MDMA and the eCBome

MDMA is a synthetic amphetamine analog that was first synthesized in 1912 by the German pharmaceutical company Merck. However, compared to amphetamines and methamphetamines, MDMA is less potent as a stimulant but with more serotonergic properties. 

The DEA classifies MDMA as a Schedule I Drug with “…a high potential for abuse, no currently accepted medical use in treatment in the United States, and a lack of accepted safety for use under medical supervision.” 

When ingested, MDMA is relatively quickly absorbed by the blood, and effects typically occur within 20-60 minutes later. Observations suggest that a full stomach delays the onset of the impact. It is estimated that it takes about 40 hours for the drug to be cleared from the body.

MDMA is known for its ability to induce diverse effects on the body, mind, and emotions that exist in a range between positive and negative. On the expansive or positive side, sensations of closeness and intimacy, enhanced sensuality and trust, reduced inhibition, vivid kinesthetic, visual, and auditory experiences (more with eyes closed), alertness, and increased energy levels. On the constricting or negative side, there are adverse effects such as involuntary jaw clenching, nausea and vomiting, restless legs, anxiety, and panic attacks. 

MDMA is often used in clubs or at Raves, where dancing for more extended periods in a hot environment can lead to dehydration, hyponatremia, and signs and symptoms akin to heat stroke. Many users try to compensate by drinking lots of water as a preventative response. However, MDMA increases the levels of an antidiuretic hormone (arginine vasopressin), leading to fluid retention. Thus, excessive water intake may lead to electrolyte abnormalities such as hyponatremia and associated complications, including relatively rare comas.

Since MDMA is illegal, purveyors commonly offer adulterated products containing several potentially unhealthy compounds. MDMA is available in a typical dosing range of 50 mg to 200 mg per session.

The Emerging Therapeutic Potential of MDMA-assisted Therapy:

Interest in the drug’s therapeutic potential has been highlighted in several recent clinical trials, suggesting that MDMA-assisted therapy sessions may represent a potentially effective and novel treatment for some patients. 

Supportive data:

• PTSD (J. Mitchell et al., 2023)
• Alcohol Dependencies (B. Sessa et al., 2021),(C.R. Nicholas et al., 2022)
• End-of-Life Anxieties and Quality of Life (P. Wolfson et al., 2020), (W. Barone et al., 2022)
• Social Anxieties in Autistic Adults (A. Danforth et al., 2018)

Negative data:

• MDMA may cause neuropsychiatric symptoms (S. Karlsen et al., 2007)
• MDMA-assisted therapy may work with PTSD but worsen distress in patients with a psychiatric history (A. Parrott 2014)

Ongoing clinical trials:

• MDMA-assisted therapy is currently being investigated for the treatment of Major Depressive Disorder (T-M Kvam et al., 2022)

MDMA and the Endocannabinoid System (ECS):

Observations have shown that MDMA users often co-administer cannabis in an attempt to self-medicate against the common adverse effects that occur after the euphoric phase has dissipated. Here are a few of the earlier study results:

• The first study to suggest a link between the ECS and MDMA comes from an animal trial providing evidence that the ECS modulates MDMA’s reinforcing effects (D. Braida et al., 2002).
• The author of a Ph.D. dissertation suggests that THC exerts a protective effect against MDMA-induced neurotoxicity. More specifically, she argues that MDMA with hyperlocomotor, hyperthermic, anxiogenic-like, and neurotoxic effects is contrasted by Δ9-THC with its relaxant, hypolocomotor, hypothermic, and neuroprotective properties (C. Tourino 2009).
• Later research discovered similarly that acute administration of MDMA induced a physiological increase in CB2 expression that was associated with neuroprotection against the drug’s toxic effects (E. Torres et al., 2010). 
• Δ9-THC reduces MDMA-induced hyperthermia in Rhesus Monkeys (M. A. Taffe 2012).
• Furthermore, researchers from Japan suggest that CB1 antagonism may be used in the treatment of MDMA dependence (Y. Nawata et al., 2016). Of note: THCV is an antagonist at CB1.