The current study applied data-driven methods to identify and explain novel cognitive phenotypes of HIV. Methods: 388 people with HIV (PWH) with an average age of 46 (15.8) and median plasma CD4+ T-cell count of 555 copies/mL (79% virally suppressed) underwent cognitive testing and 3T neuroimaging. Demographics, HIV disease variables, and health comorbidities were recorded within three months of cognitive testing/neuroimaging. Hierarchical clustering was employed to identify cognitive phenotypes followed by ensemble machine learning to delineate the features that determined membership in the cognitive phenotypes. Hierarchical clustering identified five cognitive phenotypes. Cluster 1 (n=97) was comprised of individuals with normative performance on all cognitive tests. The remaining clusters were defined by impairment on action fluency (Cluster 2; n=46); verbal learning/memory (Cluster 3; n=73); action fluency and verbal learning/memory (Cluster 4; n=56); and action fluency, verbal learning/memory, and tests of executive function (Cluster 5; n=114). HIV detectability was most common in Cluster 5. Machine learning revealed that polysubstance use, race, educational attainment, and volumes of the precuneus, cingulate, nucleus accumbens, and thalamus differentiated membership in the normal vs. impaired clusters. The determinants of persistent cognitive impairment among PWH receiving suppressive treatment are multifactorial nature. Viral replication after ART plays a role in the causal pathway, but psychosocial factors (race inequities, substance use) merit increased attention as critical determinants of cognitive impairment in the context of ART. Results underscore the need for comprehensive person-centered interventions that go beyond adherence to patient care to achieve optimal cognitive health among PWH.

Importance: Despite the legalization and widespread use of cannabis products for a variety of medical concerns in the US, there is not yet a strong clinical literature to support such use. The risks and benefits of obtaining a medical marijuana card for common clinical outcomes are largely unknown. Objective: To evaluate the effect of obtaining a medical marijuana card on target clinical and cannabis use disorder (CUD) symptoms in adults with a chief concern of chronic pain, insomnia, or anxiety or depressive symptoms. Design, Setting, and Participants: This pragmatic, single-site, single-blind randomized clinical trial was conducted in the Greater Boston area from July 1, 2017, to July 31, 2020. Participants were adults aged 18 to 65 years with a chief concern of pain, insomnia, or anxiety or depressive symptoms. Participants were randomized 2:1 to either the immediate card acquisition group (n = 105) or the delayed card acquisition group (n = 81). Randomization was stratified by chief concern, age, and sex. The statistical analysis followed an evaluable population approach. Interventions: The immediate card acquisition group was allowed to obtain a medical marijuana card immediately after randomization. The delayed card acquisition group was asked to wait 12 weeks before obtaining a medical marijuana card. All participants could choose cannabis products from a dispensary, the dose, and the frequency of use. Participants could continue their usual medical or psychiatric care. Main Outcomes and Measures: Primary outcomes were changes in CUD symptoms, anxiety and depressive symptoms, pain severity, and insomnia symptoms during the trial. A logistic regression model was used to estimate the odds ratio (OR) for CUD diagnosis, and linear models were used for continuous outcomes to estimate the mean difference (MD) in symptom scores. Results: A total of 186 participants (mean [SD] age 37.2 [14.4] years; 122 women [65.6%]) were randomized and included in the analyses. Compared with the delayed card acquisition group, the immediate card acquisition group had more CUD symptoms (MD, 0.28; 95% CI, 0.15-0.40; P < .001); fewer self-rated insomnia symptoms (MD, -2.90; 95% CI, -4.31 to -1.51; P < .001); and reported no significant changes in pain severity or anxiety or depressive symptoms. Participants in the immediate card acquisition group also had a higher incidence of CUD during the intervention (17.1% [n = 18] in the immediate card acquisition group vs 8.6% [n = 7] in the delayed card acquisition group; adjusted odds ratio, 2.88; 95% CI, 1.17-7.07; P = .02), particularly those with a chief concern of anxiety or depressive symptoms. Conclusions and Relevance: This randomized clinical trial found that immediate acquisition of a medical marijuana card led to a higher incidence and severity of CUD; resulted in no significant improvement in pain, anxiety, or depressive symptoms; and improved self-rating of insomnia symptoms. Further investigation of the benefits of medical marijuana card ownership for insomnia and the risk of CUD are needed, particularly for individuals with anxiety or depressive symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT03224468.

The primary cannabinoid in cannabis, Δ9-tetrahydrocannabinol (THC), causes intoxication and impaired function, with implications for traffic, workplace, and other situational safety risks. There are currently no evidence-based methods to detect cannabis-impaired driving, and current field sobriety tests with gold-standard, drug recognition evaluations are resource-intensive and may be prone to bias. This study evaluated the capability of a simple, portable imaging method to accurately detect individuals with THC impairment. In this double-blind, randomized, cross-over study, 169 cannabis users, aged 18-55 years, underwent functional near-infrared spectroscopy (fNIRS) before and after receiving oral THC and placebo, at study visits one week apart. Impairment was defined by convergent classification by consensus clinical ratings and an algorithm based on post-dose tachycardia and self-rated "high." Our primary outcome, prefrontal cortex (PFC) oxygenated hemoglobin concentration (HbO), was increased after THC only in participants operationalized as impaired, independent of THC dose. ML models using fNIRS time course features and connectivity matrices identified impairment with 76.4% accuracy, 69.8% positive predictive value (PPV), and 10% false-positive rate using convergent classification as ground truth, which exceeded Drug Recognition Evaluator-conducted expanded field sobriety examination (67.8% accuracy, 35.4% PPV, and 35.4% false-positive rate). These findings demonstrate that PFC response activation patterns and connectivity produce a neural signature of impairment, and that PFC signal, measured with fNIRS, can be used as a sole input to ML models to objectively determine impairment from THC intoxication at the individual level. Future work is warranted to determine the specificity of this classifier to acute THC impairment.ClinicalTrials.gov Identifier: NCT03655717.

BACKGROUND AND AIMS: Electronic cigarette use has escalated rapidly in recent years, particularly among youth. Little is known about the genetic influences on e-cigarette use. This study aimed to determine whether genetic risk for regular use of combustible cigarettes or for number of cigarettes smoked per day confers risk for ever e-cigarette use or frequency of e-cigarette use. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We used data from 9541 young adults from the Spit for Science longitudinal cohort study (2011-2019). Polygenic scores (PGS) of regular combustible cigarette use (PGS-RCU) and cigarettes per day (PGS-CPD) were constructed using summary statistics from the two largest available genome-wide association study (GWAS) meta-analysis of European ancestry and East Asian ancestry of combustible cigarette use and used to test whether the PGS of RCU or CPD predicted lifetime e-cigarette use and frequency of past 30-day e-cigarette use in a diverse sample of young adults of African (AFR), Admixed American (AMR), East Asian (EAS), European (EUR), and South Asian (SAS) ancestry. FINDINGS: The PGS-RCU was associated with lifetime e-cigarette use in the EUR sample (OR = 1.27, 95% CI = 1.19-1.36, P = 7.53 × 10-12 ), but not in the other subsamples (ps > 0.12). This association remained significant after excluding regular combustible cigarette smokers (OR = 1.21, 95% CI = 1.12-1.31, P = 3.36 × 10-6 ). There was no statistically significant association between PGS-CPD and lifetime e-cigarette use and neither the PGS-RCU nor the PGS-CPD were associated with frequency of e-cigarette use in the past 30 days in any of the subsamples. CONCLUSIONS: Genetic factors associated with regular combustible cigarette use appear to be associated with ever e-cigarette use in young adults. We did not find evidence for shared genetic factors influencing heaviness of use of combustible cigarettes and current e-cigarette use frequency.

OBJECTIVE: Cannabis and alcohol use are correlated behaviors among youth. It is not known whether discontinuation of cannabis use is associated with changes in alcohol use. This study assessed alcohol use in youth before, during, and after 4 weeks of paid cannabis abstinence. METHODS: Healthy, non-treatment seeking, cannabis users (n = 160), aged 14-25 years, 84% of whom used alcohol in the last month, were enrolled for a 4-week study with a 2-4 week follow-up. Participants were randomly assigned to 4 weeks of either biochemically-verified cannabis abstinence achieved through a contingency management framework (CB-Abst) or monitoring with no abstinence requirement (CB-Mon). Participants were assessed at baseline and approximately 4, 6, 10, 17, 24, and 31 days after enrollment. A follow-up visit with no cannabis abstinence requirement for CB-Abst was conducted after 2-4 weeks. RESULTS: Sixty percent of individuals assigned to the CB-Abst condition increased in frequency and quantity of alcohol consumption during the 4-week period of incentivized cannabis abstinence. As a whole, CB-Abst increased by a mean of 0.6 drinking days and 0.2 drinks per day in the initial week of abstinence (p's < 0.006). There was no evidence for further increases in drinking frequency or quantity during the 30-day abstinence period (p's > 0.53). There was no change in drinking frequency or quantity during the 4-week monitoring or follow-up periods among CB-Mon. CONCLUSIONS: On average, 4 weeks of incentivized (i.e., paid) cannabis abstinence among non-treatment seeking youth was associated with increased frequency and amount of alcohol use in week 1 that was sustained over 4 weeks and resolved with resumption of cannabis use. However, there was notable variability in individual-level response, with 60% increasing in alcohol use and 23% actually decreasing in alcohol use during cannabis abstinence. Findings suggest that increased alcohol use during cannabis abstinence among youth merits further study to determine whether this behavior occurs among treatment seeking youth and its clinical significance.

Background: Cannabis use is prevalent among adolescents, and many report using in attempts to alleviate negative mood and anxiety. Abstinence from substances such as alcohol and tobacco has been reported to improve symptoms of anxiety and depression. Few studies have examined the effect of cannabis abstinence on symptoms of anxiety and depression. Objective: To test the effect of 4 weeks of continuous cannabis abstinence on depressive and anxious symptoms. Methods: Healthy, non-treatment seeking adolescents who used cannabis at least weekly (n = 179) were randomized to either 4 weeks of cannabis abstinence achieved through a contingency management paradigm (CB-Abst) or cannabis use monitoring without an abstinence requirement (CB-Mon). Abstinence was assessed by self-report verified with quantitative assay of urine for cannabinoids. Anxiety and depressive symptoms were assessed weekly with the Mood and Anxiety Symptom Questionnaire (MASQ). Results: Symptoms of depression and anxiety decreased throughout the study for all participants (MASQ-AA: stnd beta = -0.08, p = 0.01, MASQ-GDA: stnd beta = -0.11, p = 0.003, MASQ-GDD: stnd beta = -0.08, p = 0.02) and did not differ significantly between randomization groups (p's > 0.46). Exploratory analyses revealed a trend that abstinence may be associated with greater improvement in symptoms of anxiety and depression among those using cannabis to cope with negative affect and those with potentially hazardous levels of cannabis use. Conclusions: Among adolescents who use cannabis at least weekly, 4 weeks of cannabis abstinence was not associated with a significant change in anxiety or depressive symptoms compared to continued use. For recreational cannabis users who may be concerned about reducing their use for fear of increased symptoms of anxiety and depression, findings suggest that significant symptom worsening may not occur within the first 4 weeks of abstinence. Further studies are needed in clinical populations where anxiety and depression symptoms are measured more frequently and for a longer period of abstinence. Future studies are also needed to determine whether there are subgroups of adolescents who are uniquely impacted by sustained cannabis abstinence.

Marijuana (MJ) use and post-traumatic stress disorder (PTSD) have both been associated with abnormalities in brain white matter tracts, including the cingulum and the anterior thalamic radiations (ATR), which project from subcortical regions to frontal cortex. Studies have not assessed the integrity of these tracts in patients with comorbid PTSD and MJ use. To examine effects of PTSD and MJ use on brain structure, we performed diffusion tensor imaging scans on seventy-two trauma-exposed participants, categorized into four groups: those with PTSD who used MJ at least weekly (PTSD+MJ; n = 20), those with PTSD with no regular MJ use (PTSD; n = 19), trauma-exposed controls without PTSD who used MJ (TEC+MJ; n = 14) and trauma-exposed controls with no PTSD or MJ use (TEC; n = 19). White matter integrity was evaluated by calculating fractional anisotropy (FA). Results showed that while FA values in the right ATR and the cingulum differed across groups, there were no significant interactions between PTSD and MJ in any white matter tracts, indicating that MJ exposure neither normalizes nor worsens white matter abnormalities in those with PTSD. Further study is needed to evaluate the impact of MJ use on other neurobiological markers of PTSD.

The primary psychoactive compound in cannabis, Δ9-tetrahydrocannabinol (THC), binds to cannabinoid receptors (CB1) present in high concentrations in the prefrontal cortex (PFC). It is unknown whether the PFC hemodynamic response changes with THC intoxication. We conducted the first double-blind, placebo-controlled, cross-over study of the effect of THC intoxication on functional near infrared spectroscopy (fNIRS) measures of PFC activation. Fifty-four adult, regular (at least weekly) cannabis users received a single oral dose of synthetic THC (dronabinol; 5-50 mg, dose individually tailored to produce intoxication) and identical placebo on two visits at least one week apart. fNIRS recordings were obtained during a working memory task (N-Back) at three timepoints: before THC/placebo, at 100 min (when peak effects were expected), and at 200 min after THC/placebo administration. Functional data were collected using a continuous-wave NIRS device, with 8 sources and 7 detectors arrayed over the forehead, resulting in 20 channels covering PFC regions. Participants also completed frequent heart rate measures and subjective ratings of intoxication. Approximately half of participants reported significant intoxication. Intoxication ratings were not correlated with dose of THC. Increases in heart rate significantly correlated with intoxication ratings after THC dosing. Results indicated that 100 min after THC administration, oxygenated hemoglobin (HbO) response significantly increased from pre-dose HbO levels throughout the PFC in participants who reported significant intoxication. Changes in HbO response significantly correlated with self-reported intoxication at 100 min after THC administration. Among those who reported intoxication, HbO response decreased at 200 min after THC, when intoxication had largely resolved, compared to the peak THC time point. This study demonstrates that THC intoxication causes increased PFC activity, and fNIRS of the PFC can measure this effect. Increased neural activation in PFC represents a potential biomarker for cannabis intoxication.

Marijuana (MJ) use and major depressive disorder (MDD) have both been associated with deficits in verbal learning and memory as well as structural brain abnormalities. It is not known if MJ use by those with MDD confers additional impairment. The goal of this study was to examine unique and combined effects of MDD and MJ use on verbal memory and brain structure. Young adults (n=141) aged 18-25 years with MJ use and no lifetime MDD (MJ, n=46), MDD and no MJ use (MDD, n=23), MJ use and lifetime MDD (MDD+MJ, n=24), and healthy controls without MDD or MJ use (CON, n=48) were enrolled. Participants completed the California Verbal Learning Test, Second Edition (CVLT-II), a measure of verbal learning and memory. A sub-sample of 82 participants also underwent a structural magnetic resonance imaging (MRI) scan. Group differences in CVLT-II performance, cortical thickness, and hippocampal volume were assessed. We found an additive effect of MDD and MJ on memory recall. Only MDD, but not MJ, was associated with poorer initial learning, fewer words recalled, more intrusion errors, and lower percent retention. There was also an additive effect of MDD and MJ use on reduced cortical thickness in the middle temporal gyrus. Findings indicate that MJ use and MDD have additive adverse associations with verbal recall and cortical thickness in the middle temporal gyrus, suggesting that MJ use among those with MDD may be contraindicated. Prospective studies are warranted to determine whether this association may be causal.

BACKGROUND: Suggestibility, defined as an individual's inclination to accept and internalize messages, has not been studied in relation to alcohol use. Peer conformity, a component of suggestibility, may be related to alcohol use, as peer groups show similarities in patterns of alcohol use. Few studies have assessed how suggestibility and peer conformity relate to alcohol self-administration or to reinforcing effects of alcohol. AIMS: This study assessed whether suggestibility and peer conformity were associated with drinking behavior, alcohol self-administration, subjective response to alcohol, and drinking motives and expectancies. METHODS: Study 1 participants were alcohol drinkers (n=20), who completed a laboratory study of free-access intravenous alcohol self-administration. Study 2 participants were adolescents and young adults, age 14-25 (n=150), with lifetime alcohol use. Participants completed surveys of suggestibility and drinking patterns (Study 1 and 2), subjective alcohol effects (Study 1 only), and alcohol motives and expectancies (Study 2 only). RESULTS/OUTCOMES: In Study 1, participants with higher levels of suggestiblity self-administered more alcohol, and reported greater subjective alcohol effects. Peer conformity, though correlated with suggestibility, was not related to these measures. In Study 2, participants with higher suggestiblity reported more alcohol consumption, higher drinking motives and alcohol expectancies. Peer conformity was not related to alcohol consumption, but was related to coping and enhancement drinking motives, and all expectancies measures. CONCLUSIONS/INTERPRETATION: Results indicate that suggestibility, beyond peer conformity, may be a critical factor to study when examining alcohol consumption behavior, and may provide insight into the development of alcohol use disorder.

Relapse to smoking after initial abstinence is a major clinical challenge with significant public health consequences. At the brain and behavioral level, those who relapse to tobacco smoking have both greater cue-reactivity and lower inhibitory control than those who remain abstinent. Little is known about neural activation during inhibitory control tasks in the presence of drug-related cues. In the current study, tobacco smokers (SMK; n = 22) and non-smoking controls (CON; n = 19) completed a Go/NoGo task involving smoking cues during a functional magnetic resonance imaging (fMRI) scan. Following the scan session, smokers were required to quit smoking, and maintenance of abstinence was evaluated as part of a 12-week smoking cessation trial. We evaluated pre-cessation brain activity during NoGo trials in smokers who were versus were not able to quit smoking. We then compared fMRI and inhibitory control measures between smokers and non-smokers. We did not find differences between SMK and CON in performance or activation to smoking or neutral cues. However, compared to SMK who relapsed, SMK who attained biochemically-validated abstinence at the end of the smoking cessation trial had greater neural activation in the anterior insula during NoGo trials specifically with smoking-related cues. Results indicate that within SMK, decreased inhibitory control activation during direct exposure to drug-related stimuli may be a marker of difficulty quitting and relapse vulnerability.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) symptoms, even those below diagnostic threshold, enhance the likelihood of nicotine dependence, suggesting a neurobiological link between disorders. Of particular interest is the salience network (SN), which mediates attention to salient internal/external stimuli to guide behavior and is anchored by the dorsal anterior cingulate cortex (dACC) and bilateral anterior insula (AI). Disrupted interactions between the SN and the default mode (DMN) and central executive networks (CEN) have been noted in both ADHD and nicotine dependence. Further, enhanced intra-SN coupling between the dACC-AI influences aspects of nicotine dependence such as reactivity to smoking cues. METHODS: To identify links between SN functional connectivity and ADHD symptoms in nicotine dependence, we compared 21 nicotine dependent individuals with 17 non-smokers on ADHD symptoms as measured by the ADHD self-report scale (ASRS) and resting state intra and inter-SN functional connectivity. RESULTS: Relative to healthy controls, nicotine dependent individuals had significantly higher ASRS scores and greater dACC-AI coupling. No group differences were noted on inter-SN network coupling. A significant association was found between ASRS and dACC-AI coupling both in the entire cohort and specifically when evaluating nicotine dependent individuals alone. CONCLUSIONS: The greater ASRS scores in nicotine dependent individuals is in line with existent literature and the stronger dACC-AI coupling in smokers further supports the role of this network in nicotine dependence. The significant association between dACC-AI coupling and ASRS suggests that intra-SN coupling strength may impact neurocognitive functioning associated with both ADHD symptoms and nicotine dependence.

Introduction: Memory impairment is one of the most commonly reported effects of cannabis use, especially among those who initiate use earlier, perhaps due to the effects of delta-9- tetrahydrocannabinol on cannabinoid (CB1) receptors in the brain. Studies have increasingly investigated whether cannabis use is associated with impairments in verbal memory, and with alterations in brain structures underlying verbal memory. The uncinate fasciculus (UF), a long-range white matter tract, connects regions with densely localized CB1 receptors that are important in verbal memory. This study investigated the impact of cannabis use on UF structures and its association with memory performance in young adult cannabis users (CU) and non-using controls (CON). Materials and Methods: Nineteen CU and 22 CON completed a verbal memory task and a neuroimaging protocol, in which diffusion tensor imaging and structural scans were collected. We compared memory performance, diffusion and tractography measures of the UF, and cortical thickness of regions connected by the UF, between CU and CON. In regions showing a significant group effect, we also examined associations between verbal memory performance, cortical thickness, and age of onset of cannabis use. Results: Compared to non-users, CU had worse memory performance, decreased fiber bundle length in the UF, and decreased cortical thickness of brain regions along the UF such as the entorhinal cortex and fusiform gyrus. Verbal memory performance was significantly associated with age of onset of cannabis use, indicating that those who initiated cannabis use at an earlier age performed worse. Cortical thickness of the entorhinal cortex was significantly correlated with age of first use and memory performance. Conclusion: This study provides evidence that cannabis use, especially when initiated at a young age, may be associated with worse verbal memory and altered neural development along the UF. Reductions in cortical thickness in regions implicated in memory processes may underlie weaknesses in verbal memory performance.

PURPOSE OF REVIEW: Although peer influence is an important factor in the initiation and maintenance of cannabis use, few studies have investigated the neural correlates of peer influence among cannabis users. The current review summarizes research on the neuroscience of social influence in cannabis users, with the goal of highlighting gaps in the literature and the need for future research. RECENT FINDINGS: Brain regions underlying peer influence may function differently in cannabis users. Compared to non-using controls, regions of the brain underlying reward, such as the striatum, show greater connectivity with frontal regions, and also show hyperactivity when participants are presented with peer information. Other subcortical regions, such as the insula, show hypoactivation during social exclusion in cannabis users, indicating that neural responses to peer interactions may be altered in cannabis users. SUMMARY: Although neuroscience is increasingly being used to study social behavior, few studies have specifically focused on cannabis use, and therefore it is difficult to draw conclusions about social mechanisms that may differentiate cannabis users and controls. This area of research may be a promising avenue in which to explore a critical factor underlying cannabis use and addiction.

INTRODUCTION: The ability to direct smoking cessation treatment based on neuroscientific findings holds incredible promise. However, there is a strong need for consistency across studies to confirm neurobiological targets. While our prior work implicated enhanced insula reactivity to smoking cues in tobacco smoking relapse vulnerability, this finding has not been confirmed. METHOD: Using functional magnetic resonance imaging (fMRI), we evaluated the pre-cessation brain reactivity to smoking vs. neutral cues in nicotine dependent smokers who were and were not able to maintain subsequent abstinence. RESULTS: Of the 23 (7 women) individuals assessed, 13 relapsed and there were no demographic differences between those who did and did not relapse. However, smokers who relapsed showed enhanced reactivity to smoking cues in the right insula and dorsal striatum, showing significant overlap between our current and prior work despite methodological differences, including the fact that our previous work only included women. CONCLUSION: The current work supports our prior results and builds on the concept that the insula and dorsal striatum work in concert to maintain nicotine dependence. Specifically, dorsal striatal-mediated habitual responding may be triggered both by the external drug-associated cues, and the insula-mediated internal states that provide additional context motivating drug use. This replicated finding also mirrors preclinical work that finds the same individualized distinction, as only some rodents attribute incentive salience to drug cues and are more likely to reinstate drug seeking after extinction. To effectively treat addiction, these individual characteristics and their underlying neurobiological foundations must be considered.

Intoxication from cannabis impairs cognitive performance, in part due to the effects of Δ9-tetrahydrocannabinol (THC, the primary psychoactive compound in cannabis) on prefrontal cortex (PFC) function. However, a relationship between impairment in cognitive functioning with THC administration and THC-induced change in hemodynamic response has not been demonstrated. We explored the feasibility of using functional near-infrared spectroscopy (fNIRS) to examine the functional changes of the human PFC associated with cannabis intoxication and cognitive impairment. Eighteen adult regular cannabis users (final sample, n = 13) performed a working memory task (n-back) during fNIRS recordings, before and after receiving a single dose of oral synthetic THC (dronabinol; 20-50 mg). Functional data were collected using a continuous-wave NIRS device, in which 8 Sources and 7 detectors were placed on the forehead, resulting in 20 channels covering PFC regions. Physiological changes and subjective intoxication measures were collected. We found a significant increase in the oxygenated hemoglobin (HbO) concentration after THC administration in several channels on the PFC during both the high working memory load (2-back) and the low working memory load (0-back) condition. The increased HbO response was accompanied by a trend toward an increased number of omission errors after THC administration. The current study suggests that cannabis intoxication is associated with increases in hemodynamic blood flow to the PFC, and that this increase can be detected with fNIRS.

Previous studies have reported that peer groups are one of the most important predictors of adolescent and young adult marijuana use, and yet the neural correlates of social processing in marijuana users have not yet been studied. In the current study, marijuana-using young adults (n = 20) and non-using controls (n = 22) participated in a neuroimaging social exclusion task called Cyberball, a computerized ball-tossing game in which the participant is excluded from the game after a pre-determined number of ball tosses. Controls, but not marijuana users, demonstrated significant activation in the insula, a region associated with negative emotion, when being excluded from the game. Both groups demonstrated activation of the ventral anterior cingulate cortex (vACC), a region associated with affective monitoring, during peer exclusion. Only the marijuana group showed a correlation between vACC activation and scores on a self-report measure of peer conformity. This study indicates that marijuana users show atypical neural processing of social exclusion, which may be either caused by, or the result of, regular marijuana use.