Dosing and Pharmacokinetics of MDMA

Below are the events that take place after the oral administration of MDMA.

Please ensure that you read through all events before proceeding by using the arrows to navigate through the timeline.

Dosing

The following doses have been used in clinical trials to date.

Initial Dose	80-120mg (Mitchell et al., 2021)
Supplemental Dose	40-60mg (Half of the initial dose) (Mitchell et al., 2021)

FDA approval and more empirical evidence are needed to provide a recommended dosing mechanism.

During clinical trials for FDA New Drug Applications, varying doses are investigated in earlier stage research in order to determine optimal dosing. In clinical trials to date, MDMA has been administered in 75, 80, 120, and 125 mg initial doses, and in most cases, each was followed within 75 minutes by an optional, supplemental dose that is 50% of the starting dose. The New Drug Application for MDMA-assisted therapy will include a flexible initial dose of 80 or 120 mg MDMA Hydrochloride, followed by a supplemental dose of 40 or 60 mg. This dosing regimen has been identified by the drug developer (MAPS Public Benefit Corporation) as the optimal starting dose after performing clinical trials investigating different doses.

References

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

de la Torre, R., Farré, M., Ortuño, J., Mas, M., Brenneisen, R., Roset, P. N., . . . Camí, J. (2000). Non-linear pharmacokinetics of MDMA ('ecstasy') in humans. Br J Clin Pharmacol, 49(2), 104-109. https://doi.org/10.1046/j.1365-2125.2000.00121.x

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

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

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.

Mitchell, J.M., Bogenschutz, M., Lilienstein, A., Harrison, C., Kleiman, S., Parker-Guilbert, K., Ot’alora G., M., Garas, W., Paleos, C., Gorman, I., Nicholas, C., Mithoefer, M., Carlin, S., Poulter, B., Mithoefer, A., Quevedo, S., Wells, G., Klaire, S.S., van der Kolk, B., Tzarfaty, K., Amiaz, R., Worthy, R., Shannon, S., Woolley, J.D., Marta, C., Gelfand, Y., Hapke, E., Amar, S., Wallach, Y., Brown, R., Hamilton, S., Wang, J.B., Coker, A., Matthews, R., de Boer, A., Yazar-Klosinski, B., Emerson, A., & Doblin, R. (2021). MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine, 27, 1025–1033.

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

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