Adverse Impact of Cannabis on Human Health.

Cannabis, the most commonly used recreational drug, is illicit in many areas of the world. With increasing decriminalization and legalization, cannabis use is increasing in the United States and other countries. The adverse effects of cannabis are unclear because its status as a Schedule 1 drug in the United States restricts research. Despite a paucity of data, cannabis is commonly perceived as a benign or even beneficial drug. However, recent studies show that cannabis has adverse cardiovascular and pulmonary effects and is linked with malignancy. Moreover, case reports have shown an association between cannabis use and neuropsychiatric disorders. With growing availability, cannabis misuse by minors has led to increasing incidences of overdose and toxicity. Though difficult to detect, cannabis intoxication may be linked to impaired driving and motor vehicle accidents. Overall, cannabis use is on the rise, and adverse effects are becoming apparent in clinical data sets.

Women are taking the hit: Examining the unique consequences of cannabis use across the female lifespan.

Cannabis use has risen dramatically in recent years due to global decriminalization and a resurgence in the interest of potential therapeutic benefits. While emerging research is shaping our understanding of the benefits and harms of cannabis, there remains a paucity of data specifically focused on how cannabis affects the female population. The female experience of cannabis use is unique, both in the societal context and because of the biological ramifications. This is increasingly important given the rise in cannabis potency, as well as the implications this has for the prevalence of Cannabis Use Disorder (CUD). Therefore, this scoping review aims to discuss the prevalence of cannabis use and CUD in women throughout their lifespan and provide a balanced prospective on the positive and negative consequences of cannabis use. In doing so, this review will highlight the necessity for continued research that goes beyond sex differences.

Chronic cannabis use alters the spontaneous and oscillatory gamma dynamics serving cognitive control.

Regular cannabis use is associated with cortex-wide changes in spontaneous and oscillatory activity, although the functional significance of such changes remains unclear. We hypothesized that regular cannabis use would suppress spontaneous gamma activity in regions serving cognitive control and scale with task performance. Participants (34 cannabis users, 33 nonusers) underwent an interview regarding their substance use history and completed the Eriksen flanker task during magnetoencephalography (MEG). MEG data were imaged in the time-frequency domain and virtual sensors were extracted from the peak voxels of the grand-averaged oscillatory interference maps to quantify spontaneous gamma activity during the pre-stimulus baseline period. We then assessed group-level differences in spontaneous and oscillatory gamma activity, and their relationship with task performance and cannabis use metrics. Both groups exhibited a significant behavioral flanker interference effect, with slower responses during incongruent relative to congruent trials. Mixed-model ANOVAs indicated significant gamma-frequency neural interference effects in the left frontal eye fields (FEF) and left temporoparietal junction (TPJ). Further, a group-by-condition interaction was detected in the left FEF, with nonusers exhibiting stronger gamma oscillations during incongruent relative to congruent trials and cannabis users showing no difference. In addition, spontaneous gamma activity was sharply suppressed in cannabis users relative to nonusers in the left FEF and TPJ. Finally, spontaneous gamma activity in the left FEF and TPJ was associated with task performance across all participants, and greater cannabis use was associated with weaker spontaneous gamma activity in the left TPJ of the cannabis users. Regular cannabis use was associated with weaker spontaneous gamma in the TPJ and FEF. Further, the degree of use may be proportionally related to the degree of suppression in spontaneous activity in the left TPJ.

Longitudinal associations between insomnia, cannabis use and stress among US veterans.

Insomnia is highly prevalent among military veterans, with rates nearly double that of civilian populations. Insomnia typically co-occurs with other psychological problems, including substance use (e.g. cannabis) and perceived stress. Much of the research focused on insomnia, stress and cannabis use explores cannabis as a sleep aid and a mechanism for stress relief. However, recent theoretical and empirical evidence suggests a dynamic interplay between insomnia, cannabis use and perceived stress, yet few longitudinal studies exist. Using a sample of 1105 post-9/11 veterans assessed over four time points across 12 months, we used latent difference score modelling to examine proportional change between insomnia, perceived stress and cannabis use. Results revealed a complex interplay between all three constructs. In particular, we show that higher prior levels of insomnia are associated with greater increases in perceived stress, and greater prior levels of stress are associated with greater increases in cannabis use. Perhaps more importantly, our results also point to cannabis use as a catalyst for greater increases in both stress and insomnia severity. Our results suggest there may be both benefits and costs of cannabis use among veterans. Specifically, for veterans who experience chronic sleep problems, perceived stress may become overwhelming, and the benefit of stress reduction from increased cannabis use may come at the cost of increasing insomnia symptomology.

Effectiveness of cannabis use and cannabis use disorder interventions: a European and international data synthesis.

This data synthesis examined the effectiveness of behavioural and pharmacological approaches for cannabis treatment. We integrated findings from high level evidence studies and prioritised data from Europe when available. The synthesis found that only a relatively small number of published behavioural and pharmacological studies on cannabis interventions have been conducted in Europe. Applying both European and non-European data, it was found that Cognitive Behavioural Therapy (CBT) and/or Motivational Enhancement Therapy (MET) improved short-term outcomes in the frequency of cannabis use and dependency severity, although abstinence outcomes were less consistent. These improvements were typically not maintained nine months after treatment. CBT and MET (or combined CBT + MET) treatments that extend beyond four sessions were more effective than fewer sessions over a shorter duration. Combining CBT or MET (or combined CBT + MET) with adjunctive Contingency Management (CM) improved therapeutic outcomes. No pharmacotherapies have been approved for the management of cannabis use, cannabis use disorders or cannabis withdrawal. Despite only weak evidence to support the use of pharmacological agents, some are used 'off-label' to manage withdrawal symptoms outside clinical trials.

Predictors of effective therapy among individuals with Cannabis Use Disorder: a review of the literature.

Treatment demand for Cannabis Use Disorder (CUD) has increased in the past decade in almost all European countries, and CUD is currently the most common reason for first-time drug-related treatment admission in the European Union. Even though several therapeutic approaches have been shown to benefit individuals with CUD, there is a lack of knowledge regarding factors associated with effective therapy and the underlying mechanisms of change among individuals with CUD presenting for treatment. The aim of the present paper was to review current knowledge on factors that have been shown to contribute to positive outcomes in CUD treatment. A scoping methodology was used, focusing on empirically evaluated studies that used defined, cannabis-related outcome measures. In eligible studies, factors of investigation were categorized as either 'mediators', i.e., treatment-related factors associated with the processes or mechanisms through which patients benefit from therapy, or 'moderators' which are patient-related characteristics that predict his/her odds to benefit from treatment or patient-related (i.e., moderators). Factors categorized as mediators were then classified 'specific factors' if they were related to a certain technique or treatment modality or 'common factors' if they were assessed beyond treatment modalities. Findings suggest that in CUD treatment, specific mediators include treatment duration, addressing motivation to change, acquiring coping skills, enhancing self-efficacy, and integrating several therapeutic components. Common mediators include therapeutic alliance, empathy, expectations and cultural adaptation. Moderators in CUD treatment include sex, ethnicity, age-related factors and comorbid disorders.

Persistent increased severity of cannabis use disorder symptoms in adolescents compared to adults: a one-year longitudinal study.

Adolescence is a developmental period characterised by increased vulnerability to cannabis use disorder (CUD). However, previous investigations of this vulnerability have relied on cross-sectional comparisons and lack a detailed assessment of cannabis quantity, a potentially important confounding factor. Here, we aimed to investigate the one-year course of CUD in adolescents compared to adults who currently use cannabis, adjusting for a comprehensive measure of cannabis quantity. Data are from a one-year observational longitudinal study (CannTeen) of adolescents and adults who currently used cannabis regularly with five waves of assessment at 3-monthly intervals, based in London, UK. Participants were n = 70 adults (26-29, 45.7% female), who did not regularly use cannabis when they were under age 18, and n = 76 adolescents (16-17, 50.0% female). The exposure was adolescent (compared to adult) frequent cannabis use. The primary outcome was CUD symptoms measured using the cannabis use disorder identification test revised (CUDIT-R) at five time points. Models were adjusted for cannabis quantity using mean weekly standard THC units (one unit = 5 mg THC). Other covariates included gender, and whether each session occurred before or during the COVID-19 pandemic. In models adjusted for pre-registered covariates, adolescents scored 3.7 points higher on the CUDIT-R compared to the adult group across the 5 assessment waves (3.66 95% CIs 1.99, 5.34). There was also evidence of a linear reduction in symptoms over time in both groups (-0.47, 95%CIs -0.67, -0.27). Adolescents had persistently increased CUD symptoms compared to adults across the 12-month period. This association was robust after adjusting for the quantity of cannabis consumed and other covariates.

Prevalence of cannabis use disorder and perioperative outcomes in adult colectomy patients: A propensity score-matched analysis.

BACKGROUND: The decriminalization of cannabis across the United States has led to an increased number of patients reporting cannabis use prior to surgery. However, it is unknown whether preoperative cannabis use disorder (CUD) increases the risk of postoperative complications among adult colectomy patients. METHODS: Adult patients undergoing an elective colectomy were retrospectively analyzed from the National Inpatient Sample database (2004-2018). To control for potential confounders, patients with CUD, defined using ICD-9/10 codes, were propensity score matched to patients without CUD in a 1:1 ratio. The association between preoperative CUD and composite morbidity, the primary outcome of interest, was assessed. Subgroup analyses were performed after stratification by age (≥50 years). RESULTS: Among 432,018 adult colectomy patients, 816 (0.19%) reported preoperative CUD. The prevalence of CUD increased nearly three-fold during the study period from 0.8/1000 patients in 2004 to 2.0/1000 patients in 2018 (P-trend<0.001). After propensity score matching, patients with CUD exhibited similar rates of composite morbidity (140 of 816; 17.2%) as those without CUD (151 of 816; 18.5%) (p = 0.477). Patients with CUD also had similar anastomotic leak rates (CUD: 5.64% vs. No CUD: 6.25%; p = 0.601), hospital lengths of stay (CUD: 5 days, IQR 4-7 vs. No CUD: 5 days, IQR 4-7) (p = 0.415), and hospital charges as those without CUD. Similar findings were seen among patients aged ≥50 years in the subgroup analysis. CONCLUSIONS: Though the prevalence of CUD has increased drastically over the past 15 years, preoperative CUD was not associated with an increased risk of composite morbidity among adult patients undergoing an elective colectomy.

A phase III multisite randomised controlled trial to compare the efficacy of cannabidiol to placebo in the treatment of cannabis use disorder: the CBD-CUD study protocol.

BACKGROUND: Cannabis use disorder (CUD) is increasingly common and contributes to a range of health and social problems. Cannabidiol (CBD) is a non-intoxicating cannabinoid recognised for its anticonvulsant, anxiolytic and antipsychotic effects with no habit-forming qualities. Results from a Phase IIa randomised clinical trial suggest that treatment with CBD for four weeks reduced non-prescribed cannabis use in people with CUD. This study examines the efficacy, safety and quality of life of longer-term CBD treatment for patients with moderate-to-severe CUD. METHODS/DESIGN: A phase III multi-site, randomised, double-blinded, placebo controlled parallel design of a 12-week course of CBD to placebo, with follow-up at 24 weeks after enrolment. Two hundred and fifty adults with moderate-to-severe CUD (target 20% Aboriginal), with no significant medical, psychiatric or other substance use disorders from seven drug and alcohol clinics across NSW and VIC, Australia will be enrolled. Participants will be administered a daily dose of either 4 mL (100 mg/mL) of CBD or a placebo dispensed every 3-weeks. All participants will receive four-sessions of Cognitive Behavioural Therapy (CBT) based counselling. Primary endpoints are self-reported cannabis use days and analysis of cannabis metabolites in urine. Secondary endpoints include severity of CUD, withdrawal severity, cravings, quantity of use, motivation to stop and abstinence, medication safety, quality of life, physical/mental health, cognitive functioning, and patient treatment satisfaction. Qualitative research interviews will be conducted with Aboriginal participants to explore their perspectives on treatment. DISCUSSION: Current psychosocial and behavioural treatments for CUD indicate that over 80% of patients relapse within 1-6 months of treatment. Pharmacological treatments are highly effective with other substance use disorders but there are no approved pharmacological treatments for CUD. CBD is a promising candidate for CUD treatment due to its potential efficacy for this indication and excellent safety profile. The anxiolytic, antipsychotic and neuroprotective effects of CBD may have added benefits by reducing many of the mental health and cognitive impairments reported in people with regular cannabis use. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry: ACTRN12623000526673 (Registered 19 May 2023).

High-Risk Cannabis Use: A Proposal of an Operational Definition through Delphi Methodology for Scientific Consensus.

INTRODUCTION: Cannabis ranks as one of the most widely used psychoactive substances worldwide. Its usage has been reported as a risk factor for developing a variety of physical and mental health issues, alongside social and economic problems. According to the World Health Organization (WHO), hazardous (or high-risk) substance use is defined as "a pattern of substance use that increases the risk of harmful consequences for the user." The primary objective of this study was to achieve a consensus on an operational definition of high-risk cannabis use suitable for a European jurisdiction (Spain). METHODS: A three round Delphi study was conducted. The Delphi technique entails group decision-making and iterative forecasting by consulting a panel of experts and conducting systematic feedback rounds. An online survey was distributed among a diverse expert panel comprising professionals from Spain working on fields related to cannabis use (research, policy planning, and clinical professionals). One-hundred ninety-nine invitations were sent to experts, of which forty-five (22.6%) accepted to participate. All participants were provided the option to revise a background document with the latest compiled scientific evidence and guidelines related to health and social conditions associated to cannabis usage. This background document also proposed the quantification of dose using a standardized unit established for the population of Spain (the Standard Joint Unit or SJU) based on quantity of cannabis main psychoactive constituent, 9-tetrahydrocannabinol (9-THC) (1 SJU = 1 joint = 0.25 g of cannabis = 7 mg of 9-THC). Three rounds of Likert scale and open-ended questions were administered until consensus, defined as ≥75% agreement, was attained. RESULTS: Consensus was reached on defining high-risk cannabis use as the usage of more than 4 SJU (>28 mg THC) per week or any use of cannabis with potency >10% THC. Concurrent use of cannabis with other drugs was also considered high risk, while the smoked route was considered the riskiest administration route. It was also agreed that vulnerable groups for high-risk cannabis use (for whom any pattern of cannabis use represents high risk of harm) include individuals under the age of 21, pregnant or breastfeeding women, individuals with psychiatric history, those with medical health issues related to cannabis use, professional drivers and heavy machine operators. CONCLUSION: This operational definition of high-risk cannabis use for Spain elucidates usage patterns and individual vulnerability factors predictive of heightened harm. Its adoption holds potential to inform decision-making among individuals, professionals, and policy-makers, facilitating evidence-based interventions aimed at prevention and risk reduction.

Examining the Popularity, Content, and Intersections With the Substance Abuse and Mental Health Services Administration's Definition of Recovery in a Nonclinical Online Cannabis Cessation Community: Infodemiology Study of Reddit Posts.

BACKGROUND: Cannabis consumption has increased in recent years, as has cannabis use disorder. While researchers have explored public online community discussions of active cannabis use, less is known about the popularity and content of publicly available online communities intended to support cannabis cessation. OBJECTIVE: This study aims to examine the level of engagement and dominant content of an online community for cannabis cessation through 3 specific aims. First, we examine the use of a subreddit cannabis cessation community (r/leaves) over time to evaluate the popularity of this type of resource for individuals who want to stop using cannabis. Second, we examine the content of posts in the community to identify popular topics related to cessation. Third, we compare the thematic findings relative to the 4 domains of recovery defined by the Substance Abuse and Mental Health Services Administration (SAMHSA). By examining these 3 gaps, we take the initial steps toward understanding the experiences being shared online among individuals interested in cannabis cessation and compare them with the principles outlined in the SAMHSA definition of recovery. METHODS: Using the Pushshift application programming interface, we collected the count of posts by year between 2011 and 2021 and the narrative of the 100 posts with the most comments per year in a popular cannabis cessation-focused subreddit (r/leaves). A linear model and a nonlinear model were compared to evaluate change in the number of posts by year. Mixed natural language processing and qualitative analyses were applied to identify top terms, phrases, and themes present in posts over time. Overlap between themes and the 4 SAMHSA domains of recovery (health, purpose, community, and home) were examined. RESULTS: The number of annual posts in r/leaves increased from 420 in 2011 to 34,841 in 2021 (83-fold increase), with exponential growth since 2018. The term that was the most common across posts was "smoke" (2019 posts). Five major themes were identified, and a narrative arc was represented, from motivations and perceived benefits of cannabis use to the negative consequences of use, strategies to change behaviors, and the positive and negative consequences of change. There was substantial overlap between these 5 themes and 3 of SAMHSA's 4 domains of recovery: health, purpose, and community. However, the domain of home was less commonly identified. CONCLUSIONS: Engagement in this online cannabis support community appears to be increasing. Individuals using this forum discussed several topics, including multiple aspects of recovery defined by the SAMHSA. Online communities, such as this one may, serve as an important pathway for individuals seeking to reduce or cease their consumption of cannabis.

Validation of the Reasons for Quitting Smoking Cannabis Scale Among People with Cannabis Use Disorder.

BACKGROUND: The prevalence of cannabis use disorder (CUD) has increased in the last ten years with medicinal and recreational legalization across the United States and increasing accessibility worldwide. Estimates suggest that 8-18% of individuals who use cannabis meet diagnostic criteria for CUD, leading to significant impairments across functioning. However, there are currently no measures that assess the reasons for quitting smoking cannabis to use in treatments with validation evidence in those with CUD. METHOD: We validated the Reasons for Quitting Smoking Cannabis Scale (RQSCS) in adults (n = 133) who meet the diagnostic criteria for CUD as part of a laboratory-based clinical trial on transdermal nicotine patches for cannabis withdrawal symptoms (R01DA031006). We conducted standard psychometric testing, including exploratory factor analyses, estimating internal consistencies, exploring demographic variation, and testing construct validity. RESULTS: The RQSCS demonstrated a four-factor structure, including: (1) cognitive health, (2) social functioning, (3) health problems, (4) reputation, and a single item that assesses experimental incentive; λs > .410), with acceptable to high internal consistencies for each subscale (αs > .725). The scale demonstrated strong construct validity and minor demographic variation. Finally, all subscales were sensitive to detecting reasons for quitting cannabis and differentially predicted cannabis use 31 days after the study. CONCLUSION: The RQSCS is a psychometrically robust, timely instrument for assessing the reasons for quitting smoking cannabis in individuals with CUD. The scale has the potential to provide useful information for clinicians attempting to help those with CUD reduce or cease their cannabis use, informing individualized treatment plans and enhancing motivation for change.

The Indirect Influence of Cannabis Use Disorder Symptoms on PTSD Symptom Severity Through Psychological Inflexibility.

Background: One in five college students (21%) report using cannabis in the past month, and approximately 10% develop cannabis use disorder (CUD). Further, college students have high rates of trauma exposure, and CUD is prospectively linked to posttraumatic stress disorder (PTSD). Given the high rate of co-occurrence, research is needed to understand transdiagnostic, modifiable factors that could account for the relationship between CUD and PTSD. Psychological inflexibility (PI) is one such factor and refers to difficulty adapting thoughts or behaviors to various situations that reflect of one's personal values. Objectives: PI predicts worse PTSD symptom severity and has been established as a maintaining factor between alcohol use and PTSD, albeit no studies have examined this relationship with CUD. Results: College students (N = 336) completed self-report measures of CUD, PI, and PTSD. A cross-sectional mediation model explained 54% of the variance in PTSD symptom severity, F(5, 330) = 78.86, p < .001. After controlling for age, gender, and probable alcohol use disorder, CUD was not directly associated with PTSD symptom severity, yet was indirectly associated with PTSD through higher PI. Specifically, CUD was associated with higher PI (b = 0.31, p < .05, 95% CI [0.07, 0.54]), and higher PI was associated with greater PTSD symptom severity (b = 1.07, p < .001, 95% CI [0.95, 1.19]). Conclusion: Although CUD has been previously linked with worse PTSD symptoms, results suggest that this occurs through PI. Importantly, PI is malleable, and may be an important treatment target for co-occurring CUD and PTSD in college students.

Cumulative lifetime violence, social determinants of health, and cannabis use disorder post-cannabis legalization in a community sample of men: An intersectional perspective.

Despite Canada having the highest disease burden globally for cannabis use disorder (CUD) and violence being ubiquitous in men's lives, little is known about how intersections among social determinants of health (SDOH) and cumulative lifetime violence severity (CLVS) influence CUD in men post-cannabis legalization. Using data collected in a survey with a national community sample of 597 men who self-identified as having experienced violence, we conducted a latent profile analysis using 11 subscales of the CLVS-44 scale and explored differential associations between CLVS profiles and CUD considering SDOH covariates. Four profiles were distinguished by intersections among CLVS-44 subscale severity and roles as target and perpetrator. CLVS profiles were significantly associated with CUD in the unadjusted model and in the adjusted model where age, adverse housing, and education were significant covariate controls. In the adjusted model, CUD was differentially associated with CLVS profiles and significantly higher in Profile 4 (highest severity target and perpetrator) than in Profile 1 (lowest severity target, no perpetration). Chi-square tests showed significant intersection between adverse housing, younger age, Profile 4 CLVS, and moderate to severe CUD among cannabis users. These results reveal the importance of understanding simultaneous intersections among indicators of CLVS in determining profiles of lifetime violence. Also critical are intersections among CLVS profiles and significant covariates as a basis for trauma- and violence-informed care for CUD that prioritizes men most disadvantaged by this convergence and attends to individual and structural health disparities at practice and policy levels.

A call for mindfulness-based interventions for cannabis-use disorders.

Cannabis use is being increasingly liberalized worldwide, and an increasing prevalence of cannabis-use disorder (CUD) is observed. The few current therapeutic options for CUD are only modestly effective. Mindfulness-based interventions offer promising prospects for the management of substance-use disorders. However, despite proliferating literature on mindfulness and substance use, few studies have explored mindfulness in terms of cannabis use and CUD. There are many possibilities for the implementation of mindfulness-based interventions for cannabis use reduction, especially for younger users, who are more vulnerable to cannabis-related harms. Accordingly, large controlled trials are needed to reliably assess the potential of such interventions.

Open Label Pilot of Lorcaserin (a serotonin 2C-receptor agonist) for Cannabis Use Disorder.

Background And Objective: Cannabis Use Disorder (CUD) has no FDA approved treatment. Serotonin-2c (5HT2c) agonists have preclinical and human laboratory evidence for potential efficacy for CUD. We assessed the tolerability and effects of lorcaserin (5HT2c agonist) on CUD. Methods: In a 10-week, open label, uncontrolled trial, the tolerability of lorcaserin was tested in outpatients with CUD. Adverse events (AE) were assessed weekly. Cannabis use was assessed twice weekly by the Timeline follow-back and quantitative urine metabolites. Results: 17 participants enrolled, and 14 received medication. Participants' average age was 35 years; majority were male (N=12). The medication was well tolerated in males. There were no serious adverse events (SAE). The most common AE's were headache/migraine (N=4, all females), anorexia (N=3), and irritability (N=2). Participants decreased their frequency of cannabis use significantly (p < 0.001), adjusted for baseline use. By the end of the trial, participants decreased by 1.76 (SE=0.47) cannabis using days/week. Average daily amount of cannabis and urine THC metabolite levels did not change significantly. Conclusions: Lorcaserin was well tolerated in males but not females suggesting possible sex differences. Future trials of other 5HT2c agonists (lorcaserin was withdrawn at the request of the FDA) should consider longer dose titration phases. Trial Registration: NCT02932215.

Clinical effectiveness of nirmatrelvir plus ritonavir in patients with COVID-19 and substance use disorders based on real-world data.

This study assessed the clinical efficacy of nirmatrelvir plus ritonavir (NMV-r) in treating patients with coronavirus disease-2019 (COVID-19) and substance use disorders (SUDs). This study included two cohorts: the first examined patients with SUDs, with and without a prescription for NMV-r, while the second compared patients prescribed with NMV-r, with and without a diagnosis of SUDs. SUDs were defined using ICD-10 codes, related to SUDs, including alcohol, cannabis, cocaine, opioid, and tobacco use disorders (TUD). Patients with underlying SUDs and COVID-19 were identified using the TriNetX network. We used 1:1 propensity score matching to create balanced groups. The primary outcome of interest was the composite outcome of all-cause hospitalization or death within 30 days. Propensity score matching yielded two matched groups of 10 601 patients each. The results showed that the use of NMV-r was associated with a lower risk of hospitalization or death, 30 days after COVID-19 diagnosis (hazard ratio (HR), 0.640; 95% confidence interval (CI): 0.543-0.754), as well as a lower risk of all-cause hospitalization (HR, 0.699; 95% CI: 0.592-0.826) and all-cause death (HR, 0.084; 95% CI: 0.026-0.273). However, patients with SUDs had a higher risk of hospitalized or death within 30 days of COVID-19 diagnosis than those without SUDs, even with the use of NMV-r (HR, 1.783; 95% CI: 1.399-2.271). The study also found that patients with SUDs had a higher prevalence of comorbidities and adverse socioeconomic determinants of health than those without SUDs. Subgroup analysis showed that the benefits of NMV-r were consistent across most subgroups with different characteristics, including age (patients aged ≥60 years [HR, 0.507; 95% CI: 0.402-0.640]), sex (women [HR, 0.636; 95% CI: 0.517-0.783] and men [HR, 0.480; 95% CI: 0.373-0.618]), vaccine status (vaccinated <2 doses [HR, 0.514; 95% CI: 0.435-0.608]), SUD subtypes (alcohol use disorder [HR, 0.711; 95% CI: 0.511- 0.988], TUD [HR, 0.666; 95% CI: 0.555-0.800]) and Omicron wave (HR, 0.624; 95% CI: 0.536-0.726). Our findings indicate that NMV-r could reduce all-cause hospitalization and death in the treatment of COVID-19 among patients with SUDs and support the use of NMV-r for treating patients with SUDs and COVID-19.

Cannabis use, abuse and dependence during the COVID-19 pandemic: a scoping review.

The interaction between cannabis use or addiction and SARS-COV-2 infection rates and COVID-19 outcomes is obscure. As of 08/01/2022 among 57 evaluated epidemiological/clinical studies found in Pubmed-database, most evidence for how cannabis use patterns were influenced by the pandemic was given by two systematic reviews and 17 prospective studies, mostly involving adolescents. In this age group, cannabis use patterns have not changed markedly. For adults, several cross-sectional studies reported mixed results with cannabis use having increased, decreased or remained unchanged. Two cross-sectional studies demonstrated that the severity of adults´ cannabis dependence was either increased as a consequence of increasing cannabis use during the pandemic or not changed. Regarding the effect of cannabis use on COVID-19 outcomes, we found only five retrospective/cross-sectional studies. Accordingly, (i) cannabis use did not impact mild COVID-19 symptoms; (ii) cannabis using individuals experienced more COVID-19-related hospitalizations; (iii) cannabis using veterans were associated with reduced SARS-COV-2 infection rates; (iv) frequent cannabis use was significantly associated with COVID-19 mortality, and (v) cannabis dependents were at higher risk of COVID-19 breakthrough after vaccination. It should be outlined that the validity of these retrospective/cross-sectional studies (all self-reports or register/e-health-records) is rather low. Future prospective studies on the effects of cannabis use on SARS-COV-2 infection rates and COVID-19 outcomes are clearly required for conclusive risk-benefit assessments of the role of cannabis on users' health during the pandemic. Moreover, substance dependence (including cannabis) is associated with (often untreated) somatic comorbidity, which severity is a proven key risk factor for worse COVID-19 outcomes.

Research Review: Siblings matter. A multi-level meta-analysis on the association between cannabis use among adolescent siblings.

BACKGROUND: Parents' and peers' cannabis use are well-documented predictors of youth cannabis use, however, relatively little is known about the influence of siblings' cannabis use. Hence, this meta-analysis investigated the association between sibling-youth cannabis use (disorder) and explored moderation by sibling type (monozygotic- vs. dizygotic- vs. non-twins), age, age spacing, birth order, gender, and gender constellations (same- vs. mix- gender pairs). When comparison data of parents' and peers' cannabis use (disorder) were also available in the included studies, separate meta-analyses on associations between parent-youth and peer-youth cannabis use (disorder) were additionally conducted. METHODS: Studies were selected if they included 11- to 24-year-old participants, and investigated associations between cannabis use (disorder) among those youth and their siblings. These studies were retrieved via a search in seven databases (e.g., PsychINFO). A multi-level meta-analysis using a random effects model was performed on the studies, and heterogeneity analyses and moderator analyses were also conducted. PRISMA guidelines were followed. RESULTS: We retrieved 20 studies (most of which originated from Western cultures) with 127 effect sizes for the main sibling-youth meta-analysis and found a large overall effect-size (r = .423), implying that youth had higher cannabis use rates when their sibling used cannabis, and this association was stronger for monozygotic twins and for same-gender sibling pairs. Finally, a medium effect size existed for the associations between parent-youth cannabis use (r = .300) and a large effect size for peer-youth cannabis use (r = .451). CONCLUSIONS: Youth are more likely to use cannabis when their siblings use cannabis. This sibling-youth cannabis use association existed for all sibling constellations, was larger than the association between parent-youth cannabis use, and was similar in magnitude compared to the association between peer-youth cannabis use-suggesting both genetic and environmental influences (e.g., social-learning) between siblings. Hence, it is important not to neglect sibling influences when treating youth cannabis use (disorder).

Role of neuronal nicotinic acetylcholine receptors in cannabinoid dependence.

Cannabis is among the most widely consumed psychoactive drugs around the world and cannabis use disorder (CUD) has no current approved pharmacological treatment. Nicotine and cannabis are commonly co-used which suggests there to be overlapping neurobiological actions supported primarily by the co-distribution of both receptor systems in the brain. There appears to be strong rationale to explore the role that nicotinic receptors play in cannabinoid dependence. Preclinical studies suggest that the ɑ7 nAChR subtype may play a role in modulating the reinforcing and discriminative stimulus effects of cannabinoids, while the ɑ4ß2 * nAChR subtype may be involved in modulating the motor and sedative effects of cannabinoids. Preclinical and human genetic studies point towards a potential role of the ɑ5, ɑ3, and ß4 nAChR subunits in CUD, while human GWAS studies strongly implicate the ɑ2 subunit as playing a role in CUD susceptibility. Clinical studies suggest that current smoking cessation agents, such as varenicline and bupropion, may also be beneficial in treating CUD, although more controlled studies are necessary. Additional behavioral, molecular, and mechanistic studies investigating the role of nAChR in the modulation of the pharmacological effects of cannabinoids are needed.