Safety pharmacology of acute MDMA administration in healthy subjects

In nine double-blind, placebo-controlled studies with 166 healthy subjects, single doses of MDMA (75 or 125 mg) produced acute positive subjective effects lasting about 4 hours, with the higher dose yielding stronger 'good drug effect' ratings. Moderate and transient 'bad drug effects' were greater in women than men. MDMA raised systolic blood pressure above 160 mmHg in 33% of subjects, heart rate above 100 beats/min in 29%, and body temperature above 38°C in 19%; these effects were more frequent with the 125 mg dose. Adverse effects were dose-dependent and more common in females. No serious adverse events occurred, and liver or kidney function was unaffected about a month later. MDMA was safe in healthy subjects in a medical setting, but risks are likely higher in patients with cardiovascular disease.

Study at a glance

Abstract

3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is being investigated in MDMA-assisted psychotherapy. The present study characterized the safety pharmacology of single-dose administrations of MDMA (75 or 125 mg) using data from nine double-blind, placebo-controlled, crossover studies performed in the same laboratory in a total of 166 healthy subjects. The duration of the subjective effects was 4.2 ± 1.3 h (range: 1.4–8.2 h). The 125 mg dose of MDMA produced greater ‘good drug effect’ ratings than 75 mg. MDMA produced moderate and transient ‘bad drug effect’ ratings, which were greater in women than in men. MDMA increased systolic blood pressure to >160 mmHg, heart rate >100 beats/min, and body temperature >38°C in 33%, 29% and 19% of the subjects, respectively. These proportions of subjects with hypertension (>160 mmHg), tachycardia, and body temperature >38°C were all significantly greater after 125 mg MDMA compared with the 75 mg dose. Acute and subacute adverse effects of MDMA as assessed by the List of Complaints were dose-dependent and more frequent in females. MDMA did not affect liver or kidney function at EOS 29 ± 22 days after use. No serious adverse events occurred. In conclusion, MDMA produced predominantly acute positive subjective drug effects. Bad subjective drug effects and other adverse effects were significantly more common in women. MDMA administration was overall safe in physically and psychiatrically healthy subjects and in a medical setting. However, the risks of MDMA are likely higher in patients with cardiovascular disease and remain to be investigated in patients with psychiatric disorders.