Psychedelic bliss : memory and risk taking during MDMA intoxication

Summary

MDMA (ecstasy) produces both positive effects and short-term side effects that appear early after ingestion. Early side effects such as fatigue, lack of energy, and difficulty concentrating arise about 24 hours after taking MDMA. Late short-term side effects occur up to 7 days after use and last longer. MDMA acts primarily on the serotonergic system as a powerful indirect 5-HT agonist, increasing 5-HT release, blocking reuptake, and inhibiting synthesis.

Study at a glance

Abstract

In addition to the positive effects, ecstasy use is also accompanied by short-term side effects occurring early, with respect to administration, and later on.Early short time side effects i.e. fatigue, lack of energy and difficulty concentrating, arise approximately 24 hours after MDMA ingestion.Late short-term side effects occur up to 7 days post-drug and are more or less comparable to early short time effects with the exception that they last longer (de la Torre et al., 2004).MDMA produces these positive and negative effects through the interaction with several neurotransmitter systems such as the serotonergic (5-HT), dopaminergic, noradrenergic, cholinergic and histaminergic systems.The main effect of MDMA is on the serotonergic system where it acts as a powerful indirect 5-HT agonist.MDMA causes an increased release of 5-HT, a blockade of the 5-HT reuptake mechanism, and inhibition of tryptophan hydroxylase, the precursor involved in the synthesis of 5-HT (Britt & McCance Katz, 2005; Schmidt & Kehne, 1990).Animal studies have shown that following ingestion of MDMA, there are two depletion phases of 5-HT.The increased release of 5-HT combined with the absence of reuptake and synthesis causes the 5-HT to be depleted in the first 3 to 6 hours after administration of MDMA.This first phase is depicted as the acute and reversible phase as it disappears within 12 hours, when the levels of 5-HT have returned to normal.The second depletion phase arises between 24 hours and 7 days post-drug, and is called the long-term or neurotoxic phase.This is because this second phase can be accompanied by the loss of 5-HT uptake sites, an indication of neurotoxic damage (Green, Mechan, Elliott, O'Shea, & Colado, 2003; Schmidt & Kehne, 1990).This persistent damage to neurons has been shown to occur in animals when administrated MDMA following a repeated high dosing scheme (Ricaurte, Yuan, & McCann, 2000).Whether it is justified to extrapolate these data to humans is however a topic of debate because of differences between animal studies and humans e.g.dosage, and the route of administration (De La Torre & Farre, 2004;Rattray, 1991).An indication for the second 5-HT depletion phase in humans is the existence of lowered mood, a few days after the use of ecstasy, or the so called 'mid-week depression', (Curran & Travill, 1997).Furthermore, there are also imaging studies showing signs of structural changes in heavy users e.g.lower 5-HT transporter densities, although these changes are possibly temporary (Green et al., 2003; Reneman, de Win, van den Brink, Booij, & den Heeten, 2006).Serotonin is a widespread neurotransmitter that is involved in diverse physiologic and cognitive processes.An example of a cognitive function in which 5-HT is implicated is memory performance.In several studies it has been shown DAY 1 DAY 2