Peripheral endocannabinoid concentrations are not associated with verbal memory impairment during MDMA intoxication

E Haijen, M. Farre, R. de la Torre, A.M. Pastor, E. Olesti, N Pizarro, J G Ramaekers, K P C Kuypers

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: Preclinical data have suggested involvement of the endocannabinoid (eCB) system in MDMA-induced memory impairment. Clinical research has shown that blockade of the 5-HT2 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-HT2 receptor blocker ketanserin would lead to a counteraction of the MDMA effects on eCB concentrations and memory.

METHODS: 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).

RESULTS: 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.

CONCLUSION: Current findings suggest that peripherally measured endocannabinoids are not associated with the verbal memory deficit during MDMA intoxication.

TRIAL REGISTRATION NUMBER: NTR3691.

Original languageEnglish
Pages (from-to)709-717
Number of pages9
JournalPsychopharmacology
Volume235
Issue number3
DOIs
Publication statusPublished - Mar 2018

Keywords

  • Journal Article
  • SYSTEM
  • 2-ARACHIDONOYLGLYCEROL
  • KETANSERIN
  • 5-HT2 receptor
  • HUMANS
  • THC
  • MDMA
  • Verbal memory
  • ECSTASY
  • PHARMACOKINETICS
  • 2-AG
  • PHARMACOLOGY
  • AEA
  • Endocannabinoids
  • MODULATION
  • BRAIN
  • Ketanserin

Cite this

Haijen, E ; Farre, M. ; de la Torre, R. ; Pastor, A.M. ; Olesti, E. ; Pizarro, N ; Ramaekers, J G ; Kuypers, K P C. / Peripheral endocannabinoid concentrations are not associated with verbal memory impairment during MDMA intoxication. In: Psychopharmacology. 2018 ; Vol. 235, No. 3. pp. 709-717.
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title = "Peripheral endocannabinoid concentrations are not associated with verbal memory impairment during MDMA intoxication",
abstract = "BACKGROUND: Preclinical data have suggested involvement of the endocannabinoid (eCB) system in MDMA-induced memory impairment. Clinical research has shown that blockade of the 5-HT2 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-HT2 receptor blocker ketanserin would lead to a counteraction of the MDMA effects on eCB concentrations and memory.METHODS: 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).RESULTS: 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.CONCLUSION: Current findings suggest that peripherally measured endocannabinoids are not associated with the verbal memory deficit during MDMA intoxication.TRIAL REGISTRATION NUMBER: NTR3691.",
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author = "E Haijen and M. Farre and {de la Torre}, R. and A.M. Pastor and E. Olesti and N Pizarro and Ramaekers, {J G} and Kuypers, {K P C}",
year = "2018",
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Peripheral endocannabinoid concentrations are not associated with verbal memory impairment during MDMA intoxication. / Haijen, E; Farre, M.; de la Torre, R.; Pastor, A.M.; Olesti, E.; Pizarro, N; Ramaekers, J G; Kuypers, K P C.

In: Psychopharmacology, Vol. 235, No. 3, 03.2018, p. 709-717.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Peripheral endocannabinoid concentrations are not associated with verbal memory impairment during MDMA intoxication

AU - Haijen, E

AU - Farre, M.

AU - de la Torre, R.

AU - Pastor, A.M.

AU - Olesti, E.

AU - Pizarro, N

AU - Ramaekers, J G

AU - Kuypers, K P C

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N2 - BACKGROUND: Preclinical data have suggested involvement of the endocannabinoid (eCB) system in MDMA-induced memory impairment. Clinical research has shown that blockade of the 5-HT2 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-HT2 receptor blocker ketanserin would lead to a counteraction of the MDMA effects on eCB concentrations and memory.METHODS: 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).RESULTS: 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.CONCLUSION: Current findings suggest that peripherally measured endocannabinoids are not associated with the verbal memory deficit during MDMA intoxication.TRIAL REGISTRATION NUMBER: NTR3691.

AB - BACKGROUND: Preclinical data have suggested involvement of the endocannabinoid (eCB) system in MDMA-induced memory impairment. Clinical research has shown that blockade of the 5-HT2 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-HT2 receptor blocker ketanserin would lead to a counteraction of the MDMA effects on eCB concentrations and memory.METHODS: 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).RESULTS: 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.CONCLUSION: Current findings suggest that peripherally measured endocannabinoids are not associated with the verbal memory deficit during MDMA intoxication.TRIAL REGISTRATION NUMBER: NTR3691.

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KW - HUMANS

KW - THC

KW - MDMA

KW - Verbal memory

KW - ECSTASY

KW - PHARMACOKINETICS

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KW - Endocannabinoids

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