Chronic Cannabis Users Research Articles

Multimodal examination of daily stress rhythms in chronic Cannabis users.

Chronic cannabis users frequently report stress relief as their primary reason for use. The endocannabinoid system is involved in the neuroendocrine stress response, and diurnal cortisol rhythms may be disrupted in chronic cannabis users. The objectives were to determine whether cannabis users demonstrate disruptions in diurnal stress rhythms and examine the acute effects of cannabis on stress-related outcomes in cannabis users' natural environments. Eighty-two participants (39 cannabis users, 43 non-users) collected saliva samples to quantify cortisol concentrations and provided subjective stress ratings at 8 time points throughout the day. They wore a medical-grade wearable device for 24h that recorded physiological indicators of stress (heart rate variability, electrodermal activity). Cannabis users collected additional saliva samples before and after cannabis use to examine acute effects of cannabis use. Cannabis users exhibited significant dysregulations in diurnal cortisol rhythms, including a blunted cortisol awakening response, flattened diurnal cortisol slope, and elevated afternoon cortisol concentrations. There were no differences in diurnal heart rate variability or electrodermal activity except for elevated evening heart rate in cannabis users. Finally, there were significant decreases in cortisol, subjective stress, and electrodermal activity following acute cannabis use in cannabis users' natural environment. These results provide evidence of dysregulated diurnal cortisol rhythms in cannabis users that were related to later waking times and acute stress-relieving properties of cannabis use in naturalistic environments. Future research should examine the direction of the relationship between cannabis use and diurnal cortisol rhythms and potential implications for other psychological disorders.

Contesting Cannabinoid Hyperemesis Syndrome: How Narratives of Cannabis Shape Diagnosis Contestation and Treatment Resistance.

Cannabinoid hyperemesis syndrome (CHS) is characterized by the onset of cyclic bouts of severe nausea and vomiting in chronic cannabis users. As the number of CHS diagnoses rises, it is important to understand how people experience the disease. Using a narrative framework, we explore how the symbolic meaning participants associated with cannabis shaped the way they experienced diagnosis and treatment of CHS. To do this, we relied on semi-structured interviews with 24 people who self-reported having CHS. Participants had very positive perceptions of cannabis, which contributed to them contesting the diagnosis and resisting the treatment. They initially contested the diagnosis because they believed that cannabis was beneficial and helped with nausea, that claims about the harms of cannabis were part of a larger medical conspiracy to stigmatize it, and that they had different symptoms than those with CHS. They resisted treatment recommendations of abstinence and sought to continue using cannabis by trying new routes of administration, using only certain types of cannabis, reducing the amount or frequency of use, or substituting other substances. Findings point to the importance of understanding how narratives can shape the way people respond to diagnosis and treatment.

Rare but relevant: Cannabinoid hyperemesis syndrome.

Cannabinoid hyperemesis syndrome (CHS) is a (probably) rare syndrome that occurs in frequent and chronic cannabis users. It is characterised by cyclical vomiting and gastrointestinal symptoms. CHS is frequently misdiagnosed resulting in extensive investigations and delayed diagnosis and treatment. Standard anti-emetic treatments are typically not effective, and no standardised treatment protocol exists for CHS. Bathing or showering in hot water is often reported to relieve symptoms. Little is known of the aetiology of CHS as the literature is predominantly informed by case reports and chart reviews. Similarly, little is known of the demographics and cannabis use patterns of those who develop CHS. The number of CHS cases globally appears to have risen following liberalisation of cannabis regulation and access in some countries, underscoring the need for wider recognition of CHS in emergency care and by the wider public.

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

Cannabis is the most widely used psychoactive drug in the United States. While multiple studies have associated acute cannabis consumption with alterations in cognitive function (e.g., visual and spatial attention), far less is known regarding the effects of chronic consumption on the neural dynamics supporting these cognitive functions. We used magnetoencephalography (MEG) and an established visuospatial processing task to elicit multi-spectral neuronal responses in 44 regular cannabis users and 53 demographically matched non-user controls. To examine the effects of chronic cannabis use on the oscillatory dynamics underlying visuospatial processing, neural responses were imaged using a time-frequency resolved beamformer and compared across groups. Neuronal oscillations serving visuospatial processing were identified in the theta (4-8 Hz), alpha (8-14 Hz), and gamma range (56-76 Hz), and these were imaged and examined for group differences. Our key results indicated that users exhibited weaker theta oscillations in occipital and cerebellar regions and weaker gamma responses in the left temporal cortices compared to non-users. Lastly, alpha oscillations did not differ, but alpha connectivity among higher-order attention areas was weaker in cannabis users relative to non-users and correlated with performance. Overall, these results suggest that chronic cannabis users have alterations in the oscillatory dynamics and neural connectivity serving visuospatial attention. Such alterations were observed across multiple cortical areas critical for higher-order processing and may reflect compensatory activity and/or the initial emergence of aberrant dynamics. Future work is needed to fully understand the implications of altered multispectral oscillations and neural connectivity in cannabis users.

Gynecomastia in chronic chronic cannabis cannabis users: mechanism mechanism of action and review of the literature

Gynecomastia in chronic chronic cannabis cannabis users: mechanism mechanism of action and review of the literature

The Impact of Chronic Cannabis Use on Esophageal Motility in Patients Referred for Esophageal Manometry.

Tetrahydrocannabinol, the main psychoactive compound in cannabis, binds with high affinity to the cannabinoid 1 receptor. Small randomized controlled studies using conventional manometry have shown that the cannabinoid 1 receptor can modulate esophageal function, namely transient lower esophageal sphincter relaxation frequency and lower esophageal sphincter tone. The effect of cannabinoids on esophageal motility in patients referred for esophageal manometry has not been fully elucidated using high-resolution esophageal manometry (HREM). We aimed to characterize the clinical effect of chronic cannabis use on esophageal motility utilizing HREM. Patients who underwent HREM from 2009 to 2019 were identified at 4 academic medical centers. The study group consisted of patients with a noted history of chronic cannabis use, a diagnosis of cannabis-related disorder, or a positive urine toxicology screen. Age and gender-matched patients with no history of cannabis use were selected to form the control group. Data on HREM metrics based on the Chicago classification V3, and the prevalence of esophageal motility disorders were compared. Confounding effects of BMI and medications on esophageal motility were adjusted for. Chronic cannabis use was found to be an independent negative predictor of weak swallows (β=-8.02, P =0.0109), but not a predictor of failed swallows ( P =0.6890). The prevalence of ineffective esophageal motility was significantly lower in chronic cannabis users compared with nonusers (OR=0.44, 95% CI 0.19-0.93, P =0.0384). There was no significant difference in the prevalence of other esophageal motility disorders between the 2 cohorts. In patients with dysphagia as their primary indication for HREM, chronic cannabis use was found to be independently associated with increased median integrated relaxation pressure (β=6.638, P =0.0153) and increased mean lower esophageal sphincter resting pressure (β=10.38, P =0.0084). Chronic cannabis use is associated with decreased weak swallows and reduced prevalence of ineffective esophageal motility in patients referred for esophageal manometry. In patients referred for dysphagia, chronic cannabis use is associated with increased integrated relaxation pressure and lower esophageal sphincter resting pressure, though not to levels above the normal range.

The neural oscillations serving task switching are altered in cannabis users.

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.

Association of Cannabis Use Disorder with Major Adverse Cardiac and Cerebrovascular Events in Older Non-Tobacco Users: A Population-Based Analysis.

Tobacco use disorder (TUD) adversely impacts older patients with established cardiovascular disease (CVD) risk. However, CVD risk in chronic habitual cannabis users without the confounding impact of TUD hasn't been explored. We aimed to determine the risk of major adverse cardiac and cerebrovascular events (MACCE) in older non-tobacco smokers with established CVD risk with vs. without cannabis use disorder (CUD). We queried the 2019 National Inpatient Sample for hospitalized non-tobacco smokers with established traditional CVD risk factors aged ≥65 years. Relevant ICD-10 codes were used to identify patients with vs. without CUD. Using multivariable logistic regression, we evaluated the odds of MACCE in CUD cohorts compared to non-CUD cohorts. Prevalence of CUD in the sample was 0.3% (28,535/10,708,815, median age 69), predominantly male, black, and non-electively admitted from urban teaching hospitals. Of the older patients with CVD risk with CUD, 13.9% reported MACCE. The CUD cohort reported higher odds of MACCE (OR 1.20, 95% CI 1.11-1.29, p < 0.001) compared to the non-CUD cohort. Comorbidities such as hypertension (OR 1.9) and hyperlipidemia (OR 1.3) predicted a higher risk of MACCE in the CUD cohort. The CUD cohort also had higher unadjusted rates of acute myocardial infarction (7.6% vs. 6%) and stroke (5.2% vs. 4.8%). Among older non tobacco smokers with known CVD risk, chronic cannabis use had a 20% higher likelihood of MACCE compared to those who did not use cannabis.

Risks associated with chronic cannabis use on opioid use, length of stay, and revision rate for patients undergoing posterior lumbar interbody fusion

BACKGROUND CONTEXTOpioids are commonly prescribed to treat spinal pain, especially those undergoing surgery. Cannabis has been suggested as an agent that can modulate opioid needs in these patients. PURPOSETo investigate the effect of cannabis use on perioperative opioid requirement and revision surgery rate in patients undergoing lumbar fusion. STUDY DESIGNRetrospective cross-sectional study. PATIENT SAMPLEA total of 48,499 patients from PearlDiver national database who underwent posterior lumbar interbody fusion. OUTCOME MEASURESOpioid-use rates, MME, length of stay, and revision rates. METHODSUsing PearlDiver, we identified patients for posterior lumbar interbody fusion (PLIF), cannabis use disorder, revision lumbar fusion, demographics, and comorbidities. Cannabis users and non-users were propensity matched for age, sex, and tobacco use. Pre and postoperative cumulative morphine milli equivalence (MME) were calculated. Opioid-use rates, MME, length of stay (LOS), and revision rates were compared using univariate analysis. Revision rates were compared using Kaplan-Meyer log-rank analysis, and logistic and cox regression. RESULTSOf 48,499 patients undergoing PLIF, 3.4% were identified as chronic cannabis users. They were younger, and more likely to be male and use tobacco. They had a higher rate and amount of opioid use within 90-days preoperatively, and 90- and 365-days postoperatively, after controlling for age, sex, and tobacco use. Cannabis users had longer LOS (4.4 vs 4.0 days), and a higher rate of revision surgery (6.9% vs 3.2%). Log-rank analysis, as well as logistic and cox regression confirmed an increased revision rate. Concurrent tobacco and cannabis use also had an additive effect on revision rate to 8.1%, compared with those who used only cannabis (5.4%) or tobacco (4.5%). CONCLUSIONSChronic cannabis use is associated with an increased preoperative and long-term postoperative opioid use, a longer length of stay, and an increased revision rate.

A - 93 The Impact of Motivation on Neuropsychological Performance in Chronic Cannabis Users.

Cannabis is one of the most widely used substances, and although the literature shows that it affects users' cognition, it is unclear how much that impact is affected by factors such as motivation. Previous studies utilizing validity measures showed that user motivation to perform well positively impacts California Verbal Learning Test - II performance, which was higher in cannabis users who completed it immediately after a motivational statement (Macher & Earleywine, 2012). In the present study, the authors altered the order of test administration to further delineate the role motivation plays in cannabis user performance on neuropsychological measures. Participants (48 cannabis users, 23 nonusers) completed a neuropsychological battery, including performance validity measures, with random assignment to a motivational or neutral condition. The test order was altered to evaluate whether a motivational statement had an effect on any subsequent test administered or a lasting effect throughout the battery. Analyses revealed significant differences in performance, with users in the motivational condition performing better than users in the neutral condition on the Block Design (p = 0.006, partial eta squared = 0.157) and Digit Symbol Coding (p = 0.011, partial eta squared = 0.137) subtests of the WAIS-III (both indicating large effect sizes). Nonusers in the neutral condition performed better than nonusers in the motivational condition on multiple subtests. Results indicate that cannabis users exposed to the motivational statement performed better than those given a neutral statement on several neuropsychological tests. Findings suggest that cannabis users can demonstrate better cognitive performance when sufficiently motivated.

Circulating Endocannabinoids and N-Acylethanolamines in Individuals with Cannabis Use Disorder-Preliminary Findings.

Endocannabinoids and related N-acylethanolamines (NAEs) are bioactive lipids with important physiological functions and putative roles in mental health and addictions. Although chronic cannabis use is associated with endocannabinoid system changes, the status of circulating endocannabinoids and related NAEs in people with cannabis use disorder (CUD) is uncertain. Eleven individuals with CUD and 54 healthy non-cannabis using control participants (HC) provided plasma for measurement by high-performance liquid chromatography-mass spectrometry of endocannabinoids (2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA)) and related NAE fatty acids (N-docosahexaenoylethanolamine (DHEA) and N-oleoylethanolamine (OEA)). Participants were genotyped for the functional gene variant of FAAH (rs324420, C385A) which may affect concentrations of AEA as well as other NAEs (OEA, DHEA). In overnight abstinent CUD, AEA, OEA and DHEA concentrations were significantly higher (31-40%; p < 0.05) and concentrations of the endocannabinoid 2-AG were marginally elevated (55%, p = 0.13) relative to HC. There were no significant correlations between endocannabinoids/NAE concentrations and cannabis analytes, self-reported cannabis use frequency or withdrawal symptoms. DHEA concentration was inversely related with marijuana craving (r = -0.86; p = 0.001). Genotype had no significant effect on plasma endocannabinoids/NAE concentrations. Our preliminary findings, requiring replication, might suggest that activity of the endocannabinoid system is elevated in chronic cannabis users. It is unclear whether this elevation is a compensatory response or a predating state. Studies examining endocannabinoids and NAEs during prolonged abstinence as well as the potential role of DHEA in craving are warranted.

Cannabis Users Require More Anesthetic Agents for General Anesthesia in Ambulatory Oral and Maxillofacial Surgery Procedures

The use of cannabis in the general population has steadily increased over recent years and there is limited literature regarding the anesthetic implications of chronic cannabis use, particularly in the setting of outpatient anesthesia. To determine whether chronic cannabis users undergoing deep sedation or general anesthesia during ambulatory procedures require more anesthetic agents than nonusers. A retrospective cohort study of subjects undergoing deep sedation or general anesthesia at the Oklahoma University Oral and Maxillofacial Surgery Clinic from January to December 2022 was performed. The inclusion criteria were duration of anesthetic procedure between 15 to 40minutes, use of propofol, fentanyl, ketamine, and midazolam, and extraction of at least 2 teeth. The exclusion criterion was patients undergoing adjunctive procedures other than extractions during sedation. Cannabis use status was grouped as users and nonusers. A user was defined as a subject who self-reported any regular use of cannabis. The primary outcome variable was the amount of intravenous anesthetic agents administered. Secondary outcome variables included the length of the procedure and the number of teeth extracted. Age, sex, and the senior-most resident involved in the sedation. IBM SPSS was utilized to perform descriptive statistics, paired t-tests, ANOVA, and multivariate linear regression. A level of significance of 5% (P<.05) was used for all analyses. Four hundred and ninety nine subjects were identified, 189 met the inclusion criteria, and 57 reported using cannabis. The mean age of nonusers was 28.2±7.8years and that of users was 26.6±6.4years (P=.09). Females represented 71.9% of nonusers and 72.7% of users. Cannabis users received significantly more propofol (117.5mg±71.3 vs 152.5mg±101.8; P=.004), midazolam (4.7mg±1.0 vs 5.1mg±1.5; P=.01), ketamine (40.2mg±15.7 vs 46.1mg±16.9; P=.01), and fentanyl (75.2μg±26.3 vs 88.6μg±32.8; P=.002) than nonusers, despite extracting a similar number of teeth (4.5±3.1 vs 4.4±3.5; P=.37) in a similar amount of time (25.5±7.3 vs 27.3±7.8; P=.06). Cannabis users required more propofol, midazolam, ketamine, and fentanyl than non-cannabis users during outpatient oral and maxillofacial surgery procedures.

Cannabinoid hyperemesis syndrome in pregnancy: Challenges and opportunities.

Antenatal cannabis consumption is common and associated with adverse perinatal outcomes, including low birthweight, pre-term birth and increased rates of admission to neonatal intensive care. Cannabinoid hyperemesis syndrome (CHS) comprises severe, cyclical episodes of vomiting, intractable nausea and abdominal pain observed in chronic cannabis users. CHS, particularly during pregnancy, poses a diagnostic dilemma with a tendency to be ineffectively managed secondary to reduced clinician awareness and a scarcity of available therapies. This clinical perspective explores the current literature on CHS in pregnancy, available pharmacotherapeutics, and recognises the current barriers to improving clinical care.

386. Fatty Acid Amide Hydrolase is Associated With Impulsiveness: A Pet Study in Overnight Abstinent Chronic Cannabis Users

386. Fatty Acid Amide Hydrolase is Associated With Impulsiveness: A Pet Study in Overnight Abstinent Chronic Cannabis Users

Chronic cannabis use alters dACC-striatal glutamatergic balance

Prefrontal and striatal glutamate plays an important role in modulating striatal dopamine levels and an imbalance in regional glutamate has been identified in several psychiatric conditions. We hypothesized that this imbalance also exists in cannabis use disorder (CUD). We recently quantified the difference in glutamate of dorsal anterior cingulate (dACC) and striatum regions in the frontostriatal pathway using proton MRS at baseline and on verified abstinent days 7 and 21 in chronic users of cannabis (n = 20) in comparison with age- and sex- matched non-using controls (n = 10). In addition, the Barratt Impulsiveness Scale-11 (BIS) was collected as a measure of inhibitory impulse control of the participants. We found that the difference in glutamate concentrations between the dACC and striatum (ΔdACC-strGlu) of the controls was significantly higher than that of cannabis users across the study timeline (F(1,28) = 18.32, p < 0.0005). The group difference was not affected by age, sex, or alcohol/cigarette consumption. On abstinent day 7, ΔdACC-strGlu was significantly correlated with the corresponding ΔdACC-strGABA among the users (r = 0.837, p < 0.00001). On day 21, ΔdACC-strGlu was negatively associated with monthly cannabis use days (Spearman's rho = −0.444, p = 0.05). Self-reported BIS and its subscales were significantly altered among the users compared to the controls across the study timeline (total F(1,28) = 7.0, p = 0.013; non-planning F(1,28) = 16.1, p < 0.0005; motor F(1,28) = 5.9, p = 0.022; cognitive F(1,28) = 6.1, p = 0.019). These data provide preliminary evidence that chronic cannabis use may lead to a dACC-striatal glutamate imbalance in conjunction with poor impulse control.

Chronic cannabis use and error awareness: The effect on learning from errors.

Cannabis 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. Thirty-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. While 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. It 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.

Cannabinoid Hyperemesis Syndrome - A Case Report of an uncommon condition

IntroductionThe increasing prevalence of cannabis use in the world requires awareness of cannabis-related disorders such as cannabinoid hyperemesis syndrome (CHS). CHS is characterized by cyclic episodes of nausea, vomiting and abdominal pain, affecting chronic cannabis users, who usually recur to hot showers to relief the symptoms. The pathophysiology underlying this syndrome is still unclear. Despite the well-established anti-emetic properties of cannabis, there is increasing evidence of its paradoxical effects on the gastrointestinal tract and central nervous system.ObjectivesThe authors pretend to inform the readers about the rare Cannabinoid Hyperemesis Syndrome (CHS).MethodsThe authors describe a case of a 22 years old patient with chronic cannabis use, cyclic and intractable nausea and vomiting, to bring to the attention that this condition exists and is underdiagnosed.ResultsCHS should be strongly considered in the differential diagnosis of persistent vomiting in patients who reports relief with hot showers. In the acute setting, supportive care with intravenous fluids, dopamine antagonists, topical capsaicin cream, and avoidance of narcotic medications has shown some benefit. However, cannabis cessation appears to be the best treatment.ConclusionsCHS prevalence will continue to rise in parallel with increasing worldwide cannabis use and potency. So, health professionals must be aware of this syndrome, its diagnosis, and treatment, to provide better care and avoid overlooking CHS. Further research is required to elicit the exact mechanism and additional therapies for this condition.Disclosure of InterestNone Declared

CANNABIS USE AND RISK OF FALLING IN OLDER ADULTS

Abstract The prevalence of cannabis use has significantly increased among US adults ≥ 50 years. However, the effect of chronic cannabis use on fall risk in older adults is unclear. A series of investigations were conducted to examine the intersection between cannabis use and fall risk in older adults. The findings indicated that: 1) Older (≥ 50 years) chronic cannabis users have a higher fall risk and walking impairments, 2) cannabis users might have a discrepancy between perceptual and physiological fall risk, and 3) chronic use of Δ-9-tetrahydrocannabinol (THC) might have negative influences on inhibitory control and brain activity. Future mechanistic (e.g., neuroimaging) investigations of the short- and long-term effects a variety of cannabis products (e.g., THC/CBD ratios, routes of administration) on cognitive/motor function, and fall incidence in older adults are suggested.

Long-Term Outcomes of Adolescent THC Exposure on Translational Cognitive Measures in Adulthood in an Animal Model and Computational Assessment of Human Data

Although perceived as relatively harmless and nonaddictive, adolescent cannabis use significantly increases the likelihood of developing cannabis use disorder in adulthood, especially for high-potency cannabis. Risky decision-making is associated with chronic cannabis use, but given confounds of human studies, it remains unclear whether adolescent cannabis exposure and Δ9-tetrahydrocannabinol (THC) potency specifically predicts risky decision-making or influences cognitive response to the drug later in life. To leverage a human data set of cannabis users and a rat model to evaluate the long-term outcomes of adolescent THC exposure on adult decision-making and impulse control. This translational rat study tested the link between adolescent THC exposure and adulthood decision-making. A reanalysis of a previously published dataset of human chronic cannabis users was conducted to evaluate decision-making phenotypes. Computational modeling assessed the human and animal results in a single framework. Data were collected from 2017 to 2020 and analyzed from 2020 to 2022. Decision-making was measured by the Iowa Gambling Task (IGT) and Rat Gambling Task (rGT). Impulse control was assessed in the rat model. Computational modeling was used to determine reward and punishment learning rates and learning strategy used by cannabis users and THC-exposed rats. Cell-specific molecular measures were conducted in the prefrontal cortex and amygdala. Of 37 participants, 24 (65%) were male, and the mean (SD) age was 33.0 (8.3) years. Chronic cannabis users (n = 22; mean [SE] IGT score, -5.182 [1.262]) showed disadvantageous decision-making compared with controls (n = 15; mean [SE] IGT score, 7.133 [2.687]; Cohen d = 1.436). Risky choice was associated with increased reward learning (mean [SE] IGT score: cannabis user, 0.170 [0.018]; control, 0.046 [0.008]; Cohen d = 1.895) and a strategy favoring exploration vs long-term gains (mean [SE] IGT score: cannabis user, 0.088 [0.012]; control, 0.020 [0.002]; Cohen d = 2.218). Rats exposed to high-dose THC but not low-dose THC during adolescence also showed increased risky decision-making (mean [SE] rGT score: vehicle, 46.17 [7.02]; low-dose THC, 69.45 [6.01]; high-dose THC, 21.97 [11.98]; Cohen d = 0.433) and elevated reward learning rates (mean [SE] rGT score: vehicle, 0.17 [0.01]; low-dose THC, 0.10 [0.01]; high-dose THC, 0.24 [0.06]; Cohen d = 1.541) during task acquisition. These animals were also uniquely susceptible to increased cognitive impairments after reexposure to THC in adulthood, which was correlated with even greater reward learning (r = -0.525; P < .001) and a shift in strategy (r = 0.502; P < .001), similar to results seen in human cannabis users. Molecular studies revealed that adolescent THC dose differentially affected cannabinoid-1 receptor messenger RNA expression in the prelimbic cortex and basolateral amygdala in a layer- and cell-specific manner. Further, astrocyte glial fibrillary acidic protein messenger RNA expression associated with cognitive deficits apparent with adult THC reexposure. In this translational study, high-dose adolescent THC exposure was associated with cognitive vulnerability in adulthood, especially with THC re-exposure. These data also suggest a link between astrocytes and cognition that altogether provides important insights regarding the neurobiological genesis of risky cannabis use that may help promote prevention and treatment efforts.

Cannabinoid hyperemesis syndrome in North America: evaluation of health burden and treatment prevalence.

Cannabinoid hyperemesis syndrome (CHS) is a poorly understood vomiting disorder associated with chronic cannabis use. To characterise patients experiencing CHS in North America and to obtain a population-based estimate of CHS treatment prevalence in Canada before and during the Covid-19 pandemic METHODS: Internet survey of 157 CHS sufferers in Canada and the United States. Administrative health databases for the province of Alberta (population 5 million) were accessed to measure emergency department (ED) visits for vomiting, with a concurrent diagnostic code for cannabis use. Three time periods of 1year were assessed: prior to recreational cannabis legalisation (2017-2018), after recreational legalisation (2018-2019) and during the first year of the Covid-19 pandemic (2020-2021). Problematic cannabis use (defined as a CUDIT-R score ≥8) was universal among the survey cohort, and 59% and 68% screening for moderate or worse anxiety or depression, respectively. The overall treatment prevalence of CHS across all ages increased from 15 ED visits per 100,000 population (95% CI, 14-17) prior to legalisation, to 21 (95% CI, 20-23) after legalisation, to 32 (95% CI, 31-35) during the beginning of the Covid-19 pandemic (p< 0.001). Treatment prevalence among chronic cannabis users was as high as 6 per 1000 in the 16-24 age group. Survey data suggest patients with CHS almost universally suffer from a cannabis use disorder, which has significant treatment implications. Treatment prevalence in the ED has increased substantially over a very short time period, with the highest rates seen during the Covid-19 pandemic.