We are in a critical window for linking science with cannabis policymaking. Researchers can increase the influence of their studies by using (1) stronger research designs, (2) causal inference methods, (3) improved taxonomies of treatment and control jurisdictions, (4) explicit conceptual frameworks and (5) intersectional methods to explore subpopulation effects. Amid sweeping momentum world-wide to repeal cannabis bans, evaluations of non-medical cannabis laws have proliferated. However, cross-sectional designs [1] or inappropriate design choices [2] limit many of these studies. The article by Gunadi, Zhu & Shi demonstrates the potential for using causal inference methods in longitudinal settings to overcome these methodological hurdles [3]. Their work underscores the need to refine research conceptualization and methods to more clearly inform policy discussions. Taxonomies that classify jurisdictions according to the restrictiveness of their cannabis policy environments [4] may allow researchers to identify more appropriate control and treatment locations. Currently, evaluations of non-medical cannabis legalization are too heterogeneous to meta-analyze [5]. Some of this heterogeneity may arise from the profoundly different ways jurisdictions that fall under the same stage of cannabis legalization (i.e. illegal, decriminalized, medical cannabis or non-medical cannabis) regulate cannabis sale and consumption [6-9]. When this is the case, grouping these jurisdictions together to form treatment and control conditions will probably reduce researchers’ odds of detecting associations. Increasing attention to legalization time-lines presents another opportunity to strengthen the links between non-medical cannabis policy research and policymaking processes. Building a non-medical cannabis market is a lengthy process in which different aspects emerge and stabilize at different times [9]. However, thus far, the most rigorous evaluations of non-medical cannabis legalization have focused upon the effective date of non-medical cannabis legalization policies and used short time-frames [10-12]. Reliance upon this design suggests that our best evidence thus far fails to capture the consequences of non-medical cannabis markets themselves. Instead, these studies evaluate eliminating penalties for adult cannabis use, often the sole aspect of new cannabis regulatory regimes in place on the legislation's effective date. This design also cannot differentiate between short- and long-term effects [13]. It is dangerous to design permanent laws and regulations based on the measurement of short-term effects that have more to do with penalties than the operation of formal markets. Identifying best practices and political priorities will also require greater clarity concerning the aspect(s) of non-medical cannabis legalization hypothesized to underlie studied associations. Legalizing non-medical cannabis is but the first step in a long journey of designing regulatory regimes that govern sale and consumption of non-medical cannabis, including policies on pricing, dispensary locations and operations, marketing and home-growing. These decisions may affect mechanisms such as setting prices, increasing access and/or product potency, altering the public's perception of cannabis risks, establishing social norms and shaping stigma related to the cannabis black market [8, 13]. More explicit conceptual frameworks will facilitate testing pathways for policy effects that can more clearly inform policy recommendations. Finally, researchers can facilitate the implementation of equitable non-medical cannabis policies by investigating heterogeneous treatment effects and unintended consequences of laws and regulations. The harms that arise from legalization will depend upon which subpopulations change their cannabis use after the legalization of non-medical cannabis [13]. Currently, studies tend to classify respondents into two broad populations: adolescents and adults. Separating youth and adults is an essential foundation; however, understanding the role of laws and regulations in cannabis-related disparities requires stratification, statistical interactions and/or data-driven algorithms to unpack differential responses and effects across diverse subpopulations [14]. A more intersectional approach could provide insight into whether laws and regulations designed to remedy structural racism in fact contribute to it. As the Reagan-initiated ‘War on Drugs’ in the United States demonstrated, cannabis laws can have starkly disparate consequences for historically marginalized populations. It is essential to involve community members in policy development processes and explore potential continued injustices, such as disparities in cannabis penalties [15, 16], the role of black markets [4, 17] and the potentially inequitable distribution of cannabis dispensaries [18, 19], to prevent similar injustices in the future. Researchers are in a critical window for informing non-medical cannabis policymaking. The literature has progressed far enough to identify future directions for research, but not far enough to maximize its potential for policy influence. First, ensuring methodological rigor through longitudinal designs, causal inference methods and more accurate taxonomies of treatment and control jurisdictions may increase researchers’ chances of detecting significant associations and producing defensible findings. Secondly, making conceptual frameworks explicit and using longer time-frames may clarify the public health relevance of cannabis market commercialization and specific policies and regulations, allowing policymakers to identify political priorities. Finally, engaging community members in policymaking and policy research and investigating subpopulation effects and unintended consequences of policies may produce evidence that more clearly informs larger policymaker and community concerns regarding disparities and equity. None. None. Pamela J. Trangenstein: Conceptualization; writing – original draft preparation. David H. Jernigan: Writing – review & editing.

No abstract is available for this article.

No abstract is available for this article.

To estimate the prevalence of family members affected by addictive disorders (FMA) with regard to various types of addictive disorders, and self-rated health and depression in the general population. Cross-sectional general population survey. The German Health Update study (GEDA) 2014/2015, a nationally representative panel of German residents aged 15 years or older. A total of 24 824 residents aged 15 years or older. Participants were asked if they had a family member with current or past addictive disorder, the type of addiction and the relationship status. In addition, self-rated health and depression were assessed using standardized questionnaires. Of the respondents, 9.5% [95% confidence interval (CI) = 9.0-10.0] reported being affected by a current addictive disorder of a relative (cFMA), with a further 4.5% (95% CI = 4.2-4.9) reported having been affected by the addictive disorders of a relative in the past but not within the last 12 months (pFMA). Most FMAs reported having been affected by disorders due to alcohol, followed by cannabis and other drugs. Compared with life-time non-FMAs, FMAs reported significantly (P < 0.001) higher odds ratios for depression (cFM = 2.437; 95% CI = 2.082-2.853; pFMA = 1.850; 95% CI = 1.519-2.253) and ill-health (cFMA = 1.574; 95% CI = 1.374-1.805; pFMA = 1.297; 95% CI = 1.082-1.555). In Germany, family members affected by addictive disorder are a substantial group within the general population. This group is characterized by ill-health and has not yet been adequately addressed by the addiction treatment system.

We appreciate the insightful commentary by Jauncey et al. [1] on our trial comparing intranasal and intramuscular naloxone administered by ambulance personnel [2]. We fully support their conclusion regarding early and, if necessary, repeated naloxone administration, and that bystanders always should call for an ambulance. Jauncey et al. raise concern regarding our finding that 20% in the nasal group did not reach a respiratory rate of 10/minute within 10 minutes. However, it is unlikely that these patients were apnoeic during the 2-minute interval of progressive naloxone antagonism. Regardless, a rapid response by peers in a community setting is vital to prevent cardiac arrest. In our trial intramuscular and intranasal administration were compared head-to-head, not a regimen of incremental and repeated doses. Our finding that a single intranasal naloxone dose of 1.4 mg naloxone hydrochloride restored respiration in as much as 80% in 10 minutes convinced us that this is an adequate starting-point for titration. Most community naloxone kits consist of two or more doses, and re-administration of antidote should be at the core of bystander training. In the community setting, the time to a rescue dose of naloxone should be faster than the 10-minute interval in our trial. Early administration and calling of emergency services allow for naloxone to work during the ambulance dispatch time, preventing a deepening intoxication. Fentanyl and its analogues are dangerous drugs, and the increasing number of deaths by these potent opioids is a major worry. Death from fentanyl may differ from death by other opioids, as they may induce muscular rigidity and vocal closure that hinder respiration [3-5], in addition to the development of slow or absent breathing, leading to hypoxia and hypercarbia characteristic to all opioids. There is too little scientific evidence on the naloxone doses that are needed to antagonize fentanyl overdose [6-9]. Naloxone doses in the 4–8-mg range are now being introduced without clear scientific rationale that such high doses are needed—we know without doubt that high doses of naloxone precipitate acute withdrawal. Duration of response is indeed a major worry, but the initial administration of massive doses of naloxone, rather than titration based on individual response, risks over-antagonizing not only the individual patient, but also the trust that community-based naloxone programmes need. Acute withdrawal is an avoidable harm, and not a trivial matter. In addition, the introduction of the 4-mg spray may have increased the risk for severe pulmonary complications in overdose victims [10]. The field of opioid overdose needs more quality research to move naloxone dosing from anecdotes to evidence. We are afraid that increasing the dose of naloxone may decrease willingness to use naloxone in the community. The most significant factors for successful take-home naloxone programmes are that bystanders are present at overdoses, that they can identify an overdose, that they carry naloxone and that they are willing to use it—and always call for an ambulance. None. A.K.S. and I.T. have nothing to disclose. O.D. reports grants from Regional Health Trust, Central Norway, grants from St Olav's University Hospital, Trondheim, Norway, and grants from the Laerdal Foundation during the conduct of the study, and the Norwegian University of Science and Technology (NTNU). The NTNU has signed a collaboration and licensing agreement with Dne Pharma (Oslo, Norway) to commercialize the nasal spray. Dne Pharma has received marketing authorization for a naloxone nasal spray (Ventizolve/Respinal) based on this collaboration. The formulation was invented by O.D., and the agreements ensure potential royalties for him through NTNU and NTNU's subsidiary Technology Transfer (TTO). The agreements do not restrict NTNU's opportunity to publish results from its own research on the product. O.D. was the principal investigator (no personal honorarium) for Dne Pharma on a study of naloxone spray in volunteers and has been reimbursed for project-related journeys between Oslo and Trondheim. He has received honoraria and travel support from Dne Pharma for presentations on marketing events. AKS, IT and OD has contributed equally in the writing of this letter.

To quantify the trends in frequent and occasional cannabis vaping, demographic differences and concurrent nicotine and alcohol use. Observational study. Survey-weighted multinomial logistic regression models assessed trends and disparities in past 30-day cannabis use. Trends were assessed overall and by sex, race/ethnicity, parental education and urbanicity. Multinomial logistic regression models also estimated associations of cannabis use (none, use without vaping, use with vaping) with past 2-week binge drinking and past 30-day nicotine/tobacco use. United States, 2017-19. Participants in the national Monitoring the Future (n = 51 052) survey. Past 30-day frequent cannabis use (six or more times/30 days) and past 30-day occasional use (one to five times/30 days), with and without vaping. Past 30-day frequent cannabis use with vaping and occasional use with vaping rose from 2017 to 2019. Past 30-day frequent and occasional cannabis use without vaping declined. Certain groups, such as Hispanic/Latino or lower socio-economic status adolescents, experienced particularly notable increases in frequent cannabis use with vaping (e.g. prevalence among Hispanic/Latino adolescents). Adolescents who reported smoking and vaping nicotine, and 10+ occasions of binge drinking, were 42.28 [95% confidence interval (CI) = 33.14-53.93] and 10.09 (95% CI = 4.51-22.53) times more likely to report past 30-day cannabis use with vaping, respectively, compared with no use. Cannabis use without vaping appears to be declining among adolescents in the United States, while cannabis use with vaping is accelerating; frequent cannabis vaping is especially increasing, with consistent increases across almost all adolescent demographic groups. Cannabis use among US adolescents remains highly associated with other substance use.

Paul Roman has been a researcher in the alcohol and addictions field for 55 years. He entered Cornell University in 1960, staying through the completion of his PhD in organisational behaviour. It was there he met and worked with Harry Trice, who stimulated his interest in alcoholism in industry. After a year at the University of Georgia, he spent seventeen years at Tulane University, then returning to Georgia.

In the United States, until 2018 both the prevalence of heavy alcohol use and the suicide mortality rate increased among men and women; however, women had experienced a notably higher increase in both. As heavy alcohol use may have contributed to the observed sex disparity in the suicide mortality rate increase, the aim of the current study was to estimate the temporal trend of the sex- and age-group-specific proportion of suicides that were alcohol-involved in the United States. Using restricted-access data from the National Violent Death Reporting System, we performed joinpoint regression analyses to investigate temporal trends in the sex- and age-group (young adults = 18-34 years; middle-aged adults = 35-64 years; and older adults = 65+ years)-specific proportion of suicides that were alcohol-involved. United States. A total of 115 202 suicide decedents 18+ years of age from 2003 to 2018. The sex- and age-group-specific proportion of suicides that were alcohol-involved, among all suicide decedent, for which the decedent had a blood alcohol concentration (BAC) (a) ≥ 0.04 g/dl and (b) ≥ 0.08 g/dl. For 2003-18, the proportion of suicides that were alcohol-involved wherein the decedent had a BAC ≥ 0.08 g/day significantly increased on average annually for women of all age groups [young women: 2.80%, 95% confidence interval (CI) = 1.86%, 3.75%; middle-aged women: 2.20%, 95% CI = 1.20%, 3.21%; older women: 10.48%, 95% CI = 1.17%, 20.65%], while only middle-aged men experienced a significant average annual percentage increase (0.81%, 95% CI = 0.003%, 1.62%). In the United States between 2003 and 2018, alcohol use preceding death by suicide increased among women compared with men.