Regular cannabis use modulates gamma functional connectivity with V1 during visual processing

Cannabis use has increased globally, but its effects on brain function are not fully known, highlighting the need to better determine recent and long-term brain activation outcomes of cannabis use. To examine the association of lifetime history of heavy cannabis use and recent cannabis use with brain activation across a range of brain functions in a large sample of young adults in the US. This cross-sectional study used data (2017 release) from the Human Connectome Project (collected between August 2012 and 2015). Young adults (aged 22-36 years) with magnetic resonance imaging (MRI), urine toxicology, and cannabis use data were included in the analysis. Data were analyzed from January 31 to July 30, 2024. History of heavy cannabis use was assessed using the Semi-Structured Assessment for the Genetics of Alcoholism, with variables for lifetime history and diagnosis of cannabis dependence. Individuals were grouped as heavy lifetime cannabis users if they had greater than 1000 uses, as moderate users if they had 10 to 999 uses, and as nonusers if they had fewer than 10 uses. Participants provided urine samples on the day of scanning to assess recent use. Diagnosis of cannabis dependence (per Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) was also included. Brain activation was assessed during each of the 7 tasks administered during the functional MRI session (working memory, reward, emotion, language, motor, relational assessment, and theory of mind). Mean activation from regions associated with the primary contrast for each task was used. The primary analysis was a linear mixed-effects regression model (one model per task) examining the association of lifetime cannabis and recent cannabis use on the mean brain activation value. The sample comprised 1003 adults (mean [SD] age, 28.7 [3.7] years; 470 men [46.9%] and 533 women [53.1%]). A total of 63 participants were Asian (6.3%), 137 were Black (13.7%), and 762 were White (76.0%). For lifetime history criteria, 88 participants (8.8%) were classified as heavy cannabis users, 179 (17.8%) as moderate users, and 736 (73.4%) as nonusers. Heavy lifetime use (Cohen d = -0.28 [95% CI, -0.50 to -0.06]; false discovery rate corrected P = .02) was associated with lower activation on the working memory task. Regions associated with a history of heavy use included the anterior insula, medial prefrontal cortex, and dorsolateral prefrontal cortex. Recent cannabis use was associated with poorer performance and lower brain activation in the working memory and motor tasks, but the associations between recent use and brain activation did not survive false discovery rate correction. No other tasks were associated with lifetime history of heavy use, recent use, or dependence diagnosis. In this study of young adults, lifetime history of heavy cannabis use was associated with lower brain activation during a working memory task. These findings identify negative outcomes associated with heavy lifetime cannabis use and working memory in healthy young adults that may be long lasting.

People who regularly use cannabis exhibit altered brain dynamics during cognitive control tasks, though the impact of regular cannabis use on the neural dynamics serving motor control remains less understood. We sought to investigate how regular cannabis use modulates the neural dynamics serving motor control. Thirty-four people who regularly use cannabis (cannabis+) and 33 nonusers (cannabis-) underwent structured interviews about their substance use history and performed the Eriksen flanker task to map the neural dynamics serving motor control during high-density magnetoencephalography (MEG). The resulting neural data were transformed into the time-frequency domain to examine oscillatory activity and were imaged using a beamforming approach. MEG sensor-level analyses revealed robust beta (16-24 Hz) and gamma oscillations (66-74 Hz) during motor planning and execution, which were imaged using a beamformer. Both responses peaked in the left primary motor cortex and voxel time series were extracted to evaluate the spontaneous and oscillatory dynamics. Our key findings indicated that the cannabis+ group exhibited weaker spontaneous gamma activity in the left primary motor cortex relative to the cannabis- group, which scaled with cannabis use and behavioral metrics. Interestingly, regular cannabis use was not associated with differences in oscillatory beta and gamma activity, and there were no group differences in spontaneous beta activity. Our findings suggest that regular cannabis use is associated with suppressed spontaneous gamma activity in the left primary motor cortex, which scales with the degree of cannabis use disorder symptomatology and is coupled to behavioral task performance.

AimsTo summarize and evaluate our knowledge of the relationship between heavy cannabis use, cannabis use disorder (CUD) and the brain.MethodsNarrative review of relevant literature identified through existing systematic reviews, meta‐analyses and a PubMed search. Epidemiology, clinical representations, potential causal mechanisms, assessments, treatment and prognosis are discussed.ResultsAlthough causality is unclear, heavy and dependent cannabis use is consistently associated with a high prevalence of comorbid psychiatric disorders and learning and memory impairments that seem to recover after a period of abstinence. Evidence regarding other cognitive domains and neurological consequences, including cerebrovascular events, is limited and inconsistent. Abstinence after treatment is only achieved in a minority of cases; treatment targeted at reduction in use appears have some success. Potential moderators of the impact of CUD on the brain include age of onset, heaviness of use, CUD severity, the ratio of ∆9‐tetrahydrocannabinol to cannabidiol and severity of comorbid disorders.ConclusionsCurrent evidence of long‐term effects of daily cannabis use and cannabis use disorder on brain‐related outcomes is suggestive rather than conclusive, but use is associated with psychiatric morbidity and with cognitive impairments that recover after a period of abstinence.

Cannabis use has been associated with cardiovascular risks, yet its relationship with subclinical vascular markers such as augmentation index (AIx) remains unclear. This study aimed to investigate the association between cannabis use and AIx, stratified by sex, in a middle-aged general population. We analyzed data from 20,692 participants of the UK Biobank who had available AIx and cannabis use information. Cannabis exposure was categorized by lifetime use (low, moderate, and heavy), recent vs. past use, and frequency. Linear regression models were stratified by sex and adjusted for cardiovascular and sociodemographic covariates, including blood pressure, heart rate, tobacco and alcohol use, comorbidities, and socioeconomic status. Men exhibited lower AIx than women (19.06% vs. 21.93%), but a higher prevalence of cannabis use (3.58% vs. 1.68% for heavy users and 7.11% vs. 4.25% for everyday consumption in cannabis users). In men, heavy lifetime cannabis use was associated with increased AIx (β = 1.48, 95% CI [0.76; 2.19]), whereas low use was inversely associated (β = -0.79 [-1.30; -0.27]). Daily cannabis use was associated with higher AIx (β = 1.21 [0.15; 2.27]). In women, heavy use was associated with higher Aix (β = 1.31 [0.20; 2.42]); other patterns of cannabis use were not associated with AIx. In the overall population, there was no evidence of differences in the associations by sex. Heavy cannabis use was associated with increased arterial stiffness as measured by AIx.

Cannabinoid Hyperemesis Syndrome Is Associated With High Disease Burden: An Internet-Based Survey.

A literature review and meta-analyses of cannabis use and suicidality

BackgroundDifferences in the volumes of the hippocampus and amygdala have consistently been observed between young adults with heavy cannabis use relative to their non-using counterparts. However, it remains unclear whether the subfields of these functionally and structurally heterogenous regions exhibit similar patterns of change in young adults with long-term heavy cannabis use disorder (CUD). ObjectivesThis study aims to investigate the effects of long-term heavy cannabis use in young adults on the subregional structures of the hippocampus and amygdala, as well as their longitudinal alterations. MethodsThe study sample comprised 20 young adults with heavy cannabis use and 22 matched non-cannabis using healthy volunteers. All participants completed the Cannabis Use Disorder Identification Test (CUDIT) and underwent two T1-structural magnetic resonance imaging (MRI) scans, one at baseline and another at follow-up 3 years later. The amygdala, hippocampus, and their subregions were segmented on T1-weighted anatomical MRI scans, using a previously validated procedure. ResultsAt baseline, young adults with heavy CUD exhibited significantly larger volumes in several hippocampal (bilateral presubiculum, subiculum, Cornu Ammonis (CA) regions CA1, CA2-CA3, and right CA4-Dentate Gyrus (DG)) and amygdala (bilateral paralaminar nuclei, right medial nucleus, and right lateral nucleus) subregions compared to healthy controls, but these differences were attenuated at follow-up. Longitudinal analysis revealed an accelerated volumetric decrease in these subregions in young adults with heavy CUD relative to controls. Particularly, compared to healthy controls, significant accelerated volume decreases were observed in the right hippocampal subfields of the parasubiculum, subiculum, and CA4-DG. In the amygdala, similar trends of accelerated volumetric decreases were observed in the left central nucleus, right paralaminar nucleus, right basal nucleus, and right accessory basal nucleus. ConclusionsThe current findings suggest that long-term heavy cannabis use impacts maturational process of the amygdala and hippocampus, especially in subregions with high concentrations of cannabinoid type 1 receptors (CB1Rs) and involvement in adult neurogenesis.

The degree to which cannabis use causes long term harm to mental functioning is contentious. To determine the evidence for residual and long term effects of cannabis use on mental functions. Comprehensively review human studies addressing detrimental effects on human mental and life functioning. Heavy use causes immediate effects on perception, mood and sedation, but also deficits in cognitive ability. But cessation following heavy use has withdrawal effects and is associated with residual effects on cognition that may last for several weeks. Heavy use also raises the risk of impoverishment of life outcomes and a decline in socioeconomic status as well as the risk of mental health problems. Young age at the start of heavy cannabis use causes a risk of lifelong detrimental effects, and as a worst case together with genetic vulnerability exacerbate a predisposition to schizophrenia. Heavy regular use of cannabis that begins in adolescence heightens the risk of longterm impairment of life and mental functioning.

Longitudinal associations of cannabis and illicit drug use with depression, suicidal ideation and suicidal attempts among Nova Scotia high school students

Medial temporal structures and memory functions in adolescents with heavy cannabis use

Cannabis withdrawal syndrome (CWS)-a diagnostic indicator of cannabis use disorder-commonly occurs on cessation of heavy and prolonged cannabis use. To date, the prevalence of CWS syndrome has not been well described, nor have the factors potentially associated with CWS. To estimate the prevalence of CWS among individuals with regular or dependent use of cannabinoids and identify factors associated with CWS. A search of literature from database inception to June 19, 2019, was performed using MEDLINE, Embase, PsycINFO, Web of Science, the Cumulative Index to Nursing and Allied Health Literature, ProQuest, Allied and Complementary Medicine, and Psychiatry online, supplemented by manual searches of reference lists of included articles. Articles were included if they (1) were published in English, (2) reported on individuals with regular use of cannabinoids or cannabis use disorder as a primary study group, (3) reported on the prevalence of CWS or CWS symptoms using a validated instrument, (4) reported the prevalence of CWS, and (5) used an observational study design (eg, cohort or cross-sectional). All abstracts, full-text articles, and other sources were reviewed, with data extracted in duplicate. Cannabis withdrawal syndrome prevalence was estimated using a random-effects meta-analysis model, alongside stratification and meta-regression to characterize heterogeneity. Cannabis withdrawal syndrome prevalence was reported as a percentage with 95% CIs. Of 3848 unique abstracts, 86 were selected for full-text review, and 47 studies, representing 23 518 participants, met all inclusion criteria. Of 23 518 participants included in the analysis, 16 839 were white (72%) and 14 387 were men (69%); median (SD) age was 29.9 (9.0) years. The overall pooled prevalence of CWS was 47% (6469 of 23 518) (95% CI, 41%-52%), with significant heterogeneity between estimates (I2 = 99.2%). When stratified by source, the prevalence of CWS was 17% (95% CI, 13%-21%) in population-based samples, 54% in outpatient samples (95% CI, 48%-59%), and 87% in inpatient samples (95% CI, 79%-94%), which were significantly different (P < .001). Concurrent cannabis (β = 0.005, P < .001), tobacco (β = 0.002, P = .02), and other substance use disorders (β = 0.003, P = .05) were associated with a higher CWS prevalence, as was daily cannabis use (β = 0.004, P < .001). These findings suggest that cannabis withdrawal syndrome appears to be prevalent among regular users of cannabis. Clinicians should be aware of the prevalence of CWS in order to counsel patients and support individuals who are reducing their use of cannabis.

Background Understanding the potential impact of cannabis use on cardiovascular health is increasingly important as cannabis use rises in the U.S. Objectives: This study evaluated the associations between regular cannabis use, with and without tobacco co-use, and cardiovascular outcomes. Methods Analysis of a limited dataset obtained through IBM Watson Health Explorys, a platform integrating electronic health record data. Matched controls using Mahalanobis distance within propensity score calipers were defined for: 1) cannabis-using patients (n = 8,944; 43% female); and subgroups of cannabis-using patients: 2) with an encounter diagnosis for tobacco use disorder (TUD; n = 4,682); and 3) without a TUD diagnosis (non-TUD; n = 4,262). Patients had ≥1 blood pressure measurement and blood chemistry lab result in the MetroHealth System (Cleveland, Ohio). Cannabis-using patients had an encounter diagnosis of cannabis abuse/dependence and/or ≥2 cannabis-positive urine drug screens. Control patients, with no cannabis-use-documentation, were matched to the cannabis-using patients on demographics, residential zip code median income, body mass index, and, for the total sample, TUD-status. Outcomes were encounter diagnosis (yes/no) of cerebrovascular accident (CVA), heart arrhythmia, myocardial infarction, subarachnoid hemorrhage (SAH), and all-cause mortality. Results TUD-patients had the greatest prevalence of cardiovascular disease, regardless of cannabis-use indication. In the total sample and non-TUD subgroup, regular cannabis use was significantly associated with greater risk for CVA, arrhythmia, SAH, and mortality. In the TUD subgroup, regular cannabis use was significantly associated with greater risk for arrhythmia and SAH. Conclusions Cannabis use is associated with significantly greater risk of adverse cardiovascular diagnoses and overall death, particularly in non-tobacco users.

The role of bias-based bullying in regular cannabis use among adolescents.

DRD2 and DRD4 in relation to regular alcohol and cannabis use among adolescents: Does parenting modify the impact of genetic vulnerability? The TRAILS study

Cannabis is the most widely used illicit drug worldwide, though it is unclear whether its regular use is associated with persistent alterations in brain morphology. This review examines evidence from human structural neuroimaging investigations of regular cannabis users and focuses on achieving three main objectives. These include examining whether the literature to date provides evidence that alteration of brain morphology in regular cannabis users: i) is apparent, compared to non-cannabis using controls; ii) is associated with patterns of cannabis use; and with iii) measures of psychopathology and neurocognitive performance. The published findings indicate that regular cannabis use is associated with alterations in medial temporal, frontal and cerebellar brain regions. Greater brain morphological alterations were evident among samples that used at higher doses for longer periods. However, the evidence for an association between brain morphology and cannabis use parameters was mixed. Further, there is poor evidence for an association between measures of brain morphology and of psychopathology symptoms/neurocognitive performance. Overall, numerous methodological issues characterize the literature to date. These include investigation of small sample sizes, heterogeneity across studies in sample characteristics (e.g., sex, comorbidity) and in employed imaging techniques, as well as the examination of only a limited number of brain regions. These factors make it difficult to draw firm conclusions from the existing findings. Nevertheless, this review supports the notion that regular cannabis use is associated with alterations of brain morphology, and highlights the need to consider particular methodological issues when planning future cannabis research.