Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE-4): Alcohol use disorder and cannabinoid hyperemesis syndrome management in the emergency department.

The fourth Society for Academic Emergency Medicine (SAEM) Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE-4) is on the topic of the emergency department (ED) management of nonopioid use disorders and focuses on alcohol withdrawal syndrome (AWS), alcohol use disorder (AUD), and cannabinoid hyperemesis syndrome (CHS). The SAEM GRACE-4 Writing Team, composed of emergency physicians and experts in addiction medicine and patients with lived experience, applied the Grading of Recommendations Assessment Development and Evaluation (GRADE) approach to assess the certainty of evidence and strength of recommendations regarding six priority questions for adult ED patients with AWS, AUD, and CHS. The SAEM GRACE-4 Writing Team reached the following recommendations: (1) in adult ED patients (over the age of 18) with moderate to severe AWS who are being admitted to hospital, we suggest using phenobarbital in addition to benzodiazepines compared to using benzodiazepines alone [low to very low certainty of evidence]; (2) in adult ED patients (over the age of 18) with AUD who desire alcohol cessation, we suggest a prescription for one anticraving medication [very low certainty of evidence]; (2a) in adult ED patients (over the age of 18) with AUD, we suggest naltrexone (compared to no prescription) to prevent return to heavy drinking [low certainty of evidence]; (2b) in adult ED patients (over the age of 18) with AUD and contraindications to naltrexone, we suggest acamprosate (compared to no prescription) to prevent return to heavy drinking and/or to reduce heavy drinking [low certainty of evidence]; (2c) in adult ED patients (over the age of 18) with AUD, we suggest gabapentin (compared to no prescription) for the management of AUD to reduce heavy drinking days and improve alcohol withdrawal symptoms [very low certainty of evidence]; (3a) in adult ED patients (over the age of 18) presenting to the ED with CHS we suggest the use of haloperidol or droperidol (in addition to usual care/serotonin antagonists, e.g., ondansetron) to help with symptom management [very low certainty of evidence]; and (3b) in adult ED patients (over the age of 18) presenting to the ED with CHS, we also suggest offering the use of topical capsaicin (in addition to usual care/serotonin antagonists, e.g., ondansetron) to help with symptom management [very low certainty of evidence].

Evaluation of the immune system status and hematological dyscrasias, among amphetamine and cannabis abusers at Eradah Hospital in Qassim, Saudi Arabia.

This cross-sectional study aims to evaluate the immune system status and hematological disturbances among individuals who abuse amphetamines and cannabis. Substance abuse, particularly of amphetamines and cannabis, has been associated with various adverse effects on the body, including potential impacts on the immune system and hematological parameters. However, limited research has been conducted to comprehensively assess these effects in a cross-sectional design. Additionally, fungal infections are on the rise internationally, and immune-compromised people are particularly susceptible. The study will recruit a sample of amphetamine and cannabis abusers (n = 50) at the Eradah Hospital in the Qassim Region of Buraydah and assess their sociodemographic and biochemical variables, including blood indices and differential WBC indices, liver, and kidney profiles. Additionally, 50 sputum samples in total were cultured for testing for fungus infections. To obtain the descriptive statistics, the data was imported into Microsoft Excel and subjected to statistical analysis using SPSS 22.0. Amphetamine and cannabis abuser's sociodemographic variables analysis observed that the majority (52%) were aged 18-30, with 56% in secondary school. Unemployment was a significant issue, and most had no other health issues. The majority (50%) had 5-10 years of abuse, while 32% had less than 5 years, and only 18% had been drug abusers for more than 10 years. There were significant changes (p < 0.001) in all different leukocyte blood cells, including neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Furthermore, a microscopic examination of blood films from individuals who misuse the combination of the medications "amphetamine and cannabis" reveals hazardous alterations in Neutrophils. Out of 50, 35 sputum samples showed positive growth on Sabouraud dextrose agar (SDA) with chloramphenicol antibiotic, indicating a unicellular fungal growth. The present study explores the immune system and hematological disturbances linked to amphetamine and cannabis abuse, providing insights into health risks and targeted interventions. The findings complement previous research on drug users' hematological abnormalities, particularly in white blood cells. Routine hematological tests help identify alterations in homeostatic conditions, improving patient knowledge and preventing major issues. Further research is needed on multi-drug abuse prevention, early detection, and intervention. The cross-sectional design allows for a snapshot of the immune system and hematological status among abusers, laying the groundwork for future longitudinal studies. Key Words: Drug Effect, Immunity, Epidemiology, Oxidative Stress, Inflammation.

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.

Cannabinoid hyperemesis syndrome.

SummaryCannabis use is legalised in many countries. We present a patient in their 40s who complained of recurrent abdominal pain and associated nausea and vomiting. The patient was previously seen in various hospitals, treated symptomatically, and discharged with a diagnosis of non-specific abdominal pain. The patient had a chronic history of smoking cannabis and nicotine and drinking alcohol. Abdominal examination revealed no masses, and abdominal X-ray was normal. Blood tests and gastroduodenoscopy revealed no obvious aetiology. Intravenous fluids, together with antiemetics and proton pump inhibitors, were administered. The patient also received counselling and was advised to stop cannabis use. At discharge, the patient was well and asked to come back for review in 2 weeks, and, thereafter monthly for a period of 6 months after stopping cannabis use. The patient reported no recurrent symptoms despite continued cigarette and alcohol use. A suspected cannabinoid hyperemesis syndrome (CHS) became a consideration. Awareness of cannabis-related disorders such as CHS may assist in avoiding costly hospital workups.

Unveiling the link between chronic pain and misuse of opioids and cannabis.

Over 50 million Americans endure chronic pain where many do not receive adequate treatment and self-medicate to manage their pain by taking substances like opioids and cannabis. Research has shown high comorbidity between chronic pain and substance use disorders (SUD) and these disorders share many common neurobiological underpinnings, including hypodopaminergic transmission. Drugs commonly used for self-medication such as opioids and cannabis relieve emotional, bothersome components of pain as well as negative emotional affect that perpetuates misuse and increases the risk of progressing towards drug abuse. However, the causal effect between chronic pain and the development of SUDs has not been clearly established. In this review, we discuss evidence that affirms the proposition that chronic pain is a risk factor for the development of opioid and cannabis use disorders by outlining the clinical evidence and detailing neurobiological mechanisms that link pain and drug misuse. Central to the link between chronic pain and opioid and cannabis misuse is hypodopaminergic transmission and the modulation of dopamine signaling in the mesolimbic pathway by opioids and cannabis. Moreover, we discuss the role of kappa opioid receptor activation and neuroinflammation in the context of dopamine transmission, their contribution to opioid and cannabis withdrawal, along with potential new treatments.

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.

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.

Associations between smoking and pain in early recovery in residential substance use treatment-seekers.

INTRODUCTION: A growing literature indicates bidirectional associations between pain and tobacco use. Cigarette smokers are at increased risk for chronic pain, and observational and experimental studies indicate that pain increases motivation to smoke. Tobacco use disorder frequently co-occurs with other substance use disorders, which are also associated with chronic pain vulnerability. Despite evidence that pain significantly predicts smoking and relapse, associations between smoking history/trajectory and changes in pain over the course of treatment have not been characterized. The objective of the study was to determine the association between in-treatment smoking trajectory, pack-years (i.e., number of cigarette packs smoked per day multiplied by smoking duration), pain-related interference in daily activities, and pain intensity over the course of residential treatment. METHODS: In this study, 280 adult smokers in a residential SUD treatment center in North Central Florida completed questionnaires assessing cigarette use, pain intensity, and pain interference at treatment entry and discharge (Mean = 80.3 days, SD = 25.6). Most participants were diagnosed with alcohol use disorder (66.1 %). Opioid (27.9 %) and cannabis use disorders (29.6 %) were also common. Participants were grouped by whether their smoking increased (n = 36), decreased (n = 46), or stayed the same (n = 133) from entry to discharge. RESULTS: Analyses indicated a positive association between pack-years and pain intensity at both baseline (r = 0.185, p = 0.018) and discharge (r = 0.184, p = 0.019). Smoking trajectory was associated with pack-years, with those decreasing smoking having greater pack-years than those sustaining or increasing use [F(2,136) = 8.62, p < 0.01, η2p = 0.114]. Mixed general linear models indicated pain intensity [F(1,274) = 44.15, p < 0.0001, η2p = 0.138] and interference in day-to-day activities [F(1,276) = 31.79, p < 0.0001, η2p = 0.103] decreased significantly over time. However, there was no main effect of smoking trajectory on pain intensity [F(2,212) = 2.051, p = 0.131, η2p = 0.019] or of smoking trajectory by time interaction [F(2, 212) = 1.228, p = 0.295, η2p = 0.011]. CONCLUSIONS: Overall, findings provide evidence that smoking behavior influences pain within the context of residential substance use treatment. Given that pain is associated with urge to use substances and risk of return to use, more consistent and rigorous assessment of pain and proactive pain management is likely to enhance substance use treatment outcomes among people who smoke.

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.

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.

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.