphetamine (MDMA)-induced neurotoxicity. Neuroreport. 1999 Nov 26;10(17):3675-80.

Images:

https://en.wikipedia.org/wiki/Brave_New_World

https://en.wikipedia.org/wiki/MDMA

https://en.wikipedia.org/wiki/Electric_Daisy_Carnival

https://commons.wikimedia.org/wiki/Ecstasy

https://commons.wikimedia.org/wiki/Category:Mydriasis