MDMA: The Chemistry, Effects, and Brain Science

By Tessa Eskin

MDMA, or 3,4-methylenedioxymethamphetamine, was first produced in 1912 and introduced to underground psychotherapists in the early 1970s. Over the next few decades, it would become a favorite party drug due to its euphoric and highly prosocial effects. Today, this staple of parties, raves, and music festivals goes by many colorful street names – most commonly, Molly and Ecstasy.

Recently, MAPs completed their rigorous run of clinical studies on MDMA-assisted therapy for PTSD. Last year, their findings earned the drug breakthrough status by the FDA as a legitimate treatment for the disorder. Most participants experienced a full recovery, leaving behind their PTSD diagnosis in the long-term follow up.

The substance itself doesn’t fix PTSD but weakens the initial barriers patients face while engaging in psychotherapy (talk therapy). Often, those suffering from PTSD harbor deep-rooted trust issues, which hinders open engagement with therapists. MDMA tackles this with a potent cocktail of chemical reward system hormones that induce social cooperation, openness, and trust. For PTSD patients, these prosocial effects are key to unlocking and processing traumatic memories in a therapeutic setting.

MDMA: The Love Drug

For decades, partygoers have taken MDMA and found themselves pouring their hearts and souls out to whoever will listen. This is because the entactogenic (prosocial) effects of the drug promote a sense of oneness and communion. Fear responses are muted, while the body surges with euphoria, connection, and love for fellow humanity. It’s no wonder that of all the treatments, it’s MDMA that gets PTSD patients talking. Many participants in the MAPs trials even experienced unprompted epiphanies and psychological breakthroughs, to the astonishment of their supervising therapists. So, how exactly does MDMA work its magic?

MDMA is a pure chemical substance derived from amphetamine, a psychomotor stimulant. It often comes in pill form with effects last roughly 3-6 hours, depending on dosage. The drug produces heightened energy euphoria and increased sensory awareness, including sensitivity to sound and touch. The trip includes mild hallucinations, fixations on sights and sounds, and diminished anxiety. Pupils dilate, heart-rate and blood pressure increase, and there may be jaw clenching and dry-mouth, loss of appetite, and dehydration. After the trip comes a warm afterglow, though some experience ‘fog-head’, tiredness, and low moods due to drained reward system hormones.

This is all due to a surge of neurotransmitters and hormones suddenly released in the body while on MDMA—most notably, serotonin, dopamine, and norepinephrine, all communicators which relay signals between nerve cells. Huge quantities of these hormones flow to the nucleus accumbens, which houses our brain’s reward system hormones. Let’s break this down.

A Reward System Chemical Cocktail

Serotonin is the key hormone that regulates mood, happiness and anxiety.  Depression is often attributed to low levels of serotonin, which also stabilizes sleep cycles, pain control, and digestion. At normal levels, it helps us stay “focused, emotionally stable, happier, and calmer.” MDMA releases a huge amount of serotonin into the system, inducing euphoria, heightened empathy, and the desire to be social. Our bodies can only produce limited amounts, taking roughly 14 days to replenish the system after a dose of MDMA. This is why the comedown can be quite rough on some users.

Dopamine is the ‘reenforcing’ hormone responsible for mood regulation, focus, and various central nervous system functions. Known as the ‘feel-good neurotransmitter’, the chemical passes information between neurons, cells that transmit nerve impulses. Dopamine is released when we indulge our food cravings or during sex, inducing pleasure and satisfaction so we keep coming back. Dopamine boosts mood, motivation, and attention. Those with naturally lower levels are often more prone to addictive habits, which gives them a boosted dopamine release. It is dopamine that induces the pleasurable and stimulating effects of MDMA. With a heady dose of euphoria, confidence, and hyperactivity, it feels very much like falling in love.

Norepinephrine is a hormone and neurotransmitter produced within the adrenal gland (or adrenal medulla). The adrenal gland also produces adrenaline. Together, norepinephrine and adrenaline work our fight and flight responses and regulate mood, anxiety, sleep cycles, energy, and focus. Unbalanced norepinephrine levels are associated with depression, anxiety, PTSD, and substance abuse. A surge of levels induces euphoria, but also elevates blood pressure and hyperactivity, contributing to the high-energy sensations of MDMA.

Enhanced Trust and Openness

MDMA also increases oxytocin, the love hormone that bonds us. When paired with the MDMA cocktail, oxytocin is responsible for playfulness and desire for closeness and physical affection. The hormone promotes feelings of connection, while also dimming fear responses. Oxytocin actually changes the way we perceive and interpret facial expressions. With a high surge, we’re less likely to identify anger, threats, or negative social cues, all leading to high levels of trust and openness. This effect specifically touches upon the psychological benefits of MDMA-assisted therapy for PTSD. As mentioned above, traumatic events often cause hyper-vigilance, making it difficult for patients to open up during talk-therapy. This may also be due to a decrease in the amygdala responses to threat-related social signals when on MDMA.

The cherry on the top of this hormonal sundae is prolactin, which induces a post-orgasmic state. This makes people more relaxed, satisfied, and content. Together, these hormones put patients into the “optimal arousal zone.” This is the sweet spot where therapeutic change is most possible. Now, after years of rigorous testing and FDA breakthrough approval, we should soon begin to see MDMA-assisted therapy available and integrated into the mainstream treatment of PTSD.