Peripheral endocannabinoid concentrations are not associated with verbal memory impairment during MDMA intoxication
Eline Haijen, Magı́ Farré, Rafael de la Torre, Antoni Pastor, Eulàlia Olesti, Nieves Pizarro, Johannes G. Ramaekers, Kim P. C. Kuypers
Psychopharmacology November 16, 2017 DOI: 10.1007/s00213-017-4787-2 via OpenAlex
Summary
MDMA impaired verbal memory 90 minutes after administration in a word learning task, replicating earlier findings with the same dose (75 mg). Contrary to expectations, MDMA did not affect endocannabinoid concentrations (anandamide and 2-AG) in blood, and the 5-HT2 receptor blocker ketanserin did not block MDMA-induced memory impairment. Ketanserin alone increased AEA concentrations 180 minutes after administration. The findings suggest that peripherally measured endocannabinoids are not involved in the verbal memory deficit during MDMA intoxication.
Study at a glance
| Characteristics | Double-blind placebo-controlled within-subject study Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Healthy recreational polydrug users |
| Interventions | MDMA Ketanserin Placebo |
| Dose | MDMA 75 mg, ketanserin 40 mg |
| Topics | MDMA Serotonin |
| Keywords | Ketanserin Memory impairment Placebo |
| Citations | 9 |
| Key finding | MDMA impaired verbal memory 90 minutes post-treatment, but did not affect endocannabinoid concentrations, and ketanserin did not block this impairment. |
Abstract
Preclinical data have suggested involvement of the endocannabinoid (eCB) system in MDMA-induced memory impairment. Clinical research has shown that blockade of the 5-HT 2 receptor nulls memory impairment during MDMA intoxication. Interestingly, studies have demonstrated that the eCB and the 5-HT system interact. It was hypothesized that MDMA would cause an increase in eCB concentrations together with a decrease in memory performance, and that combining MDMA with a 5-HT 2 receptor blocker ketanserin would lead to a counteraction of the MDMA effects on eCB concentrations and memory. Twenty healthy recreational polydrug users entered a double-blind placebo-controlled within-subject study. Participants received a pre-treatment (ketanserin 40 mg, placebo) followed 30 min later by a treatment (MDMA 75 mg, placebo). Verbal memory was tested by means of a 30-word learning test. Endocannabinoid concentrations (anandamide (2-AG); N -arachidonylethanolamine (AEA)) were assessed in blood at baseline, before (90 min post-treatment) and after cognitive tests (150 min post-treatment). Findings showed that MDMA impaired memory 90 min post-treatment in the word learning task. This effect was a replication of previous studies using the same dose of MDMA (75 mg) and the same learning paradigm. Contrary to our hypothesis, MDMA did not affect eCB concentrations, nor did ketanserin block MDMA-induced memory impairment. Ketanserin caused an increase in AEA concentrations, 180 min after administration. Current findings suggest that peripherally measured endocannabinoids are not associated with the verbal memory deficit during MDMA intoxication. Trial registration number: NTR3691.