Halfway through the focus group interview, participants were asked to reflect on the reasons behind elevated marijuana mis-use rates amongst youth high school students of color as well as what they believe unstable community indicator examples are for the prevalence of marijuana mis-use in South Central LA. As participants described their experiences visiting or not visiting marijuana dispensaries in their community as well as elucidated their line of reasoning behind why students of color have recently gained more access to marijuana, this substantial theme arose: marijuana mis-use amongst youth and adults of color within South Central LA have augmented due to increased marijuana accessibility and increase in the presence of marijuana outlets. In extricating this theme, it was discovered that the theme paralleled the research question initially posited which was “Do marginalized communities of color such as African American and Latinx communities experience more marijuana use due the presence of unstable community indicators such as marijuana dispensary abundance near schools and lacking communal forums that respond to marijuana mis-use prevention advocacy?” The development of this theme not only fit in Burnard’s open coding interview transcription analysis, but also affiliated with Dornfield’s live coding process of qualitative interview responses. Specifically, Stage 1 to Stage 10 sections were added to participant response transcription corresponding to this particular theme, mobile vertical rack however, I incorporated the live coding process due to the theme reinforcing the main research question. The live coding process included finding “main ideas” within the transcription that contained the same keywords as the research question.

Subsequently, a list of codes were grouped into categories which converged to form this theme. Under Burnard’s stages of transcriptional analysis, theterminology “dross” was applied to the transcript in cutting out unnecessary words that act as filler or deviate from the central idea of the statements relating to marijuana outlet abundance and accessibility within the transcript which constituted data refinement. In applying dross to the transcriptions, two subheadings developed which were “increased accessibility and outlet/dispensary increase.” When more transcripts were added under these subheadings, the theme expanded to marijuana outlet concentrations in urban areas due to cultural promotion and medicinal recreation popularity. The following data residing under the subheading of marijuana accessibility supports this theme. Diana stated that “All over, you see the big billboards and marijuana can be delivered to your home.” Maria stated that “you can use marijuana for medicinal purposes in the fact these uses are so it’s so easy to get permission for.” Soriyah stated that “They seek marijuana as well and that for medical reasons, but I also think they do it for enjoyment also.” Additionally, data was recorded which aligned with the subheading of marijuana outlet/dispensary increase which further corroborated the theme development. Janice stated that “I live fairly close to Western Avenue and Crenshaw and I see all these green pluses, I used to think they were churches.But as far as outlets and dispensaries, I’m assuming I once upon a time I saw one look like a beautiful department store up near Melrose. And so someone you know, jokingly asked me if I wanted to go shopping.” Diana stated that “I do know a few people that go to the dispensaries. And I have actually gone into the one on Melrose. It’s huge, and it’s amazing to see all of the stuff that’s in there. I don’t smoke marijuana. But I used to.” Lastly, Monica stated that “Marijuana was heavily regulated here in the Inland Empire almost to death. Until you know, folks started seeing the potential to make money and then they opened it up, but I do see it in more urbanized areas of the Inland Empire as opposed to like Redlands, I don’t know very many in Redlands.

So if I look in the geographical areas, they’llBased on the advancement of the focus group interview, the next theme devised was perceptions on current marijuana mis-use prevention education measures, connecting to the “effectiveness of educational tools in redirecting individuals to marijuana use recovery programs” component of the topic. Similar to the development of the aforementioned themes, a combination of Burnard’s interview transcript analysis and Dornfeld’s live coding analysis was utilized to extract keywords and splice these keywords into subheadings. Major subheadings included “participants have never heard of recovery programs through education” and “participants have never heard of recovery programs through visuals” as well as substantiated the theme. First, data was collected and placed into the “participants have never heard of recovery programs through education” subheading. Examples of this data included the following. Diana stated “And matter of fact, when you’re saying that they had some types of rehabilitation. I was like, Wow, no, that’s good. But that was the first time I had ever heard of it.” Elena stated that “So you really have to seek and then even, you know, at the doctor’s offices, they don’t say too much about it. So it will be very hard if you know, if you don’t know anyone to kind of find out about it, because it’s not something that’s just made readily available and unheard of often in our community.” Soriyah stated that “Okay. I don’t know of any. I’m just saying that there’s not a lot of messaging on it because it’s not seen as a problem.” Mikayla stated that “No one thinks there’s anything wrong with marijuana use. So no, I haven’t seen any programming for it.” Under the “participants have never heard of recovery programs through education” subheading, the following data was collected. Elena stated that “Oh, no, I haven’t been aware of these types of programming. I’ve seen posters, but they’ve been mostly for mental illness.” Monica stated that “I haven’t even seen any posters regarding marijuana mis-use recovery.” The data collected under these respective sub-headings corroborate the theme in that these responses explore whether the presence of educational curriculum have made individuals aware of these slightly obscure marijuana mis-use recovery programs and showcase participant reactions on the availability of marijuana mis-use education/programming tools within their community.

The last theme created in parallel with Burnard’s stages of transcription was that “participants believed that education on this marijuana mis-use is missing in communities now, but there are other community development tools which can reduce the prevalence of marijuana mis-use by safely steering users to treatment options or recovery programs.” Two subheadings resided under this theme, but equally linked the theme with the research topic. The two subheadings formed were “participants believed that there should be presentations/educational curriculum targeted towards elementary/middle school students” and “participants believed that community programming development would be effective in underscoring the implications of marijuana mis-use.” The data collected for the first subheading not only substantiated the theme development,vertical grow table but also the research topic sub-component of proposing stable community indicators in communities for creating community/youth awareness on marijuana mis-use. Data included quote transcriptions from 3 out of the 8 participants. Janice stated that “The education curriculum. I just think that it has to be started at a young age because they need to know about it because it’s everywhere.” Elena stated that “I also agree about starting at a younger age, I typically work with youth at a high school age. But I also think that elementary school is where you start because when they go to middle school, they have the pressures of trying to fit in. So I also think that it will help people and direct people towards prevention and treatment resources.” Jared stated that “Education is useful, young users tend to err on the side to focus on what is perceived as benefits.” Under the second sub-heading, a salient quote was extracted from Jared which was “creating maybe some drama classes, music, and art and stuff like that for youth” are great examples of effective educational tools for youth.” The theme encapsulates both data sets within respective sub-headings in that participants acknowledged gaps in effective educational tools tailored towards marijuana mis-use prevention and proposed ways in which marijuana mis-use education can be engaging for youth of color. As aforementioned, the research question was “What are the contributing causes for increases in marijuana mis-use amongst adolescents within communities of color? Have communities within South Central LA purported effective educational programming/community tools which spurs awareness of these topics and creates platforms for marijuana mis-use prevention advocacy, especially for youth of color?” Focus group methodology and program evaluation were included in the data collection tools to address these questions. When the marijuana mis-use presentation was given prior to the focus group interview, participants expressed that they were either unaware or aware of statistics that alluded to higher marijuana mis-use rates amongst high school youth communities of color. This suggests that there is a general lack of educational programming in the form of presentation and statistical information dissemination for marijuana mis-use within South Central LA.

The underdevelopment of these resources represent a unstable community indicator which indirectly fosters acceptability, subsequent consumption of marijuana, and mis-use within youth communities of color. Corroborated by Goldstick’s argument about the presence of socially disorganized communities as well as these communities formation of unstable organizational behaviors may be categorized as a social disorganization factor which drives maladaptive social/organizational behaviors including marijuana mis-use over consumption rates in South Central LA as well as individual investment in marijuana outlets to further promote unsafe messages on marijuana mis-use impacts on short/long term health. This connection between findings and Goldstick’s argument, addresses the primary research question in that the lack of educational programming was discussed in association with reflections on marijuana mis-use rates as well as a solicitation for increased education development to reverse the marijuana outlet development/misuse behaviors was established. Additionally, during the focus group discussion, all respondents relayed their own experiences as well as affirmed the abundance of marijuana outlets near high schools/urban areas such as Crenshaw, Melrose, and the Redlands. With this, respondents agreed that marijuana accessibility upon legalization increased due to profuse numbers of dispensaries near high schools/urban areas as well as stated that the easy access to marijuana represents a contributing cause to the increase in marijuana mis-use. These experience based results tie in with the proposed problem of youth access to marijuana and implicate that respondents may have exposure to the socially disorganized indicator of marijuana outlet presence within their area of residence or county. In South Central LA, this result further highlights that the increased presence of marijuana outlets poses a threat to the well being of the youth in that marijuana becomes not only more accessible to them, but also subjects them to mis-use marijuana in the long run which can unfavorably impact their educational pathway as well as their perceptions of their own health. Similar to Goldstick’s argument regarding the construction of alcohol outlets inurban areas within Michigan which led to adolescents engaging in “poly substance use,” findings delineate that increased density of marijuana outlets alongside other social disorganization indicators such as high level of crime are noted to further foster frequent marijuana substance mis-use and detrimental “behavioral comorbidities” within adolescents. Contrera examined the correlation between presence of marijuana dispensaries as well as crime rate violence in LA and concluded that the study literature model revealed the increase in crime rates due to marijuana outlet density. This result aligns with Contreras finding in that the concentration of marijuana outlets may not only drive the execution of crime which is a social disorganization indicator, but also may influence youth of color to access marijuana alongside their demonstration of violent behaviors. Juxtaposing Lankaneu’s argument that there is no correlation between “density of marijuana outlets and frequency of marijuana use amongst adolescents in LA,” result findings alternatively suggest that individuals who resided in South Central LA witnessed a pattern of high schoolers mis-using marijuana due to increased density of marijuana outlets near schools. This finding is not only supported by Goldstick’s and Contrera’s argument, but also connects to the research which is that indicators of social disorganization such as marijuana outlet development near schools may serve as a contributing cause to increase marijuana mis-use rates amongst high school students in CA.

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.