MDMA: Neurochemical mechanisms of action on the brain and its effectiveness in psychotherapy

Empathogens or entactogens are a class of psychoactive drugs that produce experiences of emotional communion, oneness, relatedness, emotional openness. Most entactogens are phenethylamines with 3,4-methylenedioxymethamphetamine (the “MDMA”) as being a major substance of this chemical class.

MDMA acts in the brain through three main neurochemical mechanisms: blockade of serotonin reuptake, induction of serotonin release, and induction of dopamine release [1]. The key characteristic of MDMA is its ability to block and release serotonin at the same time, whilst most drugs such as Prozac and other antidepressants are only able to do one of these neurochemical mechanisms. Essentially, MDMA floods the central nervous system with serotonin. After MDMA use, people feel self-confident, have an expansive sense of self-worth, and feel great about themselves. MDMA has strong anxiolytic properties as it affects the 5-HT1B receptor which is thought to be important in producing feelings of calmness and drugs that activate this site are known in psychedelics research as “serene”. In turn, this effect helps to significantly reduce anxiety and fear which could be particularly helpful to surface repressed and negative memories and address traumas from these experiences through psychotherapy.

There are, nonetheless, certain side effects that are linked to the way in which MDMA acts in the brain. One such side effect is serotonin syndrome. Serotonin syndrome is the accumulation of too much serotonin in the human body. After MDMA metabolizes out of the body, people may experience episodes of depression or low mood due to the depletion of serotonin. Serotonin levels can then take between 24 hours and a few weeks of abstinence to restore.[2] Another side effect that pertains to the dopamine release can be nausea and irregularity of one’s heartbeat.[3]

Secondly, since MDMA also has a methamphetamine base and releases dopamine, MDMA users are also awake, alert, and cognizant of their surroundings. This is what makes MDMA truly unique in psychotherapy. It is both stimulating and relaxing. In psychiatry, almost all anxiolytics are sedating. In this regard, MDMA is a fast-acting and non-sedating anxiolytic. People have enhanced memories of the MDMA experience and as well as memories of early repressed traumas. Hence, MDMA is particularly well-suited for psychotherapy. The cornerstone of psychotherapy for the treatment of post-traumatic stress disorders (the “PTSD’’) is exposure and desensitization. The traumatized patient needs to encounter distressing memories until they gradually lose their power. Naturally, this is very disturbing to most patients. MDMA has the potential to make negative memories less vivid while increasing feelings of safety and trust.[4]

Thirdly, MDMA is not a typical hallucinogen. Although MDMA boosts serotonin levels in the central nervous system, it has a slight affinity with one of the serotonergic receptors, 5-HT2A, which is responsible for hallucinations. MDMA induces an altered state of consciousness with much milder forms of hallucinations compared to tryptamine psychedelics and this subtle shift in consciousness creates an opportunity for the person to get in contact or touch with his deeper self and become a more genuine and authentic person. This is why MDMA is classed as “entactogen” or “touching within”. Feelings of authenticity are increased after MDMA resulting in a person having better self-awareness of one’s motives and desires, reducing biases in processing self-relevant information, acting by own values, and acting with sincerity and truth in relationship with close others [5]. Genuine and honest conversations with psychotherapists could be instrumental in helping people to address their fears and anxiety stemming from traumatic experiences.

Finally, another unique quality of MDMA is its ability to induce a sense of connectedness with other people and empathy. MDMA increases the level of oxytocin hormones known to be important in bonding and affiliative behaviours. For example, oxytocin is released during breastfeeding which strengthens the bond between mother and infant. Oxytocin is also released in affiliative behaviours when you feel belonging to a certain community or team in sport or work. This is particularly a key attribute of MDMA which makes it so effective in psychotherapy. An important predictor for the successful outcome of psychotherapy is an alliance with a psychotherapist. Patients are more trusting of the therapist with MDMA use which further enhances this therapeutic alliance proving to be highly effective in addressing and processing tragic and difficult memories.

In summary, MDMA’s neurochemical mechanisms of action on the brain are unique and a combination of its certain qualities such as being anxiolytic, non-hallucinogenic, entactogenic, and enhancement of therapeutic alliance could make MDMA-assisted psychotherapy effective in the treatment of PTSD. In our next Leafy Tunnel article on MDMA, we will explore the latest developments on clinical trials with MDMA-assisted psychotherapy.

Further recommended reading:

1. https://www.drugabuse.gov/publications/drugfacts/mdma-ecstasymolly
2. https://drugpolicy.org/drug-facts/can-mdma-be-used-medicine-or-therapy
3. M. C. Mithoefer et al., “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 25, no. 4 (2011).
4. https://maps.org/research/mdma/ptsd/phase3
5. Rick Doblin, Ph.D., Testimony to US Sentencing Commission Re: MDMA, Prepared in collaboration with Ismail L. Ali, JD, and Natalie Lyla Ginsberg, MSW
6. https://www.amazon.co.uk/dp/0892818573/ref=cm_sw_r_u_apa_fabc_uT1aGbX2T8QTA
7. https://www.neuroscientificallychallenged.com/blog/2014/5/23/ecstasy-oxytocin-mdma

[1] Ecstasy The Complete Guide : A Comprehensive Look at the Risks and Benefits of MDMA by Julie Holland

[2] https://www.psycom.net/serotonin-syndrome

[3] https://www.webmd.com/mental-health/what-is-dopamine

[4] https://www.scientificamerican.com/article/how-molly-works-in-the-brain/

[5] Beyond Fear: MDMA and Emotion — Matthew Baggott, Goldman and Kernis, 2002, Sheldon, Ryan et al, 1997

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