Gender differences in the subjective effects of MDMA

This pooled analysis (n= 74) of three studies, investigated gender differences in the (perceived) effects of MDMA use. Equal doses of MDMA per kg body weight produced stronger psychoactive effects in women compared to men.


Rationale: 3,4-Methylenedioxymethamphetamine (MDMA) mainly releases serotonin (5-HT) and is contained in the recreational drug Ecstasy. 5-HT is known to play an important role in mood and anxiety disorders, for which there is a female preponderance. To date, there are no systematic data on gender differences in the subjective effects of MDMA. 

Objectives: The present work analyzed the pooled data from three controlled studies on the psychological and physiological effects of MDMA in healthy volunteers with no or minimal MDMA experience. A particular focus of the analyses were possible gender differences. 

Methods: A total of 74 subjects (54 male, 20 female) participated in all three studies. MDMA in oral doses ranging from 70–150 mg (1.35–1.8 mg/kg) was administered under double-blind placebo-controlled conditions. Subjective peak changes were assessed by standardized psychometric rating scales. Physiological measures were blood pressure, heart rate, and peripheral body temperature. Adverse drug effects were assessed during the experimental session and after 24 h. 

Results: Psychoactive effects of MDMA were more intense in women than in men. Women especially had higher scores for MDMA-induced perceptual changes, thought disturbances, and fear of loss of body control. The dose of MDMA positively correlated with the intensity of perceptual changes in women. Acute adverse effects and sequelae were also more frequent in female than in male subjects. In contrast, men showed higher increases in blood pressure than women. 

Conclusions: The fact that equal doses of MDMA per kilogram body weight produce stronger responses in women compared to men is consistent with increased susceptibility of women to the 5-HT-releasing effects of MDMA. Our results also indicate that increasing doses of MDMA produce more hallucinogen-like perceptual alterations, particularly in women.”

Authors: Matthias E. Liechti, Alex Gamma & Franz X. Vollenweider


Materials and methods

This analysis summarizes data from three published double-blind, placebo-controlled within-subject studies performed in our laboratory between 1996 and 2000. The studies were conducted in calm and comfortable laboratory environments, and the subjects’ psychological state and regional cerebral blood flow were assessed.

Subjective experience during the peak drug effect was assessed by psychometric ratings, and side effects were assessed by the List of Complaints both during the session and after 24 h. There were no correlations for age with any dependent measure.

All three studies were approved by the Ethics Committee of the University Hospital of Psychiatry, Zurich, and the Swiss Federal Health Office, Department of Pharmacology and Narcotics, Bern. The doses of MDMA used were very unlikely to produce neurotoxicity or lasting behavioral or functional consequences.

All 74 subjects were recruited from the University hospital staff and the Medical School of Zurich. They were screened by a semi-structured psychiatric interview, the Freiburg Personality Inventory, and by clinical examination. Sixty-nine subjects were MDMA-na, and 22 had received MDMA in combination with a pretreatment prior to the MDMA-alone session that was entered into the present analysis. No drug screenings were performed during the study.

Psychometric ratings were used to assess the psychological effects of MDMA, including efficiency-activation, self-confidence, heightened mood, apprehension-anxiety, depressiveness, thoughtfulness-contempla- tiveness, extroversion, introversion, inactivation, dazed state, tiredness, sensitivity, aggression-anger, and emotional excitation.

The Oceanic Boundlessness (OB) and Anxious Ego Dissolution (AED) measures derealization and depersonalization associated with positive mood, and the Visionary Restructuralization (VR) measures ego-disintegration and loss of autonomy and self-control associated with arousal and anxiety.

Pure racemic MDMA was obtained from the Swiss Federal Health Office, Department of Pharmacology and Narcotics, Bern, and was taken orally as a single dose.

Data were analyzed using Statistica 5.5 for Windows. ANOVAs were performed with drug and gender as within-subjects factors, and Tukey’s post hoc tests were performed based on significant main effects or interactions.

MDMA increased scores in all dimensions of the Altered States of Consciousness rating scale, and women scored significantly higher than men in all dimensions of the OAV.

Table 1 shows the main effects of MDMA and its interactions with gender, and post hoc results for 54 male and 20 female subjects.

Acute and short-term adverse effects of MDMA include: anxiety, depressiveness, heightened mood, THO thoughtfulness-contemplativeness, EXT extroversion, INT introversion, INA inactivation, DZT dazed state, TRD tiredness, SNS sensitivity, AGG aggression-anger, EXC emotional excitability.

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