Adverse Effects

The adverse effects of MDMA listed in this section are not an exhaustive list, however they are the most common adverse effects or the adverse effects that cause the greatest concern in a clinical setting.

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Vital Signs

During MDMA-assisted therapy, the medicine can produce the following adverse effects:

  • Tachycardia

  • Dehydration

  • Overheating

  • Pupil dilation

  • Hypertension (Cami et al., 2000; Harris et al., 2002; Liechti et al., 2001; Mas et al., 1999; Schwartz & Miller, 1997)

Physical Adverse Effects

Some physical adverse effects of MDMA administration include:

  • Sweating

  • Muscle spasms (jaw clenching)

  • Fatigue

  • Muscular, hepatic, renal, and central nervous system dysfunction

  • Nausea

  • Lack of appetite

  • Jaw clenching and teeth grinding

  • Headache

  • Dizziness

  • Feeling unusually hot or cold dependent or independent of their body temperature

  • Paresthesia (Harris et al., 2002; Liechti et al., 2001; Mithoefer et al., 2019; Schwartz & Miller, 1997; Vollenweider et al., 1998)

Behavioural Adverse Effects

In addition to the physical adverse effects, clients may also experience some of these behavioural adverse effects.

  • Increased anxiety

  • Panic

  • Irritability

  • Depressed mood (Cami et al., 2000; Harris et al., 2002; Liechti et al., 2001; Mas et al., 1999; Mithoefer et al., 2019)

MDMA is associated with sympathomimetic effects such as increases in heart rate and blood pressure; however these effects tend to be transient and self-limiting and are generally tolerated well by healthy individuals (Bedi et al., 2009; Downing, 1986; Grob, 1998; Harris et al., 2002; Kirkpatrick et al., 2012; Kolbrich et al., 2008; Lester et al., 2000; Liechti et al., 2001; Mas et al., 1999; Mithoefer et al., 2011; Oehen et al., 2013).

Health Professional Tip

"When providing MDMA-assisted therapy, your clients may experience jaw tightness or jaw clenching during the session. One practical piece of advice I’ve received to support my clients through this is to have either a wet rag they can bite down on or gum available for them to chew, which should help relieve discomfort associated with that."

- Dr. Reid Robison, Numinus Chief Clinical Officer

Post-MDMA Adverse Effects

As previously mentioned, there are some adverse effects that may be experienced following the Medicine Session. However, these are more common in recreational settings (Sessa et al., 2019 as cited in Rush et al., 2022). These include:

  • Low mood and depressive effects

  • Irritability

  • Fatigue (Sessa et al., 2019 as cited in Rush et al., 2022)

References

Bedi, G., Phan, K. L., Angstadt, M., & de Wit, H. (2009). Effects of MDMA on sociability and neural response to social threat and social reward. Psychopharmacology (Berl), 207(1), 73-83. https://doi.org/10.1007/s00213-009-1635-z

Cami, J., Farré, M., Mas, M., Roset, P. N., Poudevida, S., Mas, A., . . . de la Torre, R. (2000). Human pharmacology of 3,4-methylenedioxymethamphetamine ("ecstasy"): psychomotor performance and subjective effects. J Clin Psychopharmacol, 20(4), 455-466. https://doi.org/10.1097/00004714-200008000-00010

Downing, J. (1986). The psychological and physiological effects of MDMA on normal volunteers. J Psychoactive Drugs, 18(4), 335-340. https://doi.org/10.1080/02791072.1986.10472366

Grob, C. (1998). MDMA research: Preliminary investigations with human subjects. Int J Drug Policy, 9(2), 119-124.

Harris, D. S., Baggott, M., Mendelson, J. H., Mendelson, J. E., & Jones, R. T. (2002). Subjective and hormonal effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans. Psychopharmacology (Berl), 162(4), 396-405. https://doi.org/10.1007/s00213-002-1131-1

Kirkpatrick, M. G., Gunderson, E. W., Perez, A. Y., Haney, M., Foltin, R. W., & Hart, C. L. (2012). A direct comparison of the behavioral and physiological effects of methamphetamine and 3,4- methylenedioxymethamphetamine (MDMA) in humans. Psychopharmacology (Berl), 219(1), 109- 122. https://doi.org/10.1007/s00213-011-2383-4

Kolbrich, E. A., Goodwin, R. S., Gorelick, D. A., Hayes, R. J., Stein, E. A., & Huestis, M. A. (2008). Physiological and subjective responses to controlled oral 3,4-methylenedioxymethamphetamine administration. J Clin Psychopharmacol, 28(4), 432-440. https://doi.org/10.1097/JCP.0b013e31817ef470

Lester, S. J., Baggott, M., Welm, S., Schiller, N. B., Jones, R. T., Foster, E., & Mendelson, J. (2000). Cardiovascular effects of 3,4-methylenedioxymethamphetamine. A double-blind, placebo- controlled trial. Ann Intern Med, 133(12), 969-973. https://doi.org/10.7326/0003-4819-133-12- 200012190-00012

Liechti, M. E., Gamma, A., & Vollenweider, F. X. (2001). Gender differences in the subjective effects of MDMA. Psychopharmacology (Berl), 154(2), 161-168. https://doi.org/10.1007/s002130000648

Mas, M., Farré, M., de la Torre, R., Roset, P. N., Ortuño, J., Segura, J., & Camí, J. (1999). Cardiovascular and neuroendocrine effects and pharmacokinetics of 3, 4-methylenedioxymethamphetamine in humans. J Pharmacol Exp Ther, 290(1), 136-145.

Mithoefer, M. C., Feduccia, A. A., Jerome, L., Mithoefer, A., Wagner, M., Walsh, Z., . . . Doblin, R. (2019). 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), 236(9), 2735-2745. https://doi.org/10.1007/s00213-019-05249-5

Mithoefer, M. C., Wagner, M. T., Mithoefer, A. T., Jerome, L., & Doblin, R. (2011). 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(4), 439-452. https://doi.org/10.1177/0269881110378371

Oehen, P., Traber, R., Widmer, V., & Schnyder, U. (2013). A randomized, controlled pilot study of MDMA (± 3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD). J Psychopharmacol, 27(1), 40-52. https://doi.org/10.1177/0269881112464827

Rush, B., Marcus, O., Shore, R., Cunningham, L., Thomson, N., and Rideout, K. (2022). Psychedelic Medicine: A Rapid Review of Therapeutic Applications and Implications for Future Research. Homewood Research Institute. https://hriresearch.com/research/exploratory- research/research-reports/

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

Vollenweider, F. X., Gamma, A., Liechti, M., & Huber, T. (1998). Psychological and cardiovascular effects and short-term sequelae of MDMA ("ecstasy") in MDMA-naive healthy volunteers. Neuropsychopharmacology, 19(4), 241-251. https://doi.org/10.1016/s0893-133x(98)00013-x