Cannabis use and mood disorders: a systematic review.

Background: Problematic cannabis use is highly prevalent among people with mood disorders. This underscores the need to understand the effects of cannabis and cannabinoids in this population, especially considering legalization of recreational cannabis use. Objectives: We aimed to (1) systematically evaluate cross-sectional and longitudinal studies investigating the interplay between cannabis use, cannabis use disorder (CUD), and the occurrence of mood disorders and symptoms, with a focus on major depressive disorder (MDD) and bipolar disorder (BD) and; (2) examine the effects of cannabis on the prognosis and treatment outcomes of MDD and BD. Methods: Following PRISMA guidelines, we conducted an extensive search for English-language studies investigating the potential impact of cannabis on the development and prognosis of mood disorders published from inception through November 2023, using EMBASE, PsycINFO, PubMed, and MEDLINE databases. Results: Our literature search identified 3,262 studies, with 78 meeting inclusion criteria. We found that cannabis use is associated with increased depressive and manic symptoms in the general population in addition to an elevated likelihood of developing MDD and BD. Furthermore, we observed that cannabis use is linked to an unfavorable prognosis in both MDD or BD. Discussion: Our findings suggest that cannabis use may negatively influence the development, course, and prognosis of MDD and BD. Future well-designed studies, considering type, amount, and frequency of cannabis use while addressing confounding factors, are imperative for a comprehensive understanding of this relationship. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023481634.

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

BACKGROUND: 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). METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Evidence for sex differences in the impact of cytochrome P450 genotypes on early subjective effects of cannabis.

Early positive subjective effects of cannabis predict the development of cannabis use disorder (CUD). Genetic factors, such as the presence of cytochrome P450 genetic variants that are associated with reduced Δ9-tetrahydrocannabinol (THC) metabolism, may contribute to individual differences in subjective effects of cannabis. Young adults (N = 54) with CUD or a non-CUD substance use disorder (control) provided a blood sample for DNA analysis and self-reported their early (i.e., effects upon initial uses) and past-year positive and negative subjective cannabis effects. Participants were classified as slow metabolizers if they had at least one CYP2C9 or CYP3A4 allele associated with reduced activity. Though the CUD group and control group did not differ in terms of metabolizer status, slow metabolizer status was more prevalent among females in the CUD group than females in the control group. Slow metabolizers reported greater past year negative THC effects compared to normal metabolizers; however, slow metabolizer status did not predict early subjective cannabis effects (positive or negative) or past year positive effects. Post-hoc analyses suggested males who were slow metabolizers reported more negative early subjective effects of cannabis than female slow metabolizers. Other sex-by-genotype interactions were not significant. These initial findings suggest that genetic variation in CYP2C9 and CYP3A4 may have sex-specific associations with cannabis-related outcomes. Slow metabolizer genes may serve as a risk factor for CUD for females independent of subjective effects. Male slow metabolizers may instead be particularly susceptible to the negative subjective effects of cannabis.

Morning cannabis use in young adults: Associations with overall levels of use, negative consequences, and cannabis use disorder symptoms across 2.5 years.

BACKGROUND: Emerging research suggests morning cannabis use may be associated with using more cannabis and experiencing more cannabis-related consequences. This paper examined whether months when young adults reported morning cannabis use (use between 6:00AM and 12:00PM) were associated with cannabis use frequency, negative cannabis-related consequences, and changes in cannabis use disorder (CUD) symptoms. METHODS: Participants were 778 young adults (Mage=21.11 years, 58.5% female) enrolled in a longitudinal study on substance use and social role transitions. Eligible participants were 18-23 years old at screening and reported past-year alcohol use. Participants completed a baseline survey, 24 consecutive monthly surveys, and a follow-up survey 30 months after baseline. Aims were tested using multilevel models and multiple regression. RESULTS: Analyses were limited to cannabis use months (N=4719; 28.9% of sampled months) and participants who reported cannabis use at least once (N=542; 69.7% of all participants). Morning use was reported in 12.3% of cannabis use months and at least once by 23.6% of participants who reported using cannabis. Relative to non-morning use months, morning use months were associated with greater cannabis use frequency and more negative consequences. However, the association between morning use and negative consequences was not statistically significant after controlling for cannabis use frequency. The percentage of cannabis use months with morning use was positively associated with increased CUD symptoms at the 30-month follow-up, relative to baseline. CONCLUSIONS: Morning cannabis use may be a useful marker of high-risk cannabis use and may contribute to the maintenance and worsening of CUD over time.

The separate and joint effects of recent interpersonal abuse and cannabis use on psychotic experiences: findings from students in higher education in the United States.

BACKGROUND: Various forms of interpersonal abuse (e.g., physical, emotional, sexual) and cannabis use across the lifespan have both been known to increase odds of psychotic experiences; however, there have been few studies examining their separate and joint effects in the United States. METHODS: We analyzed data from the Healthy Minds Study (2020-2021) and used multivariable logistic regression and interaction contrast ratios to assess separate and joint effects of interpersonal abuse (past 12 months) and cannabis use (past 30 days) on psychotic experiences (past 12 months). RESULTS: Students who only used cannabis had significantly greater odds of psychotic experiences (aOR: 1.70; 95% CI 1.58-1.82), as well as those who only experienced interpersonal abuse (aOR: 2.40; 95% CI 2.25-2.56). However, those who reported both cannabis use and interpersonal abuse had the greatest odds, exceeding the sum of these individual effects (the combined effect aOR: 3.46; 95% CI 3.19-3.76). CONCLUSIONS: Recent interpersonal abuse and recent cannabis use both separately and jointly increase odds of having recent psychotic experiences. Future research should continue to examine the potential interactive and additive impact of multiple known exposures to better inform primary and secondary prevention efforts.

Assessing evidence supporting cannabis harm reduction practices for adolescents at clinical high-risk for psychosis: a review and clinical implementation tool.

Cannabis use is consistently associated with both increased incidence of frank psychotic disorders and acute exacerbations of psychotic symptoms in healthy individuals and people with psychosis spectrum disorders. Although there is uncertainty around causality, cannabis use may be one of a few modifiable risk factors for conversion to psychotic disorders in individuals with Clinical High Risk for Psychosis (CHR-P) syndromes, characterized by functionally impairing and distressing subthreshold psychotic symptoms. To date, few recommendations beyond abstinence to reduce adverse psychiatric events associated with cannabis use have been made. This narrative review synthesizes existing scientific literature on cannabis' acute psychotomimetic effects and epidemiological associations with psychotic disorders in both CHR-P and healthy individuals to bridge the gap between scientific knowledge and practical mental health intervention. There is compelling evidence for cannabis acutely exacerbating psychotic symptoms in CHR-P, but its impact on conversion to psychotic disorder is unclear. Current evidence supports a harm reduction approach in reducing frequency of acute psychotic-like experiences, though whether such interventions decrease CHR-P individuals' risk of conversion to psychotic disorder remains unknown. Specific recommendations include reducing frequency of use, lowering delta-9-tetrahydrocannabinol content in favor of cannabidiol-only products, avoiding products with inconsistent potency like edibles, enhancing patient-provider communication about cannabis use and psychotic-like experiences, and utilizing a collaborative and individualized therapeutic approach. Despite uncertainty surrounding cannabis' causal association with psychotic disorders, cautious attempts to reduce acute psychosis risk may benefit CHR-P individuals uninterested in abstinence. Further research is needed to clarify practices associated with minimization of cannabis-related psychosis risk.

Cannabis use Disorder and Complications After Anterior Cervical Diskectomy and Fusion.

OBJECTIVE: The aim of this study, a retrospective database analysis, was to assess the impact of baseline cannabis use disorder (CUD) on perioperative complication outcomes in patients undergoing primary 1- to 2-level anterior cervical diskectomy and fusion (ACDF) surgery. METHODS: The PearlDiver Database was queried from January 2010 to December 2021 for patients who underwent primary 1- to 2-level ACDF surgery for degenerative spine disease. Patients with CUD diagnosis 6 months before the index ACDF surgery (i.e., CUD) were propensity matched with patients without CUD (i.e., control in a ratio of 1:1, employing age, gender, and Charlson Comorbidity Index as matching covariates). Univariate and multivariable analysis models with adjustment of confounding variables were used to evaluate the risk of CUD on perioperative complications between the propensity-matched cohorts. RESULTS: The 1:1 matched cohort included 838 patients in each group. Following multivariate analysis, CUD was demonstrated to be associated with an increased incidence of hospital readmission at 90 days (odds ratio [OR] = 2.64, 95% confidence interval: [1.19 to 6.78], [P = 0.027]) and revision surgery at 1 year postoperative (OR = 3.36, 95% confidence interval: [1.17 to 14.18], [P = 0.049]). CUD was additionally associated with reduced risk of overall medical complications at both 6 months and 1 year postoperative (OR = 0.55, [P = 0.021], and OR = 0.54, [P = 0.015], respectively). CONCLUSIONS: These findings indicate that isolated baseline CUD is associated with an increased risk of hospital readmission at 90 days postoperative and cervical spine reoperation at 1 year after primary 1- to 2-level ACDF surgery with a decrease in overall medical complications, cardiac arrhythmias, and acute renal failure.

Cannabis use disorder and adverse cardiovascular outcomes: A population-based retrospective cohort analysis of adults from Alberta, Canada.

AIM: To measure the association between cannabis use disorder (CUD) and adverse cardiovascular disease (CVD) outcomes. DESIGN AND SETTING: We conducted a matched, population-based retrospective cohort study involving five linked administrative health databases from Alberta, Canada. PARTICIPANTS: We identified participants with CUD diagnosis codes and matched them to participants without CUD codes by gender, year of birth and time of presentation to the health system. We included 29 764 pairs (n = 59 528 individuals in total). MEASUREMENTS: CVD events were defined by at least one incident diagnostic code within the study period (1 January 2012-31 December 2019). Covariates included comorbidity, socio-economic status, prescription medication use and health service use. Using mortality-censored Poisson regression models, we computed survival analyses for time to incident CVD stratified by CUD status. In addition, we calculated crude and stratified risk ratios (RRs) across various covariates using the Mantel-Haenszel technique. FINDINGS: The overall prevalence of documented CUD was 0.8%. Approximately 2.4% and 1.5% of participants in the CUD and unexposed groups experienced an incident adverse CVD event (RR = 1.57; 95% confidence interval = 1.40-1.77). CUD was significantly associated with reduced time to incident CVD event. Individuals who appeared to have greater RRs for incident CVD were those without mental health comorbidity, who had not used health-care services in the previous 6 months, who were not on prescription medications and who did not have comorbid conditions. CONCLUSIONS: Canadian adults with cannabis use disorder appear to have an approximately 60% higher risk of experiencing incident adverse cardiovascular disease events than those without cannabis use disorder.

Randomized controlled trial of zolpidem as a pharmacotherapy for cannabis use disorder.

BACKGROUND: Sleep disturbance is commonly reported among individuals meeting criteria for cannabis use disorder (CUD), and people who use cannabis frequently report sleep disturbance as a contributor to failed quit attempts. The purpose of this study was to measure sleep in individuals enrolled in treatment for CUD, and to determine whether use of hypnotic medication during treatment increased abstinence rates. METHOD: The study enrolled 127 adults seeking treatment for CUD in a 12-week clinical trial and randomized to receive extended-release zolpidem (zolpidem-XR) or placebo. All participants received computerized behavioral therapy and abstinence-based contingency management. The study conducted in-home ambulatory polysomnography (PSG) assessments at baseline and during treatment to objectively measure sleep. Self-report measures of recent sleep, Insomnia Severity Index (ISI), and drug use (Timeline Follow-Back) were collected at each study visit, and the study confirmed self-reported abstinence via quantitative urine drug testing. RESULT: Participants randomized to placebo, but not zolpidem-XR exhibited significant sleep disturbance during week 1 of treatment. Sleep disturbance emerged in the zolpidem-XR group after study medication was stopped at the end of treatment. Though participants assigned to the zolpidem-XR condition had qualitatively greater rates of abstinence compared with placebo (27 % versus 15 % negative at end of treatment), the difference was not statistically significant. Treatment retention was poor (about 50 % drop out in both groups) and medication adherence was a challenge without the use of contingent incentives. CONCLUSION: Results from this randomized controlled trial suggest that zolpidem-XR can attenuate abstinence-induced sleep disturbance early in treatment for CUD, but that sleep problems are likely to emerge after the medication is stopped. Further research should identify alternative pharmacotherapies and behavioral treatments for CUD and elucidate the role of sleep disturbance in the development and maintenance of CUD.

Prevalence and impact of cannabis use disorder on acute ischemic stroke and subsequent mortality in elderly peripheral vascular disease patients: A population-based analysis in the USA (2016 - 2019).

BACKGROUND: Given current evidence linking peripheral atherosclerotic disease, also known as cannabis arteritis, and acute ischemic stroke (AIS) in individuals with cannabis use disorder (CUD), we investigated the frequency and implications of CUD in relation to AIS risk and outcomes among elderly patients with peripheral vascular disease (PVD). METHODS: The National Inpatient Sample (2016-2019) was used to compare geriatric patients with PVD and cannabis use disorder CUD. CUD was correlated with AIS admissions. Adjusted multivariable regression models assessed in-hospital mortality rates. RESULTS: Of 5,115,824 geriatric admissions with PVD, 50.6 % were male and 77.5 % were white. 21,405 admissions had cardiovascular and CUD co-occurrence. 19.7 % of CUD patients had diabetes mellitus (DM), compared to 33.7 % of non-CUD patients. Smoking and HTN rates were comparable between groups. Patients with CUD used more recreational drugs concurrently than those without CUD. AIS prevalence was 5.2 % in CUD patients and 4.0 % in controls (p < 0.001). In the geriatric population with PVD, the presence of CUD was found to be associated with increased odds of hospitalizations due to AIS, with an adjusted odds ratio (aOR) of 1.34 (95 % confidence interval [CI] 1.18-1.52, p < 0.001). All-cause in-hospital mortality was not statistically significant, with an aOR of 0.71 (95 %CI 0.36-1.37, p = 0.302). In our study, older patients with PVD and hypertension (aOR 1.73) had a greater risk of AIS. Intriguingly, when we analyzed AIS predictors in elderly PVD patients with concurrent tobacco use disorder, we identified a counterintuitive protective effect (aOR 0.58, 95 % CI 0.42-0.79, p < 0.001). CONCLUSIONS: Our findings indicate that among geriatric patients with PVD and concurrent CUD, there is a notable 34 % risk of AIS. Importantly, this risk persists despite controlling for other CVD risk factors and substance use. Further investigations are warranted to elucidate and validate the intriguing phenomenon known as the smoker's paradox.

Cannabis Exposure and Adverse Pregnancy Outcomes Related to Placental Function.

Importance: Cannabis use is increasing among reproductive-age individuals and the risks associated with cannabis exposure during pregnancy remain uncertain. Objective: To evaluate the association between maternal cannabis use and adverse pregnancy outcomes known to be related to placental function. Design, Setting, and Participants: Ancillary analysis of nulliparous individuals treated at 8 US medical centers with stored urine samples and abstracted pregnancy outcome data available. Participants in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort were recruited from 2010 through 2013; the drug assays and analyses for this ancillary project were completed from June 2020 through April 2023. Exposure: Cannabis exposure was ascertained by urine immunoassay for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol using frozen stored urine samples from study visits during the pregnancy gestational age windows of 6 weeks and 0 days to 13 weeks and 6 days (visit 1); 16 weeks and 0 days to 21 weeks and 6 days (visit 2); and 22 weeks and 0 days to 29 weeks and 6 days (visit 3). Positive results were confirmed with liquid chromatography tandem mass spectrometry. The timing of cannabis exposure was defined as only during the first trimester or ongoing exposure beyond the first trimester. Main Outcome and Measure: The dichotomous primary composite outcome included small-for-gestational-age birth, medically indicated preterm birth, stillbirth, or hypertensive disorders of pregnancy ascertained by medical record abstraction by trained perinatal research staff with adjudication of outcomes by site investigators. Results: Of 10 038 participants, 9257 were eligible for this analysis. Of the 610 participants (6.6%) with cannabis use, 32.4% (n = 197) had cannabis exposure only during the first trimester and 67.6% (n = 413) had ongoing exposure beyond the first trimester. Cannabis exposure was associated with the primary composite outcome (25.9% in the cannabis exposure group vs 17.4% in the no exposure group; adjusted relative risk, 1.27 [95% CI, 1.07-1.49]) in the propensity score-weighted analyses after adjustment for sociodemographic characteristics, body mass index, medical comorbidities, and active nicotine use ascertained via urine cotinine assays. In a 3-category cannabis exposure model (no exposure, exposure only during the first trimester, or ongoing exposure), cannabis use during the first trimester only was not associated with the primary composite outcome; however, ongoing cannabis use was associated with the primary composite outcome (adjusted relative risk, 1.32 [95% CI, 1.09-1.60]). Conclusions and Relevance: In this multicenter cohort, maternal cannabis use ascertained by biological sampling was associated with adverse pregnancy outcomes related to placental dysfunction.