Discrete memory impairments in largely pure chronic users of MDMA

Abstract

Abbreviated running title:Discrete memory impairments in pure users of MDMA Original Article Submitted:Number of words in the abstract: 241/250 Number of words in the main text: 4493/5000 Number of Tables: 3 Number of Figures: AbstractChronic use of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") has repeatedly been associated with deficits in working memory, declarative memory, and executive functions. However, previous findings regarding working memory and executive function are inconclusive yet, as in most studies concomitant stimulant use, which is known to affect these functions, was not adequately controlled for. Therefore, we compared the cognitive performance of 26 stimulant-free and largely pure (primary) MDMA users, 25 stimulant-using polydrug MDMA users, and 56 MDMA/stimulantnaïve controls by applying a comprehensive neuropsychological test battery. Neuropsychological tests were grouped into four cognitive domains. Recent drug use was objectively quantified by 6-month hair analyses on 17 substances and metabolites. Considerably lower mean hair concentrations of stimulants (amphetamine, methamphetamine, methylphenidate, cocaine), opioids (morphine, methadone, codeine), and hallucinogens (ketamine, 2C-B) were detected in primary compared to polydrug users, while both user groups did not differ in their MDMA hair concentration. Cohen's d effect sizes for both comparisons, i.e., primary MDMA users vs. controls and polydrug MDMA users vs. controls, were highest for declarative memory (dprimary=.90, dpolydrug=1.21), followed by working memory (dprimary=.52, dpolydrug=.96), executive functions (dprimary=.46, dpolydrug=.86), and attention (dprimary=.23, dpolydrug=.70). Thus, primary MDMA users showed strong and relatively discrete declarative memory impairments, whereas MDMA polydrug users displayed broad and unspecific cognitive impairments. Consequently, even largely pure chronic MDMA use is associated with decreased performance in declarative memory, while additional deficits in working memory and executive functions displayed by polydrug MDMA users are likely driven by stimulant co-use.

Social Cognition and Interaction in Chronic Users of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”)

“…All participants gave written informed consent and were compensated for their participation. Both MDMA users and MDMA-naïve healthy controls were already published in Wunderli et al (2017) ; however, polydrug users with hair concentrations of stimulants (e.g., cocaine and amphetamine) exceeding the values of MDMA were excluded from the present analysis. Moreover, the present MDMA user sample did not overlap with the samples of previous publications from the ZuCo 2 St, including cocaine users and stimulant-naïve controls (e.g., Preller et al, 2013 , 2014 ; Vonmoos et al, 2013b ; Hulka et al, 2014 ).…”

“…First, MDMA users often co-use other drugs ( Schifano et al, 1998 ; Curran, 2000 ), and previous MDMA research has been criticized for measuring drug consumption only via self-reports ( Cole, 2014 ). Second, drug users might be motivated to give a biased self-report or simply over- or underestimate their own consumption because of consistently shown memory alterations ( Magura and Kang, 1996 ; Quednow et al, 2006 ; Wunderli et al, 2017 ).…”

Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine

“…172,173,174,175 Those with a history of only moderate MDMA use do not seem to exhibit memory impairments. 176 However, acute MDMA intoxication produces memory deficits.…”

Clinical and Medical Management of Conditions Caused by MDMA or ‘Ecstasy’

“…Many of the neurocognitive and related problems of MDMA users are also similar in some ways to those caused by other recreational drugs, such as amphetamine or cocaine (Table 15.3; Parrott et al, 2011). So that while retrospective memory deficits are found in 'relatively pure' MDMA users, the memory problems may be worsened by additional drug usage (Mohamed et al, 2011;Wunderli et al, 2017).…”