Effects of MDMA On The Human Body

Effects Of MDMA On The Human Body

The effects of MDMA on the human brain and body are complex. It induces serotonin, dopamine, and norepinephrine release, and can act directly on a number of receptors, including α2-adrenergic (adrenaline) and 5HT_2A(serotonin) receptors. (DHEA), and the antidiuretic hormone vasopressin (which may be important in its occasional production of water intoxication or hyponatremia).

It's not fully understood why MDMA induces these unusual psychoactive effects. Most explanations focus on serotonin release. MDMA causes serotonin vesicles in the neurons to release quantities of serotonin into the synapses. Studies using pretreatment with an SSRI to block the ability of MDMA to release serotonin in volunteers suggest serotonin release is necessary for most effects of MDMA in humans. Released serotonin is believed to stimulate several receptors that contribute to the experiential effects of MDMA. Laboratory rodent experiments have shown MDMA to activate oxytocin-containing neurons in the hypothalamus by stimulating 5-HT_1A receptors. This appears to contribute to some of the social effects of MDMA: upon administering a drug that blocked brain receptors for oxytocin, the effects of the drug on social behavior were reduced. A second serotonin receptor, 5-HT_2A receptors (which are important for the effects of hallucinogens), makes mild contributions to MDMA effects. When the receptor was blocked, volunteers given MDMA reported decreases in MDMA-induced perceptual changes, emotional excitation, and acute adverse responses. In contrast, blocking these 5-HT_2A receptors had little effect on MDMA-induced positive mood, well-being, extroversion, and most short-term sequelae. One possible explanation for some of these 5-HTA-mediated effects is that 5-HT_2A stimulation inhibits dopamine release.

Although serotonin is important to the effects of MDMA, other drugs that release serotonin, such as fenfluramine, do not have effects like MDMA. This indicates that other neurochemical systems must be important for the MDMA experience. In addition to serotonin, dopamine and noradrenaline may play important roles in producing MDMA effects. The dopaminergic D2 receptor antagonist haloperidol selectively reduced the euphoric effects of MDMA in volunteers while increasing feelings of anxiety. Although not yet examined in humans, several studies in rodents, indicate the noradrenergic mechanisms contribute to the stimulating effects of MDMA. Finally, currently unexplored effects of MDMA may turn out to be important, such as trace amine receptors.

The effects of MDMA on regional cerebral blood flow (CBF) have been studied in humans using -Positron Emission Tomography (PET) MDMA was found to produce alteration of brain activity in cortical, limbic, and paralimbic structures. The dose of MDMA, 1.7 mg/kg, was psychoactive and participants reported heightened mood, increased extroversion, feelings of altered reality, and mild perceptual alterations. Feelings of "extroversion" correlated with CBF in the temporal cortex, amygdala, and orbitofrontal cortex.