In the Fundamentals of Psychedelic-Assisted Therapy course, we looked at the overall harm of hallucinogenic substances compared with other common substances of abuse. If you haven’t yet taken Fundamentals, we have provided sufficient context below.
In the course, we learned that a landmark study published in the Lancet in 2010 examined the individual, societal, and global harms associated with 20 commonly used substances.
The chart below is interactive. Click the coloured boxes in the legend to toggle between seeing the values together or separately.
Adapted from Lancet, 2010.
Note
This study focused primarily on the harm levels of these substances used primarily in a recreational setting, and the term ecstasy is used as a result instead of MDMA.
Harm Potential
While the harm score for MDMA is relatively low in a clinical setting, there are some important considerations that health professionals should be mindful of.
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While MDMA does not have the same addictive properties as other substances, there is a potential for abuse given that MDMA impacts the same neurotransmitters as substances which are highly addictive. It has been noted that prolonged use of MDMA can cause changes in the serotonin and dopamine systems in the brain which are typically associated with a substance use disorder, however more studies are needed to determine the degree to which MDMA is addictive (NIDA, 2021). In addition, in clinical trials to date for MDMA-assisted therapy for PTSD, no participants have developed MDMA substance use disorders post-study termination (MAPS, 2021).
As discussed in Fundamentals of Psychedelic-Assisted Therapy, an important aspect of integration is facilitating ways for clients to keep the positive changes engendered by psychedelic experiences alive. In the course, we provide some recommendations for how to keep the psychedelic experience alive without the need for ingesting medicines recreationally outside of a clinical setting.
The combination of MDMA with MAOI medications may present a risk for causing serotonin syndrome and increasing sympathetic activity; 4 deaths have already been reported as a result of concomitant recreational use of MDMA and moclobemide (Leonardi & Azmitia, 1994; Pilgrim et al., 2012).
Existing literature based on animal data estimates a median lethal dose (LD50) to be between 10 and 20 mg/kg in humans (700-1400mg in 70kg adult) which is about ten times more than what is recommended to be used in MDMA-assisted therapy.
As mentioned earlier, when used recreationally, MDMA is also referred to as ecstasy (a name coined in 1984 in California), molly, and various other street names (Freudenmann et al., 2006). Its recreational use has been associated with triggering long-term depression and anxiety, although research has shown this to be more closely linked to polydrug use rather than the use of MDMA itself (MacInnes et al., 2001; Medina & Shear, 2007; Milani et al., 2004; Parrott et al., 2000; Sumnall et al., 2004). In a recreational setting, MDMA can cause perceptual shifts (sensory enhancement, distortion, illusion without true hallucination), delirium, intense dysphoria, and confusion (Schwartz & Miller, 1997).
Substance Purity
Illegal material sold as MDMA is often of limited purity, sometimes actually containing no MDMA whatsoever; when present, the actual MDMA content can vary greatly (Baggott et al., 2000; Cole et al., 2002; Tanner-Smith, 2006). Such products may contain a range of other compounds (some not even psychoactive), such as ephedrine, caffeine, ketamine, cathinones, paramethoxyamphetamine (PMA), paramethoxymethamphetamine (PMMA), dextromethorphan, methamphetamine, and amphetamine (Brunt et al., 2017; Tanner-Smith, 2006).
The use of MDMA in controlled settings is fundamentally different than its use in recreational settings, and the abuse potential within MDMA-assisted therapy programs is considered to be very low (MAPS, 2021). It is important to note that the MDMA used in psychedelic-assisted therapy should be pure and obtained from a reputable supplier, ensuring the safety of our clients and quality of our programs.
References
Baggott, M., Heifets, B., Jones, R. T., Mendelson, J., Sferios, E., & Zehnder, J. (2000). Chemical analysis of ecstasy pills. JAMA, 284(17), 2190. https://doi.org/10.1001/jama.284.17.2190
Brunt, T. M., Nagy, C., Bücheli, A., Martins, D., Ugarte, M., Beduwe, C., & Ventura Vilamala, M. (2017). Drug testing in Europe: monitoring results of the Trans European Drug Information (TEDI) project. Drug Test Anal, 9(2), 188-198. https://doi.org/10.1002/dta.1954
Cole, J. C., Bailey, M., Sumnall, H. R., Wagstaff, G. F., & King, L. A. (2002). The content of ecstasy tablets: implications for the study of their long-term effects. Addiction, 97(12), 1531-1536. https://doi.org/10.1046/j.1360-0443.2002.00222.x
Freudenmann, R. W., Oxler, F., & Bernschneider-Reif, S. (2006). The origin of MDMA (ecstasy) revisited: the true story reconstructed from the original documents. Addiction, 101(9), 1241-1245. https://doi.org/10.1111/j.1360-0443.2006.01511.x
Leonardi, E. T., & Azmitia, E. C. (1994). MDMA (ecstasy) inhibition of MAO type A and type B: comparisons with fenfluramine and fluoxetine (Prozac). Neuropsychopharmacology, 10(4), 231- 238. https://doi.org/10.1038/npp.1994.26
MacInnes, N., Handley, S. L., & Harding, G. F. (2001). Former chronic methylenedioxymethamphetamine (MDMA or ecstasy) users report mild depressive symptoms. J Psychopharmacol, 15(3), 181-186. https://doi.org/10.1177/026988110101500310
MAPS. (2021). Multidisciplinary Association for Psychedelic Studies Investigator's Brochure. In (13 ed.). San Jose: MAPS.
Medina, K. L., & Shear, P. K. (2007). Anxiety, depression, and behavioral symptoms of executive dysfunction in ecstasy users: contributions of polydrug use. Drug Alcohol Depend, 87(2-3), 303- 311. https://doi.org/10.1016/j.drugalcdep.2006.09.003
Milani, R. M., Parrott, A. C., Turner, J. J., & Fox, H. C. (2004). Gender differences in self-reported anxiety, depression, and somatization among ecstasy/MDMA polydrug users, alcohol/tobacco users, and nondrug users. Addict Behav, 29(5), 965-971. https://doi.org/10.1016/j.addbeh.2004.02.044
NIDA. (2021). Is MDMA Addictive?. Retrieved from https://nida.nih.gov/publications/research-reports/mdma-ecstasy-abuse/mdma-addictive
Parrott, A. C., Sisk, E., & Turner, J. J. (2000). Psychobiological problems in heavy 'ecstasy' (MDMA) polydrug users. Drug Alcohol Depend, 60(1), 105-110. https://doi.org/10.1016/s0376- 8716(99)00146-5
Pilgrim, J. L., Gerostamoulos, D., Woodford, N., & Drummer, O. H. (2012). Serotonin toxicity involving MDMA (ecstasy) and moclobemide. Forensic Sci Int, 215(1-3), 184-188. https://doi.org/10.1016/j.forsciint.2011.04.008
Schwartz, R. H., & Miller, N. S. (1997). MDMA (ecstasy) and the rave: a review. Pediatrics, 100(4), 705-708. https://doi.org/10.1542/peds.100.4.705
Sumnall, H. R., Wagstaff, G. F., & Cole, J. C. (2004). Self-reported psychopathology in polydrug users. J Psychopharmacol, 18(1), 75-82. https://doi.org/10.1177/0269881104040239
Tanner-Smith, E. E. (2006). Pharmacological content of tablets sold as "ecstasy": results from an online testing service. Drug Alcohol Depend, 83(3), 247-254. https://doi.org/10.1016/j.drugalcdep.2005.11.016
