Raul Gonzalez

Acute and non-acute effects of cannabis on brain functioning and neuropsychological performance.

Cannabis has an ancient history of human use and is currently one of the most commonly used drugs worldwide. Understanding its impact on neurobehavioral functioning is of significant public health concern. In recent decades, substantial progress has been made in understanding the impact of cannabis use on neurobehavioral functioning. This has been fueled, in part, by characterization of an endocannabinoid signaling system in the brain through which cannabis exerts its psychoactive effects. Acute intoxication with cannabis causes marked changes in subjective mental status, brain functioning, and neuropsychological performance. Some of these changes are consistently detected and well characterized, yet others are not. Changes in brain functioning and neuropsychological performance are also reported after abstinence, but appear to be mild, circumscribed, and transient. On the other hand, functional neuroimaging often reveals subtle differences in the brain functioning of abstinent cannabis users compared with controls. The persistence and clinical significance of these differences, however, remains to be determined. Neuropsychological deficits and differences in brain functioning are most consistently observed only among frequent, heavy users, who are those most likely addicted to cannabis. The dire impact of drug addiction on a person’s life and everyday functioning suggests that the large number of individuals addicted to cannabis experience substantial negative effects from its use. This manuscript reviews the scientific literature on the aforementioned topics in detail, providing evidence for converging findings, and highlighting areas in need of further investigation.

Executive functions among individuals with methamphetamine or alcohol as drugs of choice: preliminary observations

Substance dependent individuals (SDIs) are frequently, but not invariably, impaired on tasks of executive functions. In this study, we examine patterns of executive performance among subjects with different self-reported “drug of choice” (defined as substance used >80% of the time prior to abstinence). Subjects were 33 abstinent SDIs receiving inpatient treatment and 19 non-SDI normal controls (NC) well-matched on age, sex, ethnicity, and VIQ, who were assessed using the Iowa Gambling Task (GT) and a delayed non-match to sample task (DNM): measures of decision making and working memory, respectively. Seventeen SDIs identified alcohol (AL group) and 16 SDIs identified methamphetamine (METH group) as their drug of choice. Overall, the METH group performed more poorly than the NC and AL groups on both tasks, with the largest differences observed in working memory. The AL group was not significantly impaired overall compared to NCs on either task, but showed subtle abnormalities of GT performance similar to the METH group. These preliminary findings suggest that self-reported drug of choice on admission to treatment may be associated with different patterns of executive performance during early recovery.

Deficient strategic control of verbal encoding and retrieval in individuals with methamphetamine dependence

Methamphetamine (MA) dependence is associated with deficits in episodic verbal memory, but the cognitive mechanisms underlying such impairments are not known. The authors evaluated a component process model of episodic verbal memory in 87 persons with MA dependence (MA+) and 71 demographically similar non-MA-using controls (MA-). Compared with MA- controls, MA+ participants demonstrated deficient overall learning, free recall, and utilization of semantic clustering, as well as higher rates of repetitions and intrusions. No between-groups differences were evident on measures of serial clustering, retention, or recognition discrimination. Taken together, these findings indicate that MA dependence is associated with deficient strategic (i.e., executive) control of verbal encoding and retrieval, which is consistent with the sequelae of MA-related prefronto-striatal circuit neurotoxicity.

The influence of executive functions, sensation seeking, and HIV serostatus on the risky sexual practices of substance-dependent individuals

From a public health standpoint, identifying factors that contribute to risky sexual practices among substance-dependent individuals is critical, particularly in the context of HIV infection. This study examines the respective contributions of executive neurocognitive functions, sensation seeking, and HIV serostatus in predicting risky sexual practices among poly-substance users (with a history of dependence primarily for cocaine or cocaine/heroin). HIV+ (n=109) and HIV- (n=154) substance-dependent individuals were assessed using three neurocognitive tasks of executive functions: Stroop reaction time, delayed non-matching to sample, and the Iowa Gambling Task. Sensation seeking was assessed using the Sensation Seeking Scale-V. Greater sensation seeking was associated with more risky sexual practices among HIV+ participants, particularly among those who performed best on the Iowa Gambling Task. Our findings indicate that continued risk behavior among HIV+ drug users may be driven by sensation seeking (a personality trait common among drug users); however, the impact of executive functions is less clear.

Performance of young adult cannabis users on neurocognitive measures of impulsive behavior and their relationship to symptoms of cannabis use disorders

Recent studies suggest that abstinent cannabis users show deficits on neurocognitive laboratory tasks of impulsive behavior. But results are mixed, and less is known on the performance of non-treatment-seeking, young adult cannabis users. Importantly, relationships between performance on measures of impulsive behavior and symptoms of cannabis addiction remain relatively unexplored. We compared young adult current cannabis users (CU, nu2009=u200965) and nonusing controls (NU, nu2009=u200965) on several laboratory measures of impulsive behavior, as well as on a measure of episodic memory commonly impacted by cannabis use. The CU group performed more poorly than the NU group on the Hopkins Verbal Learning Test–Revised Total Immediate Recall and Delayed Recall. No significant differences were observed on the measures of impulsive behavior (i.e., Iowa Gambling Task, IGT; Go–Stop Task; Monetary Choice Questionnaire; Balloon Analogue Risk Task). We examined relationships between neurocognitive performance and symptoms of cannabis use disorder symptoms (Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition, DSM–IV CUD) among the CU group, which revealed that poorer IGT performance was associated with more symptoms of DSM–IV CUD. Our results show poorer memory performance among young adult cannabis users than among healthy controls, but no differences on measures of impulsive behavior. However, performance on a specific type of impulsive behavior (i.e., poorer decision making) was associated with more cannabis use disorder symptoms. These results provide preliminary evidence to suggest that decision-making deficits may be more strongly associated with problems experienced from cannabis use, rather than solely being a consequence of cannabis use, per se. This publication was supported by Grants K23DA023560 and R01DA031176 (PI: Gonzalez) and F31DA032244 (PI: Schuster) from the National Institute on Drug Abuse (NIDA), as well as P01 CA098262 (PI: Mermelstein) from the National Cancer Institute (NCI). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

Additive deleterious effects of methamphetamine dependence and immunosuppression on neuropsychological functioning in HIV infection.

Methamphetamine (MA) dependence and HIV infection are independently associated with cerebral dysfunction, especially within frontal-basal ganglia circuits. Recent evidence indicates that MA dependence has an additive effect on neuropsychological (NP) deficits associated with HIV infection. This study extends prior findings by examining the combined effects of MA dependence (MA+) and immunosuppression (i.e., CD4 lymphocyte count <200) on NP functioning in 284 HIV+ individuals. Prevalence of NP impairment was examined in four demographically comparable groups: (1) MA+/CD4xa0<xa0200; (2) MA+/CD4xa0≥xa0200; (3) MA−/CD4xa0<xa0200; and (4) MA−/CD4xa0≥xa0200. Results revealed that both MA dependence and immunosuppression were significant predictors of NP impairment. More importantly, additive effects were evident whereby the MA+/CD4xa0<xa0200 group exhibited the highest rate of NP impairment. Findings indicate that MA dependence conveys an additive deleterious impact on NP status in immunosuppressed persons with HIV infection, perhaps reflecting the combined effects of neuropathophysiological mechanisms in fronto-striatal circuits.

Characteristics of prospective memory deficits in HIV-seropositive substance-dependent individuals: preliminary observations.

The construct of “prospective memory” (PM) refers to a type of episodic memory for a future intention or “remembering what one must do.” This function has been proposed as a candidate mechanism underlying behaviors of critical importance in HIV disease, including adherence with medication regimens and continued engagement in risk behavior. We administered tasks of time-based and event-based prospective memory and control tasks of retrospective and working memory to 31 HIV-seropositive and 35 HIV-seronegative substance-dependent individuals (SDIs). We found that compared with HIV− controls HIV+ participants showed deficits in time-based but not event-based PM. Retrospective, but not working, memory performance correlated significantly with time-based PM performance. In addition, performance on the time-based PM task was a significant predictor of scores on a self-report measure of risky sexual and injection practices. These preliminary data provide new and unique findings regarding the components of executive function mediated by prefrontal cortical systems that are impaired among HIV+ SDIs and their relevance to “real-world” behaviors.

Nonacute (residual) neuropsychological effects of cannabis use: a qualitative analysis and systematic review.

Because there is a possibility that cannabis or cannabis‐like molecules might be used as treatments for certain conditions in the future, it becomes important to consider the possible adverse effects of these compounds. In this paper, the authors review the evidence for persisting effects of nonacute cannabis use on the central nervous system, as reflected by alteration in neuropsychological performance. From the 40 articles that met criteria for inclusion in this review, the authors could not detect consistent evidence for persisting neuropsychological deficits in cannabis users; however, 22 of the 40 studies reported at least some subtle impairments. The inability to reach a firm conclusion results largely from methodological limitations inherent in most studies. These are considered in detail to inform future studies on (nonacute) consequences of cannabis consumption on cognitive abilities.

Iowa Gambling Task performance and emotional distress interact to predict risky sexual behavior in individuals with dual substance and HIV diagnoses

HIV+ substance-dependent individuals (SDIs) show emotional distress and executive impairment, but in isolation these poorly predict sexual risk. We hypothesized that an executive measure sensitive to emotional aspects of judgment (Iowa Gambling Task; IGT) would identify HIV+ SDIs whose sexual risks were influenced by emotional distress. We assessed emotional distress and performance on several executive tasks in 190 HIV+ SDIs. IGT performance interacted significantly with emotional distress, such that only in better performers were distress and risk related. Our results are interpreted using the somatic marker hypothesis and indicate that the IGT identifies HIV+ SDIs for whom psychological distress influences HIV risk.

The influence of inhibitory control and episodic memory on the risky sexual behavior of young adult cannabis users

Cannabis use is associated with risky sexual behavior (RSB) and sex-related negative health consequences. This investigation examined the role of inhibitory control and episodic memory in predicting RSB and sex-related negative consequences among current cannabis users. Findings indicated that the relationships among cannabis, neurocognition, and sexual-risk varied according to the dimension of neurocognition and the parameter of RSB in question. Specifically, more risk-taking was associated with more RSB. Furthermore, amount of recent cannabis use was associated with more RSB and sex-related negative consequences, but only among those with worse performances on a measure of decision-making and of risk-taking. Contrary to hypotheses, worse episodic memory also significantly predicted higher overall sexual-risk and decreased safe-sex practices. Results indicate that worse neurocognitive performance in the areas of risk-taking, decision-making, and episodic memory may influence the degree to which cannabis users engage in RSB and experience negative health consequences as a result. (JINS, 2012, 18, 1-7).