Additionally, longitudinal epigenetic studies will allow for the examination of the impact of interventions on epigenetic changes. For example, longitudinal examination of smoking-induced DNA methylation patterns identified dynamic and stable markers across time and also observed reversal of smoking induced methylation changes after smoking cessation. Using repeated measures of DNA methylation and marijuana use, we crosssectionally identified numerous marijuana associated epigenetic markers associated at one time point but not the other , including 6 and 10 loci associated with both recent and cumulative marijuana use at Y15 and Y20, respectively. Additionally, one stable epigenetic marker, cg05575921, was associated with both marijuana variables across the examination years with consistent effect estimates . We also performed longitudinal analyses to investigate changes in methylation and marijuana use across the examinations and identified 12 CpGs that varied with change in marijuana use, including markers in AHRR, COL11A2, and TFEB. Together, these results suggest a majority of the observed marijuana associated epigenetic associations are dynamic, although stable epigenetic patterns maybe observed with marijuana use. Furthermore, the identification of dynamic markers across time suggests both recent and cumulative marijuana use may modulate epigenetic changes differently during the aging process. A possible explanation for the observation of different CpGs, as well as biological pathways and diseases, across the time points may relate to the pharmacokinetic properties influenced by age. For example,cannabis drying rack reductions in hepatic and renal clearance can increase the bio-availability of marijuana metabolites with prolongation of its half-life and subsequently, may impact molecular and cellular processes differently by age.

Consistent with our findings, dynamic epigenetic markers are more likely to be identified compared to stable markers during longitudinal analyses. However, further studies investigating the modulatory effects of marijuana on the epigenome on different age groups may provide additional insight. Moreover, changes in marijuana use may alter DNA methylation signatures, which may serve as biomarkers to evaluate continued or ceased marijuana use. Although additional studies are needed to evaluate these markers, our findings demonstrate marijuana may induce dynamic and stable epigenetic signatures that may have utilityas biomarkers for recent and cumulative marijuana use across time. The impact of lifestyle factors and behaviors on health is complex and often involves an integrative approach to elucidate the underlying biological processes. By investigating genetic contributions to methylation markers associated with marijuana use, we identified 650 cis-meQTLs, including 56 cis-meQTLs that mapped to traits in the NHGRI-EBI GWAS Catalog. Among the mapped traits, we observed consistent terms related to immunological factors, cardiovascular traits, and brain measurements. Marijuana use has been associated with alterations in white blood cell counts, blood pressure, and brain structures. Caffeine is the most consumed psychoactive substance in the world and induces dopamine release in the nucleus accumbens, a brain structure mediating pleasure and reward processing. Analogously, marijuana exerts similar effects on the nucleus accumbens via the endocannabinoid system, suggesting the pleasure and reward of caffeine and marijuana use share the same reward center. Additionally, we identified 198 DMRs associated with recent and cumulative use of marijuana at Y15 and Y20. Among the top DMRs, several regions have previously been associated with cognitive function, psychiatric disorders, and immune function. RNF39 was the most significant DMR in two of the four analyses and has previously been associated with general cognitive function and bipolar and major depressive disorders. TRIOBP is the most significant DMR associated with recent marijuana use at Y20 and has been associated with general cognitive function, schizophrenia, and basophil count.

Similarly, SH3RF3 has been associated with general cognitive ability, schizophrenia, and eosinophilia. Lastly ZFP57 has been associated with general cognitive ability, schizophrenia, autism, and rheumatoid arthritis. In sum, these findings suggest marijuana use shares common genetic and epigenetic pathways associated with immunological factors, cognitive function, and brain structures and may regulate similar molecular mechanisms and biological processes. These insights could help lead to the development of new preventive and predictive tools for marijuana-associated health outcomes. As a psychoactive substance, marijuana may modulate pathways and diseases associated with homeostasis and health outcomes. Our pathway analysis revealed differentially methylated markers over represented in pathways associated with cellular proliferation, hormone signaling, and infection. The MAPK signaling cascades are signaling pathways that regulate cellular proliferation, differentiation, and apoptosis; studies have suggested potential therapeutic benefits of CBD on cancer treatment via these pathways. With regard to hormones, the endocannabinoid system modulates dopaminergic neurons and acute use of tetrahydrocannabinol increases dopamine release and neuron activity, whereas long-term use has been associated with diminishing of the dopamine system. THC has also been shown to modulate oxytocin and areas of the brain associated with reward and addiction behaviors. Moreover, cannabinoids have been reported to promote progression of human papillomavirus positive head and neck squamous cell carcinoma, primarily through MAPK activation. Notably, a previous genome-wide DNA methylation study of marijuana identified the latter two pathways during pathway analysis. In addition to these biological pathways, differentially methylated genes associated with marijuana use were over represented in psychiatric diseases and spasticity. Marijuana use has been associated with several psychotic disorders including schizophrenia, bipolar disorder, autism, and psychosis , as well as substance-related disorders. Additionally THC and smoked marijuana have been shown to reduce spasticity among patients with multiple sclerosis and spinal cord injuries. Additionally, connections between the top marijuana associated pathways and diseases have been previously reported. For example, abnormalities in the MAPK signaling and dopamine pathways have been associated with schizophrenia, as well as the use of oxytocin for treatment of substance related disorders.

Collectively, we identified pathways and diseases over represented with marijuana-associated methylation markers, suggesting common epigenetic regulations which could serve as potential diagnostic and therapeutic targets for these related traits. The current CARDIA study leveraged repeated methylation levels and marijuana data to examine the association of marijuana use on DNA methylation. The availability of genetic data enabled the examination of potential genetic modulation of methylation markers associated with marijuana via meQTL analyses. Moreover, compared to other countries where residents use a mixture of marijuana and tobacco, CARDIA is a US-based cohort where mixing of marijuana and tobacco is less prevalent, allowing for a more complete examination of the independent associations of marijuana and tobacco smoking on DNA methylation. This study, however, is not without limitations. Although we identified biologically relevant epigenetic loci and replicated previously reported methylation markers, we were unable to replicate our findings in an independent study, and as such, the findings presented warrant validation. Residual confounding from additional factors, e.g., use of other or co-drug use and social support,vertical grow system may partially explain the observed associations. As marijuana use was considered illegal for most yearly examinations in CARDIA, use may have been under reported. However, at each examination, marijuana use was self-reported , collected at a research site , and participants’ responses were confidential . The route of administration of marijuana can also affect the onset, intensity, and duration of the psychoactive effects, as well as organ systems. Investigations into marijuana use via other routes of administration may provide novel additional insights, including the latter, which was not present during the time points in the current study but is becoming more widely used. Additionally, this study examined acute exposure to marijuana , compared to hyperacute exposure and investigations into DNA methylation changes due to hyperacute exposure may provide further insight into the acuity of exposure on epigenetic factors. And lastly, although CARDIA is a diverse cohort, Black and White participants were sampled from four centers across the US. As such, additional studies from more diverse populations across different geographical locations will enable for better generalizability of the findings presented here.Mas biomarkers for recent and cumulative marijuana use across time. The impact of lifestyle factors and behaviors on health is complex and often involves an integrative approach to elucidate the underlying biological processes. By investigating genetic contributions to methylation markers associated with marijuana use, we identified 650 cis-meQTLs, including 56 cis-meQTLs that mapped to traits in the NHGRI-EBI GWAS Catalog. Among the mapped traits, we observed consistent terms related to immunological factors, cardiovascular traits, and brain measurements. Marijuana use has been associated with alterations in white blood cell counts, blood pressure, and brain structures. We found the most significant mapped cis-meQTL has previously been associated with coffee consumption. Caffeine is the most consumed psychoactive substance in the world and induces dopamine release in the nucleus accumbens, a brain structure mediating pleasure and reward processing. Analogously, marijuana exerts similar effects on the nucleus accumbens via the endocannabinoid system, suggesting the pleasure and reward of caffeine and marijuana use share the same reward center.

Additionally, we identified 198 DMRs associated with recent and cumulative use of marijuana at Y15 and Y20. Among the top DMRs, several regions have previously been associated with cognitive function, psychiatric disorders, and immune function. RNF39 was the most significant DMR in two of the four analyses and has previously been associated with general cognitive function and bipolar and major depressive disorder. TRIOBP is the most significant DMR associated with recent marijuana use at Y20 and has been associated with general cognitive function, schizophrenia,and basophil count. Similarly, SH3RF3 has been associated with general cognitive ability, schizophrenia, and eosinophilia. Lastly ZFP57 has been associated with general cognitive ability , schizophrenia, autism, and rheumatoid arthritis. In sum, these findings suggest marijuana use shares common genetic and epigenetic pathways associated with immunological factors, cognitive function, and brain structures and may regulate similar molecular mechanisms and biological processes. These insights could help lead to the development of new preventive and predictive tools for marijuana-associated health outcomes. As a psychoactive substance, marijuana may modulate pathways and diseases associated with homeostasis and health outcomes. Our pathway analysis revealed differentially methylated markers over represented in pathways associated with cellular proliferation, hormone signaling, and infection. The MAPK signaling cascades are signaling pathways that regulate cellular proliferation, differentiation, and apoptosis; studies have suggested potential therapeutic benefits of CBD on cancer treatment via these pathways. With regard to hormones, the endocannabinoid system modulates dopaminergic neurons and acute use of tetrahydrocannabinol increases dopamine release and neuron activity, whereas long-term use has been associated with diminishing of the dopamine system. THC has also been shown to modulate oxytocin and areas of the brain associated with reward and addiction behaviors. Moreover, cannabinoids have been reported to promote progression of human papillomavirus positive head and neck squamous cell carcinoma, primarily through MAPK activation. Notably, a previous genome-wide DNA methylation study of marijuana identified the latter two pathways during pathway analysis. In addition to these biological pathways, differentially methylated genes associated with marijuana use were over represented in psychiatric diseases and spasticity. Marijuana use has been associated with several psychotic disorders including schizophrenia, bipolar disorder, autism, and psychosis, as well as substance-related disorders . Additionally THC and smoked marijuana have been shown to reduce spasticity among patients with multiple sclerosis and spinal cord injuries. Additionally, connections between the top marijuana associated pathways and diseases have been previously reported. For example, abnormalities in the MAPK signaling and dopamine pathways have been associated with schizophrenia, as well as the use of oxytocin for treatment of substance related disorders. Collectively, we identified pathways and diseases over represented with marijuana-associated methylation markers, suggesting common epigenetic regulations which could serve as potential diagnostic and therapeutic targets for these related traits. The current CARDIA study leveraged repeated methylation levels and marijuana data to examine the association of marijuana use on DNA methylation. The availability of genetic data enabled the examination of potential genetic modulation of methylation markers associated with marijuana via meQTL analyses. Moreover, compared to other countries where residents use a mixture of marijuana and tobacco, CARDIA is a US-based cohort where mixing of marijuana and tobacco is less prevalent, allowing for a more complete examination of the independent associations of marijuana and tobacco smoking on DNA methylation. This study, however, is not without limitations. Although we identified biologically relevant epigenetic loci and replicated previously reported methylation markers, we were unable to replicate our findings in an independent study, and as such, the findings presented warrant validation. Residual confounding from additional factors, e.g., use of other or co-drug use and social support, may partially explain the observed associations.

Though more respondents provided negative evaluations of marijuana use under the condition that it was determined conclusively to be harmful, the effect was not significant . This may have been due to other considerations that outweighed the consideration of harm and led these respondents to maintain that marijuana use is all right even if it was certainly harmful to the user . As expected, respondents reported significantly different evaluations of the stealing and music issues and justified their evaluations with moral and personal reasons, respectively. Under each of the proposed conditions , stealing was consistently evaluated negatively and music was consistently evaluated positively. Similarly, results showed significant differences between judgments of the legality of these issues: All the respondents agreed with a law against stealing and none agreed with a law against purchasing music. The results mainly supported the hypothesis that judgments about marijuana use contrast with judgments about the prototypically moral and personal issues. Although respondents’ marijuana use evaluations clearly contrasted with their consistently negative evaluations of stealing, results indicated that, like their evaluations of the music items, respondents were significantly more likely to report positive evaluations of each marijuana use item . Notably, however, their positive evaluations of marijuana use were not as consistent as their evaluations of purchasing music. Whereas all respondents provided positive evaluations of the general music question ,pruning marijuana only 57% of the sample provided a positive evaluation of the general marijuana question . Respondents’ evaluations of each of the additional questions about purchasing music were likewise more consistently positive than their evaluations to the same questions posed about marijuana use.

For example, almost all evaluations of purchasing music under the common practice condition were positive, whereas responses about the acceptably of marijuana use under the common practice condition yielded only 68% positive evaluations . Similarly, though none of the respondents agreed with a law prohibiting the purchase of music, 30% agreed with a law prohibiting marijuana use. These differences suggest that, despite respondents’ significantly more favorable views toward the marijuana items than the stealing items, evaluations of the marijuana use items were not as overwhelmingly positive as they were to the music issue. This lends support to the hypothesis that marijuana is a more ambiguous social issue as compared to the purchasing music and the stealing issues that show the more consistent response patterns expected of prototypically personal and moral issues. The hypothesis is further supported by comparing findings from the items aimed at assessing criterion judgments associated with prototypical issues to similar items regarding the marijuana use issue. Results generally followed expected patterns. Significantly more respondents judged stealing as not all right 1) in general , 2) in the case that it is legal for those ages 21 and older , nor 3) if it is a commonly practiced act . Moreover, all the respondents reported that this act should be not be legal. That the significant majority of evaluations remained negative despite these added contingencies is indicative of the moral reasoning about this issue . Responses to the music items were somewhat more variable than responses to the stealing items. This was primarily due to respondents’ compliance with the legal contingencies posed. Though still significantly higher than those who reported negative or mixed evaluations of the act, fewer respondents maintained that purchasing music would be acceptable even if there was a law prohibiting the act. Some respondents did, however, disagree with the acceptability of purchasing music if there was a law prohibiting the act. These respondents typically cited legal reasons for their negative evaluations , but often also stated that such a law would be unfair or unwarranted.

These results suggest that, while most respondents thought of music-purchasing as a non-moral issue that should not be part of the conventionally regulated system , some felt that the legal prohibition of an act was enough to make the act unacceptable. Responses to the criterion judgment questions for the stealing and music issues were compared with similar questions about marijuana use and were expected to demonstrate differences. It was hypothesized, that because marijuana use is an ambiguous social issue, there would be greater variability among evaluations of this issue under the various contingencies than among evaluations of the stealing and music issues. This hypothesis was partially supported. Respondents provided a mix of positive, negative, or depends evaluations of marijuana when asked to consider whether marijuana use would be all right in the presence of a law prohibiting use, or in the absence of a law prohibiting use. This variability in evaluations contrasts with findings from the stealing and music items , which respectively showed significantly higher negative and positive evaluations despite the legal contingency conditions. This suggests that respondents’ evaluations of marijuana use were more susceptible to conditions of legality. On the other hand, respondents maintained positive evaluations of marijuana under the common practice condition posed; significantly more respondents reported that marijuana use would be all right even in places where it was not commonly practiced. Taken together, these findings suggest that the legality of marijuana showed a greater impact on their positive evaluations than did the common practice condition . A review of respondents’ justifications also provided evidence for the hypothesis that marijuana use is an ambiguous issue that contrasts with prototypically moral and personal issues, which are more consistently judged within their respective domains. As expected, evaluations of stealing were explained by references to the moral domain justifications . The music items, on the other hand, were mostly justified by references to the Personal Choice category.

Comparisons of these effects were significant; that is, the moral domain justifications were more likely than expected to be referenced for the stealing items than for the marijuana use or music item sets, and the personal domain justification was more likely to be referenced for the music items than for the marijuana use or stealing item sets. In contrast to the stealing and music items, justifications for marijuana use items showed greater heterogeneity ,trimming weed plants thereby suggesting the ambiguity of the issue. Whereas justifications for the stealing and music items were significantly more likely to reference the moral domain and the personal domain, respectively, justifications of marijuana use, were equally as likely to reference the prudential and conventional domains. These findings are generally consistent with results from previous research suggesting that adolescents report a mix of domain considerations when reasoning about marijuana or drug use . Moreover, marijuana use justifications spanned a greater number of justification categories; considerations of the medical use of marijuana, the commonality or acceptability of marijuana use practices, the system of shared expectations around use, self-imposed physical consequences related to marijuana use, and individuals’ preferences and rights to choose were all frequently referenced when reasoning about marijuana use. This is in contrast with the stealing and music items set that showed considerably higher Justice/Rights justifications and the Personal Choice justifications, respectively. Findings from the present study thus suggest that marijuana use is an ambiguous social issue that elicits multi-domain considerations. These multi-faceted considerations may in turn result in more variable judgments of this issue than of prototypical issues.Some results were inconsistent with hypothesized findings or otherwise were surprising. Overall, respondents in this sample provided a higher number positive evaluations of marijuana use across the survey’s proposed questions/conditions. Though evaluations of marijuana use were not as homogenous as they were for the stealing and music issues, that respondents provided significantly more positive evaluations of marijuana use across this item set was somewhat surprising. Respondents were expected to report greater variability in their evaluations to these items, especially to items proposing breaks from conventional norms . Respondents’ positive evaluations of marijuana use under the absence of common practice condition were particularly surprising; evaluations of marijuana use did not significantly shift in the expected direction with the introduction of this condition. While some respondents reasoned that it is important to maintain shared expectations and avoid disrespecting others by engaging in acts considered inappropriate or unacceptable in that context, the majority did not think that the absence of commonality/acceptability necessarily made the act not all right. This suggests that, for this sample of adolescents, these considerations were insufficient for a negative act evaluation. However, as discussed above, the legal status of the act did effect evaluations in the expected directions. Certain results from the harm manipulation conditions were also particularly interesting.

For the respondents who believed that marijuana use was not harmful, the hypothetical condition of the certainty of harm did not have as significant of an impact on act evaluations as expected: Responses to this item were mixed, suggesting that the certainty of harm was not enough to result in significantly higher negative act evaluations as was expected. However, it is important to note the mixed evaluations of marijuana use under the condition of certain harm did in fact contrast with respondents’ initial general evaluations of marijuana use, which was overall significantly positive. Thus, though not enough to significantly sway the response pattern in the negative direction, the mix of responses to this item does suggest that the addition of the harm condition had some degree of impact on evaluations.The present study was founded on two primary concepts from social domain theory: that some social issues are multi-faceted and that informational assumptions play an essential role in judgment formations . These concepts provide structures for understanding the process of adolescents’ reasoning about non-prototypical social issues and the bases for their judgments about these issues. The findings from this study demonstrate adolescent reasoning about ‘ambiguous’ issues, as well as the role of informational assumptions in reasoning about social issues relevant to their age group .According to social domain theory, the adolescent period is one in which individuals expand their capacity for incorporating and assimilating the myriad of facets that may be involved in a single issue . These multiple facets may be considered and weighed against one another to arrive at a judgment that accounts for the various circumstantial components of the issue: “Decision-making involves weighing and balancing different considerations and goals in particular situations. The decision making process is not bounded within a domain, but includes a coordination of different domains like morality, prudence, convention, and personal jurisdiction. A variety of judgments, which coexist across ages, are brought to bear in making decisions” . Thus, there are processes of coordinating social concepts that can take many forms depending on the time and/or circumstances in which the issue is examined and on the salience of the various facets the individual has come to associate with the issue. The results of this study suggest that there is need for further research into the coordination processes undertaken when reasoning about ambiguous issues like marijuana use. Greater understanding of how individuals coordinate the various facets of issues can offer insights into relative the salience and impact these facets have on judgments, and ultimately, behaviors. The multiple cross-domain justifications adolescents frequently provided for their evaluations, and the shifts that took place in their evaluations as various hypothetical conditions were placed on the issue, were indicative of the factors associated with issue for these respondents. It may be that these respondents balanced these considerations against one another to form a judgment. Not only did respondents often recognize and explicitly state that there were various factors that should be considered when justifying their responses, but they at times were unable to settle on a positive or negative evaluation . Moreover, their statements typically communicated that the circumstances that were posed in the contingency questions were influential to their reasoning and judgments, or were at least considered and then dismissed as less crucial to their than other relevant factors. These qualitative components of the findings may be indicative of the composition of the coordination process involved in these adolescents’ reasoning.This was suggestive of the ambiguities involved in this issue, especially as compared to their more homogenous judgments of the prototypically moral issue . As reviewed in the Introduction, Turiel et al. explain that the uncertainties of the differing assumptions associated with these non-prototypical issues gives them their ambiguous character.

Based on their response to the question about common practice, respondents were directed to answer whether marijuana use would be all right in places where it was not common practice or generally accepted or whether it would be all right in places where it was common practice and generally accepted . Respondents were also asked whether they think that the frequent use of marijuana causes physical or psychological harm to the user and to indicate why or why not. Based on their response to this item about the harmfulness of marijuana, respondents were directed to respond to a follow-up question asking them whether it would be all right to use marijuana if scientists were able to definitively conclude that marijuana use is safe or harmless to the user , or whether it would be all right to use marijuana if scientists were able to definitively conclude that marijuana use is not safe or harmless to the user . Each item response was assigned one or more justification code according to the types of references the respondent made as he/she justified his/her evaluation. Because of the openended, short-answer format of the survey, responses to items may have referenced one or more of the categories. That is, a respondent may have mentioned considerations pertaining to any of the above justification categories, and so, a single response could have been assigned one or more of the justification codes. For example, a single item response could have referred to considerations about rules or laws regarding the act and the safety of engaging in the act, while also noting considerations of one’s right to choose to engage in the act –such a response would thereby yield three justification codes. Also due to the open-ended nature of the survey, respondents at times provided ‘uncodeable’ responses. Uncodable responses were typically either insubstantial to determine what the respondent meant ,drying curing or did not clearly answer the question being asked . Informational Assumptions. Respondents’ informational assumptions about the harm involved in marijuana use assessed by item 5 and the two sub-questions of this item.

Item 5 asked respondents whether they think frequent use of marijuana causes physical or psychological harm to the user, and why or why not they think it does or doesn’t. Responses were assigned a Yes, No, or Uncertain/Mixed code to the first part of this question. The second part of this question was not coded, as this information was not relevant to the aims of this study. However, respondents’ verbatim responses to this item were transcribed and are presented in Appendix D. Based on their response to whether or not they think marijuana use causes harm, respondents were directed to then answer either Item 5a or Item 5b. Those who reported thinking marijuana use does cause harm were asked to suppose that scientists were able to conclude without a doubt that marijuana use is safe or harmless to the user and to judge whether use would be all right or not all right in this hypothetical case. The opposite scenario was presented to those who reported thinking that marijuana use does not cause harm to the user. Planned pairwise contrasts using chi-squared tests were used to analyze whether statistically significant differences exist between participants’ responses to different questions. Correlations between variables were calculated using Spearman’s rank correlation coefficient . For these tests, the null hypothesis was that there is no difference in the way the sample of participants responded to the questions. The alternative hypothesis was that there is enough evidence to reject the null hypothesis. In all tests, an alpha value of .05 is considered significant for rejection. Respondents’ evaluations were also tested to determine whether a statistical difference existed in how they responded within each item. Multi-nomial goodness-of-fit was tested for each item. The test evaluated the probability of the observed count in each response category being equal to the expected count in each category. A p-value < .05 was taken as evidence that the observed cell counts were statistically improbable enough to reject the null hypothesis that there is no difference between expected and observed counts. Due to the small sample nature of the experiment, Monte Carlo exact tests were used to compute goodness-of fit. A log linear regression was used to analyze domain use within each of the three issues for the justification results. The Poisson function in Stata15 was used to model counts of how often participants referenced each category within a particular issue. Coefficients were reported as odds relative to the reference category, which was always the most frequently referenced domain, and p-values are derived from Wald tests.

The distribution of responses was compared between races. Pairwise contrasts for item and self-report race were conducted using chi-squared tests. The contingency tables were very sparse, suggesting that the results of this analysis should be interpreted with caution. Furthermore, the pairwise contrasts produced results that were not statistically significant aside for one item. For the one item that showed a statistically significant difference between race , 15 out of 25 cells were sparse , with many expected values being below 1 and some at 0. Due to the lack of compelling evidence for statistically significant differences in responses between race/ethnicities and the presence of very sparse tables created by the analysis, the race variable was removed from the analysis. The first research question asked how adolescents evaluate the use of marijuana. Respondents were asked for their evaluations on marijuana use in order to assess overall attitudes toward the issue and to compare judgments on this issue with judgments on stealing and purchasing music. Respondents’ judgments about marijuana use was further assessed through questions asking for respondents’ evaluations of the legality of the act and the acceptability of the act if it is commonly practiced or legal for individuals ages 21 and older. Table 3 shows respondents’ answers to the initial set of marijuana questions. Generally, results suggest that the majority respondents indicated that marijuana use is all right across the conditions presented and should be not be prohibited by law. However,dry cannabis they also reported that frequent use causes harm to the user. Results of multinomial goodness-of-fit tests are presented to demonstrate the statistical significance of respondents’ evaluation patterns by item. Pairwise contrasts between respondents’ general act evaluations of marijuana and their evaluations to each of the other marijuana items were also conducted as points of comparison . Note that, throughout this chapter, percentages that do not add up to 100 indicate the presence of ‘uncodeable’ or incomplete data. Respondents’ evaluations of marijuana use were expected to show variance and thereby support the hypothesis that marijuana is an ambiguous issue. This hypothesis was expected to be further supported by comparisons with the stealing and purchasing music items that were expected to show little to no response variance. The contrast between the marijuana use response pattern and the prototypically moral and personal domain issues was thus expected to further demonstrate the ambiguous nature of the marijuana use issue. The first item on the survey was used to investigate respondents’ general evaluations about marijuana use. Results indicated that respondents’ evaluations of marijuana use varied significantly = 36.14, p < .0001, with more respondents reporting positive or uncertain evaluations of marijuana use than negative evaluations of use. Item 2 asked respondents whether they think marijuana use should be prohibited by law. A comparison of responses with this item to similar items asking respondents to judge the legality stealing and purchasing music were intended to see if the marijuana use issue differs from these prototypical issues.

Results indicate that significantly fewer respondents reported favoring a law prohibiting the use of marijuana = 14.73, p = .0002. Most respondents thought that there should not be a law prohibiting marijuana use. Only 30% of respondents agreed that there should be a law prohibiting marijuana use . A pairwise contrast with item 1 shows that there was a statistically significant difference between how respondents initially evaluated marijuana and how they responded to the question about marijuana legality = 20.89, p < .001). The effect size is medium . Thus, responses to the question about marijuana use in general were different than responses to evaluations about the legality of marijuana. Respondents’ answers to these questions were moderately negatively correlated . This suggests providing a positive evaluation of marijuana use is associated with a negative evaluation of a law prohibiting use . Most respondents reported positive evaluations to the question asking whether marijuana use would be all right under the condition that it was commonly practiced or accepted. Results indicated that respondents reported significantly higher positive evaluations to marijuana use when asked about the acceptability of use under the condition that it is commonly practiced = 38.12 p < .0001). Most respondents stated that marijuana use would be all right in this case. However, 25% of respondents maintained that marijuana use would not be all right even if it was a common practice and 12% provided mixed or uncertain responses . A pairwise contrast between the common practice question and item 1 was statistically significant = 25.4, p < .001and had a medium effect size . Follow up analyses indicated that shifts from respondents’ general marijuana use evaluations to their evaluations under the common practice condition were primarily due to respondents changing their uncertain evaluations to negative evaluations. Thus, those who had initially provided uncertain evaluations about the acceptability of marijuana use were not persuaded to think use was all right under the common practice condition. Rather, they were more likely to shift to a negative evaluation when judging the act solely on the contingency of common practice. This suggests that other considerations were more prominent in these respondents’ reasoning process; that is, the common practice of the act was not an adequate contingency to shift these respondents’ judgments to a positive evaluation. Little shift occurred from positive responses to item 1 to positive responses to the common practice item. The second research question asked whether adolescents evaluated the use of marijuana by adults differently than use in general. In order to determine whether respondents’ judgments about the act were contingent on the age of the user, they were asked whether use by adults of a certain age would be acceptable if it was permitted by law. Respondents provided significantly higher positive evaluations of marijuana use under this contingency = 104.4, p < .0001. In fact, responses to this item had the highest rate of positive evaluations of marijuana use . A pairwise contrast of this item with the general marijuana use evaluation item was statistically significant = 35.7, p < .001 and had a medium effect size . This suggests that adolescents judge marijuana use under the legal age contingency more favorably than use in general . Results thus indicate that respondents judge marijuana use by adults differently than they how they judge marijuana use generally; they are more likely to find that marijuana use is acceptable for adults 21 years of age or older in the presence of a law permitting such use. Respondents’ evaluations of marijuana use for adults conditional on their general evaluations of marijuana use were further compared using a cross tabulation of responses to these two items. Results are presented in Table 4, showing that 91% of those who initially agreed that marijuana use was acceptable also reported thinking that use would be all right under the age contingency condition. Of the few respondents who initially disagreed that marijuana use is acceptable , most shifted to agree that marijuana use would be all right under the age contingency condition. Respondents who initially had uncertain general evaluations about marijuana use also tended to shift their judgments under the age contingency condition. Of these respondents, 77% went on to say use would be all right for adults 21 and older. Comparison of marijuana use evaluations to prototypically moral and personal act evaluations. The fifth research question asked how adolescents’ evaluations of marijuana use compares to those of a prototypical moral issue and a prototypical personal issue . Comparisons between results from the marijuana use issue and results from the prototypical issues were intended to ascertain if marijuana use is an ambiguous issue that is judged with greater variability than issues that fall more clearly within moral or personal domains.

Pain severity change was calculated by subtracting the baseline PEG from the last recorded PEG; thus, negative values indicate a decrease in pain severity. To examine the impact of pain severity on changes in marijuana use, we constructed general linear models with change in pain severity as the outcome variable and change in marijuana use as independent variables. Residual diagnostics were performed to determine if linear model assumptions were satisfied. Opioid initiation and discontinuation outcomes: For the relationship between marijuana use and opioid initiation and discontinuation, we only considered marijuana use at baseline. This allowed us to explore the assertion that marijuana use facilitates tapering of opioids. We constructed multi-variable binary logistic regression models with opioid initiation and discontinuation as the outcome variables and marijuana use at the index visit as an ordinal variable . Due to small sample size and data separation, each logistic regression was performed using Firth’s penalized maximum likelihood estimation to reduce bias in the parameter estimates. We considered covariates at baseline that are potentially associated with these exposures and outcomes: age, race, gender, other substance use and mood symptoms. Viral load and CD4+ T-cell count were collected for descriptive purposes. Virologic failure was defined as plasma HIV RNA >1000 copies/mL at any time during the study period, without a repeated test within 30 days that found ≤1000 copies/mL31. Analyses were adjusted for CNICS site. All analyses were performed in SAS 9.4 . Most participants were from UAB and UCSD , consistent with prior studies from this cohort. Demographic and clinical variables are summarized in Table 1. Just over half of participants were aged >50 years. Most participants were male and nearly half identified as non-Hispanic Black. The median CD4+ T-cell count at the index visit was 582 cells/mm3, and only 16% of participants had a detectable viral load. Clinically significant symptoms of depression and anxiety were common,drying cannabis occurring in more than one third of the sample. Marijuana use varied by site, with the highest current and past marijuana use reported by participants recruited from Washington .

Overall, most participants reported no marijuana use in the past 3 months; 8% reported daily, 5% weekly, 3% monthly, and 13% 1–2 times in the past 3 months. Of participants who reported less than daily use, 11% reported increased use during follow-up. Of participants reporting having used any marijuana, 10% reported decreased use during follow-up. Median pain severity at baseline was 6.3/10 , and median change in pain severity during the follow-up was 0 . The most common chronic pain locations were low back and hands/feet. During the year prior to the index visit, 47% of participants were prescribed LTOT; 8% were initiated during the study period, and 10% were discontinued during the study period. Table 2 summarizes the analyses of the relationship between change in marijuana use and chronic pain severity during the study period. Among PLWH with chronic pain, neither increases nor decreases in marijuana use were associated with changes in pain severity. As described in Table 3, marijuana use at the index visit was not associated with either lower odds of opioid initiation or higher odds of opioid discontinuation. Notably, marijuana use at the index visit was associated with increased opioid initiation in the unadjusted analysis which did not achieve statistical significance in either the unadjusted or adjusted analyses, .In this study, we investigated potential benefits of marijuana use in PLWH. We did not find evidence that, among patients with chronic pain, marijuana use was associated with improvements in pain or reductions in opioid prescribing. This study adds to the evidence base from which HIV providers can draw when discussing marijuana use with their patients. Over the past several years, there has been a proliferation of research on the association between marijuana and health outcomes in the general population and in PLWH. Some studies have produced concerning findings, while other studies are more equivocal. For example, with regard to PLWH, studies suggest that marijuana use may be associated with sub-optimal HIV primary care visit adherence and cognitive impairment, but not with antiretroviral adherence, virologic suppression, or mortality.

Non–HIV-related harms of marijuana use include impaired driving, hyperemesis syndrome, cognitive impairment, psychosis, and other mood symptoms. Our findings suggest that these harms are not counterbalanced by benefits in terms of pain or reductions in opioid prescribing. We note that there are other conditions, such as multiple sclerosis and post-traumatic stress disorder, that are listed as an indication for medical marijuana in many states but have a similarly limited evidence base. Some states have legalized recreational and medical marijuana as a result of voter petitions or legislative mandates and not as a result of scientific inquiry. Similarly, indications for medical marijuana use published by states may not have depended on evidence, but rather community and political input. Our data suggest that at least in PLWH, this is putting “the cart before the horse”. Additional observational studies in populations with other chronic conditions will be essential to establishing which groups, if any, are most likely to benefit from medical marijuana. Our study has limitations. First, it was conducted in a clinical cohort of PLWH who are in clinical care – that is, they attend clinic visits, and are mostly virologically suppressed. Our findings may not be generalizable to other populations of PLWH who are not as engaged in care. While our analysis was longitudinal, it was drawn from only one year of follow-up data. A longer longitudinal study would address this issue and allow for more robust investigations of causal inference. Also, due to lack of reliable opioid dose data, we were only able to investigate initiation and discontinuation of opioid prescribing, rather than an increase or decrease, which may be an outcome more sensitive to change over a one-year period. Despite CNICS being one of the largest prospective cohort studies of PLWH, our sample size of PLWH with chronic pain, with or without changes in marijuana use, was small. It is not possible to definitively determine whether we were under powered to detect associations between marijuana use and pain/opioid outcomes, or whether these associations do not exist. Also, people with the heaviest marijuana use and people who did not use marijuana were excluded from some analyses, and sensitivity analyses could not be performed due to their small numbers. CNICS asks about “non-medical” use of marijuana, and participants’ interpretation of this question may vary. Individuals may use illicit marijuana to treat pain and other symptoms, and/or may not have access to medical marijuana in their state.

CNICS does not specifically query medical marijuana use. Another limitation is the inability to assess “intent”—that is, if medical providers and patients intended to use marijuana with a specific goal of reducing opioid dependency. Future clinical trials likely will focus on this as an intervention. Finally, we acknowledge that marijuana use is diverse in terms of route of administration and dose . Therefore, we were only able to consider marijuana use status and frequency. In conclusion, we did not find evidence that marijuana use in PLWH is associated with improved pain outcomes, or changes in opioid prescribing. This suggests that caution is warranted when counseling PLWH about potential benefits of recreational or medical marijuana. Further studies, including prospective trials of medical marijuana and large observational studies, are needed to understand what impact, if any, marijuana use can have on pain in PLWH.In the past few decades,cannabis curing the social and political atmosphere around marijuana use has led to increased divergence of public opinions and understandings about the issue. Variability in how common, how accepted, how practical, and even how lawful the use of marijuana is among communities and social groups frequently makes this a contentious issue. However, it is the very prominence and divisiveness of this issue that make it a timely topic of investigation. Marijuana use is an issue that may call to mind several considerations, making the matter complex and difficult to decisively judge. It can involve concerns about legality, safety, personal rights, social-cultural acceptability, and perhaps even morality. Some or all of these considerations may be involved in evaluations and judgments about marijuana use. While reasoning about marijuana use may undoubtedly be complicated for adults in the population who recognize the numerous facets involved in the issue, evaluations and judgments may be more complex for adolescents in the midst of a particularly transformative period of social and cognitive development. Though children begin to learn about their social worlds early on through their interactions and exchanges with their environments, it is not until adolescence they are able to incorporate a greater number of more complex components of their world into their thinking . In this way, reasoning becomes more complex and responses to social dilemmas more nuanced. The reasoning process does not, however, always produce clear and definitive conclusions. Because adolescents are still in the nascent stages of forming their understanding of social matters, a certain degree of opaqueness in their reasoning and evaluations is typical and expected. This can particularly be the case with regard to more complicated matters like drugs . Given the various features of the issue of marijuana use, as well as inconsistency in the “facts” and legislations on marijuana, this issue can be especially unclear for teenagers. Arguably, however, the multitude of factors that can be involved when forming judgments about marijuana use make investigating adolescents’ conceptualizations of the issue particularly instructive and revelatory of processes of adolescent reasoning. In the present study, adolescents’ evaluations and judgments about marijuana use were examined. The principal aim of this investigation is to shed light upon adolescents’ judgments about marijuana use, and to assess which particular informational assumptions their evaluations are based upon. The study also aimed to uncover the various considerations that teens find to be most salient and applicable to the matter. The present investigation is guided by Social Domain Theory , a framework regarding how children and adolescents think about their social world.

For over thirty years, this theory has provided a framework for investigating how children and adolescents construct their understanding of the world and the social cognitive processes they engage in when forming judgments about social matters. The key features of this theory and the value of using this framework for the investigation at hand are reviewed in the following sections.According to social domain theory, children come to understand their social world through their interactions with others, and in the process, construct different domains of social knowledge, such as the moral and conventional domains. The moral domain refers to concepts of justice, welfare, and rights that are obligatory, universal, and unchangeable. In contrast, the conventional domain refers to prescribed and generally accepted social norms and rules that are contextually determined. Though these domains may overlap in some cases , research has indicated that individuals distinguish between moral and conventional matters from a young age . The social domain framework also includes a third domain, referred to as the personal domain . The personal domain encompasses issues that are primarily related to concepts of the self, such as personal preferences, choices, and behaviors that do not directly affect others. An important distinction has been made between reasoning about issues that are personal matters and judgments about prudential matters . According to Tisak and Turiel , the prudential domain is similar to the moral domain in that it involves the issue of harm done unto persons. However, judgments about prudential issues focus on how particular actions impact the self, and in that sense are non-social and therefore lack the key social-interactional characteristic of moral issues. Research has shown that children and adolescents make distinctions among moral, conventional, personal, and prudential issues from a very early age, and understand and make judgments about their social worlds according to the domains .The literature in the field has consistently revealed the following criteria to be characteristic of issues evaluated as moral: judgment that the act is wrong, the wrongfulness of the act is not based on the existence of rules and is not contingent on rules , the wrongfulness of the act is not based on authority commands, so the act would be judged as wrong even if an authority states the act is acceptable, and the wrongfulness of the act is not based on common practice, so the act would be wrong even if it was an accepted practice among a group.

All analyses were performed with R statistical software .Overall, residents of states where marijuana was legalized for recreational purposes were more likely to endorse the belief that marijuana had benefits compared with residents of other states . Specifically, residents in recreationally legal states were more likely to believe marijuana could be beneficial for pain management ; provide relief from stress, anxiety, or depression ; and improve appetite . Pain management was endorsed as the most important benefit regardless of state of residence . Residents of nonlegal states were more likely to endorse the belief that marijuana had no benefits compared with those in recreationally legal states . Multivariate analyses confirmed that residents of recreational states were less likely to believe marijuana had ‘‘no benefits’’ and more likely to believe that marijuana use had benefits in pain management, helped with reducing or stopping other medications, provided relief from stress, anxiety, and depression, improved sleep and appetite, and improved creativity compared with residents of medical and nonlegal states after adjusting for baseline characteristics .Residents of recreational, medical, and nonlegal states all endorsed addiction as the most important risk associated with use . Multivariate analyses revealed that residents of recreational states were more likely to believe that marijuana use impaired memory, and also caused a decrease in intelligence and energy compared with residents of other medically legal and nonlegal states after adjusting for baseline characteristics .Residents in recreational states were significantly more likely to believe that smoking one marijuana joint a day is somewhat or much safer than smoking 1 cigarette a day . Residents of recreationally and medically legal states were more likely to believe second-hand marijuana smoke was somewhat or much safer than second-hand tobacco smoke .

Opinions regarding other relevant public health concerns were largely similar across states: most residents,plant nursery benches regardless of legal status in state of residence, agreed that it is unsafe for children and adults to be exposed to second-hand marijuana smoke, and that marijuana use was unsafe for pregnant women. Multivariate analyses confirmed that residents of recreational states were more likely to believe that smoking 1 marijuana joint a day was safer than smoking 1 cigarette a day compared with residents of other medically legal and nonlegal states after adjusting for baseline characteristics . Residents of recreational states were also more likely to believe second-hand smoke from marijuana was safer than second-hand smoke from tobacco compared with residents of other medical and nonlegal states after adjusting for baseline characteristics .In this national study, we found that residents of states that had legalized recreational marijuana use more commonly attributed some benefit to marijuana than residents of medically legal or nonlegal states. We also found that the perception of risks from marijuana use was similar across states. In addition, we found that residents of states where marijuana was legalized were more likely to believe that marijuana smoke was less harmful than tobacco smoke. Finally, use of all forms and multiple forms of marijuana was more common among residents of recreationally legal states. Several national surveys, including the NSDUH and MTF, assess individual risk perception of marijuana use among national samples, and recent research suggests that risk perception has decreased nationwide . Previous research demonstrates that marijuana legalization is associated with decreases in risk perception, as evident from studies examining California pre and post medical legalization in 1999 . More recent research supports this assertion , and while research into the role of recreational legalization specifically is limited, initial data in adolescents suggest recreational legalization has been associated with a considerable decrease in risk perception .

While such surveys have adequately examined the decrease in risk perception associated with marijuana, there exists no detail on the types of risks individuals associate with marijuana use or potential benefits individuals assign to marijuana use. Our results show that residents of states where marijuana has been legalized for recreational use have an overall more favorable view towards potential benefits of marijuana use and were more likely to attribute benefits to marijuana use that are not supported by evidence. For example, a majority of respondents endorsed pain relief as a benefit of marijuana use, despite only limited evidence supporting its effect in managing chronic neuropathic pain and no evidence in treating other types of chronic pain . There is no evidence currently available that suggests second-hand marijuana smoke is safer than tobacco smoke and some evidence suggesting it is toxic . There is no data suggesting that marijuana is an effective and safe treatment for insomnia . When taken in context with previous research demonstrating the decrease in risk perception associated with marijuana use, our findings are significant as they illustrate the need for targeted public health campaigns to combat misinformation specifically in states with recreational marijuana legalization. We found that residents of recreationally legal states expressed less concern regarding second-hand marijuana smoke compared with second-hand tobacco smoke, and were more likely to believe that smoking marijuana is somewhat or much safer than smoking tobacco. These differences in perception are concerning, given the evidence that inhalation of particulate matter in any form is associated with increased cardiovascular risk . The perception that marijuana smoke is relatively safe compared with tobacco smoke has been perpetuated by the spread of inaccurate information on the internet . Some highly frequented internet sites suggest that smoking marijuana has many health benefits, such as improvement of lung health or the slowing of Alzheimer symptoms .

There is currently no data to suggest that smoking marijuana improves lung health. On the contrary, recent evidence demonstrates smoking marijuana is associated with coughing, wheezing, and sputum production . The lack of a clear federal public health response to the growing legalization of marijuana and proliferation of pro-marijuana marketing has left a vacuum that is filled by commercial interests . Unlike the tobacco industry, the marijuana industry has remained largely unchallenged by a coordinated regulatory response, and is aggressively advertising its product in states with rapidly expanding commercial markets . Over half of adults living in states with recreational marijuana are frequently exposed to pro-marijuana advertising in numerous forms , and research indicates that greater exposure to pro-marijuana advertising is associated with heavier marijuana use among adolescents and heavier use among adult persons who use . More stringent regulations of marijuana product marketing, and also a cohesive public health messaging campaign, are necessary to combat misinformation and communicate the potential risks associated with marijuana use so consumers can make informed choices about use. With the exception of smoking rates, which were roughly equivalent among residents in recreationally legal and medically legal states, prevalence of use among all forms of marijuana and use of multiple forms of marijuana was higher among residents in recreationally legal states. This is not surprising, given that novel forms of marijuana are more accessible in states with robust recreational markets. For example,metal greenhouse benches in the first year with an active recreational marijuana market, Colorado dispensaries sold 4.81 million units of edible cannabis product . The popularity of marijuana products in forms other than smoking is a cause for some concern as such products are increasingly available with THC content at high levels not yet studied. Previous research suggests that some edible products exceed state-mandated THC thresholds and can reach as high as 7000 mg per package . Given the growing popularity of marijuana in forms like edibles or extracts, increased focus should be directed towards understanding the health effects of THC at such concentrated levels. In the absence of evidence of harms, states may be reluctant to more stringently regulate the form and content of edible products. There are several limitations to this study. The generalizability of our results may have been limited by the use of an internet survey as the population who choose to join an ongoing internet panel may be different from individuals who choose not to participate. However, GfK’s KnowledgePanel has demonstrated no evidence of non-response bias in the panel on core demographic and socioeconomic variables . We did not conduct reliability testing of the survey items. As a result, it is possible the interpretation of our questions might differ between participants. For example, though pain management was endorsed as the most important benefit across residents of all states, we did not distinguish between types of chronic pain, and this may have been interpreted differently between participants. Additionally, we did assess the extent of individual marijuana use among participants, medical reasons for use among marijuana users, and sources of information regarding beliefs about marijuana. However, the data were not sufficiently relevant when stratified by state legalization status.

Furthermore, it is important to note that we did not differentiate between state legal status beyond the designation of ‘‘recreationally legal, medically legal, or nonlegal,’’ and marijuana accessibility can vary greatly within states with the same legal status due to differences in state-based implementation. Nonetheless, we found clear differences in opinions of residents of recreationally legal states compared with other states. Finally, the study was cross-sectional. Therefore, it is unknown if people in states where marijuana was legalized for recreational use developed their beliefs before legalization, which then led to legalization in their state, or if the opinions assessed in this survey were a result of recreational legalization of marijuana.The prevalence of marijuana use has increased in the past decade in the United States population and worldwide. In tandem with increasing marijuana use, there has also been a substantial drop in the public’s perception of risks from marijuana use in the US and other Western countries.Moreover, the marijuana industry has experienced tremendous growth in the past decade and is projected to exceed $57 billion in annual revenue within the next decade.In tandem with the growth in marijuana marketing, sales, and use, there has been a proliferation of misinformation.National surveys suggest the perception of Bgreat risk^ from weekly marijuana use has dropped from 50.4% in 2002 to 33.3% in 2014 and has dropped further since.A recent national survey demonstrated that the public attributes benefit to marijuana without any evidence to support such beliefs . Moreover, recent data also suggests that many Americans believe that marijuana has no risks and that it prevents health problems.The main drivers of this favorable perception in the US are unclear, but it is likely multi-factorial and includes the liberalization of medical marijuana laws and promotion by advocacy organizations and business interests. For example, Business Insider, a website with an audience of over 100 million visitors a month,recently touted the ability of marijuana to Breverse carcinogenic effects of tobacco and improve lung health.^ The source research article cited by Business Insider did not support such a claim.In addition, legalization has been accompanied by the commercialization of marijuana, with projections estimating that marijuana sales will exceed $25 billion by 2025.There is overt marketing to consumers of marijuana on the Internet and social media with inadequate regulatory oversight.It is possible that sources of information are playing a role in furthering misinformation among the public, which in turn is resulting in decreases in risk perception, particularly among adolescents.Determining the public’s main sources of information about marijuana use is essential to curbing misinformation and improving public health outcomes. In this national survey of US adults, we examined where US adults receive information about marijuana. We also examined whether the sources of information were associated with believing unsupported claims about marijuana.We conducted a survey of a nationally representative sample of 16,280 US adults on risks and benefits of marijuana use. The survey was conducted using Knowledge Panel , a nationally representative panel of civilian, non-institutionalized US adults aged 18 years and older that has been used to survey public opinion since 1999. GfK created a representative sample of US adults by random sampling of addresses. The address-based sampling covers 97% of the country and encompasses a statistical representation of the US population. Households without Internet access are provided with an Internet connection and a tablet to ensure participation. All participants in the panel are sampled with a known probability of selection. No one can volunteer to participate and are instead selected randomly by GfK based on address.

The proportion of counties in Colorado with prohibitions was also greater than that found in a policy surveillance study from California.Our results add to existing reports that numerous counties are opting to prohibit recreational marijuana facilities in states where recreational marijuana can be legally purchased and consumed . We found local stakeholders were publicly engaged in county policy decisions. We did not identify stakeholders who represented industry groups or external entities, which appear to play a limited public role in local debates. It is feasible that industry groups or other external advocates were involved in private lobbying efforts as opposed to public facing advocacy strategies. Our findings about the predominance of local stakeholders in policy debates are similar to research examining a local medical marijuana policy debate in California involving internal actors, and the arguments namely reflected a struggle between identity and social order within the region.The involvement of local stakeholders also suggests marijuana commercialization is currently a cottage industry. In the absence of targeted regulatory policy to retain small-scale growers and retailers, a large marijuana industry could emerge, prioritizing lobbying and aggressive advertising strategies.Tobacco companies may potentially enter marijuana policy debates given their long-standing interest in entering into legalized marijuana markets based on the sales potential.Based on our qualitative data, whereas some stakeholders were likely to support allowing marijuana facilities as a way of attracting outside tourism, other stakeholders used concerns about legal liability or additional crime from outsiders as rationale to prohibit these facilities. Future work should further explore how county policymakers balance local-level politics and perspectives with state policy directives and policies over time. Additional research could examine factors influencing enactment of local recreational marijuana policies and closely examine the effect of population density and county-state borders on local marijuana policy decisions.

Arguments in favor of permissive cannabis dry rack county ordinances included economic benefits 60 and increased access to medicinal and therapeutic treatment. Early evidence on cannabis markets in Washington suggests increased cannabis retail access is associated with more frequent use among adults in the state.Sales data from Washington indicate a large and growing marijuana market, yielding a substantial source of state revenue allocated to the general fund, basic health, local municipalities, prevention and education, research, and other issues. In fiscal year 2019, Washington collected $395.5 million in legal marijuana taxes and license fees.62 During the COVID-19 pandemic, monthly recreational marijuana sales in Colorado were $183 million in July 2020 alone.As state and local governments continue to be impacted by the economic losses associated with COVID-19, economic gain arguments might become increasingly attractive to offset diminishing revenues from other sources. The gradient of local marijuana policy is more nuanced than these three categories because some counties allowing all types of marijuana facilities also have restrictive zoning conditions, limit the maximum number of facilities, or limit acreage for cultivation or processing facilities. Additionally, our study did not closely examine other local marijuana policy elements such as minimum buffer distances, business hour limits, public health messaging, or advertising restrictions.Another study limitation is the exclusion of cities and towns from the sample. It is important to note that counties are limited in their regional authority and can include cities with marijuana policies that differ from the county policy. Prior studies on similar topics and geographies have examined marijuana policy in Washington cities with more than 3,000 residents3 and all cities in California.6 Given our additional focus on policy stakeholders, arguments, and advocacy efforts, we elected to solely concentrate on county-level policies. A key strength of our study is that it is the first to consider local policy variation across two states that legalized recreational marijuana use at the same time. The typology we created and employed can serve as the basis for future legal epidemiology work to examine the effects of policy on public health, health, and social outcomes.

Other strengths are the inclusion of qualitative research and newspaper article data for the purpose of providing rich descriptions of the county policy environments and change. Prior cross-sectional policy surveillance studies lacked these elements. Further, our findings convey the value of ongoing local policy surveillance data because four counties identified as having moratoriums/bans in place as of July 2014 allowed recreational marijuana facilities by mid-2019, indicating considerable local policy change processes occurred within these jurisdictions in the span of a few years.Since 2012, several other states have legalized recreational marijuana for adults and have permitted local-level jurisdictions to regulate local markets. States may benefit from the results of our findings as they create their own frameworks to regulate marijuana and take into consideration similar fundamental local government concerns, such as public safety, health, and environmental impact issues. Opponents of permissive marijuana policies point to perceived public health, safety, and welfare issues related to marijuana facilities and use, including addiction, increased crime, and detrimental health effects for minors. Early results from Colorado suggest legalization has led to increased marijuana-related hospitalizations, an initial surge in poison control center calls mentioning marijuana, and increased DUIs for which marijuana was identified as the primary impairing substance.In Colorado and Washington, commercial marijuana legalization is significantly associated with increased rates of fatal motor vehicle accidents.There is also evidence on the harms of marijuana secondhand smoke on cardiovascular health.Use of high-potency cannabis concentrate products has also been associated with negative consequences like psychosis and emergency department visits.These public health outcomes should be considered and used to inform policy decisions. Research about associations between crime and legal recreational marijuana facilities and local markets can also help address perceived concerns about increased crime. Findings from existing studies are mixed, likely due in part to challenges in interpreting law enforcement data.

We found that advocates of allowing local marijuana facilities claimed legalization could reduce local marijuana black market activities; however, opponents were concerned about additional enforcement or implementation costs, as well as crime. Cost-effectiveness studies comparing the cost of additional enforcement or implementation mechanisms to local revenues are needed. Potential associations between local marijuana policy and health effects and crime have gone largely unexplored due to restrictions and limitations on federal funding for marijuana research. Studies on the implementation and management of marijuana prevention and control programs have also been constrained by a lack of federal funding. However, interest in the public health and safety impact of local marijuana businesses expressed by local stakeholders in our study indicates a critical demand for policy effectiveness research to inform local decisions. Youth access to and use of marijuana, driving under the influence of marijuana, marijuana dependence and addiction,botanicare rolling benches unwanted contaminants in marijuana products, uncertain potency of marijuana products, and concurrent use of marijuana and alcohol have previously been identified as important topics for public health research and evaluation to inform policy.Public concern about noxious odors was a frequent argument against permitting marijuana cultivation and processing facilities in local jurisdictions, as well as a reason to overturn permissive marijuana ordinances. This is an issue that policymakers and marijuana producers need to address and mitigate with regulatory policy and practice. As the legal market continues to grow, more research is needed on the impact of operating marijuana cultivation and processing facilities on the environment,including studies of the use of pesticides and cannabis cultivation and regulation standards.Concerns have been raised regarding the concentration of cultivation licenses in agricultural areas and environmental health concerns for vulnerable populations,who often disproportionately face environmental injustices. Research is also needed to explore the role of state and local public health departments in regulating marijuana in states where recreational marijuana is legal, since a public health framework would designate them as the lead regulatory agency.Studying the impact of marijuana legalization on public health departments’ scope of work and health education and promotion efforts in marijuana prevention and control programs is also important. States such as Washington that have earmarked revenue for prevention, control, and research may have made further progress than counterparts in this area for developing educational campaigns .Co-occurring marijuana and tobacco use have been associated with increased rates of psychiatric disorders and psychosocial problems . Further, co-use has been linked to more days of past month marijuana use and higher rates of marijuana dependence relative to marijuana only smokers . Despite the negative health related consequences of tobacco and marijuana co-use, a recent review found only three studies focusing on co-use prevention and two studies on treatment . Since that review, a few treatment studies for marijuana and tobacco co-use have been published . However, additional research is needed to inform the effective development of prevention and treatment interventions for tobacco and marijuana co-users. Identifying interaction expectancies might help identify barriers and strategies that should be used in the development of prevention and treatment interventions for co-users .

High expectations may pose barriers to cessation of either substance, therefore underlying low motivation to quit. The Nicotine and Other Substance Use Interaction Expectancies Questionnaire was developed by Rohsenow et al. to investigate expectations regarding the relationship between smoking and other substance use held by treatment seeking substance users. Participants reported that substance use almost always increased their smoking or urges to smoke, but smoking only increased their substance use or urges about half of the time . More recently, Ramo et al. adapted the NOSIE to examine cigarette and marijuana interaction expectancies . In a non-treatment seeking sample of young adult marijuana and tobacco co-users, Ramo et al. found that young adults who used more tobacco and marijuana held higher expectancies regarding the interaction of the two substances. In addition, days of past month marijuana use and thoughts about abstinence, significantly predicted responses to the NAMIE scales. The current study examines presence and predictors of tobacco and marijuana interaction expectancies among African American young adults participating in an anonymous online survey. African Americans were chosen as the population of interest, as co-use is considerably high among this population of young adults and they experience higher rates of negative drug-related consequences of substance use comparable to other racial/ethnic groups . Further, African Americans are more likely to smoke blunts than other racial/ethnic groups , and little is known about whether this form of co-use may be associated with unique patterns of interaction expectancies compared to other forms of co-use. The purpose of the current study was to determine if there are differences in tobacco and marijuana co-use expectations among blunt and cigarette co-users [hereafter referred to as blunt co-users] and non-blunt and cigarette co-users [non-blunt co-users] and determine if expectancies among blunt co-users and non-blunt co-users were associated with variables that have been linked with expectations about drug use in previous studies , including age at first tobacco use, age at first marijuana use, days of past month marijuana use, and days of past month tobacco use.Participants were African American young adults who completed an anonymous online survey. The survey was designed to assess patterns of and factors associated with marijuana and tobacco co-use among non-treatment seeking young adults. Participants were recruited via flyers distributed in predominately African American communities , word of mouth, and a free campaign on Craigslist in a Midwestern city in the United States. The survey link, along with a Quick Response code, was included on the flyer, which directed participants to the consent form, screening questions, and a secure survey within Qualtrics. Participants who met the following criteria were eligible to participate in the survey: were between the ages of 18–29, self-reported as being a non-Hispanic African American or Black woman or man, self-reported smoking marijuana at least four times in the past month, self-reported smoking tobacco at least 20 of the past 30 days, were not enrolled in outpatient or residential substance abuse treatment for marijuana or not engaged in formal smoking cessation treatment in the past year and had a personal email account to receive an electronic gift card. Eligible participants were invited to complete a brief survey, and received a $20 online gift card for their time and effort. Of the 185 participants who completed the survey screener, 162 participants met eligibility criteria to complete the survey. Of those, 144 completed the survey. For the current study, we used data from participants who reported past month marijuana and cigarette use .

There has been growing interest in standardized trials to determine efficacy and side effects using standardized dosing . Marijuana is also increasingly recognized as a promising therapeutic target in various digestive disorders including inflammatory bowel disease, irritable bowel syndrome, secretion and motility related disorders. Cross-sectional studies  have reported a correlation between daily marijuana use and increase in liver fibrosis and steatosis among hepatitis C patients. However, several subsequent cohort studies did not confirm the association between marijuana use and accelerated progression to fibrosis or cirrhosis in HCV or HIV/HCV coinfected patients. Whether marijuana use should be a contraindication for liver transplant is unclear. In a recent survey of transplant physicians, 47% identified marijuana use as a “controversial characteristic”. In fact, there is little consensus within the LT community whether marijuana users should be eligible for transplant listing at all . Despite this debate, there are few reports on overall survival among chronic liver disease patients who use marijuana. Consequently, marijuana use among LT candidates remains a controversial topic . Yet, in July 2015, California adopted Assembly Bill 258, the Medical Cannabis Organ Transplant Act, which prohibits transplant institutions from denying transplantation to medical marijuana users based on their use of marijuana alone. In fact, 6 other states have adopted similar measures protecting medical cannabis users: Arizona, Delaware, Illinois, Minnesota, New Hampshire and Washington. In addition, 6 states passed legislation or ballot measures to legalize medical marijuana in 2016 alone, bringing the total number of states with legalization of marijuana to twenty-eight in addition to the District of Columbia. Given the increasing trend towards legalization and protection of medical marijuana,indoor grow lights shelves understanding the impact of marijuana use on LT outcomes is not only practical but also essential. In the only prior study assessing LT-related outcomes among marijuana users, Ranney et al found no survival difference among LT candidates whether they consumed marijuana or not.

However, in this study, more than a third of eligible patients on the LT wait list were excluded due to missing tobacco, toxicology or psychiatric history. This large proportion of patients with missing toxicology data is likely to include many substance users who might be reluctant to undergo drug screening for fear of delisting or had poor follow up. Despite exclusion of these potentially high-risk patients, marijuana users were significantly less likely to receive LT . Given the proportion of missing data, it is plausible that this study may not have adequately captured adverse outcomes like death or delisting among marijuana users on the LT wait list. In light of the limited data on LT wait list outcomes, in the present study, we aimed to assess several outcomes among historical marijuana users who were evaluated for LT at our institution, including death or delisting on the LT waiting list and probability of receiving LT. In addition, we also sought to evaluate the prevalence of and factors associated with marijuana use among all patients undergoing LT evaluation at our center to guide future studies among this population. All adults presenting for a LT evaluation at University of California, San Francisco over a 2-year period, from January 1, 2012 through December 31, 2013, were included in this retrospective cohort study. The study was reviewed and approved by the UCSF institutional review board. During the study period, the UCSF LT program had a policy of not listing patients with active marijuana use. Prior to listing, patients were required to abstain from marijuana use and, therefore, all marijuana use among listed patients is likely to be historical. Marijuana use was defined as ‘recent’ if subjects self-reported ongoing marijuana use at the time of first LT evaluation and/or had positive drug toxicology on screening laboratory evaluation. These patients were generally asked to abstain from marijuana use before being listed for LT. ‘Prior’ use refers to self-reported historical use of marijuana. Similarly, tobacco, alcohol and illicit substance use was defined by combination of self-report and urine toxicology and further categorized as ‘prior’ and ‘recent’. Patient demographic and clinical data were collected by individual health record review and/or programmed capture from electronic medical record databases .

Substance use, including marijuana, information was obtained from review of detailed psychosocial assessment conducted by trained social workers at the time of first LT evaluation. Statistical analyses were performed using STATA versions 12 and 14 software . Marijuana use was defined as combination of self-report on psychosocial assessment or positive urine toxicology during initial LT evaluation and work up. Urine drug screening was performed at the discretion of the LT team based on perceived risk of drug use on the LT wait list. Our study includes the initial urine drug screen with further data captured at the end of the study period via final LT status . Marijuana use was further categorized as ‘prior’ or ‘recent’ at the time of first LT evaluation, as described previously. Factors associated with marijuana use were analyzed using a multi-variable log-link Poisson regression with robust standard errors to estimate adjusted incidence rate ratios . Using this method, the calculated IRR approximates the prevalence ratio. All risk factors with p-values of less than 0.05 were retained in the multi-variable model. Among those listed for LT, we calculated the cumulative incidence of death or delisting within strata of marijuana use. Similarly, we also calculated the cumulative incidence of receiving LT within strata of marijuana use. Observation time was measured from date of first LT evaluation to the first of dropout, wait list death, or transplant. Cumulative incidence estimates accounted for competing events and patients remaining on the waiting list were censored at the last known date on the list. Using Fine and Gray competing risk regression 19 we estimated the hazard ratios and 95% CI for risk of the 2 outcomes of interest, wait list death or delisting and receiving transplant on the wait list. Factors with a univariate p<0.2 and the primary explanatory variable, marijuana use, were included in the multi-variable modeling process. The final multi-variable models were selected by backward elimination with p>0.05 for removal while retaining marijuana use. Of all 884 LT candidates, 585 were listed for LT. Among them, 205 died or were delisted while 287 received LT. Among never users of marijuana, 69% were listed for LT. While, 65% and 51% of prior and recent users of marijuana were listed for LT, respectively. Listing and wait list outcomes for all participants are outlined in Figure 2. Among those listed for LT, there was no statistically significant difference in the cumulative incidence of death or delisting on the LT waiting list within strata of marijuana use .

Similarly, there was no statistically significant difference in the cumulative incidence of receiving LT within strata of marijuana use . Reasons for delisting from the LT wait list are presented in Table 4. The most common reasons for delisting included ‘too sick for transplant’ and ‘death’ . There were isolated cases of ‘substance abuse relapse’ with no significant differences between recent, prior and never users of marijuana . Our study presents a comprehensive assessment of marijuana use among LT candidates. We found no statistically significant association between the risk of wait list removal or death and historical marijuana use. On the other hand, notably,vertical indoor growing system a history of recent illicit drug use was associated with higher risk of death or delisting. This finding could be related to a number of possibilities including recidivism to drug abuse which would prompt delisting from LT wait list, or perhaps higher rate of medical illness from complications of drug use resulting in death or delisting. Illicit drug use may also reflect worse social circumstances and lack of support leading to delisting. On the other hand, a similar association with marijuana use was not found. This observation supports major differences in the impact of a history of marijuana use vs. illicit drug use among LT candidates. Similarly, in unadjusted and adjusted competing risk regression, we were unable to detect a statistically significant association between receiving LT and history of marijuana use. Factors associated with higher chance of receiving LT included MELD score ≥20 and HCC – both of which are consistent with and reflect current LT allocation practices . Marijuana use was highly prevalent among LT candidates at our institution. Almost half of all evaluated patients had a history of marijuana use and a considerable proportion were recent users at the time of evaluation. Among users, 13% had a self-reported history of weekly use while 16% had been daily users. Substance use, beyond marijuana, was a common feature among LT candidates – we found high prevalence of historical tobacco use , alcohol use , illicit drug use and prescription opiate/BDZ use . More than half of all alcohol users had a history of heavy use/abuse, and a significant proportion of candidates were recent users of illicit substances. We also found that almost a quarter of evaluated patients had recent opiate/BDZ prescriptions. Though detailed and systematic data about substance abuse among all LT candidates are limited, our findings are similar to prior reports, including those assessing patients with alcoholic liver disease .

We also identify several factors associated with marijuana use, including younger age and white race. Marijuana use was closely associated with other substance use – persons with alcoholic and HCV cirrhosis were more likely to have been marijuana users compared to those with HBV cirrhosis. Tobacco use, both prior and recent, was also associated with higher prevalence of marijuana use. Similarly, prior and recent illicit drug users had higher prevalence of marijuana use. Notably, never users of alcohol had much lower prevalence of marijuana use – this likely reflects a small proportion of LT candidates who have been abstinent or had very limited exposure to any substance use. There have been prior conflicting reports regarding an association between marijuana use and lower BMI. In univariate analysis, marijuana users were less likely to be obese compared to overweight , though this association was not significant after multi-variable adjustment . This is the first study to present detailed data on prevalence and multi-variable adjusted factors associated with marijuana use among LT candidates. Our findings are consistent with limited prior reports of marijuana use patterns among LT candidates. Recent national drug use surveys 27 have found that 6.5% of adults older than 25 had active marijuana use. These nationally representative estimates are in close agreement with our finding of 7% recent marijuana use among LT candidates. It is also important to note that marijuana use was not just limited to those with a history of substance abuse but was rather distributed across the spectrum of substance use, as demonstrated in Figure 1. Yet, in our study, despite noting a high prevalence of marijuana use and its associations with other substance use, we were unable to detect worse outcomes with historical marijuana use itself; whereas, illicit substance use did confer higher risk of death or delisting on the wait list. In a recent study, Greenan et al 28 also found that isolated recreational marijuana was not associated with poorer outcomes among kidney transplant patients. Though most patients underwent urine drug screening in addition to psychosocial evaluation to identify marijuana use in our cohort, we assessed for differences in sensitivity of marijuana use assessment between urine drug screening and psychosocial screening. Most marijuana users had positive urine toxicology – among ‘recent’ marijuana users 80% had positive urine toxicology while an additional 20% were identified based on self-report alone. Therefore, sensitivity of drug screening alone was 80% while that of self-report alone was 62% . We also assessed for differences in outcomes between those who tested negative for marijuana and those who were not tested with urine drug screening. A similar proportion of subjects with and without urine drug screen were positive for marijuana use – 48% and 46% , respectively, with no statistical difference detected . When comparing subjects without marijuana use by presence or absence of the urine test, risk of death/delisting and LT failed to differ statistically. Regardless of screening method, a similar proportion of patients were positive for marijuana use and wait list outcomes were similar.

Gaining better understanding how psychological distress and social supports or deficits relate to marijuana use among young adults may inform tailored intervention development. Marijuana has become more socially acceptable in California since medical marijuana laws passed in 1996, and acceptability is likely to increase further if marijuana is legalized. A 2015 study of Northern California teens reported that marijuana was perceived as more socially acceptable, normative, and safer than cigarettes.However, it remains unclear how this social context may interact with sociodemographic and psychosocial characteristics in marijuana use among young adults. Although the evidence base for understanding the health effects of marijuana is limited as a result of the difficulties with conducting research on a drug classified as Schedule 1 under the United States Controlled Substances Act, early studies have indicated associations between long-term heavy marijuana use and increased risk of addiction, chronic bronchitis, cognitive impairment and psychosis disorders in people predisposed to them.Additionally, studies of marijuana use among adolescents have demonstrated associations with decreased academic achievement and increases in use of other illicit drugs as well as suicide attempts.Marijuana use has further been associated with risky health behaviors, such as tobacco use and binge drinking, and secondhand marijuana smoke has been shown to compromise vascular function similar to secondhand cigarette smoke.30 This study’s objective is to describe the sociodemographic correlates of marijuana use in a diverse population-based sample of young adults residing in San Francisco and Alameda Counties, and to investigate associations between psychological distress, social support,clone rack loneliness and marijuana use. Specifically, we hypothesize that: 1) there will be differences in marijuana use by sociodemographic characteristic; 2) psychological distress will be positively associated with use; and 3) social support and loneliness will moderate the association between psychological distress and marijuana use.

We additionally control for known correlates of marijuana use among young adults, including perceived harms of marijuana, sleep quality, cigarette smoking, and alcohol use.Data for this study are from the 2014 San Francisco Bay Area Young Adult Health Survey, a probabilistic multi-mode household survey of 18–26 year old young adults, stratified by race/ethnicity, in Alameda and San Francisco Counties in California. Potential respondent households were identified in two ways – first from address lists obtained from Marketing Systems Group wherein there was an approximately 40% chance that an eligible young adult resided at the selected addresses , and second using 2009–2013 American Community Survey and 2010 decennial census data in a multistage sampling design to identify Census Block Groups and subsequently Census Blocks in which at least 15% of residents were adults in the eligible age range; address lists were compiled for each selected block and households were randomly selected from these lists for face-to-face visits . The survey was conducted using three modes – mail/web, telephone, and face-to-face interviews. Mailings, including the survey questionnaire, informed consent document, and $2 incentive were sent to each of the 15,000 addresses identified, followed by two additional mailings. Respondents could return the questionnaire by mail, or complete it online. Subsequently, the ~13,000 households for which we had phone numbers and from which we had not already received a response received up to three calls to determine eligibility and attempt questionnaire completion. Finally, a random selection of addresses was drawn from the households lacking a mail or phone response, and research assistants visited each of these households, as well as all of the randomly selected housing units from the block sample, in person up to three times. The final number of observations was 1,363 for a survey response rate of 30%. Approximately 2/3 of respondents replied via mail or online with most of the remaining responses completed in the face-to face phase; only a handful of questionnaires were completed via telephone. Individual sample and post-stratification adjustment weights were constructed after data collection.

We assessed respondent age, sex, race/ethnicity, sexual orientation, maternal education and marital status. Age is a continuous variable in years; self-reported race/ethnicity is measured as a categorical indicator and the remaining measures are dichotomous. Respondents were given the opportunity to select multiple race categories, and those who selected more than one category and were not Latino were classified as “multi-race.” Sex was coded as ‘1’ if the respondent was male, 0 otherwise; LGBT was coded as ‘1’ if the respondent identified as homosexual or bisexual; mother’s college education was coded as ‘1’ if the respondent’s mother had at least graduated college; married was coded as ‘1’ if the respondent was currently married. Psychological distress was measured with the K6 scale,which asks respondents how frequently in the past month they felt nervous, hopeless, restless, depressed, worthless and like everything was an effort. Participants were classified as having serious psychological distress if the K6 value was equal to or greater than the validated cutoff of 13.Social support is a composite variable based on five items, derived from the Multidimensional Scale of Perceived Social Support, indicating agreement with the following statements: 1) there are people I can count on when I need help; 2) there is a special person in my life who cares about my feelings; 3) my family really tries to help me; 4) my friends really try to help me; and 5) I get the emotional support I need from people in my life. Responses were on a five-point Likert scale from strongly disagree to strongly agree. Loneliness was measured using two items, derived from the Loneliness Scale,employing the same Likert response scale: 1) no one really knows me well; and 2) my interests and ideas are not shared by those around me. Each of the two composite variables were standardized, and higher response values indicate greater levels of social support and loneliness. These items were based on longer versions of validated scales; and we conducted confirmatory factor analyses to ensure that the abbreviated scales each conform to one factor . Perceived harm of marijuana use was measured continuously with respondents indicating how harmful they think marijuana is to general health, from “not at all” harmful to “extremely” harmful .

We assessed three other health behaviors possibly related to marijuana use: current cigarette smoking, number of days respondents engaged in binge drinking and respondent sleep quality. Current smoking was coded as ‘1’ if the respondent smoked a cigarette at least one day in the previous. Days binge drinking was measured continuously as the number of days respondents reported drinking five or more alcoholic beverages “within a few hours” in the past 30 days. Sleep quality was also measured continuously; respondents rated their sleep quality from “very bad” to “very good” .We used Stata 13 to examine bivariate relationships between each of our predictors and marijuana use , followed by a hierarchical logistic regression, reflected in Table 2, using the “svyset” command to adjust for the complex sampling design. Data for the analysis were retained for 1324 of the total 1363 observations. Twenty-seven respondents were missing values for marijuana use, and the remaining observations were dropped due to incomplete data across several of the independent variables in the model. In conducting the hierarchical regression,hydroponic shelves we first assessed relationships between exogenous and socioeconomic characteristics and marijuana use, before entering serious psychological distress, followed by social support and loneliness and adding perceived harm and other health behaviors in the final model. The series of models addressed how covariates and serious psychological distress were independently associated with marijuana use and whether social support or loneliness moderated those associations. We hypothesized that marijuana use would have a positive association with marijuana use and that social support would diminish this association while loneliness would amplify it. Weighted characteristics for the study sample are shown in Table 1. Average age in the young adult sample was 22.7 years and approximately half of respondents were male. The race/ethnic distribution of the sample closely mirrors the distribution found in the young adult population in Alameda and San Francisco Counties.Approximately 10% of respondents identified as LGBT and 3.2% were married. Almost 9% of young adult respondents were classified as having serious psychological distress, which is substantially higher than the three percent of 18–64 year old adults estimated to be distressed in the most recent National Health Interview Survey.Approximately 15% reported current cigarette smoking, consistent with national estimates of smoking in this age group, but higher than the California adult prevalence rate of 12%.Marijuana users were more likely than non-users to be male and identify as LGBT . Non-Hispanic Asian/Pacific Islanders were the least likely race/ethnic group to use marijuana with only 10% reporting past 30 day use. Marijuana users were also more likely to have a mother with at least a bachelors degree , and had higher rates of serious psychological distress , much higher smoking rates and more reported days of binge drinking .Non-Hispanic Asian/Pacific Islander young adults had significantly lower odds of using marijuana, while non-Hispanic multiracial young adults had twice the odds of using marijuana compared to non-Hispanic White young adults. This is relatively consistent with prior studies showing lower substance use among Asians and the limited research that exists on multiracial adults indicates higher rates of substance use in this group.Few studies evaluate outcomes specifically for multiracial populations, often because the data are unavailable or the sample is too small, yet people who identify as multi-race are one of the fastest growing populations in the United States.

Younger populations in particular increasingly identify as multi-race, and it will be important to gain better understanding of how health behavior manifests among these individuals. Maternal education also demonstrated a significant positive correlation with marijuana use, a finding counter intuitive to prior health research suggesting protective effects of maternal education and family socioeconomic status on health outcomes.However, at least one prior study has found that those in the middle income range may be most likely to use marijuana, and given how little information is currently available on the characteristics and effects of marijuana use it may be premature to expect that marijuana use behavior shares the same features as more demonstrated problematic health behaviors, such as smoking and heavy alcohol use.While we cannot account for other measures of family SES, in our sample marijuana use peaked among young adults whose mothers had a bachelor’s degree. We did not find support for our second hypothesis; although positive, the relationship between psychological distress and marijuana use was not significant. We could locate only one other study that assessed serious psychological distress in relation to marijuana use among young adults, and studies of this relationship in adolescents had mixed findings.As social norms around marijuana change, reasons for using marijuana may also be changing in ways not directly measured in our study. Rather than to cope with psychological distress, young adults may use marijuana for recreational purposes or to mitigate physical pain, and these and other explanatory factors warrant further investigation. We found mixed support for our third hypothesis as social support and loneliness did not appear to moderate any association of psychological distress on marijuana use, but they both demonstrated significant positive correlations with marijuana use. While the finding concerning loneliness lends support to the idea that marijuana may be used as a coping method, the positive association with social support is less straightforward. Social capital, broadly conceived, is generally thought to be inversely associated with poor health outcomes and potentially risky health behavior, but some research in recent years has called this into question, arguing that peers and social networks may influence substance use, including that of marijuana.The extent to which the association between social support and marijuana use may be a social network effect in our analysis is unknown. Another possibility is that marijuana use, unlike cigarette smoking, does not carry a distinct stigma, and young adults may not use marijuana in similar ways to tobacco, alcohol or other substances. Similar to prior research,we found lower perceived harm of marijuana to be significantly related to marijuana use. Marijuana legalization advocates argue that portraying marijuana as safer than alcohol both in terms of health risks and societal harms is the strategy that brought the ballot victory to the legalization attempt in Colorado, and the same tactics were repeated successfully in Alaska campaign.It is likely that the same arguments will be used to push for legalization in other states and may lead to reduced perceptions of harm and increased use. Lastly, current cigarette smoking was associated with four times greater odds of using marijuana, while an additional day of binge drinking correlated to a 13% greater likelihood of using marijuana.

Given the high number of analyses performed across subgroups and multiple ECG abnormalities studied, there is high risk of a statistically significant false positive finding. Minor ECG abnormalities are common in healthy black people and associated with physical activity; we might have not been able to fully adjust for that. Minor abnormalities have not been associated with future CVD in young adults. While these elements inherently limit our confidence in the measures of association, CARDIA is to our knowledge the only cohort with ECG data which assessed marijuana exposure over such a long time and in such a large cohort. While the study of daily marijuana users is of evident interest, few participants use marijuana daily, and we still need to know if marijuana use is associated with changes in ECG, even at lower exposures or from past exposure. The strength of the CARDIA dataset lies in the possibility to study the full spectrum of marijuana use intensity typical of the exposure in the general population. No other longitudinal study assessed the association between marijuana use and ECG. In this study, we did not find an association between cumulative or past use of marijuana and ECG abnormalities. Compared to the previous studies assessing the association between marijuana use and ECG, most of them published more than 4 decades ago and including only very few participants, we can now report results from a cohort more than 100 times larger than previous studies. We were able to adjust for a rich set of covariables repeatedly measured at 7 examinations and a dozen phone follow-ups. We cannot exclude the possibility of informative censoring, which is a source of bias,vertical farming equipment suppliers but addressed that issue by using IPAW, as stated in the methods section.The District of Columbia and 15 States – Alaska, Arizona, California, Colorado, Illinois, Maine, Massachusetts, Michigan, Montana, Nevada, New Jersey, Oregon, South Dakota, Vermont, and Washington have legalized recreational marijuana use.

As a result, involuntary exposure to secondhand marijuana smoke has become much more common in everyday settings across the country. Studies have shown that secondhand exposure close to tobacco smoking or vaping is substantially higher than farther away – this “proximity effect” will also be an issue near marijuana smoking or vaping. The initial research investigating the proximity effect and spatial variation of exposure near a source used a tracer gas to mimic the transport of emitted air pollutants. For example, McBride et al released carbon monoxide as a tracer in a residential living room while using 12 real time CO monitors to measure concentrations at different indoor positions. Acevedo-Bolton et al deployed a larger monitoring array in the same residential living room to characterize exposure as a function of the distance from a continuous CO source. Klepeis et al measured real-time CO concentrations at up to 36 points in a residential backyard to consider the proximity effect outdoors near a building. These tracer gas studies provided insight into how different environmental conditions influence the proximity effect; however, they did not account for the characteristics of real smoking or vaping emissions, such as the exhalation of mainstream smoke and the buoyancy of sidestream smoke that can also affect proximity exposure greatly. Studies involving real human smoking or vaping were conducted mostly in prescribed settings. Acevedo-Bolton et al performed controlled experiments inside 2 homes and 16 outdoor locations, using a small group of investigators wearing personal exposure monitors to measure PM2.5 exposure close to prescribed tobacco cigarette smoking. Ott et al used a similar small-group monitoring approach to measure PM2.5 exposure near prescribed tobacco cigarette smoking at 6 outdoor bus stops on California roadways. Zhao et al measured indoor PM2.5 concentrations at 4 different distances from volunteers performing e-cigarette vaping, using a standardized puff frequency indoors in an 80 m3 patient room in a clinical research center. Using a heated mannequin, Martuzevicius et al measured indoor particle exposures at 3 different distances from e-cigarette vaping, adopting the same 30 s puff frequency.

Nguyen et al investigated particle concentrations at personal-space, social-space, public-space distances from non-prescribed vaping activities in California vaping shops. These studies provided valuable data for the levels of exposure close to tobacco smoking or vaping in real-world indoor and outdoor settings. Marijuana is most often smoked in homes . Using a commercial real-time sensor , a recent research study monitored particle number concentrations in ~300 California residences. This study provided the first set of data on particle levels inside real homes with marijuana smoking. However, this large-scale study did not allow spatial measurement of exposure inside a home or accurate mass concentration measurements based on gravimetric calibration. Little is known about the PM2.5 exposure close to a marijuana smoker. There also is virtually no knowledge of how different source types and environments affect the proximity effect. Our first goal was to examine, for the first time, PM2.5 exposure close to a marijuana smoker and how the exposure can be reduced by increasing the distance from the source; we measured real-time PM2.5 concentrations at 1, 2, and 3 m distances from marijuana emissions in a smoker’s home and assessed both the level and frequency of exposure versus distance. Our second goal was to investigate whether choosing a different source type, a different location, or a different environmental setting can reduce the proximity exposure; we tested two common marijuana source types along with their corresponding exhalation patterns in an indoor and an outdoor location under different ventilation and air mixing conditions. Given the collected exposure data, an additional goal of our research was to explore data analysis methods that can potentially be useful for evaluating the recommended physical distance from marijuana sources to minimize involuntary exposure. We performed field research inside a residential property in San Jose, CA . This single-family home has two stories and a private backyard, and the marijuana smoker is the only occupant in this property. Five AM510 SidePakTM monitors were deployed near the indoor chair in the 4.3×3.7×2.4 m family room or the outdoor chair in the backyard where the participant normally smokes or vapes marijuana . Both chairs backed up to a wall, and the outdoor chair had a small table 0.7 m high to its immediate left.

The 5 SidePak monitors were placed radially with 15o angle spacing at an equal distance from the source in each session , measuring PM2.5 concentration every 1 s; they were facing the front of the smoker to account for the worst-case exposure. Three monitors were placed at 1 m height ,grow lights shelves whereas two monitors were at 1.5 m height to consider typical adult breathing heights while sitting and standing, respectively . The actual measured breathing heights of the smoker sitting on the indoor and outdoor chairs were 1.2 m and 1.1 m, respectively. Using these monitoring settings, we performed 35 experiments . For the indoor experiments, 17 were performed with all windows and interior or exterior doors closed in the house – “base case” while 3 involved opening the family-room door and two dining room windows while running the fan of the centralized HVAC system – “alternative case”. For outdoor experiments, 12 were carried out with a fully-opened outdoor umbrella above the smoker – “base case” – while 3 were carried out with this umbrella fully closed – “alternative case”. We hypothesize opening or closing the umbrella would noticeably affect the air mixing and proximity effect close to the source. For the base-case experiments, all 5 monitors were underneath the umbrella when placed at 1 m distance from the smoker. We used the VelociCalc 8386 anemometer to measure and log the indoor and outdoor air velocities near the smoking or vaping locations every 2 s during each experiment. This instrument has a 6-mm diameter sensor probe with a 25 mm long anemometer at its tip, and its minimum detectable air speed is 0.01 m/s. It was not possible to release carbon monoxide or sulfur hexafluoride tracer gas in the participant’s house. As a way to estimate the magnitude of ventilation, we burned matches inside the house while using the Optical Particle Sizer 3330 to measure the particle number concentrations every 1 min. The air change rate was estimated by the log linear regression between concentration of the smallest particle size range and time after the well-mixed condition was reasonably achieved. Given the timescale of the experiments , diffusional and gravitational losses of particles within this size range were expected to be negligible compared with air exchange; this method has been used to estimate ACH in a residence where tracer gas releases were not feasible . These air change rate tests were performed outside the regular smoking or vaping experiments, because they involved particle emissions. We investigated two types of marijuana sources regularly used by the participant: a cigarette-like marijuana joint with 0% CBD and 9.6% THC, and an electronic vaping pen with the “Care by Design” 2:1 cartridge . A standardized smoking or vaping protocol that consisted of 5 puffs over a 5-minute period was used. After inhaling, the participant exhaled at the starting point of every minute ; we defined the 5 min period as the source period. This protocol was intended to enable comparisons between experiments with different source types or source distances based on the same exhalation or emission frequency . Zhao et al and Martuzevicius et al have adopted this approach but with a different frequency for ecigarette vaping. In our study, the participant chose the 1-min time interval for the 5-puff sequence to not exceed his normal habit of smoking and vaping. We did not choose a specific volume and duration for each puff, since we wanted to preserve the behavioral differences embedded in each puff for different source types and to investigate how they may affect the spatial variation of exposure close to a source.

The participant did not permit sensors to be used in contact with his body; therefore, puff topography or spirometry measurement involving sensor mouthpiece breathing was not conducted in this study. As a surrogate approach, we placed the VelociCalc anemometer in front of the smoker during the 5-min source period at 0.1 m horizontal distance from the mouth position to record the “exhalation peak velocity” – the maximum air velocity produced by each exhalation . This approach enabled us to investigate human exhalation via air environment measurement. We discovered the temporal fluctuations of air velocities outdoors were comparable to the magnitudes of exhalation peak velocities. Therefore, we were not able to measure the exhalation peak velocities in the outdoor experiments. The durations of the exhalation were measured by the participant using a stopwatch. A test examining how consistently exhalation peak velocities can be produced and measured by the environmental sensing method is available in the Supplementary Material . PM2.5 Calibration. To ensure consistent measurements between monitors, we conducted a separate quality assurance study in which we placed 17 SidePak monitors inside a car chamber with a smoke source, simultaneously measuring PM2.5 concentrations every 1 min. After the emission stopped and well-mixed condition was reasonably achieved , the exponentially decaying measurements of the SidePak monitors were compared by linear regression with our reference SidePak monitor, giving R 2 > 0.999 for the 5 SidePak monitors used . The SidePak monitors measure PM2.5 concentration based on light scattering properties, which are affected by the particle size and composition. To accurately represent the actual PM2.5 concentration, the calibration factor – the ratio of gravimetrically-to-optically-measuredPM2.5 concentration is needed for each source type . In a previously published paper, we determined the CFs for the two marijuana source types: 0.35 for joint smoking and 0.44 for vaping for the reference SidePak monitor; they were applied along with the inter-monitor slopes to rescale all PM2.5 measurement in this study where i = 1-5. Jiang et al found that CFs for SidePak monitors remained relatively constant over time; for a 16-month period, the average difference was ~3%. The particle zero filter was attached to the inlet of each SidePak monitor immediately before each experiment for zero calibration. The PM2.5 measurements at the 3 different distances were collected from separate experiments, not simultaneously.