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

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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.

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Acknowledgements

This study was aided by a grant to H.V.C. from the University of London Central Research Fund. S.V. was supported by a Medical Research Council (UK) studentship. The authors are extremely grateful to all the people who generously gave up their time to participate in this study. They also thank Dr. Martin Boback for providing medical cover, Prof. John Henry for helpful discussion and Dr. Mike Franklin for analyses of tryptophan levels.A preliminary report of this study was presented at the National Institute of Drug Abuse conference: "MDMA/Ecstasy Research: Advances, Challenges and Future Directions", July 19–20th, 2001. Neither author has any involvement, financial or otherwise, that might potentially bias their work.

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  1. Clinical Psychopharmacology Unit, Clinical Health Psychology, University College London, Gower Street, London, WC1 6BT, UK

    H. Valerie Curran & Suzanne L. Verheyden

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  1. H. Valerie Curran
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  2. Suzanne L. Verheyden
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Correspondence to H. Valerie Curran.

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Curran, H.V., Verheyden, S.L. Altered response to tryptophan supplementation after long-term abstention from MDMA (ecstasy) is highly correlated with human memory function. Psychopharmacology 169, 91–103 (2003). https://doi.org/10.1007/s00213-003-1463-5

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