Effects of MDMA

MDMA's prosocial or "empathogenic" effects have largely been responsible for interest in its use as an adjunctive medication in psychedelic-assisted therapy (Bershad et al., 2016).

Subjective Effects

In a clinical setting, MDMA can produce the following subjective effects:

Reduction in negative distortions of self-relevant facts
Dampening of fears of social rejection
Reduced response to negative social experiences and emotional stimuli
Ability to speak more freely due to lowered fear of social rejection
Increased feelings of safety and acceptance
Increased self-compassion
Increased empathy, compassion, and empathic rapport
Changes in mood and perception (sensory enhancement, distortion, illusion without true hallucination)
Reprocessing of traumatic memories with clearer recall and increased equanimity without emotional numbing or dissociation
Enhanced therapeutic rapport with psychotherapy providers, known to be important for positive outcomes
Increased ability to confront fear-related memories
Altered recognition of and response to facial expressions (Bedi et al., 2009; Bershad et al., 2016; Grob & Poland, 2005; Hysek et al., 2012; Bouso et al., 2008; Greer & Tolbert, 1986; Mithoefer et al., 2011; Schwartz & Miller, 1997; Feduccia & Mithoefer, 2018)

When combined with therapy, MDMA allows for the consideration—and at times, confrontation—of emotionally intense thoughts, feelings, and memories (Bouso et al., 2008; Greer & Tolbert, 1986; Mithoefer et al., 2011). MDMA's role in producing these sorts of effects has been proven through placebo-controlled studies (Bedi et al., 2010; Cami et al., 2000; Dumont et al., 2009; Farré et al., 2007; Harris et al., 2002; Hysek et al., 2012; Liechti et al., 2001; Tancer & Johanson, 2003; van Wel et al., 2012).

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Increased Self-Compassion

“The first place I saw was this maze. I went in. There was so much trauma. I had never remembered these terrible, terrible things. And before MDMA, I really did think it was my fault. I felt it in my bones that something was so wrong with me, that I deserved those things. Being on MDMA was the first time I ever felt compassion for myself. I realized that I was a child when it happened. I had no choice.”

— Phase 2 Research Participant (Feduccia & Mithoefer, 2018).

Increased Ability to Confront Fear-Related Memories

“One thing the MDMA facilitates is thinking about traumatic experiences in a neutral, safe manner. I could objectively think about them and talk about them. Then, it seems those memories are put back in their place in the brain in a different configuration — a configuration that does not cause as many problems, such as bad dreams, intrusive thoughts all the time or having horrible insomnia. This has continued to this day, a year and a half after the last MDMA session.”

— Participant from MAPS-sponsored MDMA-assisted therapy clinical trial (Feduccia & Mithoefer, 2018).

References

Bedi, G., Hyman, D., & de Wit, H. (2010). Is ecstasy an "empathogen"? Effects of ±3,4- methylenedioxymethamphetamine on prosocial feelings and identification of emotional states in others. Biol Psychiatry, 68(12), 1134-1140. https://doi.org/10.1016/j.biopsych.2010.08.003

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

Bershad, A. K., Miller, M. A., Baggott, M. J., & de Wit, H. (2016). The effects of MDMA on socio- emotional processing: Does MDMA differ from other stimulants? J Psychopharmacol, 30(12), 1248-1258. https://doi.org/10.1177/0269881116663120

Bouso, J. C., Doblin, R., Farré, M., Alcázar, M. A., & Gómez-Jarabo, G. (2008). MDMA-assisted psychotherapy using low doses in a small sample of women with chronic posttraumatic stress disorder. J Psychoactive Drugs, 40(3), 225-236. https://doi.org/10.1080/02791072.2008.10400637

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

Dumont, G. J., Sweep, F. C., van der Steen, R., Hermsen, R., Donders, A. R., Touw, D. J., . . . Verkes, R. J. (2009). Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4- methylenedioxymethamphetamine) administration. Soc Neurosci, 4(4), 359-366. https://doi.org/10.1080/17470910802649470

Farré, M., Abanades, S., Roset, P. N., Peiró, A. M., Torrens, M., O'Mathúna, B., . . . de la Torre, R. (2007). Pharmacological interaction between 3,4-methylenedioxymethamphetamine (ecstasy) and paroxetine: pharmacological effects and pharmacokinetics. J Pharmacol Exp Ther, 323(3), 954- 962. https://doi.org/10.1124/jpet.107.129056

Feduccia, A. A. & Mithoefer, M. C. (2018). MDMA-assisted psychotherapy for PTSD: Are memory reconsolidation and fear extinction underlying mechanisms? Progress in Neuro-Psychopharmacology and Biological Psychiatry, 84(A), 221-228. https://doi.org/10.1016/j.pnpbp.2018.03.003

Greer, G., & Tolbert, R. (1986). Subjective reports of the effects of MDMA in a clinical setting. J Psychoactive Drugs, 18(4), 319-327. https://doi.org/10.1080/02791072.1986.10472364

Grob, C. S., & Poland, R. E. (2005). MDMA. In J. H. Lowinson, P. Ruiz, R. B. Millman, & J. G. Langrod (Eds.), Substance Abuse: A Comprehensive Textbook (4 ed., pp. 274-286). Williams and Wilkins.

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

Hysek, C. M., Domes, G., & Liechti, M. E. (2012). MDMA enhances "mind reading" of positive emotions and impairs "mind reading" of negative emotions. Psychopharmacology (Berl), 222(2), 293-302. https://doi.org/10.1007/s00213-012-2645-9

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

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

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

Tancer, M., & Johanson, C. E. (2003). Reinforcing, subjective, and physiological effects of MDMA in humans: a comparison with d-amphetamine and mCPP. Drug Alcohol Depend, 72(1), 33-44. https://doi.org/10.1016/s0376-8716(03)00172-8

van Wel, J. H., Kuypers, K. P., Theunissen, E. L., Bosker, W. M., Bakker, K., & Ramaekers, J. G. (2012). Effects of acute MDMA intoxication on mood and impulsivity: role of the 5-HT2 and 5-HT1 receptors. PLoS One, 7(7), e40187. https://doi.org/10.1371/journal.pone.0040187