Background Through increasing cannabis availability, state cannabis legalization has been posited as one potential solution to the opioid crisis by providing an alternative to long-term opioid use for treating chronic pain. Forty U.S. states have legalized cannabis for medical use and 25 for recreational use. We systematically reviewed the literature to investigate the relationship of state medical and recreational cannabis legalization (MCL and RCL, respectively) to rates of opioid prescriptions, nonmedical use, opioid use disorder (OUD), opioid-related hospitalizations and emergency department visits, and overdose deaths. Methods We searched EconLit, EMBASE, MEDLINE, and Web of Science Core Collection for English-language studies published through 10/21/25 that estimated MCL or RCL enactment effects on opioid outcomes compared to states that did not enact such laws. This study is registered with PROSPERO, CRD42023416119. Findings Of 43 eligible studies, 18 investigated MCL, 11 investigated RCL, and 14 investigated both. Findings on MCL, RCL and opioid prescribing were mixed. No study found decreases in non-medical opioid use after MCL enactment; only one study found decreased non-medical use after RCL enactment. No studies found that MCL or RCL decreased OUD. MCL enactment was associated with lower opioid overdose mortality rates in earlier but not more recent studies; studies of RCL and opioid overdose fatalities had inconsistent results.Interpretations.The mixed study findings suggest that MCL and RCL are just two factors in a complex set of influences on opioid outcomes that require further study. Meanwhile, cannabis legalization should not be considered an effective policy for curbing the opioid epidemic.

STUDY OBJECTIVES:Rates of cannabis use disorder (CUD) appear to be increasing nationally, with increases greater in states that legalized cannabis use. However, as legalization has progressed and stigma declined, some of these apparent increases could be due to greater willingness of survey respondents and patients to acknowledge cannabis involvement. Biological indicators of cannabis use overcome some concerns about trends denoted by self-report data whose validity is potentially changing over time. Our objective was to investigate the relationship between medical cannabis laws (MCL) and recreational cannabis laws (RCL) and the prevalence of cannabis-positive urine drug screens (UDS) in a large patient sample. METHODS:Veterans Health Administration (VHA) emergency department (ED) patients aged 18-75 years with ≥1 ED visit for any reason in a given year from 2008 to 2019 were included. Staggered-adoption difference-in-difference analysis was used to estimate the association between MCL and RCL enactment on cannabis-positive UDS, fitting adjusted linear binomial regression models. RESULTS:Adjusted cannabis-positive UDS prevalences increased from 16.4 % to 25.6 % in states with no cannabis law, 16.6 % to 27.6 % in MCL-only-enacting states, and 18.2 % to 33.8 % in RCL-enacting states. MCL-only and RCL enactment was associated with a 0.8 % (95 % CI, 0.4-1.0) and 2.9 % (95 % CI, 2.5-3.3) increase in prevalence of cannabis-positive UDS, respectively. CONCLUSIONS:MCL and RCL enactment played a significant role in the overall increases in cannabis-positive UDS among ED patients. The increase in a biological measure of cannabis use helps reduce concerns about reporting bias as cannabis becomes increasingly legalized.

Background:We investigated whether the associations of state medical and recreational cannabis legalization (MCL, RCL enactment) with increasing prevalence of Cannabis Use Disorder (CUD) differed among patients in the United States (US) Veterans Health Administration (VHA) who did or did not have common psychiatric disorders. Methods:Electronic medical record data (2005-2022) were analyzed on patients aged 18-75 with ≥1 VHA primary care, emergency department, or mental health visit and no hospice/palliative care within a given year (sample sizes ranging from 3,234,382 in 2005 to 4,436,883 in 2022). Patients were predominantly male (>80%) and non-Hispanic White (>60%). Utilizing all 18 years of data, CUD prevalence increases attributable to MCL or RCL enactment were estimated among patients with affective, anxiety, psychotic-spectrum disorders, and Any Psychiatric Disorder (APD) using staggered difference-in-difference (DiD) models and 99% Confidence Intervals (CIs), testing differences between patient groups with and without psychiatric disorders via non-overlap in the 99% CIs of their DiD estimates. Findings:Among APD-negative patients, CUD prevalence was <1.0% in all years, while among APD-positive patients, CUD prevalence increased from 3.26% in 2005 to 5.68% in 2022 in no-CL states, from 3.51% to 6.35% in MCL-only states, and from 3.41% to 6.35% in MCL/RCL states. Among the APD group, DiD estimates of MCL-only and MCL/RCL effects were modest-sized, but the lower bound of the 99% CI for the DiD estimate for MCL-only and MCL/RCL effects was larger than the upper bound of the 99% CI among the no-APD group, indicating significantly stronger MCL-only and MCL/RCL effects among patients with APD. Results were similar for MCL-only and MCL/RCL effects among disorder-specific groups (depression, post-traumatic stress disorder [PTSD], anxiety or bipolar disorders) and for MCL/RCL effects among patients with psychotic-spectrum disorders. Interpretation:Cannabis legalization contributed to greater CUD prevalence increases among patients with psychiatric disorders. However, modest-sized DiD estimates suggested operation of other factors, e.g., commercialization, changing attitudes, expectancies. As cannabis legalization widens, recognizing and treating CUD in patients with psychiatric disorders becomes increasingly important. Funding:This study was supported by National Institute on Drug Abuse grant R01DA048860, the New York State Psychiatric Institute, and the VA Centers of Excellence in Substance Addiction Treatment and Education.

Background: Wider availability of cannabis through medical and recreational legalization (MCL alone and RCL+MCL) has been hypothesized to contribute to reductions in opioid use, misuse, and related harms. We examined whether state adoption of cannabis laws was associated with changes in opioid outcomes overall and stratified by cannabis use. Methods: Using National Survey on Drug Use and Health (NSDUH) data from 2015 to 2019, we estimated cannabis law associations with opioid (prescription opioid misuse and/or heroin use) misuse and use disorder. All logistic regression models (overall models and models stratified by cannabis use), included year and state fixed effects, individual level covariates, and opioid-related state policies. Stratified analyses were restricted to individuals who reported lifetime cannabis use prior to law adoption to reduce potential for collider bias. Estimates accounted for multiple comparisons using false discovery rate (FDR) corrections and sensitivity to unmeasured confounding using e-values. Results: Overall, MCL and RCL adoption were not associated with changes in the odds of any opioid outcome. After restricting to respondents reporting past-year cannabis use, we observed decreased odds of past year opioid misuse (adjusted odds ratio [AOR]: 0.57 [95 % confidence interval [CI]: 0.38, 0.85]; FDRp-value: 0.07), among individuals in states with MCL compared to those in states without cannabis laws. RCLs were not associated with changes in the odds of any opioid outcome beyond MCL adoption. Conclusion: Comparing individuals in MCL alone states to those in states without such laws, we found an inconsistent pattern of decreased odds of opioid outcomes, which were more pronounced among people reporting cannabis use. The pattern did not hold for individuals in RCL states. In line with a substitution-oriented perspective, findings suggests that MCLs may be associated with reductions in opioid use among people using cannabis but additional work to replicate and expand on these findings is needed.

BACKGROUND:Understanding sex differences in the effects of cannabis legalization and increasing risk for cannabis use disorder (CUD) is important. We hypothesized that from 2005 to 2019, increases in CUD prevalence due to state medical or recreational cannabis laws (MCL; RCL) would differ among male and female veterans treated at the U.S. Veterans Health Administration (VHA), with greater increases among females. METHODS:Data obtained through the VHA Corporate Data Warehouse included veterans 18-75 years with ≥1 VHA primary care, emergency department, or mental health visit in a given year, 2005-2019. Staggered-adoption difference-in-difference analyses were used to estimate the role of MCL and RCL on trends in CUD diagnostic prevalence, fitting a linear binomial regression model with fixed effects for state and categorical year, time-varying cannabis law status, state-level sociodemographic covariates, patient-level age group (18-35, 36-64, 65-75 years), race and ethnicity. RESULTS:CUD prevalences increased in both sexes. CUD increased more in states enacting MCL and RCL than in states that did not enact CL. However, no CUD prevalence increases attributable to the change from no-CL to MCL-only or MCL to RCL differed significantly by sex, with one exception (greater in males aged 35-64). CONCLUSIONS:Increases in CUD prevalence following MCL or RCL enactment were greater than in states with no-CL, but generally did not show differences by sex. The increases in CUD prevalence occurring for males and females throughout the study years indicate the need for cannabis use screening by medical providers and the importance of offering evidence-based treatments for CUD.

In the United States (U.S.), the prevalence of anxiety and depression is increasing, yet significant barriers to mental health treatment remain. U.S. military veterans are disproportionately affected by anxiety and depression. Many veterans receive medical care within the Veterans Health Administration (VHA), an integrated healthcare system that has enacted clinical initiatives to reduce barriers to mental health treatment. We examined associations between VHA healthcare use and receipt of mental health counseling or prescription medication for anxiety or depression. Cross-sectional nationally representative study. U.S. veterans aged ≥ 18 years with past 12-month healthcare use and anxiety or depression (N = 1,161). In the 2019 National Health Interview Survey, veterans were assessed for their use of the VHA (vs. non-VHA healthcare use) and receipt of past 12-month mental health counseling, prescription medication for anxiety, or prescription medication for depression. Among all veterans with anxiety or depression, only 23

Importance In the context of the US opioid crisis, factors associated with the prevalence of opioid use disorder (OUD) must be identified to aid prevention and treatment. State medical cannabis laws (MCL) and recreational cannabis laws (RCL) are potential factors associated with OUD prevalence. Objective To examine changes in OUD prevalence associated with MCL and RCL enactment among veterans treated at the Veterans Health Administration (VHA) and whether associations differed by age or chronic pain. Design, Setting, and Participants Using VHA electronic health records from January 2005 to December 2022, adjusted yearly prevalences of OUD were calculated, controlling for sociodemographic characteristics, receipt of prescription opioids, other substance use disorders, and time-varying state covariates. Staggered-adoption difference-in-difference analyses were used for estimates and 95% CIs for the relationship between MCL and RCL enactment and OUD prevalence. The study included VHA patients aged 18 to 75 years. The data were analyzed in December 2023. Main Outcome and Measures International Classification of Diseases, Ninth Revision, Clinical Modification ( ICD-9-CM ) or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification ( ICD-10-CM ) OUD diagnoses. Results From 2005 to 2022, most patients were male (86.7.%-95.0%) and non-Hispanic White (70.3%-78.7%); the yearly mean age was 61.9 to 63.6 years (approximately 3.2 to 4.5 million patients per year). During the study period, OUD decreased from 1.12% to 1.06% in states without cannabis laws, increased from 1.13% to 1.19% in states that enacted MCL, and remained stable in states that also enacted RCL. OUD prevalence increased significantly by 0.06% (95% CI, 0.05%-0.06%) following MCL enactment and 0.07% (95% CI, 0.06%-0.08%) after RCL enactment. In patients aged 35 to 64 years and 65 to 75 years, MCL and RCL enactment was associated with increased OUD, with the greatest increase after RCL enactment among older adults (0.12%; 95% CI, 0.11%-0.13%). Patients with chronic pain had even larger increases in OUD following MCL (0.08%; 95% CI, 0.07%-0.09%) and RCL enactment (0.13%; 95% CI, 0.12%-0.15%). Consistent with overall findings, the largest increases in OUD occurred among patients with chronic pain aged 35 to 64 years following the enactment of MCL and RCL (0.09%; 95% CI, 0.07%-0.11%) and adults aged 65 to 75 years following RCL enactment (0.23%; 95% CI, 0.21%-0.25%). Conclusions and Relevance The results of this cohort study suggest that MCL and RCL enactment was associated with greater OUD prevalence in VHA patients over time, with the greatest increases among middle-aged and older patients and those with chronic pain. The findings did not support state cannabis legalization as a means of reducing the burden of OUD during the ongoing opioid epidemic.

BackgroundRates of cannabis use disorder (CUD) have increased disproportionately among Veterans Administration (VA) patients with psychiatric disorders compared to patients with no disorder. However, VA patient samples are not representative of all U.S. adults, so results on disproportionate increases in CUD prevalence could have been biased. To address this concern, we investigated whether disproportionate increases in the prevalence of cannabis outcomes among those with psychiatric disorders would replicate in nationally representative samples of U.S. adults.MethodsData came from two national surveys conducted in 2001-2002 (n = 43,093) and 2012-2013 (n = 36,309). Outcomes were any past-year non-medical cannabis use, frequent non-medical use (>= 3 times weekly), and DSM-IV CUD. Psychiatric disorders included mood, anxiety and antisocial personality disorders. Logistic regression was used to generate predicted prevalences of the outcomes, prevalence differences calculated and additive interactions compared differences between those with and without psychiatric disorders.ResultsCannabis outcomes increased more among those with psychiatric disorders. The difference in prevalence differences included any past-year non-medical cannabis use, 2.45% (95%CI = 1.29-3.62); frequent non-medical cannabis use, 1.58% (95%CI = 0.83-2.33); CUD, 1.40% (95%CI = 0.58-2.21). For most specific disorders, prevalences increased more among those with the disorder.ConclusionsIn the U.S. general population, rates of cannabis use and CUD increased more among adults with psychiatric disorders than other adults, similar to findings from VA patient samples. Results suggest that although VA patients are not representative of all U.S. adults, findings from this important patient group can be informative. Greater clinical and policy attention to CUD is warranted for adults with psychiatric disorders.

IMPORTANCE Given the personal and social burdens of opioid use disorder (OUD), understanding time trends in OUD prevalence in large patient populations is key to planning prevention and treatment services. OBJECTIVE To examine trends in the prevalence of OUD from 2005 to 2022 overall and by age, sex, and race and ethnicity. DESIGN, SETTING, AND PARTICIPANTS This serial cross-sectional study included national Veterans Health Administration (VHA) electronic medical record data from the VHA Corporate Data Warehouse. Adult patients (age >= 18 years) with a current OUD diagnosis (using International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] codes) who received outpatient care at VHA facilities from January 1, 2005, to December 31, 2022, were eligible for inclusion in the analysis. MAIN OUTCOMES AND MEASURES The main outcome was OUD diagnoses. To test for changes in prevalence of OUD over time, multivariable logistic regression models were run that included categorical study year and were adjusted for sex, race and ethnicity, and categorical age. RESULTS The final sample size ranged from 4 332 165 to 5 962 564 per year; most were men (89.3%-95.0%). Overall, the annual percentage of VHA patients diagnosed with OUD almost doubled from 2005 to 2017 (0.60% [95% CI, 0.60%-0.61%] to 1.16% [95% CI, 1.15%-1.17%]; adjusted difference, 0.55 [95% CI, 0.54-0.57] percentage points) and declined thereafter (2022: 0.97% [95% CI, 0.97%-0.98%]; adjusted difference from 2017 to 2022, -0.18 [95% CI, -0.19 to -0.17] percentage points). This trend was similar among men (0.64% [95% CI, 0.63%-0.64%] in 2005 vs 1.22% [95% CI, 1.21%-1.23%] in 2017 vs 1.03% [95% CI, 1.02%-1.04%] in 2022), women (0.34% [95% CI, 0.32%-0.36%] in 2005 vs 0.68% [95% CI, 0.66%-0.69%] in 2017 vs 0.53% [95% CI, 0.52%-0.55%] in 2022), those younger than 35 years (0.62% [95% CI, 0.59%-0.66%] in 2005 vs 2.22% [95% CI, 2.18%-2.26%] in 2017 vs 1.00% [95% CI, 0.97%-1.03%] in 2022), those aged 35 to 64 years (1.21% [95% CI, 1.19%-1.22%] in 2005 vs 1.80% [95% CI, 1.78%-1.82%] in 2017 vs 1.41% [95% CI, 1.39%-1.42%] in 2022), and non-Hispanic White patients (0.44% [95% CI, 0.43%-0.45%] in 2005 vs 1.28% [95% CI, 1.27%-1.29%] in 2017 vs 1.13% [95% CI, 1.11%-1.14%] in 2022). Among VHA patients aged 65 years or older, OUD diagnoses increased from 2005 to 2022 (0.06% [95% CI, 0.06%-0.06%] to 0.61% [95% CI, 0.60%-0.62%]), whereas among Hispanic or Latino and non-Hispanic Black patients, OUD diagnoses decreased from 2005 (0.93% [95% CI, 0.88%-0.97%] and 1.26% [95% CI, 1.23%-1.28%], respectively) to 2022 (0.61% [95% CI, 0.59%-0.63%] and 0.82% [95% CI, 0.80%-0.83%], respectively). CONCLUSIONS AND RELEVANCE This serial cross-sectional study of national VHA electronic health record data found that the prevalence of OUD diagnoses increased from 2005 to 2017, peaked in 2017, and declined thereafter, a trend primarily attributable to changes among non-Hispanic White patients and those younger than 65 years. Continued public health efforts aimed at recognizing, treating, and preventing OUD are warranted.

Purpose To synthesize the available evidence on the extent to which area-level socioeconomic conditions are associated with drug overdose deaths in the United States. Methods We performed a systematic review (in MEDLINE, EMBASE, PsychINFO, Web of Science, EconLit) for papers published prior to July 2022. Eligible studies quantitatively estimated the association between an area-level measure of socioeconomic conditions and drug overdose deaths in the US, and were published in English. We assessed study quality using the Effective Public Health Practice Project Quality Assessment Tool. The protocol was preregistered at Prospero (CRD42019121317). Results We identified 28 studies that estimated area-level effects of socioeconomic conditions on drug overdose deaths in the US. Studies were scored as having moderate to serious risk of bias attributed to both confounding and in analysis. Socioeconomic conditions and drug overdose death rates were moderately associated, and this was a consistent finding across a large number of measures and differences in study designs (e.g., cross-sectional versus longitudinal), years of data analyzed, and primary unit of analysis (e.g., ZIP code, county, state). Conclusions This review highlights the evidence for area-level socioeconomic conditions are an important factor underlying the geospatial distribution of drug overdose deaths in the US and the need to understand the mechanisms underlying these associations to inform future policy recommendations. The current evidence base suggests that, at least in the United States, employment, income, and poverty interventions may be effective targets for preventing drug overdose mortality rates.

ABSTRACT Objective Cannabis use disorders (CUD) are increasing among U.S. adults and are more prevalent among cannabis users with comorbid psychiatric disorders. Changing cannabis laws, increasing cannabis availability, and higher potency cannabis may have recently placed cannabis users with psychiatric disorders at disproportionately increasing risk for CUD. The authors used Veterans Health Administration (VHA) data to examine whether trends in CUD prevalence among VHA patients differ by whether they have psychiatric disorders. Methods VHA electronic health records from 2005 to 2019 (n range=4,332,165-5,657,277) were used to identify overall and age-specific (<35, 35-64, ≥65 years) trends in prevalence of CUD diagnoses among patients with depressive, anxiety, PTSD, bipolar, or psychotic-spectrum disorders, and to compare these to corresponding trends among patients without any of these disorders. Given transitions in ICD coding, differences in trends were tested within two periods: 2005–2014 (ICD-9-CM) and 2016–2019 (ICD-10-CM). Results Greater increases in prevalence of CUD diagnoses were observed in veterans with, compared to without, psychiatric disorders (2005-2014: difference in prevalence change=1.91%, 95% CI=1.87%-1.96%; 2016-2019: 0.34%, 95% CI=0.29%-0.38%). Disproportionate increases in CUD prevalence among those with psychiatric disorders were greatest in veterans ages <35 between 2005-2014, and in those ages ≥65 between 2016-2019. Among patients with psychiatric disorders, greatest increases in CUD prevalences were observed in those with bipolar and psychotic-spectrum disorders. Conclusions Results highlight disproportionately increasing disparities in risk of CUD among VA patients with common psychiatric disorders. Greater public health and clinical efforts are needed to monitor, prevent and treat CUD among this population.

Heavy drinking among people living with HIV (PLWH) reduces ART adherence and worsens health outcomes. Lengthy interventions are not feasible in most HIV care settings, and patients infrequently follow referrals to outside treatment. Utilizing visual and video features of smartphone technology, we developed HealthCall as an electronic means of increasing patient involvement in a brief intervention to reduce drinking and improve ART adherence. The objective of the current study is to evaluate the efficacy of HealthCall to improve ART adherence among PLWH who drink heavily when paired with two brief interventions: the National Institute on Alcoholism and Alcohol Abuse (NIAAA) Clinician’s Guide (CG) or Motivational Interviewing (MI). Therefore, we conducted a 1:1:1 randomized trial among 114 participants with alcohol dependence at a large urban HIV clinic. Participants were randomized to one of three groups: (1) CG only (n = 37), (2) CG and HealthCall (n = 38), or (3) MI and HealthCall (n = 39). Baseline interventions targeting drinking reduction and ART adherence were 25 min, with brief (10–15 min) booster sessions at 30 and 60 days. The outcome was ART adherence assessed using unannounced phone pill-count method (possible adherence scores: 0–100

Observational studies play an increasingly important role in estimating causal effects of a treatment or an exposure, especially with the growing availability of routinely collected real-world data. To facilitate drawing causal inference from observational data, we introduce a conceptual framework centered around "four targets"-target estimand, target population, target trial, and target validity. We illustrate the utility of our proposed "four targets" framework with the example of buprenorphine dosing for treating opioid use disorder, explaining the rationale and process for employing the framework to guide causal thinking from observational data. The "four targets" framework is beneficial for those new to epidemiologic research, enabling them to grasp fundamental concepts and acquire the skills necessary for drawing reliable causal inferences from observational data.

Background: Cannabis legalization for medical and recreational purposes has been suggested as an effective strategy to reduce opioid and benzodiazepine use and deaths. We examined the county-level association between medical and recreational cannabis laws and poisoning deaths involving opioids and benzodiazepines in the US from 2002 to 2020. Methods: Our ecologic county-level, spatiotemporal study comprised 49 states. Exposures were state-level implementation of medical and recreational cannabis laws and state-level initiation of cannabis dispensary sales. Our main outcomes were poisoning deaths involving any opioid, any benzodiazepine, and opioids with benzodiazepines. Secondary analyses included overdoses involving natural and semi-synthetic opioids, synthetic opioids, and heroin. Results: Implementation of medical cannabis laws was associated with increased deaths involving opioids (rate ratio [RR] = 1.14; 95% credible interval [CrI] = 1.11, 1.18), benzodiazepines (RR = 1.19; 95% CrI = 1.12, 1.26), and opioids+benzodiazepines (RR = 1.22; 95% CrI = 1.15, 1.30). Medical cannabis legalizations allowing dispensaries was associated with fewer deaths involving opioids (RR = 0.88; 95% CrI = 0.85, 0.91) but not benzodiazepine deaths; results for recreational cannabis implementation and opioid deaths were similar (RR = 0.81; 95% CrI = 0.75, 0.88). Recreational cannabis laws allowing dispensary sales was associated with consistent reductions in opioid- (RR = 0.83; 95% CrI = 0.76, 0.91), benzodiazepine- (RR = 0.79; 95% CrI = 0.68, 0.92), and opioid+benzodiazepine-related poisonings (RR = 0.83; 95% CrI = 0.70, 0.98). Conclusions: Implementation of medical cannabis laws was associated with higher rates of opioid- and benzodiazepine-related deaths, whereas laws permitting broader cannabis access, including implementation of recreational cannabis laws and medical and recreational dispensaries, were associated with lower rates. The estimated effects of the expanded availability of cannabis seem dependent on the type of law implemented and its provisions.