The effects of simultaneous alcohol and cannabis use on subjective drug effects: A narrative review across methodologies.

Over 75% of young adults who use cannabis also report drinking alcohol, leading to increased risks that include impaired cognition, substance use disorders, and more heavy and frequent substance use. Studies suggest that subjective responses to either alcohol or cannabis can serve as a valuable indicator for identifying individuals at risk of prolonged substance use and use disorder. While laboratory studies show additive effects when alcohol and cannabis are used together, the impact of co-using these substances, specifically with respect to cannabidiol, on an individual's subjective experience remains unclear. This narrative review explores the effects of simultaneous alcohol and cannabis (SAM) use on subjective drug effects, drawing from qualitative research, laboratory experiments, and naturalistic studies. Experimental findings are inconsistent regarding the combined effects of alcohol and cannabis, likely influenced by factors such as dosage, method of administration, and individual substance use histories. Similarly, findings from qualitative and naturalistic studies are mixed regarding subjective drug effects following SAM use. These discrepancies may be due to recall biases, variations in assessment methods, and the measurement in real-world contexts of patterns of SAM use and related experiences. Overall, this narrative review highlights the need for more comprehensive research to understand more fully subjective drug effects of SAM use in diverse populations and settings, emphasizing the importance of frequent and nuanced assessment of SAM use and subjective responses in naturalistic settings.

Parameter Space and Potential for Biomarker Development in 25 Years of fMRI Drug Cue Reactivity: A Systematic Review.

Importance: In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers. Objective: To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts. Evidence Review: The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders. Findings: There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes. Conclusions and Relevance: Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.

Longitudinal stability of reward and relief drinking phenotypes in community and treatment-seeking individuals who engage in heavy drinking.

BACKGROUND: Precision medicine approaches aim to improve treatment outcomes by identifying which treatments work best for specific individual phenotypes. In the treatment of alcohol use disorder (AUD), precision medicine approaches have been proposed based on phenotypes characterized by individuals who drink primarily to enhance rewarding experiences (i.e., reward drinking) or those who drink primarily to relieve negative states (i.e., relief drinking). This study examined these phenotypes across treatment- and nontreatment-seeking individuals and the stability of the phenotypes over time. METHODS: We used latent profile and latent transition analyses to identify and assess longitudinal stability (over 3 or 4 months) of reward and relief drinking subgroups within a nontreatment-seeking community sample that engaged in hazardous drinking (n = 189) and two treatment-seeking samples of individuals with AUD enrolled in two large clinical trials (n = 1726, n = 1383). We examined prospective associations with alcohol consumption and consequences at long-term follow-up (15 or 18 months). RESULTS: Results supported four subgroups: low reward/low relief, low reward/high relief, high reward/low relief, and high reward/high relief. The community sample contained more individuals classified within the high reward/low relief subgroup than treatment-seeking samples. Subgroups were generally more stable over time in the community sample than in the treatment-seeking samples. Alcohol consumption and consequences decreased over time for the treatment-seeking samples, with consequences and drinking frequency decreasing for the community sample. Participants classified within the high reward/high relief and low reward/high relief groups reported the most consequences and consumption at long-term follow-up. CONCLUSION: Reward and relief drinking phenotypes can be identified within community and treatment-seeking samples of individuals who drink heavily. The phenotypic subgroups appear to be stable over time in the absence of treatment, change somewhat during treatment, and provide utility in predicting alcohol consumption and consequences.

People who binge drink show neuroendocrine tolerance to alcohol cues that is associated with immediate and future drinking- results from a randomized clinical experiment.

Neuroendocrine tolerance to alcohol, i.e., a blunted cortisol response to alcohol, has been linked to Ventromedial Prefrontal Cortex (VmPFC) alcohol cue reactivity and relapse risk in severe Alcohol Use Disorders (AUDs), but its role in the development of AUDs is not clear. Recent work suggests that blunted cortisol responses to alcohol cues in individuals who engage in binge drinking (BD) may play a role in motivation to consume larger amounts of alcohol, but the link between this dysregulated endocrine response and BD's neural responses to alcohol cues remains unclear. To examine this, two groups of participants were recruited based on their recent drinking history. Thirty-three BD and 31 non-binging, social drinkers (SD) were exposed to alcohol cues and water cues in two separate 7 T functional magnetic resonance imaging (fMRI) scans. Each scan was followed by the Alcohol Taste Test (ATT) of implicit motivation for alcohol and a post-experiment, one-month prospective measurement of their "real world" drinking behavior. During each scan session, blood plasma was collected repeatedly to examine the separate effects of alcohol cues and alcohol consumption on cortisol levels. Relative to water cues and SD, BD demonstrated blunted cortisol cue reactivity that was negatively associated with VmPFC cue reactivity. In BD, both blunted cortisol and greater VmPFC cue reactivity were related to immediate and future alcohol consumption in the month following the scans. Thus, neuroendocrine tolerance in BD may be associated with increased incentive salience of cues and contribute mechanistically to increased alcohol consumption seen in the development of AUDs.

Affective imagery boosts the reward related delta power in hazardous drinkers.

The Reward Positivity (RewP) is an event-related potential component with a delta band spectral representation that is elicited by reward receipt. Evidence suggests that RewP is modulated by both reward probability as well as affective valuation ("liking"). Here we determined whether RewP is a marker of enhanced hedonic salience of alcohol images in hazardous drinkers. We recruited 54 participants (Hazardous Drinkers = 28, Control = 26) who completed a reinforcement learning task with affective versus alcohol imagery during feedback. The learning task used images of puppies vs. alcohol paired with reinforcing feedback. Both groups rated categories of affective images (puppies, scenery, babies, neutral) similarly, but the hazardous drinking group rated alcohol significantly higher. There were no group differences in performance or in RewP amplitudes, even as a function of alcohol imagery. Contrary to prior findings, we did not observe a significant correlation between alcohol image rating and alcohol-specific RewP amplitude, although we did observe this relationship with the alcohol-specific delta band spectral representation of RewP. Within hazardous drinking group, there was significant correlation between hazardous drinking (AUDIT score) and alcohol-specific RewP indicating an inter-individual influence of drinking habits on affect specific RewP. These findings suggest a domain-specific enhancement of reward responsiveness in hazardous drinkers.

IL-6, but not TNF-α, response to alcohol cues and acute consumption associated with neural cue reactivity, craving, and future drinking in binge drinkers.

Objective and design: Preclinical studies suggest learned immune system responses to alcohol cues and consumption may contribute to alcohol's pharmacodynamic properties and/or Alcohol Use Disorder (AUD) pathogenesis. Mechanistically, these immune alterations may be associated with increased craving and alcohol consumption, both acutely and over time. We sought to characterize this relationship in a randomized, counter-balanced, crossover neuroimaging experiment which took place between June 2020-November 2021. Methods: Thirty-three binge drinkers (BD) and 31 non-binge, social drinkers (SD), matched for demographic and psychological variables, were exposed to alcohol cues and water cues in two separate 7 T functional magnetic resonance imaging (fMRI) scans. Each scan was followed by the Alcohol Taste Test (ATT) of implicit motivation for acute alcohol. Craving measures and blood cytokine levels were collected repeatedly during and after scanning to examine the effects of alcohol cues and alcohol consumption on craving levels, Tumor necrosis factor alpha (TNF-α), and Interleukin 6 (IL-6) levels. A post-experiment one-month prospective measurement of participants' "real world" drinking behavior was performed to approximate chronic effects. Results: BD demonstrated significantly higher peak craving and IL-6 levels than SD in response to alcohol cues and relative to water cues. Ventromedial Prefrontal Cortex (VmPFC) signal change in the alcohol-water contrast positively related to alcohol cue condition craving and IL-6 levels, relative to water cue condition craving and IL-6 levels, in BD only. Additionally, peak craving and IL-6 levels were each independently related to ATT alcohol consumption and the number of drinks consumed in the next month for BD, again after controlling for craving and IL-6 repones to water cues. However, TNF-α release in the alcohol cue condition was not related to craving, neural activation, IL-6 levels, immediate and future alcohol consumption in either group after controlling for water cue condition responses. Conclusions: In sum, BD show greater craving and IL-6 release in the alcohol cue condition than SD, both of which were associated with prefrontal cue reactivity, immediate alcohol consumption, and future alcohol consumption over the subsequent 30 days. Alcohol associated immune changes and craving effects on drinking behavior may be independent of one another or may be indicative of a common pathway by which immune changes in BD could influence motivation to consume alcohol. Trial registration: Clinical Trials NCT04412824.

Heart rate variability may index emotion dysregulation in alcohol-related intimate partner violence.

Introduction: Intimate partner violence is a serious public health problem that costs the United States more than $4.1 billion in direct medical and mental health costs alone. Furthermore, alcohol use contributes to more frequent and more severe intimate partner violence incidents. Compounding this problem is treatments for intimate partner violence have largely been socially informed and demonstrate poor efficacy. We argue that improvements in intimate partner treatment will be gained through systematic scientific study of mechanisms through which alcohol is related to intimate partner violence. We hypothesize that poor emotional and behavioral regulation as indexed by the respiratory sinus arrythymia measure of heart rate variability is a key mechanism between alcohol use and intimate partner violence. Method: The present study is a placebo-controlled alcohol administration study with an emotion-regulation task that investigated heart rate variability in distressed violent and distressed nonviolent partners. Results: We found a main effect for alcohol on heart rate variability. We also found a four-way interaction whereby distressed violent partners exhibited significant reductions in heart rate variability when acutely intoxicated and attempting to not respond to their partners evocative stimuli. Discussion: These findings suggest that distressed violent partners may adopt maladaptive emotion regulation strategies such as rumination and suppression when intoxicated and attempting to not respond to partner conflict. Such strategies of emotion regulation have been shown to have many deleterious emotional, cognitive and social consequences for individuals who adopt them, possibly including intimate partner violence. These findings also highlight an important novel treatment target for intimate partner violence and suggest that novel treatments should focus on teaching effective conflict resolution and emotion-regulation strategies that may be augmented by biobehavioral treatments such as heart rate variability biofeedback.

Electrophysiological Markers of Aberrant Cue-Specific Exploration in Hazardous Drinkers.

Background: Hazardous drinking is associated with maladaptive alcohol-related decision-making. Existing studies have often focused on how participants learn to exploit familiar cues based on prior reinforcement, but little is known about the mechanisms that drive hazardous drinkers to explore novel alcohol cues when their value is not known. Methods: We investigated exploration of novel alcohol and non-alcohol cues in hazardous drinkers (N = 27) and control participants (N = 26) during electroencephalography (EEG). A normative computational model with two free parameters was fit to estimate participants' weighting of the future value of exploration and immediate value of exploitation. Results: Hazardous drinkers demonstrated increased exploration of novel alcohol cues, and conversely, increased probability of exploiting familiar alternatives instead of exploring novel non-alcohol cues. The motivation to explore novel alcohol stimuli in hazardous drinkers was driven by an elevated relative future valuation of uncertain alcohol cues. P3a predicted more exploratory decision policies driven by an enhanced relative future valuation of novel alcohol cues. P3b did not predict choice behavior, but computational parameter estimates suggested that hazardous drinkers with enhanced P3b to alcohol cues were likely to learn to exploit their immediate expected value. Conclusions: Hazardous drinkers did not display atypical choice behavior, different P3a/P3b amplitudes, or computational estimates to novel non-alcohol cues-diverging from previous studies in addiction showing atypical generalized explore-exploit decisions with non-drug-related cues. These findings reveal that cue-specific neural computations may drive aberrant alcohol-related decision-making in hazardous drinkers-highlighting the importance of drug-relevant cues in studies of decision-making in addiction.

A review of functional brain differences predicting relapse in substance use disorder: Actionable targets for new methods of noninvasive brain stimulation.

Neuroimaging studies have identified a variety of brain regions whose activity predicts substance use (i.e., relapse) in patients with substance use disorder (SUD), suggesting that malfunctioning brain networks may exacerbate relapse. However, this knowledge has not yet led to a marked improvement in treatment outcomes. Noninvasive brain stimulation (NIBS) has shown some potential for treating SUDs, and a new generation of NIBS technologies offers the possibility of selectively altering activity in both superficial and deep brain structures implicated in SUDs. The goal of the current review was to identify deeper brain structures involved in relapse to SUD and give an account of innovative methods of NIBS that might be used to target them. Included studies measured fMRI in currently abstinent SUD patients and tracked treatment outcomes, and fMRI results were organized with the framework of the Addictions Neuroclinical Assessment (ANA). Four brain structures were consistently implicated: the anterior and posterior cingulate cortices, ventral striatum and insula. These four deeper brain structures may be appropriate future targets for the treatment of SUD using these innovative NIBS technologies.

Association between empathy and drinking among a community sample of heavy drinkers: Sex differences and neural correlates.

Alcohol use disorder (AUD) is a major health problem, yet most individuals with AUD do not perceive a need for formal treatment and do not receive treatment. The lack of treatment seeking among individuals with AUD may suggest a lack of self-awareness and insight into the seriousness of AUD related problems, as well as lack of empathy for the impact of one's drinking on others. Recent work has suggested that empathy may be impaired among individuals seeking treatment for AUD. Further these impairments may differ by sex such that males with lower empathy reported more drinking consequences and greater drinking intensity, but there was no association between empathy and drinking among females. The current study used regression analyses (alpha = 0.05) to examine the association between empathy (as measured by the four scales of the Interpersonal Reactivity Index), independent components of gray matter volume in regions associated with empathy, and drinking variables among non-treatment seeking drinkers with AUD (N = 136) and also examined these effects by sex. Results showed greater perspective taking was associated with less temporoparietal and frontotemporal gray matter volume (B(SE) = -0.912 (0.043), p = 0.034). An interaction between perspective taking and sex was associated with craving, such that higher perspective taking was associated with less craving for males only (B(SE) = -0.48 (0.243), p = 0.049; R2 = 0.087). Empathic concern was related to lower percent heavy drinking days for both males and females (B(SE) = -1.57 (0.743), p = 0.035; R2 = 0.11). The current study found empathy may be an important predictor of craving for males and frequency of heavy drinking for males and females. Future work should investigate whether empathy predicts treatment seeking.

Sex moderates effects of alcohol and cannabis co-use on alcohol and stress reactivity.

BACKGROUND: Simultaneous or concurrent use (co-use) of alcohol and cannabis is associated with greater use of both substances over time, academic difficulties, more severe substance use consequences, and adverse impacts on cognitive functioning than the use of a single substance or no substance use. This study examined potential neural mechanisms underlying co-use behaviors in comparison to single substance use. Specifically, we compared alcohol cue reactivity and stress-cue reactivity among individuals who reported frequent same-day co-use of alcohol and cannabis and individuals who reported only alcohol use. METHODS: The sample included 88 individuals (41 women) who reported only alcohol use and 24 individuals (8 women) who reported co-use of alcohol and cannabis on at least 50% of drinking occasions. All participants completed fMRI stress and alcohol cue reactivity tasks. Because of known sex effects on stress reactivity and alcohol cue reactivity, we tested sex by co-use interactions. RESULTS: During alcohol cue presentation, co-users had less activation in the thalamus and dorsomedial prefrontal cortex than alcohol-only users, effects that were driven by differences in responses to neutral cues. Examination of stress cue reactivity revealed sex by co-use interactions in the lingual gyrus, with women co-users showing a greater difference between negative and neutral cue reactivity than all other groups. In addition, women co-users had greater connectivity between the nucleus accumbens and both the medial orbitofrontal cortex and the rostral anterior cingulate cortex during negative cue presentation than the other groups. CONCLUSIONS: These results provide preliminary evidence of enhanced stress cue reactivity in individuals reporting co-use of alcohol and cannabis, particularly women co-users.

A Bayesian mixed effects support vector machine for learning and predicting daily substance use disorder patterns.

Background: Substance use disorder (SUD) is a heterogeneous disorder. Adapting machine learning algorithms to allow for the parsing of intrapersonal and interpersonal heterogeneity in meaningful ways may accelerate the discovery and implementation of clinically actionable interventions in SUD research.Objectives: Inspired by a study of heavy drinkers that collected daily drinking and substance use (ABQ DrinQ), we develop tools to estimate subject-specific risk trajectories of heavy drinking; estimate and perform inference on patient characteristics and time-varying covariates; and present results in easy-to-use Jupyter notebooks. Methods: We recast support vector machines (SVMs) into a Bayesian model extended to handle mixed effects. We then apply these methods to ABQ DrinQ to model alcohol use patterns. ABQ DrinQ consists of 190 heavy drinkers (44% female) with 109,580 daily observations. Results: We identified male gender (point estimate; 95% credible interval: -0.25;-0.29,-0.21), older age (-0.03;-0.03,-0.03), and time varying usage of nicotine (1.68;1.62,1.73), cannabis (0.05;0.03,0.07), and other drugs (1.16;1.01,1.35) as statistically significant factors of heavy drinking behavior. By adopting random effects to capture the subject-specific longitudinal trajectories, the algorithm outperforms traditional SVM (classifies 84% of heavy drinking days correctly versus 73%). Conclusions: We developed a mixed effects variant of SVM and compare it to the traditional formulation, with an eye toward elucidating the importance of incorporating random effects to account for underlying heterogeneity in SUD data. These tools and examples are packaged into a repository for researchers to explore. Understanding patterns and risk of substance use could be used for developing individualized interventions.

A methodological checklist for fMRI drug cue reactivity studies: development and expert consensus.

Cue reactivity is one of the most frequently used paradigms in functional magnetic resonance imaging (fMRI) studies of substance use disorders (SUDs). Although there have been promising results elucidating the neurocognitive mechanisms of SUDs and SUD treatments, the interpretability and reproducibility of these studies is limited by incomplete reporting of participants' characteristics, task design, craving assessment, scanning preparation and analysis decisions in fMRI drug cue reactivity (FDCR) experiments. This hampers clinical translation, not least because systematic review and meta-analysis of published work are difficult. This consensus paper and Delphi study aims to outline the important methodological aspects of FDCR research, present structured recommendations for more comprehensive methods reporting and review the FDCR literature to assess the reporting of items that are deemed important. Forty-five FDCR scientists from around the world participated in this study. First, an initial checklist of items deemed important in FDCR studies was developed by several members of the Enhanced NeuroImaging Genetics through Meta-Analyses (ENIGMA) Addiction working group on the basis of a systematic review. Using a modified Delphi consensus method, all experts were asked to comment on, revise or add items to the initial checklist, and then to rate the importance of each item in subsequent rounds. The reporting status of the items in the final checklist was investigated in 108 recently published FDCR studies identified through a systematic review. By the final round, 38 items reached the consensus threshold and were classified under seven major categories: 'Participants' Characteristics', 'General fMRI Information', 'General Task Information', 'Cue Information', 'Craving Assessment Inside Scanner', 'Craving Assessment Outside Scanner' and 'Pre- and Post-Scanning Considerations'. The review of the 108 FDCR papers revealed significant gaps in the reporting of the items considered important by the experts. For instance, whereas items in the 'General fMRI Information' category were reported in 90.5% of the reviewed papers, items in the 'Pre- and Post-Scanning Considerations' category were reported by only 44.7% of reviewed FDCR studies. Considering the notable and sometimes unexpected gaps in the reporting of items deemed to be important by experts in any FDCR study, the protocols could benefit from the adoption of reporting standards. This checklist, a living document to be updated as the field and its methods advance, can help improve experimental design, reporting and the widespread understanding of the FDCR protocols. This checklist can also provide a sample for developing consensus statements for protocols in other areas of task-based fMRI.

Age dependent neural correlates of inhibition and control mechanisms in moderate to heavy drinkers.

BACKGROUND: Long-term, heavy alcohol consumption has been associated with impairments in control over alcohol use, but whether this extends to other areas of cognitive and behavioral control such as response inhibition remains unclear. Understanding individual differences in the neural correlates of response inhibition will provide further insight into the neurobiology of heavy drinking. The current study investigated response inhibition in a large sample of moderate to heavy drinkers METHODS: One hundred fifty-three individuals completed a stop signal task while undergoing functional magnetic resonance imaging. Multiple regression analyses focused on blood oxygen level-dependent (BOLD) response contrasts of correct inhibition and failed inhibition as dependent variables and included age, sex, and hazardous drinking (as measured by the Alcohol Use Disorders Identification Test (AUDIT)), and their interactions, as independent variables RESULTS: Age was negatively associated with BOLD response in lateral inferior and middle frontal gyri, anterior cingulate cortex, and inferior parietal lobe for both successful inhibition and failed inhibition contrasts. In addition, there was a significant age × AUDIT interaction in the successful inhibition contrast in the left middle frontal gyrus, with significant negative correlations between AUDIT and BOLD response in older participants, and a significant positive correlation between AUDIT and BOLD response in younger participants CONCLUSIONS: Age appears to be a particularly important factor in predicting BOLD response and may be a critical variable to include in future studies of heavy drinking and alcohol use disorder, particularly those that assess cognitive function. Finally, the age × AUDIT interaction observed in the current study may represent evidence for accelerated aging effects of alcohol on cognitive function.

Neural correlates of alcohol use disorder severity among nontreatment-seeking heavy drinkers: An examination of the incentive salience and negative emotionality domains of the alcohol and addiction research domain criteria.

BACKGROUND: The Alcohol and Addiction Research Domain Criteria (AARDoC) propose that alcohol use disorder is associated with neural dysfunction in three primary domains: incentive salience, negative emotionality, and executive function. Prior studies in heavy drinking samples have examined brain activation changes associated with alcohol and negative affect cues, representing the incentive salience and negative emotionality domains, respectively. Yet studies examining such cue-induced changes in functional connectivity (FC) are relatively sparse. METHODS: Nontreatment-seeking heavy drinking adults (N = 149, 56.0% male, 48.6% non-white, mean age 34.8 years (SD = 10.0)) underwent functional magnetic resonance imaging during presentation of alcohol, negative, and neutral pictures. We focused on FC changes involving the nucleus accumbens and amygdala in addition to activation and FC correlations with self-reported AUD severity. RESULTS: For alcohol cues versus neutral cues, we observed accumbens FC changes in the cerebellum and prefrontal cortex (PFC), and amygdala FC changes with occipital, parietal, and hippocampal regions. AUD severity correlated positively with activation in the cerebellum (p < 0.05), accumbens FC in the cingulate gyri, somatosensory gyri, and cerebellum (p < 0.05), and with amygdala FC in the PFC and inferior parietal lobule (p < 0.05) for alcohol cues versus neutral cues. For negative cues versus neutral cues, we observed accumbens FC changes in the lateral temporal, occipital, and parietal regions, and amygdala FC changes in the fusiform and lingual gyri (p < 0.05). CONCLUSIONS: The present findings provide empirical support for the AARDoC domains of incentive salience and negative emotionality and indicate that AUD severity is associated with salience and response control for reward cues. When covarying for differences in nonalcohol substance use and mood disorder diagnoses, AUD severity was also associated with emotional reactivity for negative cues.

The Effects of Alcohol and Cannabis Co-Use on Neurocognitive Function, Brain Structure, and Brain Function.

Purpose of review: Given increases in the rates of alcohol and cannabis co-use among adolescents and young adults, this review aims to summarize literature on the effects of alcohol and cannabis co-use on neurocognitive functioning, brain structure, and brain function. Recent findings: The limited existing studies examining concurrent, recent, and lifetime alcohol and cannabis co-use suggest effects on the brain are likely multifaceted. The majority of studies report that co-use is associated with negative outcomes such as impaired cognitive function and significant alterations in key structural and functional regions of the brain, while others report null effects of co-use compared to non-substance using control and single-substance use groups. Summary: Current studies lack a general consensus on methodology, definitions of concurrent and simultaneous use, and neuroimaging approaches, which makes it challenging to draw strong conclusions about the effects of co-use. More studies are needed to explore the effects of co-use in the context of simultaneous alcohol and cannabis use.

A comparison of automated and manual co-registration for magnetoencephalography.

Magnetoencephalography (MEG) is a neuroimaging technique that accurately captures the rapid (sub-millisecond) activity of neuronal populations. Interpretation of functional data from MEG relies upon registration to the participant's anatomical MRI. The key remaining step is to transform the participant's MRI into the MEG head coordinate space. Although both automated and manual approaches to co-registration are available, the relative accuracy of two approaches has not been systematically evaluated. The goal of the present study was to compare the accuracy of manual and automated co-registration. Resting MEG and T1-weighted MRI data were collected from 90 participants. Automated and manual co-registration were performed on the same subjects, and the inter-method reliability of the two methods assessed using the intra-class correlation. Median co-registration error for both methods was within acceptable limits. Inter-method reliability was in the "good" range for co-registration error, and the "good" to "excellent" range for translation and rotation. These results suggest that the output of the automated co-registration procedure is comparable to that achieved using manual co-registration.

Resting-State Connectivity in Former, Current, and Never Smokers.

INTRODUCTION: Understanding the neural mechanisms that support successful smoking cessation is vital to the development of novel treatments for nicotine dependence. METHOD: To this end, we compared resting-state functional connectivity across three smoking groups: current, never, and former smokers. We used an independent component analysis (ICA) that allowed us to compare differences in intrinsic, large-scale networks across our groups. Using this technique, we were able to compare group differences across resting-state networks without the requirement of identifying coordinate-based regions of interest. RESULTS: Overall, the ICA resulted in networks that were largely consistent with previous reports, including bilateral executive control networks, salience, and a default mode network. Group comparisons among the three groups revealed differences in three networks including sensorimotor, dorsal attention, and default mode networks, with differences localized to pre/postcentral gyrus, lateral occipital cortex, and superior parietal lobe. In all regions showing a difference, current smokers showed increased network amplitude compared to former and never smokers. CONCLUSION: Although some theoretical models of recovery have suggested an important role of frontal cortex and cognitive control, the current results seem to suggest that reductions in posterior regions including superior parietal lobe and somatosensory cortex may play a key role in maintaining long-term abstinence from cigarettes. IMPLICATIONS: The submitted research is a novel contribution to the study of successful nicotine abstinence, in part, because it includes individuals who have successfully overcome nicotine dependence. The use of ICA allowed for examination of large-scale resting-state networks throughout the brain without the need for specifying numerous regions of interest. This research supports the view that overcoming nicotine dependence may depend on reducing spontaneous activity in posterior regions of the brain rather than solely enhancing frontal control.

Decreases in the Late Positive Potential to Alcohol Images Among Alcohol Treatment Seekers Following Mindfulness-Based Relapse Prevention.

AIM: Heightened craving among individuals with alcohol use disorder (AUD) has been attributed to a hypersensitivity to alcohol cues in attentional brain networks. Active mindfulness training has been shown to help improve attentional control. Here, we examined alcohol cue-related hypersensitivity among individuals with AUD who received rolling group mindfulness-based relapse prevention (MBRP) in combination with transcranial direct current stimulation (tDCS), over right inferior frontal gyrus. METHODS: Participants (n = 68) viewed a series of emotionally negative, emotionally neutral and alcohol-related images. Following image presentation, participants were asked to rate their level of craving for the alcohol cues, and their level of negative affect evoked by neutral and negative cues. During the task, electroencephalogram (EEG) was recorded to capture an event-related component shown to relate to emotionally salient stimuli: the late positive potential (LPP). Participants who completed a follow-up EEG (n = 37) performed the task a second time after up to eight sessions of MBRP coupled with active or sham tDCS. RESULTS: We found that both craving ratings and the LPP significantly decreased in response to alcohol cues from pre- to post-treatment, but not for other image cues. The magnitude of alcohol image craving reductions was associated with the number of MBRP group sessions attended. Active tDCS was not associated with craving ratings, but it was associated with greater LPP amplitudes across image types. CONCLUSIONS: Taken together, these results suggest that disruption of alcohol-cue hypersensitivity in people with AUD may be a target mechanism of MBRP.

Effects of attentional bias modification therapy on the cue reactivity and cognitive control networks in participants with cocaine use disorders.

BACKGROUND: While attentional bias modification therapy (ABMT) alters drug-related behaviors in some substance users, results have been mixed in individuals with cocaine use disorders (CUD). OBJECTIVES: The current study examined whether ABMT affected brain functioning during independent measures of cue reactivity (i.e., cocaine versus food cues) and cognitive control (i.e., incongruent versus congruent trials), and whether brain activity was associated with baseline or post-intervention cocaine use. METHODS: 37 participants (62% male) were randomly assigned to ABMT or control therapy. Clinical and neuroimaging assessments occurred at baseline and immediately post-intervention, with additional clinical testing at 2 weeks and 3 months following intervention. Cocaine use was assessed through self-report. RESULTS: Slower reaction times and increased functional activation (prefrontal cortex, posterior parietal cortex) were observed for incongruent versus congruent stimuli and increased functional activation for cocaine relative to food videos (ventral striatum, dorsolateral prefrontal cortex and orbitofrontal cortex). The default-mode network (DMN) was not deactivated during exposure to cocaine videos. The degree of activation during cocaine relative to food cues was associated with baseline cocaine use (insula only) and reduction in use following treatment (insula and anterior DMN) above and beyond clinical variables. Cognitive control network activity was not associated with cocaine use at baseline or following treatment. ABMT therapy did not differentially affect cocaine use or functional activation during either task. CONCLUSION: Current results suggest a relationship between cue reactivity network activation and cocaine use, but question the efficacy of ABMT in changing brain function during cue reactivity or cognitive control tasks.