Cannabis cue-reactivity in cannabis use disorder: Diverging evidence in two distinct cannabis cultures.

BACKGROUND: Cannabis policies and attitudes play a role in the development and presentation of cannabis use disorder (CUD), but it is unclear how these factors are related to biomarkers of addiction. The current study examined cross-cultural differences in cannabis attitudes, cannabis cue-reactivity in the brain and its associations with cannabis use measures and cannabis attitudes. DESIGN: Cross-sectional fMRI study. SETTING: The Netherlands (NL) and Texas (TX), USA. PARTICIPANTS: 104 cannabis users with CUD (44% female; NL-CUD = 54, TX-CUD = 50) and 83 non-using controls (52% female; NL-CON = 50, TX-CON = 33). MEASUREMENTS: Self-reported positive (perceived benefits) and negative (perceived harms) cannabis attitudes and tactile cannabis cue-reactivity assessed using a 3T MRI scanner. FINDINGS: While the CUD group overall was more positive and less negative about cannabis and reported higher craving, the TX-CUD group reported significantly more positive and less negative attitudes and less craving than the NL-CUD group. Cannabis cue-reactivity was observed in the CUD group in clusters including the precuneus, lateral occipital cortex, frontal medial cortex, nucleus accumbens, and thalamus. In the TX-CUD group, a positive association was observed between symptom severity and cue-induced craving and cannabis cue-reactivity in precuneus and occipital cortex clusters, while a negative association was observed in the NL-CUD group. In these clusters, individuals with more positive attitudes exhibited a positive association between craving and cue-reactivity and those with less positive attitudes exhibited a negative association. No associations with quantity of use were observed. CONCLUSIONS: Cue-induced craving might be deferentially associated with cannabis cue-reactivity across distinct cannabis use environments.

Patterns of Use and Withdrawal Syndrome in Dual Cannabis and Tobacco Users (DuCATA_GAM-CAT): Protocol for a Mixed Methods Study.

BACKGROUND: Approximately 1 in 6 cannabis users develop a cannabis use disorder (CUD) and the odds increase to 1 in 2 for daily users. OBJECTIVE: The Dual use of Cannabis and Tobacco Monitoreing through a Gamified Web app (DuCATA_GAM-CaT) project aims to identify cannabis-tobacco patterns of use and withdrawal symptoms among individuals with CUD who are attending substance abuse programs. METHODS: The project uses a mixed methods approach consisting of 3 studies. First, a participatory qualitative study involves focus groups comprising individuals with CUD, clinicians, project researchers, and an expert gamification company to co-design a gamified web app. Second, a longitudinal prospective study to follow up individuals over 6 weeks with CUD attending substance abuse programs . Participants report their cannabis-tobacco usage patterns, type and frequency of tobacco use, nicotine dependence, withdrawal symptoms, psychoemotional factors, and motivation to quit both substances. Predictive analysis techniques are used to analyze clinical, demographic, psychological, and environmental data to predict the probability of achieving abstinence. Third, homogeneous focus groups to explore participants' experiences during their CUD treatment. RESULTS: By June 2024, the project had completed the first study, defining eligible cannabis user profiles, developed the initial web app prototype, and initiated recruitment across 10 centers, with 74 participants enrolled, aiming to reach 150 participants in total. CONCLUSIONS: All participants are required to provide informed consent, and their information is kept confidential and anonymized following confidentiality rules. The research team is committed to disseminating the results obtained to professional and patient groups, as well as informing public health agents, to positively influence political and social decision makers and design programmers. Additionally, we aim to prioritize the publication of the results in high-impact journals specialized in drug abuse, public health, and health care services research. TRIAL REGISTRATION: ClinicalTrials.gov NCT05512091; https://clinicaltrials.gov/study/NCT05512091. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/58335.

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.

Exploring the Utility of a Functional Magnetic Resonance Imaging (fMRI) Cannabis Cue-Reactivity Paradigm in Treatment Seeking Adults with Cannabis Use Disorder.

BACKGROUND: Functional magnetic resonance imaging (fMRI) studies examining cue-reactivity in cannabis use disorder (CUD) have either had small sample sizes or involved non-treatment-seeking participants. As a secondary analysis, we administered an fMRI cue-reactivity task to CUD participants entering two separate clinical trials (varenicline or repetitive Transcranial Magnetic Stimulation-rTMS) to determine the task activation patterns for treatment-seeking participants with CUD. We aimed to determine the activation patterns for the total sample and determined behavioral correlates. We additionally compared studies to determine if patterns were consistent. METHODS: Treatment-seeking participants with moderate or severe CUD had behavioral craving measured at baseline via the short form of the Marijuana Craving Questionnaire (MCQ-SF) and completed a visual cannabis cue-reactivity task during fMRI (measuring the Blood-Oxygen-Level-Dependent-BOLD response) following 24-hours of cannabis-abstinence. RESULTS: Sixty-five participants were included (37-varenicline, 28-rTMS; 32% female; mean-age 30.4±9.9SD). When contrasting cannabis-images vs. matched-neutral-images, participants showed greater BOLD response in bilateral ventromedial-prefrontal, dorsolateral-prefrontal, anterior cingulate, and visual cortices, as well as the striatum. There was stronger task-based functional-connectivity (tbFC) between the medial prefrontal cortex and both the amygdala and the visual cortex. Craving negatively correlated with BOLD response in the left ventral striatum (R2=-0.32; p=0.01) in the full sample. There were no significant differences in either activation or tbFC between studies. DISCUSSION: Among two separate treatment-seeking groups with CUD, there was increased cannabis cue-reactivity and tbFC in regions related to executive function and reward processing. Cannabis-craving was negatively associated with cue-reactivity in the left ventral striatum.

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.

Association Between Cannabis Use and Brain Structures: A Mendelian Randomization Study.

Background  Observational studies suggested that cannabis use was associated with alternation of brain structures; however, as subjected to confounding factors, they were difficult to make causal inferences and direction determinations. In this study, a two-sample Mendelian randomization (MR) analysis was employed to examine the potential causal association between cannabis use and brain structures. Methods The genome-wide association studies (GWAS) data for lifetime cannabis use (LCU), cannabis use disorder (CUD), and brain cortical and subcortical structures were utilized in this study. Cortical structures were divided into 34 distinct gyral-defined regions with surface area (SA) and thickness (TH) measured. Subcortical structures encompassed volumes from seven specified regions. The primary estimator used in our analysis was inverse-variance weighted (IVW), complemented by MR-Egger and weighted median methods to enhance the robustness of the results. The Cochran's Q test, funnel plots, and MR-Egger intercept tests were used to detect heterogeneity and pleiotropy. Results  No causal relationship was detected between LCU and global cortical SA or TH. However, at the regional cortex level, LCU was associated with decreased TH in the fusiform (ß = -0.0168 mm, SE = 0.00581, P = 0.0039) and lateral occipital (ß = -0.0141 mm, SE = 0.00531, P = 0.0079) regions, while increasing TH in the postcentral region (ß = 0.0093 mm, SE = 0.00445, P = 0.0374). At the subcortical level, LCU was found to increase the brainstem volume (ß = 0.224 mm3, SE = 0.09, P = 0.0128). CUD did not show any causal association with brain structure at either cortical or subcortical levels. Nonetheless, after applying multiple comparison corrections, the P values for the MR analysis of causal relationships between cannabis use and these brain structures did not meet the significance threshold. Conclusion  The evidence for cannabis use causally influencing brain structures is insufficient.

Cannabis use disorder and substance use treatment among U.S. adults.

INTRODUCTION: Recent expansion of cannabis legalization in multiple states calls for reexamination of the prevalence of cannabis use, cannabis use disorder (CUD), and the associations between CUD severity and substance use treatment. We used Andersen's behavioral model of healthcare use as the conceptual/analytic framework for examining treatment use. METHODS: We used data from the 2022 National Survey on Drug Use and Health (NSDUH; N = 47,100, age 18+) to describe the prevalence of past-year cannabis use, CUD and CUD severity, other substance use disorders, and substance use treatment. We compared sociodemographic, mental health, healthcare use, and cannabis and other substance use characteristics by CUD severity. Finally, we used logistic regression models to examine the associations between CUD severity and substance use treatment. RESULTS: Of the U.S. adult population, 23.0 % used cannabis in the past year; 7.0 % had a CUD (3.9 % mild, 1.9 % moderate, and 1.2 % severe CUD); and 4.7 % received substance use treatment. Of past-year cannabis users, 30.3 % had CUD (16.9 % mild, 8.4 % moderate, and 5.0 % severe CUD), and 9.6 % received substance use treatment. Cannabis users had 3-4 times higher rates of other substance use disorders than nonusers. Of those with CUD, 38.4 % had moderate/severe mental illness, 52.4 % had other substance use disorders, and 16.5 % received substance use treatment. Among all cannabis users, moderate (aOR [adjusted odds ratios] = 1.48, 95 % CI = 1.03-2.13) and severe (aOR = 2.57, 95 % CI = 1.60-4.11) CUDs were associated with greater odds of substance use treatment. Among cannabis users without nicotine dependence and alcohol, opioid, tranquilizer/sedative, and stimulant use disorders, only severe CUD (aOR = 6.03, 95 % CI = 3.37-10.78) was associated with greater odds of substance use treatment. CONCLUSIONS: This study shows increased prevalence of cannabis use and CUD among U.S. adults, and with or without other substance use disorders, CUD was associated with greater odds of substance use treatment. However, the overall low rate of treatment use among those with CUD is concerning. Healthcare providers need to provide education for both medical and recreational users on the development of tolerance and dependence. Harm reduction strategies to minimize the negative consequences of CUD are also needed.

Cannabis use patterns and association with hyperemesis: A comprehensive review.

BACKGROUND: Cannabis use in the general population is prevalent and is rising because of increased acceptance of its use, legalization in most US states, and perceived health benefits. Cannabis product potency has dramatically increased with higher delta-9-tetrahydrocannabinol content. Cannabis has documented antiemetic properties and cannabinoid pharmaceuticals are used in disorders like chemotherapy-induced nausea and vomiting. PURPOSE: Forty to eighty percent of cyclic vomiting syndrome (CVS) patients use cannabis products, which reportedly reduce stress as well as nausea and vomiting. Cannabinoid hyperemesis syndrome (CHS) has a presentation similar to CVS, but is associated with longstanding, high dose cannabis use, and is thought to be relieved by sustained cannabis abstinence. Most CHS patients have used cannabis on a daily or near-daily basis for more than 2 years. Compulsive hot-water bathing behaviors are reported by most CHS patients, but are not specific for this disorder as they are also noted by about half of CVS patients. Episodic vomiting associated with cannabis use contributes to extensive health resource use, including emergency department visits and inpatient hospitalizations, and impacts patients and their families negatively. Treatment for CHS overlaps with CVS although cannabis abstinence remains the cornerstone of its management. Challenges associated with cannabis use cessation in CHS include patient skepticism of the role of cannabis as a cause of symptoms, perceived benefits of cannabis, and a lack of other effective therapies. In this review, we highlight cannabis use patterns in the US and discuss diagnosis and management of CHS and gaps in knowledge about this disorder.

Discriminative validity of a substance use symptom checklist for moderate-severe DSM-5 cannabis use disorder (CUD) in primary care settings.

Background: The prevalence of cannabis use disorder (CUD) is increasing in the US and primary care providers need tools to identify patients with moderate-severe CUD to facilitate treatment. A single-item screen for cannabis (SIS-C) has outstanding discriminative validity for CUD. However, because the prevalence of moderate-severe CUD is typically low, the probability that an average patient who screens positive for daily cannabis has moderate-severe cannabis use disorder is low, making follow-up assessment important. Methods: This study reports the discriminative validity of a DSM-5 Substance Use Symptom Checklist ("Checklist") for moderate-severe CUD among 498 primary care patients who reported daily cannabis use on the SIS-C. We evaluated the performance of the Checklist (score 0-11) completed during routine care, compared to ≥4 DSM-5 CUD symptoms (moderate-severe CUD) on the Composite International Diagnostic Interview Substance Abuse Module from a confidential survey (reference standard). We estimated areas under receiver operating curve (AUROC), sensitivities, specificities, and post-test probabilities. Results: Of 498 eligible patients, 17 % met diagnostic criteria for moderate-severe CUD. The Checklist's AUROC for moderate-severe CUD was 0.77 (95 % CI: 0.71-0.83), and Checklist scores of 1-2 balanced sensitivity and specificity. Among patients from a population with average prevalence of CUD before screening (~6 % prevalence) and daily use on the SIS-C, a Checklist score of 3 indicated a post-test probability of 82.1 %. Conclusion: Overall performance of the Checklist was good and the high specificity made it useful for identifying patients likely to have moderate-severe CUD among those at average risk.

Urgent need for treatment addressing co-use of tobacco and cannabis: An updated review and considerations for future interventions.

BACKGROUND: There are no clinical practice guidelines addressing the treatment of tobacco-cannabis co-use and a dearth of studies to inform treatment for co-use. This narrative review aims to (1) summarize promising intervention components used in published co-use treatment studies, (2) describe key gaps and emerging issues in co-use, and (3) provide recommendations and considerations in the development and evaluation of co-use interventions. METHODS: We conducted a literature search in June 2024 across several databases to update previous reviews on tobacco-cannabis co-use treatment. We found 9 published intervention studies that specifically addressed treatment for both substances. Data from these studies were manually extracted and summarized. RESULTS: Most of the 9 included studies (1) focused on acceptability and/or feasibility, (2) provided both psychosocial/behavioral and pharmacotherapy intervention components, (3) were conducted in adults, and (4) were delivered in-person, with some having digital asynchronous components, for a 5-to-12-week duration. The most common psychosocial/behavioral strategies used were Cognitive Behavioral Therapy, Motivational Interviewing, and Contingency Management; while the most common pharmacotherapy was Nicotine Replacement Therapy. There was no evidence of compensatory use of tobacco or cannabis when providing simultaneous treatment for both substances. CONCLUSIONS: The literature to date provides support for well-integrated multi-component interventions of psychosocial/behavioral and pharmacotherapy strategies for co-use treatment. This review reinforces an urgent need for treatments targeting tobacco and cannabis co-use. Future interventions should address key gaps, including co-use of vaporized products among youth and young adults, tailored interventions for priority populations, and digital applications to increase reach and advance health equity.

Can the THC concentration predict the number of patients with cannabis-related diagnoses?

INTRODUCTION: The use of high-potency cannabis products is associated with an increased risk of mental disorders. This study investigates whether the rising THC concentration in Germany is associated with an increase in cannabis-related diagnoses. METHODS: The number of insured persons with at least one cannabis-related ICD-10 F12 diagnosis (e.g., harmful use, dependence) in outpatient care was provided by statutory health insurance funds between 2009 and 2021. The dependent variable is the ratio of (a) the number of insured persons with at least one F12 diagnosis to (b) all insured persons who have used cannabis in the last year. Information on THC concentration in cannabis flower was provided by law enforcement agencies. Using generalised mixed linear models, the dependent variable was predicted by the median THC concentration in cannabis flower. RESULTS: The regression results show that an increase in THC concentration by one percentage point is significantly associated with an increase in the proportion of diagnoses (women: +0.17; men: +0.42). THC concentration positively predicted the proportion of diagnoses in all 16 federal states for men and in 15 federal states for women. DISCUSSION AND CONCLUSIONS: Compared to low-potency products, using high-potency products may pose additional health risks, which may be particularly pronounced in men. Acknowledging the limitations of the ecological study design and uncertainties inherent to the analysed data, further investigations on the sex-specific impact of THC exposure are required. Limiting the THC concentration in cannabis products and closely monitoring THC consumption in the population appears necessary.

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.

Extended-Release Mixed Amphetamine Salts for Comorbid Adult Attention-Deficit/Hyperactivity Disorder and Cannabis Use Disorder: A Pilot, Randomized Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To determine if treatment of co-occurring adult ADHD and Cannabis Use Disorder (CUD) with extended-release mixed amphetamine salts (MAS-ER) would be effective at improving ADHD symptoms and promoting abstinence. METHOD: A 12-week randomized, double-blind, two-arm pilot feasibility trial of adults with comorbid ADHD and CUD (n = 28) comparing MAS-ER (80 mg) to placebo. Main outcomes: ADHD: ≥30% symptom reduction, measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS). CUD: Abstinence during last 2 observed weeks of maintenance phase. RESULTS: Overall, medication was well-tolerated. There was no significant difference in ADHD symptom reduction (MAS-ER: 83.3%; placebo: 71.4%; p = .65) or cannabis abstinence (MAS-ER: 15.4%; placebo: 0%; p = .27). MAS-ER group showed a significant decrease in weekly cannabis use days over time compared to placebo (p < .0001). CONCLUSIONS: MAS-ER was generally well-tolerated. The small sample size precluded a determination of MAS-ER's superiority reducing ADHD symptoms or promoting abstinence. Notably, MAS-ER significantly reduced weekly days of use over time.

Treating young adult cannabis use disorder with text message-delivered peer network counseling.

BACKGROUND: Approximately 16.5% of U.S. young adults have a cannabis use disorder (CUD) and are at risk for negative outcomes. Treatment can reduce cannabis use, but young adults are less likely to seek help than older adults. Peer Network Counseling-txt (PNC-txt) is a brief, text-delivered, Motivational Interviewing-informed substance use intervention focusing on peer relations and activity spaces as mechanisms for behavioral change. PNC-txt has shown evidence of reducing tobacco and cannabis use with adolescents and young adults, but it has not been tested in the context of legal cannabis use. The current randomized controlled trial sought to expand the evidence regarding the context of PNC-txt effects, comparing one state in which cannabis is legal (Colorado) and one state in which it is not (Tennessee). We hypothesized that participants randomized to PNC-txt would show significant reductions in cannabis use compared to controls, with larger reductions for females and those in Colorado, and that peer relations and activity space would mediate effects. METHODS: One thousand, seventy eight 18-25 year olds (CO: 551; TN: 527) who met screening criteria for CUD and biologically-verified cannabis use were randomly assigned to PNC-txt or waitlist control condition. Every other day for 4 weeks, participants assigned to PNC-txt received pre-programmed text conversations, tailored via data from the baseline assessment. Self-report and biological indicators of cannabis use were measured at 1-, 3-, and 6-months. DISCUSSION: Data analysis is underway. Results will provide evidence regarding whether, and how, PNC-txt reduces cannabis use in young adults with CUD. TRIAL REGISTRATION: This trial was prospectively registered on September 28, 2020 with ClinicalTrials.gov (NCT04567394).

Significant Psychedelic Experiences Evaluated for Mystical Characteristics Associated with Cannabis Use Reduction and Psychological Flexibility Improvement: A Naturalistic Cross-Sectional Retrospective Survey.

Treating cannabis use disorder remains a significant challenge in the field of addiction medicine. Some recent studies point to psychedelic-assisted psychotherapy as a potential treatment option for substance use disorders. The objective of this study was therefore to explore the impact of naturalistic psychedelic experiences on cannabis use and psychological flexibility. An online retrospective survey was carried out on 152 cannabis users who also reported a significant experience induced by psychedelics in the past. Following a psychedelic experience, there was a significant and sustained reduction of average CUDIT score (p < .001), frequency of cannabis use (p < .001), and acute duration of daily intoxication (p < .001). Cannabis use reduction during the first month post-experience was significantly associated with the intensity of the mystical experience (p = .01). Participants reported a concomitant increased lasting improvement of psychological flexibility following the experience (p < .001), which was correlated to the intensity of the mystical experience during the first month post-experience (p = .04). This study demonstrates that naturalistic psychedelic experiences may be followed by a decrease in cannabis use. Positive health outcomes appear potentially connected to the intensity of the mystical experience, as well as an improvement in psychological flexibility.

The moderating role of sex in the relationship between cannabis use treatment admission profile and treatment processes and outcomes: A gender perspective.

BACKGROUND: Gender-specific interventions are crucial in addressing substance use disorders -particularly cannabis use disorder - as they allow for tailored therapeutic approaches and increase the likelihood of successful outcomes. However, differences in therapeutic processes and outcomes between males and females are often not observed, making the prognosis and development of such interventions more difficult. OBJECTIVE: This study aimed to examine the moderating role of sex in the relationship between treatment admission profile characterized by indicators of cannabis use and sociodemographic sources of gender inequality (e.g., employment status) and adherence and outcome at discharge. METHOD: A multicentric retrospective observational study was conducted with a sample of 3,814 outpatients diagnosed with cannabis use disorder. Electronic health records were used for data analysis. RESULTS: The interaction between sex and the number of children, as well as pre-treatment cannabis use, predicted lower treatment adherence, particularly among females. Additionally, the interaction between sex and the number of children predicted outcomes at discharge, with females showing a higher likelihood of dropout compared to males. DISCUSSION AND CONCLUSION: Enhanced comprehensive treatment with intensified contingency management programs should be prioritized for females (especially those with children) who have consumed cannabis in the month before treatment. Adopting a treatment policy framework incorporating sex/gender-sensitive therapist training and evaluative measures is essential for optimizing treatment outcomes for all patients.

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.

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.

Changes in prenatal cannabis-related diagnosed disorders after the Cannabis Act and the COVID-19 pandemic in Quebec, Canada.

BACKGROUND AND AIMS: Public health concerns regarding pregnant women's health after the enactment of the Cannabis Act in Canada (CAC) (a law that allowed non-medical cannabis use), and the potential impact of the COVID-19 pandemic, call for a contemporary assessment of these two events. Our study measured associations between the CAC, the COVID-19 pandemic and the monthly prevalence rates of cannabis-, all drug- and alcohol-related diagnosed disorders among pregnant women in the province of Quebec. DESIGN, SETTING AND PARTICIPANTS: This was a quasi-experimental design applying an interrupted time-series methodology in the province of Quebec, Canada. The participants were pregnant women aged 15-49 years, between January 2010 and July 2022. MEASUREMENTS: Administrative health data from the Québec Integrated Chronic Disease Surveillance System were used to classify pregnant women according to cannabis-, all drug (excluding cannabis)- and alcohol-related disorders. The CAC (October 2018) and the COVID-19 pandemic (April 2020) were evaluated as (1) slope changes and (2) level changes. Cannabis-, all drug (excluding cannabis)- and alcohol-related disorders were measured by total monthly age-standardized monthly prevalence rate of each disorder for pregnant women aged 15-49 years. FINDINGS: Before the CAC, the prevalence rate of cannabis-related diagnosed disorders significantly increased each month by 0.5% [95% confidence interval (CI) = 0.3-0.6] in the pregnant population. After the CAC, there were significant increases of 24% (95% CI = 1-53) of cannabis-related diagnosed disorders. No significant changes were observed for all drug (excluding cannabis)- and alcohol-related diagnosed disorders associated with the CAC. A non-significant decrease of 20% (95% CI = -38 to 3) was observed during the COVID-19 pandemic in alcohol-related disorders. CONCLUSIONS: The monthly incidence rates of diagnosed cannabis-related disorders in pregnant women in Quebec increased significantly following the enactment of the Cannabis Act in Canada. Diagnoses of all drug (excluding cannabis)- and alcohol-related disorders remained relatively stable.