Fully Validated, Multi-Kilogram cGMP Synthesis of MDMA.
MDMA is increasingly used in clinical research, but no cGMP process has yet been reported. We describe here the first fully validated cGMP synthesis of up to 5 kg (≈30 000 patient doses) of MDMA in a four-step process beginning with a noncontrolled starting material. The overall yield was acceptable (41-53%, over four steps), and the chemical purity of the final product was excellent, exceeding 99.9% of the peak area by HPLC in each of the four validation trials. The availability of cGMP-compliant MDMA will facilitate ongoing clinical trials and provide for future therapeutic use, if encouraging results lead to FDA approval.