Pharmacological Approaches to Remediate Neurocognitive Impairment in Cocaine-Dependent Individuals

The goal of this study was to determine whether demographic (e.g. ethnicity, gender, etc.), drug use (e.g. years of cocaine use, days cocaine used in the past 30, comorbid substance use, etc.), or mood (BDI-II, LSC-R, and ASI-Lite scores) variables affected neurocognitive functioning in cocaine-dependent participants. In addition, two candidate medications were evaluated to assess whether they have the potential to improve neurocognitive functioning in cocaine-dependent individuals. There were two separate studys as part of this dissertation. Study 1 involved the investigation of demographic and drug use variables contributing to neurocognitive deficits in 125 cocaine dependent individuals. Study 2 compared the efficacy of two acetylcholinesterase inhibitors: rivastigmine and huperzine (as well as a control group randomized to receive placebo) as potential treatments for cocaine-induced neurocognitive impairment. Twenty-eight individuals were randomized to receive rivastigmine, 29 were randomized to receive huperzine, and 15 were randomized to receive placebo. Before study medication randomization, participants completed a battery of neurocognitive assessments and completed the same battery of assessments following 8 days of medication/placebo treatment. One of the factors that detrimentally affects cocaine-dependent individuals as they seek treatment is the presence of neurocognitive deficits produced or exacerbated by cocaine use. Since long-term, high-dose cocaine use is a risk factor for the onset of neurocognitive impairment in humans, it is critical that these deficits be addressed in order to improve treatment outcomes. Study 1 utilized only baseline data (independent of any medication treatment) and Study 2 used both pre-treatment (baseline, before medication administration) and post-treatment (following medication administration) data. Pearson product moment correlations and analysis of variance (ANOVA) were used to evaluate the association between demographic and drug use variables and performance on the neurocognitive measures. ANOVA was used to evaluate medication versus placebo effects on test performance pre- and post-treatment. Study 1 revealed that there were no gender or race differences in neurocognition between groups. Further, comorbid substance use (e.g. nicotine, alcohol, or marijuana) did not affect neurocognition. Study 2 showed that treatment with rivastigmine significantly improved episodic memory, though treatment with huperzine did not affect neurocognition. On the basis of outcomes from Study 1 and Study 2, we contend that cocaine associated neurocognitive impairment remains an important target of treatment. Given that cocaine addiction is associated with widespread functional difficulties, such as unemployment and relapse to dependence, it is plausible that reversing neurocognitive impairments will ameliorate these functional difficulties.