Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation.

Epidemiological studies reveal that marijuana increases the risk of cardiovascular disease (CVD); however, little is known about the mechanism. Δ9-tetrahydrocannabinol (Δ9-THC), the psychoactive component of marijuana, binds to cannabinoid receptor 1 (CB1/CNR1) in the vasculature and is implicated in CVD. A UK Biobank analysis found that cannabis was an risk factor for CVD. We found that marijuana smoking activated inflammatory cytokines implicated in CVD. In silico virtual screening identified genistein, a soybean isoflavone, as a putative CB1 antagonist. Human-induced pluripotent stem cell-derived endothelial cells were used to model Δ9-THC-induced inflammation and oxidative stress via NF-κB signaling. Knockdown of the CB1 receptor with siRNA, CRISPR interference, and genistein attenuated the effects of Δ9-THC. In mice, genistein blocked Δ9-THC-induced endothelial dysfunction in wire myograph, reduced atherosclerotic plaque, and had minimal penetration of the central nervous system. Genistein is a CB1 antagonist that attenuates Δ9-THC-induced atherosclerosis.

Crystal Structure of the Human Cannabinoid Receptor CB1.

Cannabinoid receptor 1 (CB1) is the principal target of Δ9-tetrahydrocannabinol (THC), a psychoactive chemical from Cannabis sativa with a wide range of therapeutic applications and a long history of recreational use. CB1 is activated by endocannabinoids and is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders. Here, we present the 2.8 Å crystal structure of human CB1 in complex with AM6538, a stabilizing antagonist, synthesized and characterized for this structural study. The structure of the CB1-AM6538 complex reveals key features of the receptor and critical interactions for antagonist binding. In combination with functional studies and molecular modeling, the structure provides insight into the binding mode of naturally occurring CB1 ligands, such as THC, and synthetic cannabinoids. This enhances our understanding of the molecular basis for the physiological functions of CB1 and provides new opportunities for the design of next-generation CB1-targeting pharmaceuticals.

AGA Clinical Practice Update on Diagnosis and Management of Cannabinoid Hyperemesis Syndrome: Commentary.

DESCRIPTION: The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) is to review the available evidence and provide expert advice regarding diagnosis and management of cannabinoid hyperemesis syndrome. METHODS: This CPU was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. This expert commentary incorporates important as well as recently published studies in this field, and it reflects the experiences of the authors.

Longitudinal Transitions Between Use of Combustible, Noncombustible, and Multiple Cannabis Products From Adolescence to Young Adulthood and Intersections With Nicotine Use.

Understanding transitions across use of different types of cannabis products and multiple cannabis products and how they intersect with nicotine use in young people can inform etiology and prevention. In this study, we examined transitions across use of combustible and noncombustible forms of cannabis and multiple types of cannabis from adolescence to young adulthood and the role of nicotine use in transitions. In a Southern California longitudinal cohort study (n = 3,298; baseline mean age = 16.1 (standard deviation, 0.4) years) with 9 semiannual survey waves (2015-2021), we used Markov multistate transition modeling to estimate short-term (2-wave) and long-term (9-wave) probabilities of transition across 5 cannabis use states: never use of any product, prior use with no past-6-month (P6M) use of any product, and P6M use of exclusively noncombustible products, exclusively combustible products, and multiple (noncombustible + combustible) products. Sizable transition probabilities from prior and exclusive P6M noncombustible or combustible cannabis use to P6M poly-cannabis-product use were observed in short-term (10.7%-38.9%) and long-term (43.4%-43.8%) analyses. P6M nicotine use increased risk of transitioning from never and prior use to exclusive P6M noncombustible and combustible cannabis use. Cannabis use in any form, even temporary use, during midadolescence may often be followed by poly-cannabis-product use. Nicotine use may amplify the probability of future cannabis use onset or recurrence.

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.

Cannabis use after a cancer diagnosis in a population-based sample of cancer survivors.

PURPOSE: This study aimed to characterize the prevalence and correlates of cannabis use and the methods and reasons for use among recently diagnosed cancer survivors in a population sample within Washington state. METHODS: We identified individuals diagnosed with invasive cancers in the prior 6 to 17 months from April 2020 to December 2020 using the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) cancer registry. Participants (n = 1,515) completed a questionnaire, including demographics, medical history, cannabis use, and other substance use. Cancer characteristics and date of diagnosis were obtained from SEER registry data. We calculated weighted prevalence estimates and logistic regression models to evaluate correlates of cannabis use. RESULTS: Overall, 41.3% of survivors reported cannabis use at any time after diagnosis, most commonly via edibles (60.5%) and smoking (43.8%). The most frequently reported reasons for use were sleep (54.5%), mood, stress, anxiety, and depression (44.3%), pain (42.3%), and recreation (42.3%). Cannabis use was associated with younger age, race (White vs. Asian), less education, former or current smoking, consuming more than 2 alcohol-containing drinks per day, having late-stage cancer, and cancer site. CONCLUSION: In this first evaluation of cannabis use in a registry-linked, population-based sample of survivors of all cancer types, based in a state where recreational and medical cannabis have been legal for a decade, approximately 2 in 5 survivors reported post-diagnosis use. Given how common cannabis use is among cancer survivors, there is a great need to understand its impact on cancer treatment outcomes and the overall health of cancer survivors.

The development of a next-generation sequencing panel targeting cannabinoid synthase genes to distinguish between marijuana and hemp.

Hemp and marijuana, both derived from Cannabis sativa L. (C. sativa), are subject to divergent legal regulations due to their different Δ9-tetrahydrocannabinol (Δ9-THC) contents. Cannabinoid synthase genes are considered the key enzymes that determine the chemical composition or chemotype of a particular cultivar. However, existing methods for crop type differentiation based on previous synthase gene theories have limitations in terms of precision and specificity, and a wider range of cannabis varieties must be considered when examining cannabis-based genetic markers. A custom next-generation sequencing (NGS) panel was developed targeting all synthase genes, including Δ9-THC acid synthase, cannabidiolic acid synthase, and cannabichromenic acid synthase, as well as the pseudogenes across diverse C. sativa samples, spanning reference hemp and marijuana, commercial hemp derivatives, and seized marijuana extracts. Interpretation of NGS data revealed a relationship between genotypes and underlying chemotypes, with the principal component analysis indicating a clear distinction between hemp and marijuana clusters. This differentiation was attributed to variations in both synthase genes and pseudogene variants. Finally, this study proposes a genetic cannabis classification method using a differentiation flow chart with novel synthase markers. The flow chart successfully differentiated hemp from marijuana with a 1.3% error rate (n = 147).

Cardiotoxic effects of common and emerging drugs: role of cannabinoid receptors.

Drug-induced cardiotoxicity has become one of the most common and detrimental health concerns, which causes significant loss to public health and drug resources. Cannabinoid receptors (CBRs) have recently achieved great attention for their vital roles in the regulation of heart health and disease, with mounting evidence linking CBRs with the pathogenesis and progression of drug-induced cardiotoxicity. This review aims to summarize fundamental characteristics of two well-documented CBRs (CB1R and CB2R) from aspects of molecular structure, signaling and their functions in cardiovascular physiology and pathophysiology. Moreover, we describe the roles of CB1R and CB2R in the occurrence of cardiotoxicity induced by common drugs such as antipsychotics, anti-cancer drugs, marijuana, and some emerging synthetic cannabinoids. We highlight the 'yin-yang' relationship between CB1R and CB2R in drug-induced cardiotoxicity and propose future perspectives for CBR-based translational medicine toward cardiotoxicity curation and clinical monitoring.

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.

Association Between Marijuana Use and Clinical Outcomes After Coronary Artery Bypass Grafting.

INTRODUCTION: Though marijuana use has been linked to an increase in heart failure admissions, no prior study has explored the association between its use and outcomes after coronary artery bypass grafting (CABG). This study examines the relationship between marijuana use and postoperative outcomes in CABG patients. METHODS: We utilized data from the National Inpatient Sample database from 2008 to 2018 for CABG patients ≥18 y old. Patients were divided into two groups based on marijuana use (abuse/dependency versus nonuse). Primary outcomes include in-hospital mortality, favorable discharge, and length of stay (LOS). Secondary outcomes include acute kidney injury (AKI), acute myocardial infarction (AMI), and transient ischemic attack (TIA)/stroke. A multivariable model, adjusted for confounding variables, was utilized for each outcome. RESULTS: A total of 343,796 patients met inclusion criteria for the study, 590 of which were marijuana users. In both marijuana user and nonuser groups, most patients were male and White with an average age of 56.0 and 66.3 y, respectively. There was a nonsignificant decreased odds of in-hospital mortality among marijuana users (odds ratio [OR] = 0.41, [0.141-1.124]). Marijuana users exhibited significantly decreased odds of home discharge (OR = 1.50, [1.24-1.81]), and increased odds of longer LOS (mean 10.4 d versus 9.8 d; OR = 1.14, [1.09-1.20]), AKI (OR = 1.40, [1.11-1.78]), AMI (OR = 1.56, [1.32-1.84]), and TIA/stroke (OR = 1.64, [1.21-2.22]). CONCLUSIONS: Marijuana use and dependency are associated with increased nonhome discharge, AKI, AMI, TIA/stroke, and longer LOS. Further studies are needed to delineate the pathophysiologic derangements that contribute to these unfavorable post-CABG outcomes.

Cannabis use is associated with reduced access to kidney transplantation and an increased risk of acute rejection post-transplant.

BACKGROUND: The association between cannabis use and access to waitlisting, transplantation, and post-transplant outcomes remains uncertain. METHODS: Patients referred for kidney transplant (KT) to the University Health Network from January 1, 2003, to June 30, 2020, and followed until December 31, 2020, were included. Predictors of reported cannabis use were examined using a logistic regression model. The association between cannabis use and time to clearance for KT, undergoing KT, and post-transplant outcomes was evaluated using Cox proportional hazards models. RESULTS: Among 3734 patients, the prevalence of reported cannabis use was 11.8%. Cannabis use was associated with a lower likelihood of KT clearance (adjusted hazard ratio [aHR] .82 [95% confidence interval (CI): .72, .94]). Once cleared for KT, cannabis use did not predict the subsequent receipt of KT (aHR .92, [95% CI: .79, 1.08]). Among 2091 KT recipients, cannabis use was associated with a higher likelihood of biopsy-proven acute rejection (aHR 1.55, [95% CI: 1.06, 2.27]). The relative hazard of death-censored graft failure was similarly elevated (aHR 1.60 [95% CI: .95, 2.72]). Cannabis use did not predict total graft failure (aHR 1.33 [95% CI: .90, 1.96]), death with graft function (aHR 1.06 [95% CI: .59, 1.89]), or hospital readmission in the first-year post-transplant (aHR 1.26 [95% CI: .95, 1.68]). CONCLUSIONS: Cannabis users have less access to transplantation and an increased risk of acute rejection, possibly leading to more graft loss. Further studies are warranted to understand possible mechanisms for the increased risk of allograft immune injury among cannabis users.

Cannabis use and the prevalence of current asthma among adolescents and adults in the United States.

OBJECTIVES: Cannabis use has increased among adolescents and adults in the United States (US) in recent years. Few data are available on the prevalence of asthma by frequency of cannabis use. This study aimed to estimate the prevalence of asthma by frequency of past 30-day cannabis use among US individuals. METHODS: Data were drawn from the 2020 National Survey on Drug Use and Health (NSDUH), a nationally representative, annual cross-sectional survey of US individuals aged 12 and older in the United States (N = 32,893). Logistic regression models were used to examine the relationship between frequency of any cannabis and/or blunt (i.e., cannabis smoked in a hollowed-out cigar) use in the past 30 days and current asthma, adjusting for demographics and current cigarette smoking. RESULTS: Current asthma was more common among US individuals who reported cannabis use in the past 30-days, relative to those who did not (9.8% vs. 7.4%, p < 0.0001). The odds of asthma was significantly greater among individuals reporting cannabis use 20-30 days/month (Adjusted Odds Ratio [AOR] = 1.67, 95% CI:1.21, 2.31), blunt use 6-15 and 20-30 days/month (AOR = 1.9, 95% CI:1.1, 3.2; AOR = 2.2, 95% CI:1.4, 3.6), respectively, than among those without. A positive linear relationship was observed between frequency of a) cannabis use (p < 0.0001) and b) blunt use (p < 0.0001) and current asthma prevalence. CONCLUSIONS: Findings suggest a dose-response relationship between frequency of current cannabis use and the prevalence of current asthma in the US individuals.

Distress about social problems and tobacco and cannabis use outcomes among young adults in Los Angeles County.

OBJECTIVE: To examine associations of concern, worry, and stress about discrimination, shootings/violence, and police brutality and exclusive and dual tobacco and cannabis use among young adults. METHODS: A prospective, racially/ethnically diverse cohort of young adults (n = 1960) living in Los Angeles, California completed a baseline survey in 2020 (age range: 19-23) and a follow-up survey in 2021. Exploratory factor analysis (EFA) was employed on nine variables assessing levels of concern, worry, and stress about societal discrimination, societal shootings/violence, and community police brutality at baseline. Past 30-day tobacco and cannabis use at follow-up was categorized as current exclusive tobacco, exclusive cannabis, and dual tobacco and cannabis (vs never/former) use based on eleven use variables. Multinomial logistic regressions estimated adjusted associations between each factor score (translated to standard deviation units) with exclusive and dual tobacco and cannabis use. RESULTS: The EFA produced four factor scores representing concern/worry/stress (i.e., distress) about community police brutality (F1), distress about societal shootings/violence (F2), and distress about societal discrimination (F3), as well as generalized stress about police brutality, shootings/violence, and discrimination (F4). F1, F2, and F3 were associated with subsequent exclusive current cannabis use, with F1 having the strongest association (OR: 1.35, 95% CI: 1.18-1.55), while only F1 (OR: 1.51, 95% CI: 1.27-1.78) was associated with dual tobacco and cannabis use. None of the factors were associated with exclusive tobacco use. CONCLUSIONS: Young adult concern, worry, and/or stress about social problems may increase risk of cannabis use with or without concurrent tobacco use 6-12 months later.

Perceived racism and discrimination and youth substance use in the United States - Intersections with sex and ethnicity.

OBJECTIVES: This study sought to examine associations between U.S. adolescents' perceived racism and discrimination (PRD) at school and current substance use. METHODS: Data were drawn from the Adolescent Behaviors and Experiences Survey (ABES), a probability sample of U.S. high school students in 2021 (n = 7705). Multivariable regression models were conducted to examine associations of PRD with current (past 30-day) use of tobacco products, marijuana, alcohol, and prescription opioid misuse. Interaction effects of PRD and demographic factors were tested. RESULTS: Among participants in the 2021 ABES, PRD was associated with higher odds of current use of tobacco (AOR = 1.3, p = 0.03), marijuana (AOR = 1.3, p = 0.03), alcohol (AOR = 1.2, p = 0.03), and misuse of prescription opioids (AOR = 1.6, p = 0.004). The effects of PRD on current tobacco and alcohol use differed by Hispanic and non-Hispanic adolescents (interaction effect = 0.007 and 0.01, respectively) with higher odds among Hispanic youth than among non-Hispanic counterparts. The associations of PRD and current tobacco use, marijuana use, alcohol use, and misuse of prescription opioids were moderated by sex with more pronounced effects on males than females. CONCLUSIONS: Efforts to promote awareness and create support environments that value diversity and inclusivity at school are needed to mitigate adolescent exposure to racism and discrimination.

Cannabinoid hyperemesis syndrome co-occurring with superior mesenteric artery syndrome in adolescents.

OBJECTIVES: Both superior mesenteric artery syndrome (SMAS) and cannabinoid hyperemesis syndrome (CHS) may present with abdominal pain, nausea, and emesis - making them difficult to differentiate or determine when they co-occur in adolescents who regularly use cannabis. Here, we present nine cases of CHS co-occurring with SMAS and characterize their clinical courses. METHODS: Patients admitted at Children's Hospital of Colorado between January 1, 2015, and March 23, 2023, who had both cannabis use (F12.1-F12.99) and chronic vascular disorders of the intestine (K55.1) on their problem lists were identified from the electronic medical record using ICD 10 codes. Nine met criteria for SMAS and chronic cannabis use. RESULTS: Six of nine patients were female. The most common presenting symptoms were nausea (9), vomiting (9), and weight loss (9). Four patients received cannabis cessation support. Patients lost a mean of 6.0 kg, had an average body mass index (BMI) of 15.61 percentile (17.7 kg/m2) and BMI Z-scores of -1.5. Symptoms were present for a mean of 19.6 weeks before diagnosis. CONCLUSIONS: Adolescents who experience nausea, vomiting, abdominal pain, and weight loss in association with chronic cannabis use and/or SMAS can present with confusing and overlapping symptoms. Our cohort was described as having CHS with co-occurring SMAS on imaging. Although the etiology of weight loss cannot be definitively ascertained, we postulate that the recurring emetic attacks from CHS led to weight loss resulting in SMAS. Improvement in diagnostic criteria for this population as well as cannabis cessation programming may aid in deceasing morbidity from these co-occurring conditions.

Marijuana use among community-dwelling older adults: A population-based study.

OBJECTIVES: There is a paucity of population-level data on marijuana use and mental health and functioning in older adults. METHODS: We analyzed cross-sectional data (n = 910) from a well-characterized cohort, the Monongahela-Youghiogheny Healthy Aging Team (MYHAT) study. MYHAT is an age-stratified random sample of the population age 65 years and older from a small-town in the USA. Half the sample was female and half were over 75 (Mean age = 77). Most participants were non-Hispanic White. Marijuana use was assessed by self-report and symptoms of mood disorders were screened using the modified Centers for Epidemiological Studies-Depression Scale and the Generalized Anxiety Disorder screener. Cognition was assessed by the Mini-Mental State Examination and a neuropsychological test battery; functioning using the OARS Activities of Daily Living and Instrumental Activities of Daily Living; and overall assessment using the Clinical Dementia Rating (CDR®). RESULTS: One in five MYHAT participants had a history of marijuana use and 5% reported recent use, primarily for pain (41%) and recreation/relaxation (37%). Recent use was associated with cigarette and alcohol use, symptoms of depression or anxiety, and impairments in attention. CONCLUSIONS: Twenty-percent of community-dwelling older adults living in a US state where recreational marijuana use is illegal had a history of marijuana use. Recent marijuana use was less common but, consistent with prior research, associated with other substance use and poorer mental health.

Alcohol and substance use in older adults with treatment-resistant depression.

INTRODUCTION: Alcohol and substance use are increasing in older adults, many of whom have depression, and treatment in this context may be more hazardous. We assessed alcohol and other substance use patterns in older adults with treatment-resistant depression (TRD). We examined patient characteristics associated with higher alcohol consumption and examined the moderating effect of alcohol on the association between clinical variables and falls during antidepressant treatment. METHODS: This secondary and exploratory analysis used baseline clinical data and data on falls during treatment from a large randomized antidepressant trial in older adults with TRD (the OPTIMUM trial). Multivariable ordinal logistic regression was used to identify variables associated with higher alcohol use. An interaction model was used to evaluate the moderating effect of alcohol on falls during treatment. RESULTS: Of 687 participants, 51% acknowledged using alcohol: 10% were hazardous drinkers (AUDIT-10 score ≥5) and 41% were low-risk drinkers (score 1-4). Benzodiazepine use was seen in 24% of all participants and in 21% of drinkers. Use of other substances (mostly cannabis) was associated with alcohol consumption: it was seen in 5%, 9%, and 15% of abstainers, low-risk drinkers, and hazardous drinkers, respectively. Unexpectedly, use of other substances predicted increased risk of falls during antidepressant treatment only in abstainers. CONCLUSIONS: One-half of older adults with TRD in this study acknowledged using alcohol. Use of alcohol concurrent with benzodiazepine and other substances was common. Risks-such as falls-of using alcohol and other substances during antidepressant treatment needs further study.

Legalization and retail availability of recreational marijuana and adolescent use in schools.

Legalization of use and retail sales of recreational marijuana in U.S. states and the associated potential increase in access to marijuana and normalization of its use by adults could lead to increased use by adolescents. Studies have found that states with legal recreational marijuana have higher rates of adolescent use and frequency of use compared to states without legal use. We examined changes in student office discipline referrals (ODRs) for substance use offenses in Oregon middle and high schools before and after the legalization of recreational marijuana relative to comparison schools in other states. We found that rates of substance use related ODRs in middle schools increased by 0.14 per 100 students (30% of the mean) with legalization relative to comparison schools. This increase was moderated by the presence of a marijuana outlet within one mile of the school. We found no statistically discernible changes in high school ODRs. Marijuana use in adolescence has been linked to negative health and social consequences, including academic problems, mental health issues, and impaired driving. Potential adverse impact on adolescents and investments in school-based prevention programs could be important considerations for policymakers and public health officials when evaluating marijuana legalization.

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.

Predictors of changes in marijuana consumption in Germany during the covid-19 pandemic.

During the Covid-19 pandemic Germany experienced its first increase in the proportion of heavy cannabis users since 1995. With the expected nationwide decriminalization of cannabis before 2025, we investigate the potential causes for that increase. Data were from the 2021 European Web Survey on Drugs (EWSD) including 762 12-month marijuana users from Germany (72.9% male, mean age = 29.5 years). Both heavy and regular cannabis consumers reported an increase in marijuana consumption during the pandemic, with infrequent users reporting a decrease. Using multinomial logistic regression, we found younger individuals (OR = 0.95 [95% CI = 0.92, 0.98]) and those not pursuing or completing higher education (OR = 1.86 [1.23, 2.81]) had increased use. Additionally, using cannabis to self-medicate (OR = 2.79 [1.56, 4.99]) and purchasing marijuana (OR = 2.26 [1.35, 3.77]) was associated with increased use. We found, relative to infrequent users, both regular (OR = 4.00 [2.39, 6.72]) and notably heavy users (OR = 31.17 [12.10, 80.32]) were more likely to use cannabis to self-medicate. Both regular (OR = 4.09 [2.47, 6.77]) and especially heavy users (OR = 13.53 [6.74, 27.16]) were also more likely to purchase marijuana. Heavy users were also more likely to be past 30-day tobacco users (OR = 5.92 [2.81, 12.45]). We identified the self-reported motivation of using cannabis to self-medicate as well as act of purchasing marijuana as having the strongest relation to being a heavy user and increasing marijuana use during the Covid-19 pandemic.