Altered response to tryptophan supplementation after long-term abstention from MDMA (ecstasy) is highly correlated with human memory function

Abstract

Rationale: MDMA (ecstasy; +3,4-methylenedioxymethamphetamine) damages brain serotonin (5-HT) neurons and, in non-human primates, a loss of various 5-HT axonal markers persists for several years. This raises the question of whether long lasting effects occur in human beings that persist even after they have stopped using MDMA.

Objectives: We therefore assessed the effects of an indirect 5-HT manipulation on functions thought to be affected by MDMA use in people who had stopped using MDMA (ex-users) compared with continuing users and non-users.

Methods: Ninety-six participants were recruited: 32 ex-users who had stopped using MDMA for >1 year (mean, 2.4 years); 32 current users and 32 polydrug controls who had never used MDMA but were matched with ex-users and controls on cannabis use and pre-morbid IQ. Participants were given an amino acid mixture that contained either no tryptophan (T-) or augmented tryptophan (T+) and assessed before and 5 h after the drink on measures of cognitive function and mood.

Results: T+ and T- produced plasma tryptophan augmentation and depletion, respectively, in all three groups. Ex-users' plasma tryptophan levels in response to T+ were significantly higher than other groups. Ex-users' performance on a delayed prose recall task improved after T+ and lessened after T-. Changes in ex-users' free plasma tryptophan levels correlated highly (r=-0.9) with their baseline performance on immediate and delayed prose recall; change in total plasma tryptophan correlated (r=-0.81) with delayed recall. Further, total baseline plasma tryptophan correlated with number of years they had used MDMA before quitting. Baseline differences between groups were found on learning, working memory, aggression and impulsivity. T- did not produce differential effects in the three groups.

Conclusions: Our results suggest that prolonged abstinence from MDMA might be associated with altered tryptophan metabolism. Ex-users showing the poorest memory function at baseline were also those who metabolised least tryptophan. These findings may reflect pre-morbid differences in 5-HT function of those who stop using this drug or consequences of MDMA use that emerge after abstention. Aggression is also associated with MDMA use and subsequent abstinence.