An Epidemiological Hypothesis of Policy-Shaped Drug Use Onset Curves Epidemiological Hypothesis of Policy-Shaped Drug Use Onset Curves.

show that 14 to 18 is the of for use of and most with extra-medical to encompass using the to get and by a US estimates generally show that consuming the ‘first full drink’ of an alcoholic beverage is an exception to this pattern of a single mid-adolescent peak. Age-specific incidence of drinking alcohol follows a distinctive bimodal pattern with the mid-adolescent peak followed by a sharp decline, a second peak at the US legal minimum drinking age of 21 years, and then a continuous decline as age increases [5-7]. In this paper, we use the acronym PDPD to denote this specific peak-decline-peak-decline bi-modal pattern. Cheng, et al. [7] focused on the legal minimum drinking age (LMA) in their explanation of the PDPD pattern in the age-specific estimates. They posited existence of two heterogeneous subgroups within each birth cohort. A more law-abiding subgroup of adolescents ABSTRACT Introduction: For most drugs, age-specific incidence peaks during the mid-adolescent years and then declines. Alcohol is the exception with a viable explanatory theory of heterogeneous subgroups within the US population regarding attention to the law. A natural experiment of this hypothesis is underway as states legalize and regulate cannabis similarly to alcohol. We forecast the emergence of a bimodal cannabis incidence pattern as states set minimum cannabis purchase age at 21 years. Methods: The population under study for these analyses are non-institutionalized civilian residents of the U.S., 12 years of age and older, as sampled and assessed for the National Surveys on Drug Use and Health (NSDUH), from 2010 to 2017. The sample is stratified by cannabis LMA policy- Colorado State and Washington State (CSWS) are the experimental group compared to the other 48 states as controls. We use two different methods of comparing age-specific cannabis incidence estimates by policy group. Results: The estimates using the panel study method for the 48 US states produced the traditional age-specific cannabis incidence pattern. In CSWS, however, the estimated cannabis incidence rises sharply at age 21, descending afterward. The incidence estimates at age 21 after implementation in CSWS quadrupled (from 5% to 21%). Discussion: These contrasting estimates do not yet qualify as strong evidence supporting the hypothesis that cannabis policy is shaping age-specific incidence in our hypothesized bimodal pattern. The lag time for seeing such policy effects might be as long as 5-10 years if cannabis follows the US experience with alcohol LMA.


Introduction
United States (US) estimates show that ages 14 to 18 years old is the interval of peak risk for starting extra-medical use of tobacco and most internationally regulated drugs (EMIRD), with extramedical use defined to encompass using the drug to get high and otherwise outside boundaries intended by a prescribing clinician (EMIRD as defined in supplemental material appendix S1; e.g., [1][2][3][4]). US estimates generally show that consuming the 'first full drink' of an alcoholic beverage is an exception to this pattern of a single mid-adolescent peak. Age-specific incidence of drinking alcohol follows a distinctive bimodal pattern with the mid-adolescent peak followed by a sharp decline, a second peak at the US legal minimum drinking age of 21 years, and then a continuous decline as age increases [5][6][7]. In this paper, we use the acronym PDPD to denote this specific peak-decline-peak-decline bi-modal pattern. Cheng, et al. [7] focused on the legal minimum drinking age (LMA) in their explanation of the PDPD pattern in the age-specific estimates.
They posited existence of two heterogeneous subgroups within each birth cohort. A more law-abiding subgroup of adolescents might tend to delay onset of drinking a 'first full drink' until LMA is reached at age 21 years. Another subgroup of cohort members give less attention to the LMA policy, with drinking onset soon after the first chance to try [i.e., first alcohol exposure opportunity, as discussed by Chen, et al. [8]]. If this hypothesis is correct, readers in countries with no LMA policy might find no bimodal pattern (cf. [9]). With respect to cannabis, a natural LMA experiment is underway in the United States, with some jurisdictions setting cannabis LMA at age 21 years [10]. If Cheng and colleagues are correct, the age-specific incidence patterns in these jurisdictions might shift, eventually, toward the bimodal pattern seen for alcohol.
In this short communication, we present starting estimates on this policy topic as a forecast of what might become a congruent PDPD pattern for age-specific cannabis incidence rates. Our results depict recent age-specific cannabis use incidence patterns in Colorado and in Washington State by year, each with age 21 LMA for cannabis, and we compare incidence rates in states with no cannabis LMA [11,12].

Material and Methods
For this epidemiological study, the population was specified to year of first cannabis use, from which age-specific incidence rates can be estimated from the NSDUH Restricted Data Access portal (R-DAS). The R-DAS portal provides analysis weights and variance estimate capabilities for state-specific and national estimates and 95% confidence intervals (CI).
For this research, the primary estimate is age-specific first- , where X r is the number of individuals starting to use cannabis within the 1-12 month interval before assessment, age-by-age, and N r is all persons who had not started using cannabis before that interval, stratified by cannabis LMA policy. Estimates described in this report are not readily available in R-DAS. The estimated prevalence rates ( the corresponding standard errors can be obtained. We note that the incidence can be calculated in term of p 1 and p 2 as: The corresponding variance can be calculated using the standard statistical procedures as: Where N is the projected population size in all 50 states and NCW N is the projected population size in every state except Colorado and Washington. Then, the corresponding variance of can be calculated as:    is just above 20%. Here, again, the statistical precision of estimates based on the R-DAS datasets is constrained. We must express hope for earlier rather than later access to the larger NSDUH samples and more recent data now sequestered in the restricted data enclaves until the COVID pandemic has ended.

Discussion
In this short communication, we build from the recent alcohol LMA hypothesis offered by Cheng, et al. [7] and we present evidence that a corresponding cannabis LMA hypothesis might deserve attention in future research. Acknowledging constraints on the statistical precision of the cannabis incidence estimates presented in Figures 1 & 2, we look forward to pursuit of this research line once we are allowed to tap the more complete NSDUH data in the now-restricted federal enclaves. In the meantime, readers might be interested to know how an LMA policy might exert an influence on epidemiology's patterns of age-specific incidence rates. In turn, the epidemiologically disclosed age-specific patterns can be used to guide organization and deployment of public health tactics of early outreach and intervention, as well as prevention initiatives intended to reduce hazards of drug use onsets during adolescence and the transition to early adulthood.
Limitations of the research include reliance upon self-reports about age and timing of cannabis onsets as well as uncontrolled confounding between states. In time, the public use dataset sample sizes also will be addressed when the enclave datasets become available, and re-opening of the data enclaves will make it possible to investigate sub-state variations, given that some within-CSWS jurisdictions do not permit retail cannabis sales.
Notwithstanding these limitations, these analyses demonstrate the potential for a large shift in long-standing patterns in age of first use for cannabis in the US. Additionally, the study findings are of interest because the hypothesis that LMA may be shaping agespecific drug use incidence has never been tested. However, the lag time for seeing such policy effects might take 5-10 years if cannabis follows the experience with alcohol legal minimum age in the US [13].
If this pattern continues to develop, there are new public health considerations for this age group as well as the design and implementation of cannabis prevention campaigns. Targeted prevention campaigns for alcohol and tobacco use have been one of the larger successes of public health and prevention, partly due to age-specific and appropriately timed targeting [14,15]. In a deviation from the traditional perspective that early adolescence is the optimal window for prevention, if the hypothesized development of the PDPD pattern continues, public health campaigns that seek to reduce cannabis use may be optimized in separate approaches for the law-ignoring teens who first use cannabis illegally vs.
the 21-year-olds who wait until cannabis use is legal for them.
Although more research is needed to investigate the theorized policy-induced curve, if a sufficient number of states follow in the footsteps of Colorado and Washington, we may see the age-specific incidences for first time cannabis use begin to resemble the PDPD pattern in the country overall [16,17].

BWM: MSU Graduate School University Enrichment Fellowship
• JCA: None to declare.

Conflicts of Interest
• BWM: None to declare.