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Item A national population-based study of cannabis use and correlates among U.S. veterans prescribed opioids in primary care(BMC, 2023-03-17) Zaman, Tauheed; Bravata, Dawn M.; Byers, Amy L.; Krebs, Erin E.; Leonard, Samuel J.; Sandbrink, Friedhelm; Barker, Wylie; Keyhani, Salomeh; Medicine, School of MedicineBackground: Cannabis is marketed as a treatment for pain. There is limited data on the prevalence of cannabis use and its correlates among Veterans prescribed opioids. Objective: To examine the prevalence and correlates of cannabis use among Veterans prescribed opioids. Design: Cross-sectional study. Participants: Veterans with a urine drug test (UDT) from Primary Care 2014-2018, in 50 states, Washington, D.C., and Puerto Rico. A total of 1,182,779 patients were identified with an opioid prescription within 90 days prior to UDT. Main measures: Annual prevalence of cannabis positive UDT by state. We used multivariable logistic regression to assess associations of demographic factors, mental health conditions, substance use disorders, and pain diagnoses with cannabis positive UDT. Results: Annual prevalence of cannabis positive UDT ranged from 8.5% to 9.7% during the study period, and in 2018 was 18.15% in Washington, D.C. and 10 states with legalized medical and recreational cannabis, 6.1% in Puerto Rico and 25 states with legalized medical cannabis, and 4.5% in non-legal states. Younger age, male sex, being unmarried, and marginal housing were associated with use (p < 0.001). Post-traumatic stress disorder (adjusted odds ratio [AOR] 1.17; 95% confidence interval [CI] 1.13-1.22, p < 0.001), opioid use disorder (AOR 1.14; CI 1.07-1.22, p < 0.001), alcohol use disorder or positive AUDIT-C (AOR 1.34; 95% CI 1.28-1.39, p < 0.001), smoking (AOR 2.58; 95% CI 2.49-2.66, p < 0.001), and other drug use disorders (AOR 1.15; 95% CI 1.03-1.29, p = 0.02) were associated with cannabis use. Positive UDT for amphetamines AOR 1.41; 95% CI 1.26-1.58, p < 0.001), benzodiazepines (AOR 1.41; 95% CI 1.31-1.51, p < 0.001) and cocaine (AOR 2.04; 95% CI 1.75-2.36, p < 0.001) were associated with cannabis positive UDT. Conclusions: Cannabis use among Veterans prescribed opioids varied by state and by legalization status. Veterans with PTSD and substance use disorders were more likely to have cannabis positive UDT. Opioid-prescribed Veterans using cannabis may benefit from screening for these conditions, referral to treatment, and attention to opioid safety.Item A national study of clinical discussions about cannabis use among Veteran patients prescribed opioids(Springer Nature, 2024-03-16) Zaman, Tauheed; Bravata, Dawn M.; Byers, Amy; Krebs, Erin; Leonard, Samuel; Austin, Charles; Sandbrink, Friedhelm; Hasin, Deborah S.; Keyhani, Salomeh; Medicine, School of MedicineBackground: The Veterans Health Administration tracks urine drug tests (UDTs) among patients on long-term opioid therapy (LTOT) and recommends discussing the health effects of cannabis use. Objective: To determine the occurrence of cannabis-related discussions between providers and patients on LTOT during six months following UDT positive for cannabis, and examine factors associated with documenting cannabis use. Design: We identified patients prescribed LTOT with a UDT positive for cannabis in 2019. We developed a text-processing tool to extract discussions around cannabis use from their charts. Subjects: Twelve thousand seventy patients were included. Chart review was conducted on a random sample of 1,946 patients. Main measures: The presence of a cannabis term in the chart suggesting documented cannabis use or cannabis-related discussions. Content of those discussions was extracted in a subset of patients. Logistic regression was used to examine the association between patient factors, including state of residence legal status, with documentation of cannabis use. Key results: Among the 12,070 patients, 65.8% (N = 7,948) had a cannabis term, whereas 34.1% (N = 4,122) of patients lacked a cannabis term, suggesting that no documentation of cannabis use or discussion between provider and patient took place. Among the subset of patients who had a discussion documented, 47% related to cannabis use for medical reasons, 35% related to a discussion of VA policy or legal issues, and 17% related to a discussion specific to medical risks or harm reduction strategies. In adjusted analyses, residents of states with legalized recreational cannabis were less likely to have any cannabis-related discussion compared to patients in non-legal states [OR 0.73, 95% CI 0.64-0.82]. Conclusions: One-third of LTOT patients did not have documentation of cannabis use in the chart in the 6 months following a positive UDT for cannabis. Discussions related to the medical risks of cannabis use or harm reduction strategies were uncommon.Item Alcohol Use Disorder and Cannabis Use Disorder symptomatology in adolescents is associated with dysfunction in neural processing of future events(Wiley, 2021) Aloi, Joseph; Blair, Karina S.; Meffert, Harma; White, Stuart F.; Hwang, Soonjo; Tyler, Patrick M.; Crum, Kathleen I.; Thornton, Laura C.; Mobley, Alita; Killanin, Abraham D.; Filbey, Francesca M.; Pope, Kayla; Blair, R. James; Psychiatry, School of MedicineTwo of the most commonly used substances by adolescents in the United States are cannabis and alcohol. Cannabis use disorder (CUD) and alcohol use disorder (AUD) are associated with impairments in decision-making processes. One mechanism for impaired decision-making in these individuals is thought to be an inability to adequately represent future events during decision-making. In the current study involving 112 adolescents, we used a comparative optimism task to examine the relationship between relative severity of CUD/AUD (as indexed by the CUD/AUD Identification Tests [CUDIT/AUDIT]) and atypical function within neural systems underlying affect-based neural represenation future events. Greater CUDIT scores were negatively related to responses within subgenual anterior and posterior cingulate cortex when processing high-intensity potential future positive and negative events. There was also a particularly marked negative relationship between CUD symptoms and blood oxygen level-dependent (BOLD) responses within visual and premotor cortices to high-intensity, negatively valenced potential future events. However, AUD symptom severity was not associated with dysfunction within these brain regions. These data indicate that relative risk/severity of CUD is associated with reduced responsiveness to future high-intensity events. This may impair decision-making where future significant consequences should guide response choice.Item Altered cerebellar-cortical resting-state functional connectivity in cannabis users(Sage, 2021) Schnakenberg Martin, Ashley M.; Kim, Dae-Jin; Newman, Sharlene D.; Cheng, Hu; Hetrick, William P.; Mackie, Ken; O’Donnell, Brian F.; Psychiatry, School of MedicineBackground: Cannabis use has been associated with abnormalities in cerebellar mediated motor and non-motor (i.e. cognition and personality) phenomena. Since the cerebellum is a region with high cannabinoid type 1 receptor density, these impairments may reflect alterations of signaling between the cerebellum and other brain regions. Aims: We hypothesized that cerebellar-cortical resting-state functional connectivity (rsFC) would be altered in cannabis users, relative to their non-using peers. It was also hypothesized that differences in rsFC would be associated with cannabis use features, such as age of initiation and lifetime use. Methods: Cerebellar-cortical and subcortical rsFCs were computed between 28 cerebellar lobules, defined by a spatially unbiased atlas template of the cerebellum, and individual voxels in the cerebral regions, in 41 regular cannabis users (20 female) and healthy non-using peers (N = 31; 18 female). We also investigated associations between rsFC and cannabis use features (e.g. lifetime cannabis use and age of initiation). Results: Cannabis users demonstrated hyperconnectivity between the anterior cerebellar regions (i.e. lobule I-IV) with the posterior cingulate cortex, and hypoconnectivity between the rest of the cerebellum (i.e. Crus I and II, lobule VIIb, VIIIa, VIIIb, IX, and X) and the cortex. No associations were observed between features of cannabis use and rsFC. Conclusions: Cannabis use was associated with altered patterns of rsFC from the cerebellum to the cerebral cortex which may have a downstream impact on behavior and cognition.Item Arrhythmia-related Hospitalization and Comorbid Cannabis Use Disorder: Trend Analysis in US Hospitals (2010-2014)(Cureus, 2019-09-09) Jaladi, Paul Rahul; Patel, Viralkumar; Kuduva Rajan, Shanthini; Rashid, Wahida; Madireddy, Sowmya; Ajibawo, Temitope; Imran, Sundus; Patel, Rikinkumar S.; Neurology, School of MedicineObjective To study the trends of arrhythmia hospitalizations with cannabis use disorders (CUDs) in terms of demographic characteristics and inpatient outcomes. Methods We used the nationwide inpatient sample (NIS) data during the post-legalization period (2010-2014) and included 570,556 arrhythmia inpatients (age, 15-54 years), and 14,426 inpatients had comorbid CUD (2.53%). We used the linear-by-linear association test and independent-sample T-test for assessing the change in hospital outcomes in inpatients with CUD. Results Arrhythmia hospitalizations with CUD increased by 31% (2010-2014). This increasing trend was seen in adults (45-54 years, P < 0.001) and was predominant in males (77.6%). Hypertension (40.6%), hyperlipidemia (17.6%), and obesity (15%) were prevalent medical comorbidities with variable trends over the five years. Among substance use disorders, tobacco (50.9%), and alcohol (31.4%) were major comorbidities with a variable trend (P = 0.003 for each). There was a 71.4% increase in the inpatient mortality rate between 2010 (0.7%) and 2014 (1.2%). The mean length of stay was three days, and the total hospitalization charges have been increasing (P < 0.001), averaging $35,812 per hospital admission. Conclusion Chronic cannabis use or abuse worsens hospitalization outcomes in arrhythmic patients, and more clinical studies are needed to study the causal association between these conditions due to the rising mortality risk.Item Assessment of the dopamine system in addiction using positron emission tomography(2014) Albrecht, Daniel Strakis; Hutchins, Gary D.; Saykin, Andrew J.; Kareken, David A.; Yoder, Karmen K.; Grahame, Nicholas J.Drug addiction is a behavioral disorder characterized by impulsive behavior and continued intake of drug in the face of adverse consequences. Millions of people suffer the financial and social consequences of addiction, and yet many of the current therapies for addiction treatment have limited efficacy. Therefore, there is a critical need to characterize the neurobiological substrates of addiction in order to formulate better treatment options. In the first chapter, the striatal dopamine system is interrogated with [11C]raclopride PET to assess differences between chronic cannabis users and healthy controls. The results of this chapter indicate that chronic cannabis use is not associated with a reduction in striatal D2/D3 receptor availability, unlike many other drugs of abuse. Additionally, recent cannabis consumption in chronic users was negatively correlated with D2/D3 receptor availability. Chapter 2 describes a retrospective analysis in which striatal D2/D3 receptor availability is compared between three groups of alcohol-drinking and tobacco-smoking subjects: nontreatment-seeking alcoholic smokers, social-drinking smokers, and social-drinking non-smokers. Results showed that smokers had reduced D2/D3 receptor availability throughout the striatum, independent of drinking status. The results of the first two chapters suggest that some combustion product of marijuana and tobacco smoke may have an effect on striatal dopamine concentration. Furthermore, they serve to highlight the effectiveness of using baseline PET imaging to characterize dopamine dysfunction in addictions. The final chapter explores the use of [18F]fallypride PET in a proof-of-concept study to determine whether changes in cortical dopamine can be detected during a response inhibition task. We were able to detect several cortical regions of significant dopamine changes in response to the task, and the amount of change in three regions was significantly associated with task performance. Overall, the results of Chapter 3 validate the use of [18F]fallypride PET to detect cortical dopamine changes during a impulse control task. In summary, the results reported in the current document demonstrate the effectiveness of PET imaging as a tool for probing resting and activated dopamine systems in addiction. Future studies will expand on these results, and incorporate additional methods to further elucidate the neurobiology of addiction.Item Association of a Positive Drug Screening for Cannabis With Mortality and Hospital Visits Among Veterans Affairs Enrollees Prescribed Opioids(American Medical Association, 2022-12-01) Keyhani, Salomeh; Leonard, Samuel; Byers, Amy L.; Zaman, Tauheed; Krebs, Erin; Austin, Peter C.; Moss-Vazquez, Tristan; Austin, Charles; Sandbrink, Friedhelm; Bravata, Dawn M.; Medicine, School of MedicineImportance: Cannabis has been proposed as a therapeutic with potential opioid-sparing properties in chronic pain, and its use could theoretically be associated with decreased amounts of opioids used and decreased risk of mortality among individuals prescribed opioids. Objective: To examine the risks associated with cannabis use among adults prescribed opioid analgesic medications. Design, setting, and participants: This cohort study was conducted among individuals aged 18 years and older who had urine drug screening in 2014 to 2019 and received any prescription opioid in the prior 90 days or long-term opioid therapy (LTOT), defined as more than 84 days of the prior 90 days, through the Veterans Affairs health system. Data were analyzed from November 2020 through March 2022. Exposures: Biologically verified cannabis use from a urine drug screen. Main outcomes and measures: The main outcomes were 90-day and 180-day all-cause mortality. A composite outcome of all-cause emergency department (ED) visits, all-cause hospitalization, or all-cause mortality was a secondary outcome. Weights based on the propensity score were used to reduce confounding, and hazard ratios [HRs] were estimated using Cox proportional hazards regression models. Analyses were conducted among the overall sample of patients who received any prescription opioid in the prior 90 days and were repeated among those who received LTOT. Analyses were repeated among adults aged 65 years and older. Results: Among 297 620 adults treated with opioids, 30 514 individuals used cannabis (mean [SE] age, 57.8 [10.5] years; 28 784 [94.3%] men) and 267 106 adults did not (mean [SE] age, 62.3 [12.3] years; P < .001; 247 684 [92.7%] men; P < .001). Among all patients, cannabis use was not associated with increased all-cause mortality at 90 days (HR, 1.07; 95% CI, 0.92-1.22) or 180 days (HR, 1.00; 95% CI, 0.90-1.10) but was associated with an increased hazard of the composite outcome at 90 days (HR, 1.05; 95% CI, 1.01-1.07) and 180 days (HR, 1.04; 95% CI, 1.01-1.06). Among 181 096 adults receiving LTOT, cannabis use was not associated with increased risk of all-cause mortality at 90 or 180 days but was associated with an increased hazard of the composite outcome at 90 days (HR, 1.05; 95% CI, 1.02-1.09) and 180 days (HR, 1.05; 95% CI, 1.02-1.09). Among 77 791 adults aged 65 years and older receiving LTOT, cannabis use was associated with increased 90-day mortality (HR, 1.55; 95% CI, 1.17-2.04). Conclusions and relevance: This study found that cannabis use among adults receiving opioid analgesic medications was not associated with any change in mortality risk but was associated with a small increased risk of adverse outcomes and that short-term risks were higher among older adults receiving LTOT.Item Association of Cannabis Use With Nausea and Vomiting of Pregnancy(Wolters Kluwer, 2022) Metz, Torri D.; Allshouse, Amanda A.; McMillin, Gwendolyn A.; Silver, Robert M.; Smid, Marcela C.; Haas, David M.; Simhan, Hyagriv N.; Saade, George R.; Grobman, William A.; Parry, Samuel; Chung, Judith H.; Jarlenski, Marian P.; Obstetrics and Gynecology, School of MedicineOur objective was to evaluate whether cannabis use was associated with nausea and vomiting in early pregnancy. Participants from nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be) enrolled from October 2010 through September 2013 with a PUQE (Pregnancy-Unique Quantification of Emesis) questionnaire and an available stored urine sample from the first study visit (median gestational age 12 weeks) were included. Cannabis exposure was ascertained by urine immunoassay for 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC-COOH); positive results were confirmed with liquid chromatography tandem mass spectrometry. The primary outcome was moderate-to-severe nausea by the PUQE score. Overall, 9,250 participants were included, and 5.8% (95% CI 5.4-6.3%) had detectable urine THC-COOH. In adjusted analyses, higher THC-COOH levels were associated with greater odds of moderate-to-severe nausea (20.7% in the group with THC-COOH detected vs 15.5% in the group with THC-COOH not detected, adjusted odds ratio 1.6, 95% CI 1.1-2.2 for a 500 ng/mg Cr THC-COOH increment).Item Associations Between Cannabis Use, Polygenic Liability for Schizophrenia, and Cannabis-related Experiences in a Sample of Cannabis Users(Oxford University Press, 2023) Johnson, Emma C.; Colbert, Sarah M. C.; Jeffries, Paul W.; Tillman, Rebecca; Bigdeli, Tim B.; Karcher, Nicole R.; Chan, Grace; Kuperman, Samuel; Meyers, Jacquelyn L.; Nurnberger, John I.; Plawecki, Martin H.; Degenhardt, Louisa; Martin, Nicholas G.; Kamarajan, Chella; Schuckit, Marc A.; Murray, Robin M.; Dick, Danielle M.; Edenberg, Howard J.; D'Souza, Deepak Cyril; Di Forti, Marta; Porjesz, Bernice; Nelson, Elliot C.; Agrawal, Arpana; Medical and Molecular Genetics, School of MedicineBackground and hypothesis: Risk for cannabis use and schizophrenia is influenced in part by genetic factors, and there is evidence that genetic risk for schizophrenia is associated with subclinical psychotic-like experiences (PLEs). Few studies to date have examined whether genetic risk for schizophrenia is associated with cannabis-related PLEs. Study design: We tested whether measures of cannabis involvement and polygenic risk scores (PRS) for schizophrenia were associated with self-reported cannabis-related experiences in a sample ascertained for alcohol use disorders (AUDs), the Collaborative Study on the Genetics of Alcoholism (COGA). We analyzed 4832 subjects (3128 of European ancestry and 1704 of African ancestry; 42% female; 74% meeting lifetime criteria for an AUD). Study results: Cannabis use disorder (CUD) was prevalent in this analytic sample (70%), with 40% classified as mild, 25% as moderate, and 35% as severe. Polygenic risk for schizophrenia was positively associated with cannabis-related paranoia, feeling depressed or anhedonia, social withdrawal, and cognitive difficulties, even when controlling for duration of daily cannabis use, CUD, and age at first cannabis use. The schizophrenia PRS was most robustly associated with cannabis-related cognitive difficulties (β = 0.22, SE = 0.04, P = 5.2e-7). In an independent replication sample (N = 1446), associations between the schizophrenia PRS and cannabis-related experiences were in the expected direction and not statistically different in magnitude from those in the COGA sample. Conclusions: Among individuals who regularly use cannabis, genetic liability for schizophrenia-even in those without clinical features-may increase the likelihood of reporting unusual experiences related to cannabis use.Item Associations between Oral Health and Cannabis Use among Adolescents and Young Adults: Implications for Orthodontists(MDPI, 2022-11-18) Le, Austin; Khoo, Edmund; Palamar, Joseph J.; Orthodontics and Oral Facial Genetics, School of DentistryCannabis use is prevalent among adolescents and young adults in the US. Virtually all modes of cannabis consumption involve the oral cavity, and previous studies have linked cannabis use with poorer oral health. We sought to identify associations between cannabis use and various oral health outcomes and behaviors among individuals 12–25 years of age, and to discuss implications for orthodontists who largely interact with this age group over an extended period of treatment time. We examined data from patient electronic health records (N = 14,657) obtained between 2015 and 2021. Associations between lifetime and current self-reported cannabis use and several oral health outcomes or related behaviors that reflect periodontal health, caries status, oral lesions, and physical integrity of tooth structure and restorations were examined in a bivariable and multivariable manner, controlling for patient age, sex, and self-reported tobacco and alcohol use. Reporting lifetime cannabis use was associated with higher risk for having oral lesions (aPR = 1.41, 95% CI: 1.07–1.85), bruxism (aPR = 1.31, 95% CI: 1.09–1.58), and frequent consumption of sugary beverages and snacks (aPR = 1.27, 95% CI: 1.12–1.41). Reporting current cannabis use was associated with higher risk for oral lesions (aPR = 1.45, 95% CI: 1.03–2.06) and frequent consumption of sugary beverages and snacks (aPR = 1.26, 95% CI: 1.07–1.48). Cannabis users aged 12–25 are at increased risk for bruxism, oral lesions, and frequent consumption of sugary beverages and snacks. Orthodontists and other dental professionals should probe for drug use and be cognizant of increased risk for oral health problems in patients that report actively using cannabis.