Mechanism of Action

MDMA is a "dirty drug," affecting many neurotransmitter systems. It is primarily serotonergic, and its principal mechanism of action is as an indirect seroto-nergic agonist (Ames & Wirshing, 1993; Rattray, 1991; Sprague et al., 1998). The drug's effects, and side effects (an arbitrary distinction), including anorexia, psychomotor agitation, difficulty in achieving orgasm, and profound feelings of empathy, can be explained as a result of the flooding of the serotonin system (Beck & Rosenbaum, 1994). After ingestion, MDMA is taken up by the serotonin cells through active channels, effecting the release of serotonin stores. MDMA also blocks reuptake of serotonin, and this contributes to its length of action. Although it inhibits the synthesis of new serotonin, this does not contribute to the intoxication phase, but it may contribute to sustained feelings of depression reported by some users and to a diminished magnitude of subjective effects when the next dose is taken within a few days of the first dose.

Most people who use MDMA on a regular basis tend not to increase their use as time goes on (Cohen, 1998; Peroutka, 1990). Because of its mechanism of action (the drug depletes serotonin stores and inhibits synthesis of new serotonin), subsequent doses produce a diminished high and a worsening of the drug's undesirable effects, such as psychomotor restlessness and teeth gnashing. MDMA users most typically become aware of the benefits of periodic, even rare use. First-time users are often instant advocates of MDMA, only to have their enthusiasm dampen with time. An adage about Ecstasy captures this succinctly: "Freshmen love it, sophomores like it, juniors are ambivalent, and seniors are afraid of it" (Eisner, 1993).

MDMA's effects may be arbitrarily divided into short- and long-term categories (McKenna & Peroutka, 1990). The short-term effects presumably result from the acute release of serotonin and are associated with decreases in serotonin and 5-hydoxyindoleacetic acid (5-HIAA), and in tryptamine hydroxylase (TPH) activity. The long-term effects are manifested by a steady, slow decrease in serotonin and 5-HIAA after initial recovery, persistently depressed TPH activity, and a decrease in serotonin terminal density (Demirkiran et al., 1996; Ricaurte, McCann, Szabo, & Scheffel, 2000). 5-HIAA levels most typically recover to baseline levels within 24 hours.

Anxiety and Depression 101

Anxiety and Depression 101

Everything you ever wanted to know about. We have been discussing depression and anxiety and how different information that is out on the market only seems to target one particular cure for these two common conditions that seem to walk hand in hand.

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