MDMA and its therapeutic uses: benefits and risks.

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MDMA is now a registered PTSD medicine in Australia.

MDMA and its therapeutic uses: benefits and risks

MDMA, also known as ecstasy or molly, is a synthetic drug that alters mood and perception. It is classified as a stimulant and a hallucinogen, and it can produce feelings of euphoria, empathy, and enhanced sensory awareness 1.

Therapeutic uses of MDMA

MDMA has been investigated as a potential treatment for various psychiatric disorders, such as post-traumatic stress disorder (PTSD), anxiety, depression, and addiction 1 4. The rationale behind MDMA therapy is that it can facilitate the therapeutic process by reducing fear, increasing trust, and enhancing emotional expression 4.

MDMA therapy involves taking regulated doses of MDMA under the supervision of a trained therapist, usually in conjunction with psychotherapy sessions before, during, and after the drug administration 4. The typical dose range is between 75 and 125 mg, and the effects last for about 3 to 6 hours 1.

Several studies have reported promising results from MDMA therapy, especially for PTSD. For example, a phase 2 clinical trial involving 107 participants with chronic PTSD found that MDMA-assisted psychotherapy led to significant and lasting reductions in PTSD symptoms, with 67% of the participants no longer meeting the criteria for PTSD at the 12-month follow-up 4. Based on these findings, the Food and Drug Administration (FDA) granted MDMA a breakthrough therapy designation in 2017, which means that it could expedite its development and approval 4.

Risks of MDMA use

Despite its potential benefits, MDMA also poses serious risks to health and safety. MDMA can cause acute adverse effects, such as increased heart rate, blood pressure, body temperature, sweating, nausea, jaw clenching, and anxiety 1. In rare cases, MDMA can lead to hyperthermia, dehydration, hyponatremia, serotonin syndrome, seizures, coma, or death 1.

Moreover, MDMA can cause long-term damage to the brain and the heart. Several studies have shown that MDMA can induce neurotoxicity, which means that it can harm the neurons that produce or use serotonin 2 3. Serotonin is a neurotransmitter that regulates mood, memory, sleep, and other functions. MDMA-induced neurotoxicity can result in reduced levels of serotonin and its transporter (SERT), impaired cognitive function, increased impulsivity, depression, and anxiety 2 3. One study compared regular users of MDMA with former users who had remained abstinent for two years and concluded that impairments of neuropsychological performance associated with regular ecstasy use are not reversed by prolonged abstinence 5.

MDMA can also cause cardiotoxicity, which means that it can damage the heart muscle and affect its function 1. A study in rats found that MDMA can alter cardiac gene expression and DNA methylation, which are involved in regulating heart development and function 1. Cardiotoxicity can increase the risk of heart failure, arrhythmia, or sudden cardiac death.

The need for a safer alternative

Given the serious risks associated with MDMA use, there is a need for a safer alternative that can mimic its therapeutic effects without causing neurotoxicity or cardiotoxicity. One possible approach is to develop analogs or derivatives of MDMA that have lower affinity for SERT or lower potency to release serotonin 2. This could reduce the amount of serotonin available in the synaptic clefts and thus prevent excessive stimulation of serotonin receptors and oxidative stress that contribute to neurotoxicity and cardiotoxicity 2.
BioPharm have worked in this area since the early 2000s developing and patenting new formulations.

Another possible approach is to combine MDMA with antioxidants or anti-inflammatory agents that can protect the brain and the heart from oxidative stress and inflammation induced by MDMA 2 3. For example, some studies have suggested that melatonin, N-acetylcysteine, or Acetyl-L-Carnitine may have neuroprotective or cardioprotective effects against MDMA toxicity in animal models 2 3 6 7.

However, more research is needed to confirm the safety and efficacy of these approaches in humans before they can be used in clinical settings. Until then, MDMA therapy should be used with caution and under strict medical supervision.

References

  1. Shokry IM, Shields CJ, Callanan JJ, Ma Z, Tao R. Ecstasy (MDMA) alters cardiac gene expression and DNA methylation: implications for circadian rhythm dysfunction in the heart. PLoS One. 2015;10(8):e0133967. doi: 10.1371/journal.pone.0133967. PubMed
  2. Bisagno V, Cadet JL. Methamphetamine and MDMA Neurotoxicity: Biochemical and Molecular Mechanisms. In: Aschner M., Costa L.G., Lucio M., Rocha J.B.T., Farina M. (eds) Handbook of Neurotoxicity. Springer, Cham. 2021. doi: 10.1007/978-3-030-71519-9_80-1. Springer
  3. Shokry IM, Callanan JJ, Sousa N, Tao R. Differential role of dose and environment in initiating and intensifying neurotoxicity caused by MDMA in rats. BMC Pharmacol Toxicol. 2019;20(1):47. doi: 10.1186/s40360-019-0326-6. PubMed
  4. Mithoefer MC, Feduccia AA, Jerome L, et al. MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology (Berl). 2019;236(9):2735-2745. doi: 10.1007/s00213-019-05249-5. PubMed
  5. Morgan MJ, McFie L, Fleetwood H, Robinson JA. Ecstasy (MDMA): are the psychological problems associated with its use reversed by prolonged abstinence? Psychopharmacology (Berl). 2002 Jan;159(3):294-303. doi: 10.1007/s002130100907. Epub 2001 Oct 12. PubMed
  6. Soleimani Asl S, Mousavizadeh K, Pourheydar B, Soleimani M, Rahbar E, Mehdizadeh M. Protective effects of N-acetylcysteine on 3, 4-methylenedioxymethamphetamine-induced neurotoxicity in male Sprague-Dawley rats. Metab Brain Dis. 2013 Dec;28(4):677-86. doi: 10.1007/s11011-013-9423-1. Epub 2013 Aug 24. Erratum in: Metab Brain Dis. 2014 Sep;29(3):887. Mousavizedeh, Kazem [Corrected to Mousavizadeh, Kazem]. PubMed
  7. Alves E, Binienda Z, Carvalho F, Alves CJ, Fernandes E, de Lourdes Bastos M, Tavares MA, Summavielle T. Acetyl-L-carnitine provides effective in vivo neuroprotection over 3,4-methylenedioximethamphetamine-induced mitochondrial neurotoxicity in the adolescent rat brain. Neuroscience. 2009 Jan 23;158(2):514-23. doi: 10.1016/j.neuroscience.2008.10.041. Epub 2008 Oct 30. PubMed
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