Chronic Cannabis users exhibit altered oscillatory dynamics and functional connectivity serving visuospatial processing.

Animal and cellular work has shown that central cannabinoid-1 receptors modulate neural oscillations in the gamma range (40 Hz), which may be important for normal perceptual and cognitive processes. In order to assess the effect of cannabinoids on broadband-frequency neural oscillations in humans, the current study examined the effect of chronic cannabis use on auditory steady-state responses (ASSRs) utilizing electroencephalography (EEG). Passive ASSRs were assessed using varying rates of binaural stimulation (auditory click-trains; 10-50 Hz in increments of 5 Hz; 80 dB SPL) in carefully screened cannabis users and controls. Chronic cannabis users (n=22; 12 h abstinence before study; positive 11-nor-9-carboxy-delta-9-tetrahydrocannabinol urine levels) and cannabis naïve controls (n=24) were evaluated. Time X frequency analyses on EEG data were performed using Fourier-based mean trial power (MTP) and phase-locking (inter-trial coherence; ITC). Transient ERPs to stimulus onset (auditory N100 components) were also evaluated. As predicted, a decrease in spectral power (MTP) at 40 Hz was observed in the cannabis group (p<0.018). No effects on phase-locking (ITC) or the N100 were observed. Further, within the cannabis group, lower 40 Hz power correlated with an earlier age of onset of cannabis use (p<0.04). These data suggest that chronic exposure to exogenous cannabinoids can alter the ability to generate neural oscillations, particularly in the gamma range. This is consistent with preclinical animal and cellular data, which may have implications for understanding the short- and long-term psychopharmacological effects of cannabis.

Opposing Effects of Cannabis Use on Late Auditory Repetition Suppression in Schizophrenia Patients and Healthy Control Subjects

Altered attentional control strategies but spared executive functioning in chronic cannabis users

BackgroundCannabis is the third most commonly used drug worldwide, with studies suggesting a deleterious effect on some aspects of performance monitoring. It is unknown, however, whether diminished error awareness influences adaptive behaviour in cannabis users. Therefore, this study examined the effect of error awareness on learning from errors in cannabis users.MethodsThirty-six chronic cannabis users (Mage = 23.81 years; female, 36%) and 34 controls (Mage = 21.53 years; female, 76%) completed a Go/No-Go task that allowed participants to learn from errors and adapt their behaviour. Multilevel models were specified to determine whether the effect of error awareness on learning from errors differs between cannabis users and controls, and whether cannabis-use measures predict error correction while accounting for error awareness.ResultsWhile error awareness and correction rates did not differ between the groups, there was a significant effect of age of use onset on error correction in cannabis users. Further, the effect of error awareness was dependent on age of onset, and cannabis use-related frequency and harm. That is, cannabis users reporting an earlier age of regular use or scoring higher on the cannabis use index were less likely to perform correctly following an aware error.ConclusionIt appears overall cannabis use might not be tightly coupled to behavioural indices of performance monitoring. There is evidence, however, that aspects of cannabis use predict impairments in learning from errors that may be associated with treatment outcomes.

Cannabis is increasingly used worldwide, yet its cardiovascular effects remain incompletely understood. Emerging evidence suggests that chronic cannabis use may contribute to coronary artery disease (CAD) through hemodynamic stress, endothelial dysfunction, and proinflammatory pathways. We present a report of two patients with significant CAD and long-term daily cannabis use, highlighting its potential role as a modifiable cardiovascular risk factor. We describe two patients with long-term daily cannabis use and significant CAD. The first was a 34-year-old man with minimal traditional cardiovascular risk factors who presented with acute chest pain and was found to have single-vessel disease with an 80% stenosis of the posterior left ventricular branch requiring percutaneous coronary intervention. The second was a 52-year-old man with hypertension, hyperlipidemia, and obesity who presented with exertional chest pain and was found to have severe multivessel disease requiring referral for coronary artery bypass grafting. Both patients reported daily cannabis use for over 17 years. The first case demonstrates significant CAD in a young adult with few conventional risk factors, suggesting cannabis as a potential contributing factor. The second case illustrates severe multivessel disease in a patient with traditional risk factors, where long-term cannabis exposure may have accelerated disease progression. These cases align with current epidemiologic and mechanistic evidence linking chronic cannabis use to endothelial dysfunction, oxidative stress, and atherogenesis. Clinicians should inquire about cannabis use during cardiovascular risk assessments and consider its potential contribution to CAD, particularly in younger adults or in patients with unexpectedly severe disease. While causality cannot be definitively established from case reports, these cases support the need for further research into the long-term cardiovascular effects of chronic cannabis use.

Introduction: Chronic cannabis use is associated with neuroanatomical alterations in the hippocampus. While adverse impacts of cannabis use are generally attributed to Δ9-tetrahydrocannabinol, emerging naturalistic evidence suggests cannabidiol (CBD) is neuroprotective and may ameliorate brain harms associated with cannabis use, including protection from hippocampal volume loss. This study examined whether prolonged administration of CBD to regular cannabis users within the community could reverse or reduce the characteristic hippocampal harms associated with chronic cannabis use.Materials and Methods: Eighteen regular cannabis users participated in an ∼10-week open-label pragmatic trial involving daily oral administration of 200 mg CBD, with no change to their ongoing cannabis use requested. Participants were assessed at baseline and post-CBD treatment using structural magnetic resonance imaging. Automated longitudinal hippocampal segmentation was performed to assess volumetric change over the whole hippocampus and within 12 subfields.Results: No change was observed in left or right hippocampus as a whole. However, left subicular complex (parasubiculum, presubiculum, and subiculum) volume significantly increased from baseline to post-treatment (p=0.017 uncorrected) by 1.58% (Cohen's d=0.63; 2.83% in parasubiculum). Heavy cannabis users demonstrated marked growth in the left subicular complex, predominantly within the presubiculum, and right cornu ammonis (CA)1 compared to lighter users. Associations between greater right subicular complex and total hippocampal volume and higher plasma CBD concentration were evident, particularly in heavy users.Conclusions: Our findings suggest a restorative effect of CBD on the subicular and CA1 subfields in current cannabis users, especially those with greater lifetime exposure to cannabis. While replication is required in a larger, placebo-controlled trial, these findings support a protective role of CBD against brain structural harms conferred by chronic cannabis use. Furthermore, these outcomes suggest that CBD may be a useful adjunct in treatments for cannabis dependence and may be therapeutic for a range of clinical disorders characterized by hippocampal pathology (e.g., schizophrenia, Alzheimer's disease, and major depressive disorder).

BackgroundPreclinical and human studies suggest that adolescent cannabis use may be associated with worse cognitive outcomes than adult cannabis use. We investigated the associations between chronic cannabis use and cognitive function in adolescent and adult cannabis users and controls. We hypothesised user-status would be negatively associated with cognitive function and this relationship would be stronger in adolescents than adults.MethodsAs part of the ‘CannTeen’ project, this cross-sectional study assessed cognitive performance in adolescent cannabis users (n = 76; 16–17-year-olds), adolescent controls (n = 63), adult cannabis users (n = 71; 26–29-year-olds) and adult controls (n = 64). Users used cannabis 1–7 days/week. Adolescent and adult cannabis users were matched on cannabis use frequency (4 days/week) and time since last use (2.5 days). Verbal episodic memory (VEM) was assessed using the prose recall task, spatial working memory (SWM) was assessed using the spatial n-back task, and response inhibition was assessed with the stop-signal task. Primary outcome variables were: delayed recall, 3-back discriminability, and stop signal reaction time, respectively.ResultsUsers had worse VEM than controls (F(1,268) = 7.423, p = 0.007). There were no significant differences between user-groups on SWM or response inhibition. Null differences were supported by Bayesian analyses. No significant interactions between age-group and user-group were found for VEM, SWM, or response inhibition.ConclusionsConsistent with previous research, there was an association between chronic cannabis use and poorer VEM, but chronic cannabis use was not associated with SWM or response inhibition. We did not find evidence for heightened adolescent vulnerability to cannabis-related cognitive impairment.

Regular cannabis is known to impact higher-order cognitive processes such as attention, but far less is known regarding cognitive flexibility, a component of executive function. Moreover, whether such changes are related to aberrations in the neural oscillatory dynamics serving flexibility remains poorly understood. Quantify the neural oscillatory dynamics serving cognitive flexibility by having participants complete a task-switching paradigm during magnetoencephalography (MEG). Probe whole-brain maps to identify alterations in chronic cannabis users relative to nonusers and determine how these alterations relate to the degree of cannabis use involvement. In all, 25 chronic cannabis users and 30 demographically matched nonuser controls completed neuropsychological testing, an interview regarding their substance use, a urinalysis, and a task switch paradigm during MEG. Time-frequency windows of interest were identified using a data-driven statistical approach and these were imaged using a beamformer. Whole-brain neural switch cost maps were computed by subtracting the oscillatory maps of the no-switch condition from the switch condition per participant. These were examined for group differences. Cannabis users had weaker theta switch cost responses in the dorsolateral and dorsomedial prefrontal cortices, while nonusers showed the typical pattern of greater recruitment during switch relative to no switch trials. In addition, theta activity in the dorsomedial prefrontal cortex was significantly correlated with cannabis use involvement. Cannabis users exhibited altered theta switch cost activity compared to nonusers in prefrontal cortical regions, which are critical for cognitive flexibility. This activity scaled with cannabis use involvement, indicating a link between cannabis use and aberrant oscillatory activity underlying cognitive flexibility.

Background: Acute appendicitis is the leading cause of surgical abdominal emergency in young patients. However, chronic cannabis use may alter pain perception and mask the severity of clinical presentation. We report the case of a young patient with misleading clinical signs despite generalized peritonitis. Case presentation: A 19-year-old male, chronic heavy smoker and cannabis user, was initially admitted for mild abdominal pain. After a first emergency visit, he was discharged home. One week later, he was readmitted with the same complaints. Laboratory tests revealed leukocytosis (19,000), elevated CRP (259 mg/L), renal failure, hypokalemia, and hyponatremia. CT scan showed massive intra-abdominal effusion and a borderline appendix (7 mm). Exploratory laparotomy revealed 3 liters of pus, false membranes, interloop abscesses, and both a perforated appendix and perforated Meckel’s diverticulum. An extended ileocecal resection with double stoma and abdominal drainage was performed. Postoperative recovery required intensive care unit (ICU) admission with a favorable outcome. Conclusion: Cannabis use may attenuate abdominal symptoms, delaying diagnosis and management of surgical emergencies. This case highlights the importance of detailed toxicological history in young patients.

Mismatch negativity in tobacco-naïve cannabis users and its alteration with acute nicotine administration

Many previous studies have reported that alcohol and cannabis produce additive psychomotor effects in acute combination, but few have explicitly tested whether chronic exposure to cannabis, in the absence of acute administration, alters the effects of alcohol on psychomotor performance. To test whether long-term cannabis use modulates the effects of alcohol on psychomotor skills and self-reported mood and sensation. Regular cannabis users (minimum: daily use for at least 3 years) and infrequent users (maximum: once-monthly use for at most 3 years) were matched for sex, age, alcohol intake and other drug use (14 participants in each group). Participants received alcohol (females 0.35 g/kg; males 0.45 g/kg) and placebo drinks. By urinalysis, only regular users tested positive for metabolites of Delta(9)-tetrahydrocannabinol; breath alcohol levels were similar between groups. Participants were tested on a computerised tracking task that has been used to screen drugs for adverse effects on driving. The task involved tracking a moving target on a computer screen while simultaneously responding to occasional presentations of stimuli in the periphery of the screen. Tracking accuracy was similar for both groups after placebo, but alcohol caused a significant deterioration in performance among infrequent cannabis users relative to regular users. These changes were mirrored by significant changes in self-reported scores for dizziness, measured by visual analogue scales. Alcohol slowed reaction times, but not differentially between groups. For psychomotor skills relevant to driving, chronic cannabis use (in the absence of acute administration) does not potentiate the effects of alcohol. In fact, the superior tracking accuracy of regular users relative to infrequent users after alcohol, and their lower scores for dizziness, suggest that chronic cannabis use may instead confer cross-tolerance to specific effects of alcohol on behaviour.

Rationale: Cannabis use is increasing worldwide, especially among older individuals at risk for chronic ischemic heart disease (IHD). However, little is known about the arrhythmic effects of cannabis use in IHD. Accordingly, we prospectively assessed the relationship between cannabis use, heart rate (HR), and arrhythmias in healthy age-matched controls and subjects with IHD. Methods: Healthy controls (n=37, 57% men) and subjects with IHD (myocardial infarction ≥3 months ago; n=24, 58% men) who used cannabis wore a Zio® (iRhythm Technologies) monitor for 14 days. Noncannabis using ischemic subjects (n=35, 51% males) wore Zio monitors for standard clinical indications. Baseline HR was compared with average HR measured for 4 h following consumption and changes in HR and frequency of arrhythmias were correlated with cannabis use. Results: In controls, HR increased 20 min (4.99±6.7 bpm, p=0.08) after use, then declined 4 h following use (-7.4±7.7, p<0.001). Conversely, subjects with IHD showed minimal HR increase (1.6±3.9 bpm) and blunted HR decline (-3.4±5.6 bpm, p<0.001). Supraventricular tachycardia (SVT) (29.7% vs. 58.3%; p=0.04) and nonsustained ventricular tachycardia (NSVT) (5.6% vs. 47.8%, p=0.01) were the most frequently occurring arrhythmias in controls and IHD subjects, respectively. Incidence of SVT decreased as cannabis use increased in both groups. Conversely, NSVT tended to increase with increased use in controls, and was significantly more prevalent in IHD. However, overall arrhythmia burden did not differ between cannabis users and nonusers with IHD. Conclusion: Our findings demonstrate that chronic cannabis use is associated with only mild HR changes, which are blunted in IHD. In addition, our data suggest that among cannabis users, arrhythmias are more frequent in IHD subjects that in healthy subjects.

Introduction: Chronic cannabis use has been associated with impaired cognition and elevated psychological symptoms, particularly psychotic-like experiences. While Δ9-tetrahydrocannabinol (THC) is thought to be primarily responsible for these deleterious effects, cannabidiol (CBD) is purported to have antipsychotic properties and to ameliorate cognitive, symptomatic, and brain harms in cannabis users. However, this has never been tested in a prolonged administration trial in otherwise healthy cannabis users. Here, we report the first study of prolonged CBD administration to a community sample of regular cannabis users in a pragmatic trial investigating potential restorative effects of CBD on psychological symptoms and cognition.Materials and Methods: Twenty frequent cannabis users (16 male, median age 25 years) underwent a 10-week open-label trial of 200 mg of daily oral CBD treatment, while continuing to use cannabis as usual. The majority of participants were daily cannabis users who had used cannabis for several years (median 5.5 years of regular use). Participants underwent psychological and cognitive assessments at baseline (BL) and post-treatment (PT) and were monitored weekly throughout the trial.Results: CBD was well tolerated with no reported side effects; however, participants retrospectively reported reduced euphoria when smoking cannabis. No impairments to cognition were found, nor were there deleterious effects on psychological function. Importantly, participants reported significantly fewer depressive and psychotic-like symptoms at PT relative to BL, and exhibited improvements in attentional switching, verbal learning, and memory. Increased plasma CBD concentrations were associated with improvements in attentional control and beneficial changes in psychological symptoms. Greater benefits were observed in dependent than in nondependent cannabis users.Conclusions: Prolonged CBD treatment appears to have promising therapeutic effects for improving psychological symptoms and cognition in regular cannabis users. Our findings require replication given the lack of a placebo control in this pragmatic trial, but suggest that CBD may be a useful adjunct treatment for cannabis dependence.

Cannabis, as the most widely used illicit substance in the world, also remains among the most frequently used psychoactive substances by patients with schizophrenia. It is well known that cannabis use in schizophrenia patients favors relapse, resistance to antipsychotic treatments and therefore more frequent hospitalizations. However, many studies report considerable improvement in cognitive performance in substance users, while others show the opposite. Hence, the aim of our study is to examine the relationship between schizophrenia and cannabis use in clinical and socio-de- mographic aspects. This is a cross-sectional study of patients with schizophrenia hospitalized for relapse at the Ar-Razi psychiatric hospital in Salé, Morocco. A questionnaire was established in order to search for socio- demographic data, evolutionary and prognostic criteria of the disease. Cannabis use was assessed using the Cannabis Abuse Screening Test (CAST), for the severity of schizophrenia symptoms we used the Positive And Negative Syndrome Scale (PANSS) and for perceptual and memory abilities we used the numerical version of the Rey's Complex Figure-A (RCF-A). It was found that in a sample of 115 schizophrenic patients, 47.82% (n=55) were cannabis users. The mean PANSS (negative) and (general psychopathology) scores of non-cannabis users were significantly higher than those of cannabis users with P values of (P&lt;0.001) and (P&lt;0.005) respectively. For the numerical assessment scores of the RCF-A, cannabis users had a significantly higher mean score than non-cannabis users (copy phase (P&lt;0.016) and memory (P&lt;0.001) As one of the leading risk factors for the emergence of schizophre- nia, chronic cannabis use also has a negative influence on the prognosis of patients already suffering from schizophrenia. Nevertheless, the results of our study show that cannabis-using schizophrenic patients had fewer negative symptoms according to the PANSS and an improved cognitive performance compared to non- cannabis-using patients.

With the increase in use of cannabis and its shifting legal status in the United States, cannabis use has become an important research focus. While studies of other drug populations have shown marked increases in risky decision-making, the literature on cannabis users is not as clear. The current study examined the performance of 17 cannabis users and 14 non-users on the Balloon Analog Risk Task (BART) using behavioral, fMRI and effective connectivity methods. Significant attenuation was found in a functional pathway projecting from the dorsal anterior cingulate cortex (dACC) to the nucleus accumbens (NAc) in cannabis users compared to non-using controls as well as decreases in risk-taking behaviors. These findings suggest that cannabis users may process and evaluate risks and rewards differently than non-users.