We accounted for the multiplicity of measures by correcting alpha levels via a modified Bonferroni procedure . This approach considers the mean correlation between variables and the number of tests in the adjustment of alpha levels. All alpha levels were adjusted for both traditional neurocognitive assessment and BIS-11 and their average inter-correlation coefficients in primary and secondary models and in tertiary models . The corresponding adjusted alpha levels for primary and secondary models were p ≤ 0.013 for neurocognitive domains and p ≤ 0.027 for self-reported impulsivity. The corresponding adjusted alpha levels for tertiary models, which included PSU only, were p ≤ 0.011 for neurocognitive domains and p ≤ 0.017 for BIS-11. Alpha levels for risk-taking and decision-making were not adjusted as these are individual tasks measuring separate domains of executive function. Effect sizes for mean differences between groups were calculated with Cohen’s d . We correlated cognitive functioning, risk-taking, decision making and self-reported impulsivity measures to alcohol use in PSU and AUD, and to cocaine, and marijuana use in PSU only at baseline. Since these were exploratory correlations, we chose a less restrictive alpha level of 0.05. For all other domains except fine motor skills, PSU showed numerically lower scores than AUD with effect sizes up to 0.76 but no statistically significant group differences after covariate correction . When smoking status was included as a factor in the cross-sectional group analyses of neurocognitive domains,drying rack for weed neither significant group-by-smoking interactions nor main effects of smoking were observed.
In addition, gender was not a significant predictor of neurocognitive performance at one month of abstinence, except for fine motor skills which were worse in female than male substance users. Poly substance users exhibited trends to worse decision-making than AUD [x2 = 3.64, p = 0.056, ES = 0.33]; the groups were not significantly different on risk-taking . No significant group-by-smoking interactions or main effects for smoking were observed on either IGT or BART. Poly substance users self-reported significantly higher BIS-11 total and non-planning impulsivity, a measure of cognitive control, than AUD , and being on a prescribed psychoactive medication significantly predicted higher total and non-planning impulsivity. With smoking status included in the analyses, no significant group-by-smoking interactions were observed for any of the BIS-11 measures. However, self-reported motor impulsivity showed a trend for a group-by-smoking interaction [x2 = 3.259, p = 0.071], a significant main effect for group [x2 = 2.005, p = 0.006], and a trend for a smoking effect [x2 = 1.499, p = 0.066]. Follow-up pairwise comparisons showed significantly higher motor impulsivity in smoking PSU compared to both smoking and nonsmoking AUD . Between baseline and follow-up, neurocognitive functions in abstinent PSU improved markedly in the following domains: general intelligence, cognitive efficiency, executive function, working memory, and visuospatial skills , and weaker improvements were observed for global cognition and processing speed . Abstinent PSU did not change significantly in the domains of learning and memory or fine motor skills. Preliminary analyses indicate that the lack of significant changes in the domains of visuospatial memory and fine motor skills were related to significant time-by-smoking status interactions , where only nonsmokers increased on fine motor skills and only smokers improved on visuospatial memory.
The BART scores increased significantly with abstinence , whereas the IGT scores did not change during abstinence. Self-reported total and motor impulsivity decreased significantly with abstinence and the non-planning score tended to decrease . The following changes were observed when restricting our longitudinal analysis to only those 17 PSU with baseline and follow-up data: general intelligence, executive function, working memory , visuospatial skills , global cognition , and processing speed . The 19 PSU not studied longitudinally differed from our abstinent PSU restudied on lifetime years of cocaine use . PSU not restudied performed significantly worse at baseline than abstinent PSU on cognitive efficiency, processing speed, and visuospatial learning . Furthermore, they did not differ significantly on years of education, AMNART, tobacco use severity, and proportions of smokers or family members with problem drinking, or the proportion of individuals taking a prescribed psychoactive medication. In PSU, more lifetime years drinking correlated with worse performance on domains of cognitive efficiency, executive function, intelligence, processing speed, visuospatial skills, and global cognition . More cocaine consumed per month over lifetime correlated with worse performance on executive function and greater attentional impulsivity . More marijuana consumed per month over lifetime correlated with worse performance on fine motor skills and tended to correlate with higher BIS-11 motor impulsivity ; in addition, more marijuana use in the year preceding the study correlated with higher non-planning and total impulsivity. Earlier onset age of marijuana use correlated with higher non-planning impulsivity and worse visuospatial learning . Interestingly, more lifetime years of amphetamine use correlated with better performance on fine motor skills, executive function, visuospatial skills, and global cognition . Similar to the associations found in PSU, more lifetime years drinking in AUD correlated with worse performance on cognitive efficiency, visuospatial skills, and global cognition , and worse performance on visuospatial memory correlated with greater monthly alcohol consumption averaged over the year preceding assessment and over lifetime .
In addition, longer duration of alcohol use in AUD was related to worse auditory-verbal learning and memory . Earlier age of onset of heavy drinking in AUD was associated with worse decision-making . Our primary aim was to compare neurocognitive functioning and inhibitory control in onemonth-abstinent PSU and AUD. Poly substance users at one month of abstinence showed decrements on a wide range of neurocognitive and inhibitory control measures compared to normed measures. The decrements in neurocognition ranged in magnitude from 0.2 to 1.4 standard deviation units below a zscore of zero, with deficits >1 standard deviation below the mean observed for visuospatial memory and visuospatial learning. In comparisons to AUD, PSU performed significantly worse on measures assessing auditory-verbal memory, and tended to perform worse on measures of auditory-verbal learning and general intelligence. Chronic cigarette smoking status did not significantly moderate cross-sectional neurocognitive group differences at baseline. In addition, PSU exhibited worse decision-making and higher self-reported impulsivity than AUD , signaling potentially greater risk of relapse for PSU than AUD . Being on a prescribed psychoactive medication related to higher self-reported impulsivity in PSU. For both PSU and AUD, more lifetime years drinking were associated with worse performance on global cognition, cognitive efficiency, general intelligence, and visuospatial skills. Within PSU only,vertical cannabis greater substance use quantities related to worse performance on executive function and fine motor skills, as well as to higher self-reported impulsivity. Neurocognitive deficits in AUD have been described extensively. However, corresponding reports in PSU are rare and very few studies compared PSU to AUD during early abstinence on such a wide range of neurocognitive and inhibitory control measures as administered here . To our knowledge, no previous reports have specifically shown PSU to perform worse than AUD on domains of auditory-verbal learning and general intelligence at one month of abstinence. Our studies confirmed previous findings of worse auditory-verbal memory and inhibitory control in individuals with a comorbid alcohol and stimulant use disorder compared to those with an AUD, and findings of no differences between the groups on measures of cognitive efficiency . Some of the cross-sectional neurocognitive and inhibitory control deficits described in this PSU cohort are associated with previously described morphometric abnormalities in primarily prefrontal brain regions of a subsample of this PSU cohort with neuroimaging data . Our neurocognitive findings also further complement studies in sub-samples of this PSU cohort that exhibit prefrontal cortical deficits measured by magnetic resonance spectroscopy and cortical blood flow . Our secondary aim was to explore if PSU demonstrate improvements on neurocognitive functioning and inhibitory control measures between one and four months of abstinence from all substances except tobacco. Poly substance users showed significant improvements on the majority of cognitive domains assessed here, particularly cognitive efficiency, executive function, working memory, self-reported impulsivity, but an unexpected increase in risk-taking behavior . By contrast, no significant changes were observed for learning and memory domains, which were also worst at baseline, resulting in deficits in visuospatial learning and visuospatial memory at four months of abstinence of more than 0.9 standard deviation units below a z-score of zero.
There were also indications for significant time-by-smoking status interactions for visuospatial memory and fine motor skills, however these analyses have to be interpreted with caution and considered very preliminary, considering the small sample sizes of smoking and nonsmoking PSU at followup. Nevertheless, the demonstrations of cognitive recovery in abstinent PSU, and potential effects of smoking status on such recovery, are consistent with our observations of corresponding recovery in abstinent AUD . The 19 PSU not studied at follow-up differed significantly from abstinent PSU at baseline on several important variables: they had more years of cocaine use over lifetime, and performed worse on cognitive efficiency, processing speed, and visuospatial learning. As such, these differences should be tested as potential predictors of relapse in future larger studies. Several factors limit the generalizability of our findings. Our cross-sectional sample size was modest and therefore our longitudinal sample of abstinent PSU was small; as not uncommon in clinical samples, about half of our PSU cohort relapsed between baseline and follow-up, a rate comparable to what has been reported elsewhere . This made us focus our longitudinal results reporting on the main effects of time and to de-emphasize the reporting of time-by-smoking status interactions. Larger studies are needed to examine the potential effects of smoking status and gender on neurocognitive recovery during abstinence from substances. The study sample was drawn from treatment centers of the Veterans Affairs system in the San Francisco Bay Area and a community based healthcare provider, and the ethnic breakdown of the study groups was different . Therefore, our sample may not be entirely representative of community-based substance use populations in general. Although preliminary, the within subject statistics are meaningful as they are more informative for assessing change over time than larger cross-sectional studies at various durations of abstinence. In addition, premorbid biological factors and other behavioral factors not assessed in this study may have influenced cross-sectional and longitudinal outcome measures. Nonetheless, our study is important and of clinical relevance in that it describes deficits in neurocognition and inhibitory control of detoxified PSU that are different from those in AUD, and that appear to recover during abstinence from substances, potentially as a function of smoking status. Our cross-sectional and longitudinal findings are valuable for improving current substance use rehabilitation programs. The higher impulsivity and reduced cognitive abilities of PSU compared to AUD, likely the result of long-term comorbid substance use, and the lack of improvements in learning and memory during abstinence indicate a potentially reduced ability of PSU to acquire new cognitive skills necessary for remediating maladaptive behavioral patterns that impede successful recovery. As such, PSU may require a post-detox treatment approach that accounts for these specific deficits relative to AUD. Our results show that PSU able to maintain abstinence for 4 months had less total lifetime years of cocaine use and performed better on cognitive efficiency, processing speed and visuospatial learning than those PSU not restudied ; these variables may therefore be valuable for predicting future abstinence or relapse in PSU. Additionally, and if confirmed in larger studies, our preliminary results on differential neurocognitive change in smoking and nonsmoking PSU may inform a treatment design that addresses the specific needs of these subgroups within this largely understudied population of substance users. Potentially, concurrent treatment of cigarette smoking in treatment-seeking PSU may also help improve long-term substance use outcomes, just as recently proposed for treatment seeking individuals with AUD . Finally, our findings on neurocognitive improvement in PSU imply that cognitive deficits are to some extent a consequence of long-term substance use , which have the potential for remediation with abstinence. This information is of clinical relevance and of psychoeducational value for treatment providers and treatment-seeking PSU alike. People who inject drugs are disproportionately impacted by harms associated with injecting, including overdose and infection with HIV and hepatitis C virus . Relatedly, people who experience homelessness are at increased risk of initiating injection drug use . Between 40%–61% of PWID in North America are estimated to have experienced homelessness in the prior year .