Addiction最新文献

Background and aims: Although cannabis use is widespread and prevalence of cannabis use disorder (CUD) is increasing, limited advancements have been made in CUD medication development. The objective of this study was to test the efficacy of varenicline with medical management for reducing cannabis use in treatment-seeking individuals with CUD.

Design: A phase 2, randomized, double-blind, parallel group, placebo-controlled trial was conducted.

Setting: Two outpatient research clinics in South Carolina, USA, from February 2020 to February 2023.

Participants: Eligible participants met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for CUD and used cannabis a minimum of 3 days per week. One hundred and seventy-four participants were randomized to either varenicline (n = 90) or placebo (n = 84) stratified by smoking status and sex.

Interventions: Varenicline (titrated to goal dose of 1 mg twice daily) or matching placebo for 12 weeks. Medical management was provided weekly.

Measurements: Primary outcome measure was reduction in total number of cannabis use sessions at each weekly visit (weeks 6-12).

Findings: There was no main effect of treatment on reduction of total number of cannabis use sessions per week during weeks 6 through 12 [between group difference (Δ) = 1.7; 95% confidence interval (CI) = -1.0 to 4.7; P = 0.41]; however, a statistically significant treatment by sex interaction was found (F_1,132 = 5.1; P = 0.026), with a statistically significant effect of varenicline on reduction of cannabis use sessions per week observed in men (Δ = 4.2; 95% CI = 0.6-7.8; P = 0.04) but not women (Δ = -1.4; 95% CI = -5.7 to 3.0; P = 0.18).

Conclusions: Varenicline with medical management resulted in decreased cannabis use among men with cannabis use disorder seeking treatment, but not women (no effect was observed on the overall sample of treatment-seeking individuals with cannabis use disorder).

Background and aims: While half of the states in the United States of America (USA) have approved statewide retail sales of cannabis, local governments retain the authority to opt in or out of authorizing storefront recreational cannabis retailers. This study aimed to examine local-level associations between the authorization of storefront recreational cannabis retailers and cannabis-related healthcare encounters in California, USA.

Design: A secondary data analysis of cannabis-related healthcare encounters across 482 cities in California from 2010 to 2020. A spatial difference-in-differences model was employed at the city-quarter level to assess both intracity and intercity associations, controlling for time-varying city-level policies and sociodemographic factors while accounting for spatial influence over neighboring cities.

Setting: California, USA.

Participants: All California residents from 2010 to 2020.

Measurements: Three cannabis-related healthcare encounter outcomes were assessed: (1) population-adjusted emergency department visits, (2) population-adjusted inpatient discharges, and (3) a binary indicator of any calls to poison centers. The primary policy variable was whether a city authorized storefront recreational cannabis retailers.

Findings: No statistically significant intracity association was found between the authorization of storefront recreational cannabis retailers and rate of emergency visits [-0.14 percentage points; 95% confidence interval (CI) = -18.24 to 17.97; P = 0.988], rate of inpatient discharges (-6.11 percentage points; 95% CI = -17.58 to 5.36; P = 0.297) or probability of any poison center calls (-2.58 percentage points; 95% CI = -6.18 to 1.02; P = 0.161). For intercity associations, authorizing storefront recreational cannabis retailers was associated with a 6.75 percentage point decrease (95% CI = -12.46 to -1.03; P = 0.021) in the probability of any poison center calls in neighboring cities, suggesting that local cannabis policies may have influence extending beyond their immediate jurisdictions.

Conclusions: In California, USA, the local authorization of storefront recreational cannabis retailers appears to be associated with a reduction in cannabis-related poison center calls in neighboring cities rather than within the policy-implementing cities.

Background and aims: Xylazine, an alpha-2 agonist used in veterinary anesthesia, is increasingly detected in the illicit opioid supply but little is known about the patient level factors associated with xylazine in non-fatal opioid overdose. This study aimed to determine the demographic and clinical factors associated with xylazine detection among emergency department (ED) patients with opioid overdose.

Design: Observational study. The Toxicology Investigators Consortium (ToxIC) Fentalog Study is a multicenter, prospective cohort of adult patients with suspected opioid overdose. This analysis included patients enrolled from September 2020 to September 2023.

Setting: In this multicenter study, participating sites included 10 institutions across 9 states in 4 regions of the United States (US): Northeast, Southeast, Midwest and West.

Participants: Patients were eligible for Fentalog Study inclusion if they were at least 18 years old, had a suspected opioid overdose and had waste blood available for toxicologic analysis. Only patients with qualitative serum detection of illicit opioids and/or xylazine were included in the final cohort. Of 5554 patients screened, 1289 were eligible for Fentalog Study inclusion.

Measurements: Based on results of liquid chromatography with a quadrupole time-of-flight mass spectrometer (LCQTOF-MS) and/or liquid chromatography with a triple quadrupole mass spectrometer (LC-QQQ-MS), patients were categorized into those with xylazine detected (positive cases) and without xylazine detected (negative controls). To determine clinical variables associated with xylazine detection, the primary outcome of interest was qualitative detection of xylazine on serum sampling by LCQTOF-MS.

Findings: Xylazine was detected in 238 patients. Patients with xylazine were primarily male (78%), white (48%), non-Hispanic (82%) and located in the Northeast US (75%). Bradycardia on initial ED vital signs was associated with higher likelihood of xylazine detection (adjusted odds ratio = 2.11, 95% confidence interval = 1.06-4.06).

Conclusions: Xylazine detection among emergency department opioid overdose patients appears to be more prevalent in the Northeast US and bradycardia appears to be a statistically significant clinical predictor.

Background and aims: Lower risk guidelines for safer levels of cannabis use could help to reduce the health burden posed by cannabis use disorder (CUD). We aimed to estimate risk thresholds for CUD based on delta-9-tetrahydrocannabinol (THC) consumption using standard THC units (1 unit = 5 mg THC).

Design: Data from the CannTeen study, a longitudinal observational study consisting of five assessments over a 12-month period.

Setting: London, UK.

Participants: Participants were n = 65 adults aged 26-29 (46% female, 70.77% white ethnicity) and n = 85 adolescents aged 16-17 (56% female, 65.48% white ethnicity). All participants reported at least one use of cannabis during the 12-month study period.

Measurements: Mean weekly standard THC units were estimated using the Enhanced Cannabis Timeline Followback, a comprehensive and validated assessment of quantity, frequency and potency of cannabis consumed. This was administered at 3-month intervals and averaged over a 12-month period. Past 12-month diagnosis of CUD using The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) was assessed at the final follow-up. Receiver operating characteristic curve models estimated the extent to which weekly standard THC unit consumption could discriminate no CUD from any CUD (mild, moderate or severe), and no CUD from moderate/severe CUD, in adults and adolescents separately. Risk thresholds were selected based on cut-offs that maximised sensitivity and specificity.

Findings: Discrimination accuracy of weekly standard THC units on CUD was good, with area under the curve > 0.70 for all models. Optimal cut-offs for risk of any CUD (versus no CUD) were 8.26 units per week for adults and 6.04 units per week for adolescents. For risk of moderate/severe CUD (versus no CUD) optimal cut-offs were 13.44 units per week for adults and 6.45 units per week for adolescents.

Conclusions: Weekly cannabis consumption based on standard delta-9-tetrahydrocannabinol (THC) units appears to show good discrimination accuracy of cannabis use disorder at different severities and in different age groups. Safer levels of cannabis use, defined by low weekly standard THC unit consumption, could be recommended in lower risk cannabis use guidelines.

Background and aims: The typical Marijuana Purchase Task (MPT) assesses hypothetical demand (i.e. relative reinforcing value) for cannabis across escalating prices. Cannabis demand has been related to use frequency, craving, cannabis use disorder symptoms and cue-exposure response, among other outcomes. This study assessed MPT performance for hypothetical consumption in relation to in vivo behavior in the laboratory wherein rewards were actualized.

Methods: Individuals endorsing cannabis use at least twice weekly (n = 92) participated in a laboratory cannabis self-administration study. Participants completed MPTs for Hypothetical and Actual cannabis. One trial (i.e. amount purchased at specified price) was randomly selected from the Actual MPT and participants with non-zero value trials (n = 81) were permitted to smoke up to that amount during a 1-hour session in the laboratory.

Results: Bivariate Pearson correlations demonstrated that cannabis consumption preferences were highly similar across the Hypothetical and Actual MPT at the price (rs = 0.45-0.81) and index (rs = 0.46-0.81) level. However, mean O_max (i.e. maximum expenditure), P_max (i.e. price at maximum expenditure) and breakpoint (i.e. price suppressing consumption to zero), were statistically significantly higher (ds = 0.47-0.51), and elasticity (i.e. consumption decline rate relative to price increase) was statistically significantly lower (d = -0.58) for the Actual MPT compared with the Hypothetical MPT; this was also evident at certain price points. Self-reported anticipated consumption was statistically significantly related to the amount of cannabis smoked during self-administration (R² = 0.66; P < 0.001) and was not moderated by price of the randomly selected trial.

Conclusions: High correspondence between Hypothetical and Actual Marijuana Purchase Task (MPT) performance in a laboratory setting suggests that hypothetical versions of the MPT may be broadly valid measures of cannabis demand. The robust relationship between anticipated consumption and actual cannabis quantity smoked in the laboratory suggests individual self-report accurately predicts subsequent self-administration, further supporting the construct validity of hypothetical MPTs.

Background and aims: Clinicians have little guidance on the ideal length of time patients should remain on medication treatment for opioid use disorder (MOUD) before being able to safely discontinue MOUD. This study estimated how the risk of all-cause mortality changes with the duration of MOUD, controlling for patient characteristics that change the risk profile independent of duration of therapy.

Design, setting and participants: Retrospective cohort study using electronic health record data from the US Veterans Healthcare Administration. Veterans initiating MOUD with buprenorphine, methadone or extended-release naltrexone from October 2010 to September 2020. Our analytic sample included 19 666 buprenorphine initiators, 8675 methadone initiators and 4007 extended-release naltrexone initiators.

Measurement: Duration of MOUD was measured in days. Discontinuation was defined as a gap in any MOUD coverage exceeding 28 days, regardless of MOUD type initiated. The primary outcome was all-cause mortality. We estimated multistate survival models allowing for the modeling of multiple states (i.e. on and off MOUD, death) without having to consider censoring or competing events, while adjusting for sociodemographic, clinical, prescription and facility and provider characteristics.

Findings: We observed approximately 226 000 person-years of time at risk for discontinuation or pre-discontinuation death, during which we observed 26 841 discontinuations (118.9 discontinuations per 1000 person-years). We similarly observed a total of about 106 000 person-years of post-discontinuation follow-up, during which we observed 3251 deaths (3.1 deaths per 1000 person-years). We found the largest marginal gain in probability of 6-year survival from an additional year on MOUD appears to occur around 2 years, as compared to 6 months on MOUD. Statistically significant gains continued through approximately 4-5 years of MOUD retention relative to 6-month MOUD retention. After 4-5 years, the marginal gain from one additional year of MOUD was not statistically significant.

Conclusions: Among US veterans, the benefit of retention on medication treatment for opioid use disorder (MOUD) towards overall survival continues through at least 4 years of MOUD treatment. Quality metrics based on 6-month MOUD retention may be insufficient.

Background and aims: Extensive critique of the evidence-based policy paradigm has led to new ways of considering the role of evidence; for example Katherine Smith suggests that "ideas" rather than evidence mediate "the relationship between research and policy". In this paper, we used Smith's typology on "ideas" to explore how this can be applied to a case of Australian policy making: a police diversion scheme for simple possession of drugs. We aimed to analyse the idea's journey into policy in one Australian jurisdiction (New South Wales) and assess its fit with the four different types of ideas outlined by Smith.

Method: Qualitative case study analysis using data from New South Wales, Australia, over the period 2018 to 2024. Multiple data sources were used: interviews with stakeholders (n = 26), documents [reports, non-governmental organization (NGO) advocacy documents], media and official reports of a Drug Summit. Each data source was searched for narration/text concerned with police diversion in addition to decriminalisation, extracted and analysed against Smith's typology.

Results: Features of 'institutionalised ideas' suggest that police diversion is not an institutionalised idea. It appears in this case to be a 'chameleonic idea' inasmuch as its characteristics change and are malleably deployed by different stakeholders with different interests. 'Flexian policy actors' (including police, government officials, advocates and researchers) are able to interpret, transform and shape the meaning of police diversion to suit their interests and commitments. Despite evidence synthesis and expert review recommending police diversion as a second-best option to decriminalisation, it was taken up into policy. We suggest this is because of its chameleonic nature, serving simultaneously at the hands of different policy actors as a roadblock to decriminalisation and as a Trojan horse for decriminalisation reform whilst also obscuring tensions between police diversion and decriminalisation.

Conclusions: Applying Katherine Smith's typology of ideas to an Australian police diversion scheme for simple possession of drugs shows that the scheme is not an institutionalised idea but rather a chameleonic idea. Smith's typology of ideas adds another layer to policy process frameworks, enhancing analysis seeking to understand the uptake of ideas into policy.