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Last updated Feb 10, 2005
People frequently ask whether taking anti-depressants can affect their MDMA experience in any way. The simple answer is that SSRIs (Prozac, Paxil, & Zoloft among others) may reduce the effects of MDMA. Other types of antidepressants include MAOIs, which could cause dangerous or even fatal reactions if taken with MDMA or other strong stimulants. Bupropion (Wellbutrin) alters MDMA's effects but does not appear to weaken the effects, however, the safety of this combination is not well documented. Tricyclic antidepressants, which may cause a change and increase in effects, are also not well documented.

Please also see:

Reduction of Effects

SSRIs tend to cause reduced physiological and mental effects when taken before MDMA. A study for which there was a poster at the College on Problems of Drug Dependence in June of 2002, administered 20 mg Paroxetine (Paxil, a common dosage) orally to subjects for 3 days before administering MDMA. Subjects had reduced experiential and physiological responses to the MDMA. See

An important study by Liechti et al., concerning the effects of SSRI pretreatment on subjective MDMA effects in humans, administered Citalopram (an SSRI) at 40 mg by IV and found that the Citalopram reduced physiological and emotional responses:

"The main result of this study is that the psychoactive effects of 1.5 mg/kg MDMA were substantially attenuated by pretreatment with the SSRI citalopram (40 mg iv). Citalopram inhibited most of the psychological effects of MDMA. MDMA-induced increases in positive mood, derealization and depersonalization phenomena, thought disorder, and the loss of thought and body control were all attenuated by citalopram pretreatment. MDMA-evoked intensification of sensory perception, changes in the meaning of percepts, and subjectively facilitated imagination were also inhibited by citalopram as compared to MDMA alone. Citalopram alone also lowered scores on some scales compared to placebo. Most of these changes, however, were clearly due to side effects of citalopram such as fatigue, headache, and nausea, which influenced the mood rating. MDMA also produced marked increases in emotional excitability and sensitivity that, however, were not reduced by citalopram."

"We investigated the effect of citalopram pretreatment (40 mg i.v.) on vegetative and cardiovascular effects of MDMA (1.5 mg/kg p.o.) in a double-blind placebo-controlled study in 16 healthy volunteers. MDMA moderately increased blood pressure and heart rate, slightly elevated body temperature and produced a broad range of acute and shortterm side-effects. Citalopram reduced all these MDMA-induced physiological changes except for body temperature."
A further relevant study, from the Spanish group studying MDMA In humans, is:

Segura M, Farré M, Pichini S, Peiró AM, Roset PN, Ramírez A, Ortuño J, Pacifici R, Zuccaro P, Segura J, de la Torre R (2004) Contribution of CYP2D6 to 3,4-methylenedioxymethamphetamine (MDMA) disposition in humans: use of paroxetine as a metabolic inhibitor probe. Clin Pharmacokin (in press).

As of Feb 2005 this study is still in press, but in a different paper Farre et al. state that the study shows that "...a reduced cardiovascular activity and euphoria induced by MDMA were measured in the combination treatment (paroxetine and MDMA)."

Finally, chronic use of SSRIs, as is done in the treatment of depression, seems to reduce the effects of MDMA. That is, a higher dose of MDMA is required to achieve the entactogenic effect.

Nerve Cell Damage Protection?

Some people take SSRIs (selective serotonin reuptake inhibitors) several hours after taking MDMA in an attempt to reduce or block suspected neurotoxicity (brain cell damage). See MDMA (Ecstasy) Neurotoxicity, by Baggott and Mendelson.