Natania A. Crane

Effects of cannabis on neurocognitive functioning: recent advances, neurodevelopmental influences, and sex differences.

Decades of research have examined the effects of cannabis on neurocognition. Recent advances in this field provide us with a better understanding of how cannabis use influences neurocognition both acutely (during intoxication) and non-acutely (after acute effects subside). Evidence of problems with episodic memory is one of the most consistent findings reported; however, several other neurocognitive domains appear to be adversely affected by cannabis use under various conditions. There is significant variability in findings across studies, thus a discussion of potential moderators is increasingly relevant. The purpose of this review was to 1) provide an update on research of cannabis’ acute and non-acute effects on neurocognition, with a focus on findings since 2007 and 2) suggest and discuss how neurodevelopmental issues and sex differences may influence cannabis effects on neurocognition. Finally we discuss how future investigations may lead to better understanding of the complex interplay among cannabis, stages of neurodevelopment, and sex on neurocognitive functioning.

A comprehensive examination of hookah smoking in college students: Use patterns and contexts, social norms and attitudes, harm perception, psychological correlates and co-occurring substance use

The practice of waterpipe smoking (hookah) has rapidly increased in popularity among young adults yet burgeoning research suggests that its use is associated with nicotine dependence and other negative smoking-related health consequences. Moreover, descriptive studies indicate that consumers may hold the belief that hookah smoking is safer than smoking cigarettes. The current study extended previous work by conducting a comprehensive assessment of patterns and contexts of hookah use, psychological correlates of use, co-occurring substance use as well as social norms and health perceptions surrounding the practice. Participants were 143 ethnically diverse undergraduate students at a large urban US university. Approximately half of the sample (48%) reported life-time use of hookah and 22% reported use within the past 30days. Relative to cigarette smoking, hookah smoking was associated with less perceived harm and addiction potential and higher social approval. Participants who reported life-time hookah use, as compared to those who did not, perceived less associated harm, had a greater number of friends who had tried and approved of hookah, were more likely to use cigarettes, marijuana, and alcohol and in higher frequencies and quantities and were at higher risk for problem tobacco and alcohol use. Among participants who were not current smokers, those with hookah experience were more likely to endorse intent to try a cigarette soon. Hookah users did not differ from non-users on measures of trait anxiety, depression and impulsivity though they were more likely to drink alcohol for coping, social and enhancement purposes than non-users. Implications are discussed for public health initiatives to educate young adults about the potential consequences of hookah smoking.

Increased Coupling of Intrinsic Networks in Remitted Depressed Youth Predicts Rumination and Cognitive Control

Objective Functional connectivity MRI (fcMRI) studies of individuals currently diagnosed with major depressive disorder (MDD) document hyperconnectivities within the default mode network (DMN) and between the DMN and salience networks (SN) with regions of the cognitive control network (CCN). Studies of individuals in the remitted state are needed to address whether effects derive from trait, and not state or chronic burden features of MDD. Method fcMRI data from two 3.0 Tesla GE scanners were collected from 30 unmedicated (47% medication naïve) youth (aged 18–23, modal depressive episodes = 1, mean age of onset = 16.2, SD = 2.6) with remitted MDD (rMDD; modal years well = 4) and compared with data from 23 healthy controls (HCs) using four bilateral seeds in the DMN and SN (posterior cingulate cortex (PCC), subgenual anterior cingulate (sgACC), and amygdala), followed by voxel-based comparisons of the whole brain. Results Compared to HCs, rMDD youth exhibited hyperconnectivities from both PCC and sgACC seeds with lateral, parietal, and frontal regions of the CCN, extending to the dorsal medial wall. A factor analysis reduced extracted data and a PCC factor was inversely correlated with rumination among rMDD youth. Two factors from the sgACC hyperconnectivity clusters were related to performance in cognitive control on a Go/NoGo task, one positively and one inversely. Conclusions Findings document hyperconnectivities of the DMN and SN with the CCN (BA 8/10), which were related to rumination and sustained attention. Given these cognitive markers are known predictors of response and relapse, hyperconnectivities may increase relapse risk or represent compensatory mechanisms.

Preliminary Evidence for a Sex-Specific Relationship between Amount of Cannabis Use and Neurocognitive Performance in Young Adult Cannabis Users

Accumulating evidence suggests neuropsychological deficits from cannabis use, with a burgeoning area of preclinical research indicating possible sex-differences. However, few studies have examined how cannabis use may differentially impact neurocognition in male and female cannabis users. As such, we examined potential sex-differences in associations between amount of cannabis use (across several time frames) and neurocognitive performance among young adult regular cannabis users. Consistent with previous studies, more cannabis use was generally associated with poorer episodic memory and decision-making, but not other measures of inhibitory control. However, patterns of results suggested sex-specific dissociations. In particular, more cannabis use was more consistently associated with poorer episodic memory performance in females than males. Conversely, more cannabis use was associated with poorer decision-making performance for males, but not females. These results provide further evidence for residual cannabis-associated neurocognitive deficits and suggest the importance of examining the impact of cannabis on neurocognition separately for males and females.

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).

Neuropsychological sex differences associated with age of initiated use among young adult cannabis users

Introduction. Earlier initiation of cannabis use is associated with poorer neuropsychological functioning across several domains. Given well-documented sex differences in neuromaturation during adolescence, initiation of cannabis use during this time may affect neuropsychological functioning differently for males and females. Method: In the current study, we examined sex differences in the relationship between age of initiated cannabis use and neuropsychological performance after controlling for amount of lifetime cannabis use in 44 male and 25 female young adult cannabis users. Results: We found that an earlier age of initiated use was related to poorer episodic memory, especially immediate recall, in females, but not in males. On the other hand, we found that, surprisingly, an earlier age of initiated use was associated with better decision making overall. However, exploratory analyses found sex-specific factors associated with decision making and age of initiated use, specifically that attention-deficit/hyperactivity disorder (ADHD) symptoms in females may drive the relationship between an earlier age of initiated use and better decision making. Further, an earlier age of initiated use was associated with less education, a lower IQ, and fewer years of mother’s education for females, but more lifetime cannabis use for males. Conclusions: Taken together, our findings suggest there are sex differences in the associations between age of initiated cannabis use and neuropsychological functioning. The current study provides preliminary evidence that males and females may have different neuropsychological vulnerabilities that place them at risk for initiating cannabis use and continued cannabis use, highlighting the importance of examining the impact of cannabis on neuropsychological functioning separately for males and females.

Gender differences in the associations among marijuana use, cigarette use, and symptoms of depression during adolescence and young adulthood

INTRODUCTION As prevalence of marijuana use increases, it is important that we better understand how factors like gender, cigarette use, and depression are related to marijuana use during adolescence and young adulthood. We examined longitudinal relationships among these variables in adolescents moving into young adulthood who were studied longitudinally for six years. METHODS 1263 individuals were included in the study. Participants were oversampled for ever-smoking a cigarette at baseline, when they were 15-16 years old. Frequency of cigarette smoking and marijuana use, as well as depression symptoms, were assessed at baseline, 6, 15, 24, 60 and 72 months. RESULTS Cigarette use frequency and depression symptoms were associated with frequency of marijuana use (p-values<.001), particularly in adolescence, but there were important gender differences in these relationships. Specifically, symptoms of depression were related to marijuana use frequency among males (p<.001), but not females (p=.62). In addition, frequency of marijuana use was associated with increased cigarette use frequency, especially among males who had higher symptoms of depression (p<.001). However, this effect was not seen among females. Exploratory analyses suggested that relationships between frequency of use and depression are specific to marijuana, not cigarettes. CONCLUSIONS Marijuana use is strongly related to depression symptoms and cigarette use frequency in males, indicating that in males these detrimental factors converge, whereas in females they do not. Gender differences in the factors related to marijuana use may mean that there are different risks for and consequences from use and have implications for prevention and intervention efforts.

Multidimensional prediction of treatment response to antidepressants with cognitive control and functional MRI.

Predicting treatment response for major depressive disorder can provide a tremendous benefit for our overstretched health care system by reducing number of treatments and time to remission, thereby decreasing morbidity. The present study used neural and performance predictors during a cognitive control task to predict treatment response (% change in Hamilton Depression Rating Scale pre- to post-treatment). Forty-nine individuals diagnosed with major depressive disorder were enrolled with intent to treat in the open-label study; 36 completed treatment, had useable data, and were included in most data analyses. Participants included in the data analysis sample received treatment with escitalopram (n = 22) or duloxetine (n = 14) for 10 weeks. Functional MRI and performance during a Parametric Go/No-go test were used to predict per cent reduction in Hamilton Depression Rating Scale scores after treatment. Haemodynamic response function-based contrasts and task-related independent components analysis (subset of sample: n = 29) were predictors. Independent components analysis component beta weights and haemodynamic response function modelling activation during Commission errors in the rostral and dorsal anterior cingulate, mid-cingulate, dorsomedial prefrontal cortex, and lateral orbital frontal cortex predicted treatment response. In addition, more commission errors on the task predicted better treatment response. Together in a regression model, independent component analysis, haemodynamic response function-modelled, and performance measures predicted treatment response with 90% accuracy (compared to 74% accuracy with clinical features alone), with 84% accuracy in 5-fold, leave-one-out cross-validation. Convergence between performance markers and functional magnetic resonance imaging, including novel independent component analysis techniques, achieved high accuracy in prediction of treatment response for major depressive disorder. The strong link to a task paradigm provided by use of independent component analysis is a potential breakthrough that can inform ways in which prediction models can be integrated for use in clinical and experimental medicine studies.

Tobacco may mask poorer episodic memory among young adult cannabis users

OBJECTIVE Co-occurring cannabis and tobacco use has become increasingly prevalent among young adults, but it is not clear how tobacco use may alter the neurocognitive profile typically observed among cannabis users. Although there is substantial evidence citing cannabis and tobaccos individual effect on episodic memory and related brain structures, few studies have examined the effect of combined cannabis and tobacco use on memory. METHOD This investigation examined relationships between amount of past year cannabis and tobacco use on 4 different indices of episodic memory among a sample of young adults who identified cannabis as their drug of choice. RESULTS Results indicated that more cannabis use was linked with poorer initial acquisition, total learning, and delayed recall on the Hopkins Verbal Learning Test-Revised, but only among cannabis users who sporadically smoked cigarettes in the past year. Conversely, the amount of past year cannabis use was not associated with episodic memory performance among individuals who more consistently smoked cigarettes in the past year. These differences could not be explained by several relevant potential confounds. CONCLUSIONS These findings provide important insight into a potential mechanism (i.e., attenuation of cognitive decrements) that might reinforce use of both substances and hamper cessation attempts among cannabis users who also smoke cigarettes. Ongoing and future research will help to better understand how co-use of cannabis and tobacco affects memory during acute intoxication and abstinence and the stability of these associations over time.

Attenuated intrinsic connectivity within cognitive control network among individuals with remitted depression: Temporal stability and association with negative cognitive styles.

Many individuals with major depressive disorder (MDD) experience cognitive dysfunction including impaired cognitive control and negative cognitive styles. Functional connectivity magnetic resonance imaging studies of individuals with current MDD have documented altered resting‐state connectivity within the default‐mode network and across networks. However, no studies to date have evaluated the extent to which impaired connectivity within the cognitive control network (CCN) may be present in remitted MDD (rMDD), nor have studies examined the temporal stability of such attenuation over time. This represents a major gap in understanding stable, trait‐like depression risk phenotypes. In this study, resting‐state functional connectivity data were collected from 52 unmedicated young adults with rMDD and 47 demographically matched healthy controls, using three bilateral seeds in the CCN (dorsolateral prefrontal cortex, inferior parietal lobule, and dorsal anterior cingulate cortex). Mean connectivity within the entire CCN was attenuated among individuals with rMDD, was stable and reliable over time, and was most pronounced with the right dorsolateral prefrontal cortex and right inferior parietal lobule, results that were corroborated by supplemental independent component analysis. Attenuated connectivity in rMDD appeared to be specific to the CCN as opposed to representing attenuated within‐network coherence in other networks (e.g., default‐mode, salience). In addition, attenuated connectivity within the CCN mediated relationships between rMDD status and cognitive risk factors for depression, including ruminative brooding, pessimistic attributional style, and negative automatic thoughts. Given that these cognitive markers are known predictors of relapse, these results suggest that attenuated connectivity within the CCN could represent a biomarker for trait phenotypes of depression risk. Hum Brain Mapp 38:2939–2954, 2017.