Strategic control, consolidation and poly-drug use; the relative contributions to verbal memory impairment in recreational ecstasy users

Tests of verbal learning and memory have frequently been used to examine memory performance in frequent 3,4-methylendioxymethamphetamine (“ecstasy”) consumers, and meta-analyses have identified verbal learning and memory as the cognitive domain most adversely affected by regular ecstasy use (eg. Kalechstein, et al., 2007; Zakzanis, Campbell & Jovanovski, 2007). Tests of verbal memory are diverse however and include prose recall, multi-trial free recall and recognition tests. As such, it is unclear which specific measures of verbal learning and memory are most impaired by ecstasy use. Ascertaining which measures are most affected by chronic ecstasy use can inform as to which neural networks may be more likely candidates for explaining ecstasy related cognitive impairments. Study 1 therefore aimed to clarify which measure was most impacted by ecstasy use, by separating the domain of verbal learning and memory into three dependent variables that are commonly reported in the ecstasy and memory literature; Trial 1, Total and Delayed recall. This meta-analysis showed that ecstasy use does not impact on these three measures equally, with only a trivial effect of ecstasy use (g = -.15) found for Trial 1 (immediate recall), and moderate magnitude effects for Total (g = -.71) and Delayed recall scores (g = -.67) scores. The Working with Memory model (Moscovitch & Winocur, 1992; Moscovitch & Winocur, 2002; Moscovitch, 2008) posits that networks in the prefrontal cortex work with the hippocampus to organise information to enhance encoding and retrieval efficiency. Using this model as a framework, Study 2 sought to examine the relative contributions of frontal and hippocampal cognitive processes contributing to the Total and Delayed recall deficits for ecstasy and poly-drug users. This was achieved by recruiting regular consumers of ecstasy only (n = 15), cannabis only (n = 17) regular consumers of both ecstasy and cannabis (n = 20) and drug naïve participants (n = 17). Participants completed two multi-trial word learning tasks; one of which consisted of non-related words and the other comprised of semantically related words. Indices of semantic and subjective clustering were calculated to ascertain the involvement of frontal/strategic processes to memory scores, as well as several non-traditional memory indices that specified which words were gained and lost between list learning trials and assessed patterns of forgetting over multiple trials. Results showed moderate to large magnitude effects of ecstasy use for traditional measures such as Total recall (unrelated list; g = -.92, related list; g = -1.10) and Delayed recall (unrelated list only; g = -1.02) and these effects were independent of the effects of cannabis and other drug use. A clear inter-trial consolidation deficit was also apparent for ecstasy users, who lost more words between each learning trial than non-users (g = -.67) however ecstasy users did not make fewer gains relative to the other drug groups. The lack of difference in gains suggests intact acquisition/encoding for ecstasy users, however the higher number of “losses” on the subsequent trial indicate these gains were not able to be consolidated and hence were “lost.” This poor consolidation was also evident on the measures of forgetting, with ecstasy users more likely to forget words that had previously been recalled once (g = .73) and twice (g = -.63) compared with non-users. Strategic organisation of to-be-remembered words were also associated with moderate to large magnitude effects for ecstasy (g = -.53 for the unrelated list and g = -.97 for the related list) and not cannabis use, implicating deficient engagement of the prefrontal cortex as a contributor to verbal memory deficits associated with ecstasy use. In Study 3, two source memory tasks which differed in degree of difficulty were used to assess source memory performance for ecstasy users for the first time. Source judgements require the specific recollection of the context in which the encoding occurred, such as the colour a word was presented in. Poor source judgements have been observed in drug-naïve volunteers during acute tryptophan depletion, suggesting episodic recollection processes may be sensitive to reduced 5-HT functioning (McAllister-Williams, Massey & Rugg, 2004). The pattern of results for ecstasy users resembled source judgements of older adults, with no differences apparent on the easier version of the task between drug groups, however a significant moderate ecstasy related effect was observed for the more difficult, strategic version of the task (g = -.57). This result was thus consistent with the previous finding that ecstasy users are deficient in strategic processes that assist memory performance, and also suggest that source binding associated with the hippocampus may be impaired by ecstasy exposure. With regard to poly-drug use, this thesis found limited evidence for an effect of cannabis use on the various memory measures, with one notable exception; the number of specific words lost between the final learning trial and delayed recall was significantly greater for both cannabis and ecstasy users, suggesting the often reported Delayed recall deficit for ecstasy users may be confounded by concomitant cannabis use. Overall, the current thesis has found significant strategic/organisational deficits which are associated with impaired prefrontal functioning, as well as consolidation and source memory deficits associated with hippocampal dysfunction for regular ecstasy users, and these deficits were best accounted for by ecstasy rather than poly-drug use. As such, conclusions that verbal memory deficits reported for regular consumers of ecstasy are primarily a consequence of poly-drug use are at present, premature