Rachel A. Rabin

The effects of cannabis use on neurocognition in schizophrenia: A meta-analysis

Patients with schizophrenia frequently report cannabis use, yet its effects on neurocognitive functioning in this population are still unclear. This meta-analysis was conducted to determine the magnitude of effect of cannabis consumption on cognition in schizophrenia without the confounding effects of other co-morbid substance use disorders. Eight studies met inclusion criteria yielding a total sample of 942. Three hundred and fifty six of these participants were cannabis users with schizophrenia, and 586 were patients with no cannabis use. Neuropsychological tests were grouped into seven domains (general cognitive ability and intelligence; selective, sustained and divided attention; executive abilities; working memory and learning; retrieval and recognition; receptive and expressive language abilities and visuo-spatial and construction abilities). Effect sizes were computed for each cognitive domain between cannabis-using patients and patients with no history of cannabis use. Effect size differences in cognitive performance in the schizophrenia group as a function of cannabis use were in the small to medium range, denoting superior performance in cannabis-using patients. Explanations for these findings are discussed and suggestions for future research in this area are recommended.

Effects of cigarette smoking status on delay discounting in schizophrenia and healthy controls

BACKGROUND Delay discounting is a measure of future-oriented decision-making and impulsivity. Cigarette smoking is associated with rapid discounting of the value of delayed outcomes. In schizophrenia, however, cigarette smoking improves certain neurocognitive impairments associated with the disorder which may explain the high smoking rates in this population. This study examined the relationship between cigarette smoking and delay discounting in schizophrenia and control participants. METHODS A total of N=130 participants, including those with schizophrenia (n=68) and healthy controls (n=62) were assessed on the Kirby Delay Discounting Task and compared across smoking status (smokers; non-smokers) and smoking history (current, former; never smokers). RESULTS Smokers exhibited higher discounting rates (i.e., were more impulsive) than non-smokers of the same diagnostic group. Current and former smokers with schizophrenia exhibited similar and significantly higher discounting rates than never smokers, suggesting that in schizophrenia delay discounting is a trait-dependent phenomenon independent of current cigarette smoking. Consistent with previous studies, there was a trend for higher discounting rates in control current smokers compared to control former and never smokers. CONCLUSIONS Smokers with and without schizophrenia have higher rates of delay discounting than non-smokers. However, in schizophrenia, rapid delay discounting appears to be a trait associated with having ever been a smoker (i.e., current and former smoking).

A review of co‐morbid tobacco and cannabis use disorders: Possible mechanisms to explain high rates of co‐use

BACKGROUND Tobacco and cannabis are among the most commonly used psychoactive substances worldwide, and are often used in combination. Evidence suggests that tobacco use contributes to an increased likelihood of becoming cannabis dependent and similarly cannabis use promotes transition to more intensive tobacco use. Further, tobacco use threatens cannabis cessation attempts leading to increased and accelerated relapse rates among cigarette smokers. Given that treatment outcomes are far from satisfactory among individuals engaged in both tobacco and cannabis use highlights the need for further exploration of this highly prevalent co-morbidity. OBJECTIVE Therefore, this review will elucidate putative neurobiological mechanisms responsible for facilitating the link between co-morbid tobacco and cannabis use. METHOD We performed an extensive literature search identifying published studies that examined co-morbid tobacco and cannabis use. RESULTS Evidence of both synergistic and compensatory effects of co-morbid tobacco and cannabis use have been identified. Following, co-morbid use of these substances will be discussed within the context of two popular theories of addiction: the addiction vulnerability hypothesis and the gateway hypothesis. Lastly, common route of administration is proposed as a facilitator for co-morbid use. CONCLUSIONS & SCIENTIFIC SIGNIFICANCE While, only a paucity of treatment studies addressing co-morbid tobacco and cannabis use have been conducted, emerging evidence suggests that simultaneously quitting both tobacco and cannabis may yield benefits at both the psychological and neurobiological level. More research is needed to confirm this intervention strategy and future studies should consider employing prospective systematic designs.

Neurocognitive Endophenotypes in Schizophrenia: Modulation by Nicotinic Receptor Systems

Cigarette smoking is the leading preventable cause of death in the Western world, with a considerably higher prevalence observed in schizophrenia compared to the general population. Despite the negative health consequences of smoking heavily, it has been proposed that individuals with schizophrenia may maintain smoking behaviors to remediate symptoms associated with the disorder. Neurocognitive deficits are a core feature of schizophrenia and are present in approximately 80% of patients. Further, these deficits constitute an endophenotype of schizophrenia, as they are stable across disease phases, and are heritable. The neurocognitive deficits that are present in schizophrenia are especially debilitating, since they are associated with poor clinical and functional outcomes and community integration. Interestingly, these deficits may also constitute a vulnerability factor towards the initiation and maintenance of tobacco use. Contributing to the potential shared vulnerability between schizophrenia and tobacco dependence is a dysregulation of the nicotinic acetylcholine receptor (nAChR) system. Pre-clinical evidence has shown that nicotine affects several neurotransmitter systems, including dopamine (DA), glutamate, and γ-aminobutyric acid (GABA), and certain neuropsychological deficits associated with these neurotransmitters (reaction time, spatial working memory, sustained attention, and sensory gating) are improved after nicotine administration in patients with schizophrenia. These positive effects on neurocognition appear to be more pronounced in smokers with schizophrenia, and may be an important mechanism that explains the co-morbidity of schizophrenia and tobacco dependence.

Effects of cannabis use status on cognitive function, in males with schizophrenia.

Cognitive impairment and cannabis use are common among patients with schizophrenia. However, the moderating role of cannabis on cognition remains unclear. We sought to examine cognitive performance as a function of cannabis use patterns in schizophrenia. A secondary aim was to determine the effects of cumulative cannabis exposure on cognition. Cognition was assessed in male outpatients with current cannabis dependence (n=18) and no current cannabis use disorders (n=29). We then parsed non-current users into patients with lifetime cannabis dependence (n=21) and no lifetime cannabis dependence (n=8). Finally, as an exploratory analysis, we examined relationships between cumulative cannabis exposure and cognition in lifetime dependent patients. Cross-sectional comparisons suggest that lifetime cannabis users demonstrate better processing speed than patients with no lifetime dependence. Exploratory analyses indicated that patients with current dependence exhibited robust negative relationships between cumulative cannabis exposure and cognition; these associations were absent in former users. Cannabis status has minimal effects on cognition in males with schizophrenia. However, cumulative cannabis exposure significantly impairs cognition in current, but not former users, suggesting that the state dependent negative effects of cannabis may be reversed with sustained abstinence. Prospective studies are needed to confirm these findings.

Co‐morbid tobacco use disorder and depression: A re‐evaluation of smoking cessation therapy in depressed smokers

BACKGROUND AND OBJECTIVES To provide a critical evaluation of nicotine use disorder co-morbidity in persons with major depressive disorder (MDD) or its subsyndromal presentations. We focus on how a diagnosis of current or past MDD may shape access to smoking cessation therapy, and highlight the unique challenges that this group of smokers has to overcome to receive adequate treatment. METHODS A literature search was performed using PubMed for studies published between January 1995 and March 2015 using the following keywords and combination of keywords (co-morbidity, co-occurrence, and dual-diagnosis) and (nicotine dependence, cigarette smoking, tobacco dependence, tobacco use disorder) and (depression, major depression, unipolar mood disorders) and (self-medication). A total of 93 articles were identified. Of these, 31 studies were included in the analysis. RESULTS We found that: a) depressed smokers are motivated to quit; b) smoking cessation does not exacerbate symptoms of depression; c) depression does not have a negative impact on smoking cessation outcomes, and d) the self-medication hypothesis does not account for tobacco dependence and depression co-morbidity. DISCUSSION AND CONCLUSIONS Our review of the relevant evidence suggests the importance and clinical significance of undertaking smoking cessation treatment for depressed smokers. SCIENTIFIC SIGNIFICANCE Our findings support the need for increased attention to developing and implementing smoking cessation treatments for depressed smokers. SCIENTIFIC SIGNIFICANCE Our findings support the need for increased attention to developing and implementing smoking cessation treatments for depressed smokers.

Correlations between executive function, decision-making and impulsivity are disrupted in schizophrenia versus controls

Schizophrenia (n=68) and control (n=62) participants matched on cigarette smoking history were assessed on executive function, decision-making and impulsivity tasks. In controls, executive function and decision-making correlated positively with each other and negatively with impulsivity. There were no inter-task correlations in schizophrenia participants. The significance of these findings is discussed.

Does cannabis use moderate smoking cessation outcomes in treatment-seeking tobacco smokers? Analysis from a large multi-center trial.

BACKGROUND AND OBJECTIVE Tobacco and cannabis are frequently used in combination and cannabis co-use may lead to poor tobacco cessation outcomes. Therefore, it is important to explore if cannabis co-use is associated with a reduced likelihood of achieving successful tobacco abstinence among treatment-seeking tobacco smokers. The present study examined whether current cannabis use moderated tobacco cessation outcomes after 12 weeks of pharmacological treatment (varenicline vs. nicotine patch vs. placebo) with adjunctive behavioral counseling. METHODS Treatment-seeking tobacco smokers (N = 1,246) were enrolled in an intent-to-treat study, of which 220 were current cannabis users. Individuals were randomly assigned to 12 weeks of placebo (placebo pill plus placebo patch), nicotine patch (active patch plus placebo pill), or varenicline (active pill plus placebo patch), plus behavioral counseling. The primary endpoint was biochemically verified 7-day point prevalence abstinence at the end of treatment. RESULTS Controlling for rate of nicotine metabolism, treatment arm, age, sex, alcohol, and level of nicotine dependence, cannabis users were as successful at achieving biochemically verified 7-day point prevalence abstinence compared to tobacco-only smokers. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE Findings suggest that cannabis use does not hinder the ability to quit tobacco smoking. Future tobacco cessation studies should employ prospective, longitudinal designs investigating cannabis co-use over time and at different severity levels. (Am J Addict 2016;25:291-296).

Effects of extended cannabis abstinence on clinical symptoms in cannabis dependent schizophrenia patients versus non-psychiatric controls

BACKGROUND Rates of cannabis use among patients with schizophrenia are high, however little is understood about clinical effects of continued cannabis use and cessation after illness onset. Therefore, we investigated the effects of 28-days of cannabis abstinence on psychotic and depressive symptomatology in cannabis dependent patients with schizophrenia. METHOD Males with cannabis dependence and co-morbid schizophrenia (n=19) and non-psychiatric controls (n=20) underwent 28-days of monitored cannabis abstinence. Clinical symptoms were assessed at baseline and then weekly. Abstinence was encouraged using weekly therapy sessions and contingency reinforcement, confirmed by twice-weekly urine assays. RESULTS Forty-two percent (8/19) of patients and 55% (11/20) of controls achieved 28-days of sustained cannabis abstinence. In patients, PANSS subscores did not change over time irrespective of abstinence status. In contrast, patient abstainers demonstrated a more pronounced reduction in depression scores compared to non-abstainers, however, the Abstinence Status x Time interaction was non-significant. DISCUSSION Short-term (28-days) cannabis abstinence is not associated with improvement in psychotic symptoms, but may be associated with improvement in depressive symptomatology in patients with schizophrenia. Future studies employing larger samples as well as a continuous cannabis-using group may help to better characterize the causal effects of cannabis on symptom outcomes in this disorder.

Relationship between tobacco and cannabis use status in outpatients with schizophrenia

BACKGROUND AND OBJECTIVE While high prevalence of tobacco and cannabis use are well established in schizophrenia, reports on their co-morbid use is limited. We explored the links between tobacco and cannabis use in an outpatient population meeting DSM-IV criteria for schizophrenia. METHODS Cigarette smoking behaviors were assessed in an outpaitent population with schizophrenia (N=54) with current (n=18), former (n=24), and no lifetime cannabis dependence (n=12). RESULTS We found significant differences in cigarettes per day (CPD) across groups: current dependent patients smoked less CPD than patients with former dependence and those with no history of dependence; former dependent patients smoked significantly less than patients with no history of cannabis dependence. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE Preliminary results support an effect of cannabis use status on tobacco consumption. In the absence of cannabis, patients may increase cigarette smoking, suggesting state-dependent effects of cannabis on tobacco. Prospective designs should further examine this relationship between cannabis and tobacco in schizophrenia versus non-psychiatric controls.