UNLV Retrospective Theses & Dissertations 1-1-2007 The effect of concomitant ecstasy-marijuana use on auditory verbal learning and memory performance Kimberly M Cramer University of Nevada, Las Vegas Follow this and additional works at: https://digitalscholarship.unlv.edu/rtds Repository Citation Cramer, Kimberly M, "The effect of concomitant ecstasy-marijuana use on auditory verbal learning and memory performance" (2007). UNLV Retrospective Theses & Dissertations. 2785. http://dx.doi.org/10.25669/iz5s-qjxn This Dissertation is protected by copyright and/or related rights. It has been brought to you by Digital Scholarship@UNLV with permission from the rights-holder(s). You are free to use this Dissertation in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s) directly, unless additional rights are indicated by a Creative Commons license in the record and/or on the work itself. This Dissertation has been accepted for inclusion in UNLV Retrospective Theses & Dissertations by an authorized administrator of Digital Scholarship@UNLV. For more information, please contact [email protected]. THE EFFECT OF CONCOMITANT ECSTASY-MARIJUANA USE ON AUDITORY VERBAL LEARNING AND MEMORY PERFORMANCE by Kimberly M. Cramer Bachelor of Science University of Nevada, Las Vegas 1997 Master of Science University of Nevada, Las Vegas 2001 Master of Arts University of Nevada, Las Vegas 2005 A dissertation submitted in partial fulfillment of the requirements for the Doctor of Philosophy Degree in Psychology Department of Psychology College of Liberal Arts Graduate College University of Nevada, Las Vegas May 2008 UMI Number: 3319125 INFORMATION TO USERS The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleed-through, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, If unauthorized copyright material had to be removed, a note will indicate the deletion. UMI UMI Microform 3319125 Copyright 2008 by ProQuest LLC. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. ProQuest LLC 789 E. Eisenhower Parkway PO Box 1346 Ann Arbor, Ml 48106-1346 Copyright by Kimberly M. Cramer 2008 All Rights Reserved Dissertation Approval imm The Graduate College University of Nevada, Las Vegas April 18 ■ 20 08 The Dissertation prepared by Kimberly M. Cramer Entitled The Effect of Concomitant Ecstasy-Marijuana Use on Auditory Verbal Learning and Memory Performance is approved in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Psychology Exafmnation Committee Chair Dean of the Graduate College '.xatnination Cqm m th fer Examination Committee Member Graduate College Faculty Representative 11 ABSTRACT The Effect of Concomitant Ecstasy-Marijuana Use on Auditory Verbal Learning and Memory Performance by Kimberly M. Cramer Dr. Douglas Ferraro, Examination Committee Chair Professor of Psychology University of Nevada, Las Vegas Previous research indicates that ecstasy users exhibit deficits of verbal learning and memory. This research has not considered polydrug use in ecstasy users, especially marijuana. Marijuana is an important confound because 90 percent of ecstasy users also use marijuana. Several studies have suggested that marijuana use alters verbal memory functioning; consequently, it is difficult to ascertain whether the observed memory deficits in ecstasy users are attributable to ecstasy, marijuana, or other drug use. The present study examined the effects of marijuana and ecstasy on verbal memory function. Marijuana use was accounted for by recruiting concurrent ecstasy-marijuana users’ and ecstasy-naïve marijuana-only users. Furthermore, the extent of marijuana use was controlled for in the combined ecstasy-marijuana and marijuana-only groups by assigning marijuana users to either the marijuana light or marijuana heavy experimental groups. Recent animal findings suggest that at low frequencies marijuana may exert neuroprotective effects against ecstasy-induced neurotoxicity. Alternatively, other animal iii findings have demonstrated negative synergistic effects between ecstasy and marijuana and working memory performance. Polydrug use was controlled for by restricting other drug use to not more than 15 occasions. Based upon responses to a drug use history questionnaire, 109 students were retrospectively assigned to one of five groups; marijuana-only heavy users, marijuana-only light users, ecstasy-marijuana heavy users, ecstasy-marijuana light users, and non-drug using controls. Participants were matched for age, gender, education, and intelligence as measured by the Wechsler Adult Intelligence Scale, Third Edition. Verbal learning and memory performance was assessed using the Auditory Verbal Learning Test (AVLT) (Rey, 1964; Schmidt, 1996). The Biber Figure Learning Test-Extended version (BFLT-E) was administered during the 20-minute delay of the AVLT. AVLT performance was compared between the two marijuana-only groups and the controls to determine the impact of marijuana use on mnemonic function. The marijuana-only user groups were compared with the ecstasy-marijuana groups to evaluate the effects of ecstasy on verbal memory. Overall, findings in the present study suggest that marijuana use more than ecstasy were associated with AVLT. Additionally, drug use other than ecstasy and marijuana explained some of the impairment observed on the AVLT and even more so for BFLT-E performance IV TABLE OF CONTENTS ABSTRACT............................................................................................................................iii LIST OF TABLES................................................................................................................ vii LIST OF FIGURES.................................... viii ACKNOWLEDGEMENTS.................................................................................... ix CHAPTER 1 INTRODUCTION.......................................... 1 Explicit Long-Term Verbal Memory Studies in Ecstasy Users ......................................... 6 Explanations for the Diversity of Findings ........................................................................14 The Marijuana Confound ..................................................................... 15 Evidence Demonstrating Interactive Effects of MDMA and Marijuana ........................ 18 The Proposed Investigation .................................................................................................23 CHAPTER 2 REVIEW OF RELATED LITERATURE............................................... 25 History of MDMA ............... 25 Neuropharmacology of MDMA ........................................................................................ 26 The Serotonin System ......................................................................................................... 28 Serotonergic Neuron Distribution and Pathways ..............................................................29 Serotonergic Receptors ....................................................................................................... 32 MDMA and Serotonin Receptors ...................................................................................... 39 Neuropsychopharmacological Effects of MDMA in Experimental Animals ................ 42 Acute Subjective Effects of MDMA in Humans ..............................................................44 Long-Lasting Subjective Effects of Ecstasy in Humans .................................................. 44 Mechanisms of MDMA-Induced Neurotoxicity ...............................................................45 Evidence of the Neurotoxic Effects of MDMA in Animals ............................................49 Evidence of Neurotoxic Effects of MDMA in Humans ..................................... 51 Evidence that MDMA Induces Residual Effects on Cognition ........................... 55 Executive Function ..............................................................................................................67 Methodological Challenges ................................................................................................ 71 Directions for Future Research ...........................................................................................74 Summary and Conclusions ................... 76 Marijuana ..................................... 77 Metabolism of Cannabinoids ...............................................................................78 Carmabinoid Receptors ....................................................................................................... 79 Mechanisms of Action .........................................................................................................81 Does Marijuana Produce Dependence, Tolerance and Withdrawal? ...............................82 Acute Physiological Effects of Marijuana .........................................................................83 Acute Psychological Effects of Marijuana ....................................................................... 83 Appetite, Noiception and Anti-Emetic Acute Effects of Marijuana ................................84 Acute