Altered cortical maturation in adolescent cannabis users with and without schizophrenia

Background: Preliminary reports have suggested a link between cannabis use and heart failure (HF); however, with inconclusive literature on the subject, there exists an unmet need for contemporary data on outcomes of HF patients with cannabis use. The rising prevalence of Heart Failure with Preserved Ejection Fraction (HFpEF) incited us to assess the impact of cannabis use disorder (CUD) on in-hospital outcomes of HFpEF using nationwide multicenter data. Methods: Adult admissions related to HFpEF with vs. without CUD were identified using the National Inpatient Sample (Oct 2015-Dec 2017). Demographically matched cohorts, HFpEF-CUD+ vs. HFpEF-CUD-, were obtained and compared for comorbidities and in-hospital outcomes. Multivariable regression analyses were performed after controlling for confounders (demographic/hospital characteristics, comorbidities and substance abuse) to assess the risk of adverse outcomes including all-cause mortality, arrhythmia (atrial fibrillation/flutter, ventricular arrhythmia & cardiac arrest) and stroke. Results: Of 3,835,473 HFpEF-related admissions, 10980 (0.3%) patients were cannabis users. Matched cohorts, CUD+ and CUD- were comparable for demographics (median age 55 vs. 54 years, >60% male, >80% white/black). The CUD+ cohort had a lower rate of comorbidities including hypertension (87.5% vs 88.5%), diabetes (33.7% vs 43.7%), hyperlipidemia (38.4% vs 42.1%), obesity (26.7% vs 36.2%), and renal failure (32.8% vs 39.8%) (Table 1). Despite a lower comorbidity burden, the CUD+ cohort was often admitted non-electively (95.2% vs. 92.8%) and had considerably higher odds of all-cause mortality (aOR 2.24, 95%CI:1.81-2.78), arrhythmia (aOR 1.15, 95%CI:1.05-1.25) and cardiac arrest (aOR 3.87, 95%CI: 2.88-5.21) (p<0.05) (Fig. 1). Conclusions: This nationwide multicenter analysis revealed HFpEF admissions in patients with CUD had a significantly higher risk of adverse in-hospital outcomes despite a lower CVD risk.

Cannabis use disorder (CUD) is common in youth, with elevated rates among youth with bipolar disorder (BD). Cannabis use among youth is also associated with anomalous neurostructural phenotypes. While neurophysiological mechanisms associated with cannabis use may contribute to these differences, genetic predisposition to CUD may also be contributory. Given the lack of prior studies on this topic, we examined polygenic risk scores for CUD (CUD-PRS) in relation to brain structure among youth with and without BD. T1-weighted magnetic resonance imaging (MRI) was collected for 114 participants ages 13-20 (n = 67 BD, n = 47 healthy controls (HC)). CUD-PRS was calculated using PRS-CS-auto, based on summary statistics from a genome-wide association study conducted in adults. Covariate-adjusted vertex-wise analyses examined the association of CUD-PRS with cortical volume, surface area (SA), and thickness in the whole sample, and within BD and HC. In the whole sample, higher CUD-PRS was associated with significantly lower volume and SA in the right superior frontal gyrus (β = -0.31, p < 0.01; β = -0.33, p < 0.01), and with significantly lower SA in the left paracentral lobule (β = -0.37, p = 0.0002). Within HC, higher CUD-PRS was associated with significantly lower volume and SA in the left and right superior frontal gyrus (β = -0.78, p < 0.002; β = -0.66, p < 0.028; β = -0.79, p < 0.0001; β = -0.68, p < 0.0001). There were no significant within-BD results. Present findings demonstrate a consistent pattern of higher CUD-PRS corresponding with lower regional brain structure, even in the absence of CUD. Future studies are needed to understand the mechanisms, developmental trajectories, and diagnosis-related differences in the observed findings.

CANNABIS USE DISORDER: FRIEND OR FOE IN PULMONARY EMBOLISM AND ASSOCIATED MORTALITY IN YOUNG ADULTS (AGED 18-44 YEARS)?

BackgroundIn the United States, both cannabis use disorder (CUD) and opioid use disorder (OUD) have increased in prevalence. The prevalence, demographics, and costs of CUD and OUD are not well known in heart failure (HF) admissions. This study aimed to use a national database to examine the prevalence, demographics, and costs associated with CUD and OUD in HF.MethodsThis study used the National Inpatient Sample from 2008 to 2018 to identify all primary HF admissions with and without the co-diagnosis of OUD or CUD using International Classification for Diagnosis, diagnosis codes. Demographics, costs, and trends were examined.ResultsBetween 2008 and 2018, we identified 11,692,995 admissions for HF of which 84,796 (0.8%) had a co-diagnosis of CUD only, and 67,137 (0.6%) had a co-diagnosis of OUD only. The proportion of HF admissions with CUD significantly increased from 0.3% in 2008 to 1.3% in 2018 (p<0.001). The proportion of HF admissions with OUD significantly increased from 0.2% in 2008 to 1.1% in 2018 (p<0.001). Patients admitted with HF and either CUD or OUD were younger, more likely to be Black, and from lower socioeconomic backgrounds (p<0.001, all). HF admissions with OUD or CUD had higher median costs compared to HF admissions without associated substance abuse diagnoses ($8,611 vs. $8,337 for CUD HF and $10,019 vs. $8,337 for OUD HF, p<0.001 for both).ConclusionsAmong discharge records for HF, CUD and OUD are increasing in prevalence, significantly affect underserved populations and are associated with higher costs of stay. Future research is essential to better delineate the cause of these increased costs and create interventions, particularly in underserved populations.

Posttraumatic stress disorder (PTSD) is the most highly co-occurring psychiatric disorder among veterans with cannabis use disorder (CUD). Despite some evidence that cannabis use prospectively exacerbates the course of PTSD, which in turn increases the risk for CUD, the causal nature of the relationship between cannabis and psychiatric comorbidity is debated. The longitudinal relationship between PTSD diagnosis and traumatic intrusion symptoms with cannabis use and CUD was examined using cross-lagged panel model (CLPM) analysis. Prospective data from a longitudinal observational study of 361 veterans deployed post-9/11/2001 included PTSD and CUD diagnoses, cannabis use, and PTSD-related traumatic intrusion symptoms from the Inventory of Depression and Anxiety Symptoms. A random intercept CLPM analysis that leveraged three waves (baseline, 6 months and 12 months) of cannabis use and PTSD-related intrusion symptoms to account for between-person differences found that baseline cannabis use was significantly positively associated with 6-month intrusion symptoms; the converse association was significant but reduced in magnitude (baseline use to 6-month intrusions: β = 0.46, 95% CI 0.155-0.765; baseline intrusions to 6-month use: β = 0.22, 95% CI -0.003 to 0.444). Results from the two-wave CLPM reveal a significant effect from baseline PTSD to 12-month CUD (β = 0.15, 95% CI 0.028-0.272) but not from baseline CUD to 12-month PTSD (β = 0.12, 95% CI -0.022 to 0.262). Strong prospective associations capturing within-person changes suggest that cannabis use is linked with greater severity of trauma-related intrusion symptoms over time. A strong person-level directional association between PTSD and CUD was evident. Findings have significant clinical implications for the long-term effects of cannabis use among individuals with PTSD.

Although they often co-occur, the longitudinal relationship between depression and substance use disorders during adolescence remains unclear. This study estimated the effects of cumulative depression during early adolescence (ages 13-15years) on the likelihood of cannabis use disorder (CUD) and alcohol use disorder (AUD) at age 18. Prospective cohort study of youth assessed at least annually between 6th and 9th grades (~ age 12-15) and again at age 18. Marginal structural models based on a counterfactual framework that accounted for both potential fixed and time-varying confounders were used to estimate cumulative effects of depressive symptoms over early adolescence. The sample originated from four public middle schools in Seattle, Washington, USA. The sample consisted of 521 youth (48.4% female; 44.5% were non-Hispanic White). Structured in-person interviews with youth and their parents were conducted to assess diagnostic symptom counts of depression during early adolescence; diagnoses of CUD and AUD at age 18 was based the Voice-Diagnostic Interview Schedule for Children. Cumulative depression was defined as the sum of depression symptom counts from grades 7-9. The past-year prevalence of cannabis and alcohol use disorder at the age 18 study wave was 20.9 and 19.8%, respectively. A 1 standard deviation increase in cumulative depression during early adolescence was associated with a 50% higher likelihood of CUD [prevalence ratio (PR)=1.50; 95% confidence interval (CI)=1.07, 2.10]. Although similar in direction, there was no statistically significant association between depression and AUD (PR=1.41; 95% CI=0.94, 2.11). Further, there were no differences in associations according to gender. Youth with more chronic or severe forms of depression during early adolescence may be at elevated risk for developing cannabis use disorder compared with otherwise similar youth who experience fewer depressive symptoms during early adolescence.

Integrated cognitive behavioral therapy for cannabis use and anxiety disorders: Rationale and development

Associations of cannabis use, use frequency, and cannabis use disorder with violent behavior among young adults in the United States

To evaluate the relative contributions of peers cannabis use or non use, parental approval of such use, adolescents' own beliefs about use, self-esteem, and depressive and symptoms of borderline personality disorder, in the prediction of cannabis use and dependence. Participants were 257 high-school students who completed questionnaires assessing cannabis use frequency, cannabis dependence, the number of peers using cannabis, the number of peers opposed to cannabis use, parental attitude toward cannabis use, participants' attitude toward use, self-esteem, depressive and borderline symptomatology. Logistic regression analyses were conducted to predict cannabis use, daily use and dependence. The number of peers using cannabis, participants' approval of cannabis use, and the intensity of symptoms of borderline personality disorder were risk factors for use whereas the number of peers opposed to cannabis use was a protective factor. Parental attitudes toward use and participants' depressive symptomatology were not significant independent predictors of use. There were no significant predictors of probable cannabis dependence. To inform adolescents that a significant proportion of them disapprove of cannabis use may be an effective component of prevention of use. Symptoms of borderline personality disorder may account for the association between depression and cannabis use. The social influences and psychopathological factors evaluated in this study did not appear to play a major role in the development of cannabis dependence.

Background: With the growing trends in recreational marijuana use, our study aims at analyzing the association between acute coronary syndromes (ACS) and ventricular fibrillation (Vfib) and cannabis use disorder in young adults (18–45). Methods: Young adult hospitalizations (18–45 years) with documented ACS/ventricular fibrillation and documented cannabis use were identified from the National Inpatient Sample (2019). Primary outcomes included prevalence and odds of ACS/ventricular fibrillation with cannabis use disorder. Patient factors that held significant association with adverse cardiovascular events in young cannabis users were studied. Propensity scoring and neighbor matching were used to compare resource utilization and in-hospital outcomes in the study population. Results: Among young patients (18–45) admitted for ACS, documented cannabis use disorder (CUD) had a statistically significant association with an odds ratio of 2.29 (2.48–3.04) after adjusting for age, sex, race, household income, smoking, cocaine use, uncontrolled hypertension, diabetes and hyperlipidemia. Documented CUD had a significant association with ventricular fibrillation in the population with an odds ratio of 2.29 (1.51–3.49) after adjusting for the above-mentioned factors. Among admissions with documented CUD, patient factors that held significant association with admitting diagnosis of ACS/Vfib were: black race (OR: 1.73), uncontrolled hypertension (OR: 4.08) and diabetes (OR: 2.45). Propensity-matched cohorts with documented CUD and ACS had significantly higher mean length of hospital stay 3.28 (2.98–3.53) days when compared to the cohort without documented CUD, 2.69 (2.32–2.82) days. The mean of total hospital charges was higher in the cohort with documented CUD at $92,390.64 (92,240.31–92,445.76) compared to $90,886.44 (89,932.21–91,042.56) in the cohort without cannabis use disorder. Conclusions: Documented diagnosis of cannabis use disorder had statistically significant association with admission diagnosis of ACS/Vfib even after accounting for confounders. A documented race as black and co-existing diagnosis of uncontrolled hypertension and diabetes had a significant association with admission diagnosis of ACS in the population with documented cannabis use disorder. Propensity-matched cohorts with cannabis use disorder with the main admitting diagnosis of ACS/Vfib were associated with a higher mean length of hospital stay and a higher mean of total charges compared to the matched cohorts without documented cannabis use disorder.

Parental cannabis use disorder (CUD) and low positive parenting (monitoring, support, and consistency) are risk factors for adolescent cannabis use. However, it is unclear whether parental cannabis use without CUD is sufficient to increase risk for low positive parenting and adolescent cannabis use. Additionally, parents may not treat each of their adolescents the same, and risk for adolescent cannabis use may increase as a result of low levels of positive parenting in families or low positive parenting unique to each adolescent. The current study prospectively tested low positive parenting as a mediator of the relation between parental cannabis use history (with parental cannabis use and CUD considered separately) and adolescent cannabis use at the family level and individual level. Participants were 363 adolescents from a multigenerational longitudinal study who reported on positive parenting when they were ages 9-16 (M = 11.6, SD = 1.40) and on cannabis use when they were ages 13-19 (M = 16.3, SD = 1.84). Parents reported on their own cannabis use and CUD. Results showed that parental CUD was associated with adolescent cannabis use (OR = 3.62, p = .047) but parental cannabis use without CUD was not, and only parental CUD predicted low positive parenting (B = -0.28, p < .05). Average levels of low positive parenting within a family partially mediated the association between parental CUD and offspring cannabis use. These findings suggest parental cannabis use alone may not impair parenting, but parental use that meets criteria for CUD does impair parenting. Additionally, average levels of positive parenting in families may be a mechanism underlying the intergenerational transmission of cannabis use. (PsycINFO Database Record

This study examined associations among cannabis use disorder (CUD), 12-step program participation, and cannabis and other drug use at baseline and 3- and 6-month follow-ups. Participants were age 50 or older in a study of veterans receiving medical management of alcohol and/or opioid withdrawal ( N = 171). Generalized estimating equations examined the extent to which time point, 12-step program participation, and CUD were associated with change in number of cannabis and non-cannabis drug use days. Also examined was whether having CUD was associated with 12-step program participation. From baseline through the 6-month follow-up, 12-step program participation increased, non-cannabis drug use decreased, and cannabis use remained stable. Twelve-step program participation at baseline was associated with better outcomes at follow-ups. Participants with CUD reported less 12-step program participation and more cannabis use days at follow-ups. Older adults with CUD may need other types of psychosocial treatments due to low participation in 12-step programs.

The objective of this study was to provide rates of cannabis use and dependence and risk factors, proposing a conditional path model for cannabis addiction. A subsample of adult participants from a Brazilian household survey was analyzed to estimate cannabis dependence. Estimation of prevalence rates and association between dependence and age of cannabis use initiation were performed. The conditional model was applied to investigate the mediation of depressive symptoms and alcohol consumption in the association of early cannabis use and dependence. Lifetime and last year cannabis use were 6.47% and 2.81%, respectively. Moderate and severe cannabis dependence were 0.74% and 0.18% in the population, and 26.47% and 6.38% among last year’s cannabis users. A Parallel Multiple Mediator Model revealed strong association between cannabis use initiation age and dependence, when depressive symptoms or alcohol consumption mediate this association. The proportion of cannabis users displaying dependence symptoms is elevated and it is associated with the age of cannabis use initiation. The results show the importance of primary prevention interventions, prioritizing the delay of cannabis and alcohol experimentation. Our findings can enrich the debate on drugs policies and legislation, reinforcing the need for stronger restrictions of adolescent drug access and ensuring its enforcement.

With the increase in popularity of cannabis and its use and the lack of large-scale data on cannabis use and venous thromboembolism and pulmonary embolism (PE), we used a nationally representative cohort of young adults (aged 18-44 years) to compare the odds of admissions and in-hospital mortality of PE with and without cannabis use disorder (CUD). Identified patients with PE using the National Inpatient Sample (2018) were compared for baseline, comorbidities, and outcomes. Multivariable regression analysis, adjusted for covariates, was used to compare the odds of PE in young patients with CUD (CUD+) versus those without (CUD-) and those with prior venous thromboembolism. Propensity score-matched analysis (1:6) was also performed to assess in-hospital outcomes. A total of 61 965 (0.7%) of 8 438 858 young adult admissions in 2018 were PE related, of which 1705 (0.6%) had CUD+. On both unadjusted (odds ratio, 0.80 [95% CI, 0.71-0.90]; P<0.001) and adjusted regression analyses, the CUD+ cohort had a lower risk of PE admission. The CUD+ cohort had fewer routine discharges (58.3% versus 68.3%) and higher transfers to short-term (7.9% versus 4.8%) and nursing/intermediate care (12.6% versus 9.5%) (P<0.001). The PE-CUD+ cohort of in-hospital mortality did not differ from the CUD- cohort. Propensity score-matched (1:6) analysis revealed comparable mortality odds with higher median hospital stay and cost in the CUD+ cohort. Young adults with CUD demonstrated lower odds of PE hospitalizations without any association with subsequent in-hospital mortality. The median hospital stay of the CUD+ cohort was longer, they were often transferred to other facilities, and they had a higher cost.

4 - Cannabis Abuse and Dependence