Research on adult marijuana users has shown alterations in brain response via fMRI scanning

Marijuana use in adolescence causes significant concern since marijuana use may impact the brain, which is still developing throughout adolescence. Though overall brain size stabilizes around age five , important progressive and regressive developmental processes continue throughout adolescence, including myelination , synaptic refinement , reductions of grey matter volumes and improved cognitive and functional efficiency . It is unclear how heavy marijuana use at this time could influence neural development. The long-term effects of marijuana have not yet been determined, but could potentially have major implications on social, academic, and occupational functioning. Although a good deal of research has been done on the effects of marijuana in chronic adult users, very little is known about adolescent users. Studies have shown that chronic marijuana has an influence on the neuropsychological performance of adults within a week of use. Specifically differences have been found in attention and executive functioning , memory , psychomotor speed and manual dexterity . One study demonstrated verbal learning deficits among marijuana users compared to controls 0, 1, and 7 days following use, but that these impairments subsided after a 28-day abstinence period . However, others have identified impairments in memory, executive functioning, psychomotor speed, and manual dexterity after 28 days of verified abstinence compared to published norms . Furthermore, adults who began use early in adolescence demonstrated greater decrements on verbal IQ after a 28-day abstinence period those who began late in adolescence and non-using controls,cannabis grow tent suggesting an adolescent vulnerability .

Due to its high safety profile and good spatial resolution, functional magnetic resonance imaging has become a powerful method for visualizing neural activation. More specifically, these studies have demonstrated an increase in spatial working memory brain response in marijuana users compared to normal age-matched controls in the pre-frontal cortex, anterior cingulate, and the basal ganglia . This suggests a compensatory neural response as well as recruitment of additional brain areas to achieve necessary task requirements, as seen in a recent study of task performance and brain functioning in marijuana users . However,because this study was done on adults who were abstinent for only 6-36 hours prior to the scan, it may be that these effects reflect recent use and not persisting effects . Others have characterized visuospatial attention among 12 recent marijuana users who had used 2 – 24 hours earlier, 12 abstinent users who not used for an average of 38 months, and 19 non-using controls . Both active and abstinent users showed decreased brain response in prefrontal, parietal, and cerebellar regions that normally sub-serve visual attention, and increased activation in alternate regions, suggesting brain response alterations even after extended abstinence. These adult fMRI studies point to altered neural functioning among marijuana using adults during visuospatial tasks, particularly in frontal and parietal regions. Less is known about neurocognitive functioning in adolescent marijuana users. A longitudinal study of ten adolescent marijuana users showed incomplete recovery of learning and memory impairments even after six weeks of abstinence . Recent fMRI studies of SWM involving alcohol-abusing adolescents and marijuana and alcohol-abusing adolescents have found that marijuana and alcohol were associated with greater changes than alcohol alone.

Specifically, after an average of 8 days of abstinence, adolescent marijuana users showed an increase in dorsolateral prefrontal activation and reduced inferior frontal response compared to alcohol users and non-using controls, suggesting compensatory working memory and attention activity associated with heavy marijuana use during youth . Adolescent marijuana users demonstrated increased right hippo campal activity and poorer attention and verbal working memory performance compared to demographically similar tobacco smokers and non-using controls, suggesting compensatory neural recruitment, even after a month of abstinence . In a follow-up study, marijuana using youths who were abstinent at least two weeks performed similarly as non-users on verbal working memory during ad libitum smoking and again during nicotine withdrawal, but exhibited increased parietal activation and poorer verbal delayed recall during nicotine withdrawal compared to non-marijuana users . Together, these studies suggest altered working memory functioning among adolescent marijuana users that may persist after a month of abstinence. Yet it is unclear how variability in task performance might contribute to brain activation patterns. Among normal adolescents, spatial working memory task performance is associated with activation in bilateral prefrontal and posterior parietal brain regions . Adult studies have suggested increased frontal and parietal activity associated with greater spatial working memory task difficulty . FMRI studies of adolescent and adult marijuana users have suggested that increased neural responding associated with marijuana use may be evidence of compensatory neural recruitment to maintain task performance . Therefore, the relationship between task performance and neural response may differ between marijuana users and controls, with a stronger positive relationship among marijuana users. The interaction between task performance and fMRI response to SWM has not yet been studied in adolescent marijuana users. The goal of the present study was to understand how task performance patterns contribute to neural activation in abstinent adolescent marijuana users. We studied blood oxygen level dependent fMRI neural activation during a SWM task which typically activates bilateral prefrontal and posterior parietal networks in adolescents and adults . This SWM task has been shown to be sensitive to brain response abnormalities in adolescent alcohol and marijuana users. In this study, both adolescent users and controls were required to abstain from all drugs and alcohol for 28 days prior to their fMRI scan, and all were free from psychiatric disorders and learning disabilities.

Based on our previous work we predicted that after 28 days of abstinence, marijuana users as a group would perform as well as controls; however, the task performance would vary within each group resulting in a group by task performance interaction that would be associated with brain response. Specifically, we hypothesized that there would be interactions between task performance and fMRI response in the bilateral dorsolateral prefrontal and posterior parietal cortices,grow lights for cannabis such that marijuana users show a stronger positive association between performance and brain response than controls in these regions. Flyers were distributed at local high schools, community colleges and universities to recruit 16- to 18-year-old adolescents . Adolescent participants provided written informed assent or consent for their participation, and guardians provided consent for youths under age 18, we well as consent for their own participation. This included an interview about their adolescent’s health and development history. The University of California San Diego Human Research Protections Program approved this study. Participants were initially screened for eligibility and then were given a 45-minute phone interview to collect information about general health, psychiatric disorders, and lifetime substance use. Participant parents gave consent for their own participation and were interviewed for detailed information about family health history and prenatal conditions. The computerized NIMH Diagnostic Interview Schedule for Children Predictive Scale was conducted separately with the youth and a parent to exclude adolescents with a potential psychiatric disorder . Other exclusion criteria included prenatal substance exposure, birth complications, psychotropic medication use, physical health problems, neurological dysfunction, head injury, family history of bipolar I or psychotic disorder , left-handedness, learning disability, or MRI incompatibility. Teens found to meet diagnostic criteria for alcohol use disorder were not excluded due to high comorbidity with marijuana use . Two subjects, both in the marijuana group, met criteria for alcohol abuse. Groups consisted of 17 heavy marijuana users and 17 non-using demographically similar controls. Users reported 477 episodes of lifetime marijuana use, on average, and control participants reported no more than five lifetime uses of marijuana. Groups were comparable in age, gender, ethnicity, family history of substance use disorders, and depressed and anxious mood . Marijuana users and control teens showed similar levels of IQ, as prorated by the Wechsler Abbreviated Scale of Intelligence Vocabulary and Block Design subtests , and socioeconomic status . Even though marijuana users reported more use of other drugs than controls, lifetime use of other drugs was less than 27 times across all substance types besides nicotine, alcohol, and marijuana. MJ users reported higher rates of alcohol than controls, and both groups had low rates of tobacco use . Measures Substance Use. Substance intake was assessed using the Customary Drinking and Drug Use Record .

Self-reported information was collected about lifetime and past three-month use of marijuana, alcohol, nicotine, and other drugs. Strong internal consistency, test-retest and inter-rater reliability have been shown with adolescent Customary Drinking and Drug Use Record assessments . The Timeline Follow back was used to assess drug and alcohol use for the previous 28 days. Participants were asked to point out for each day whether they used or drank. If they disclosed use, they were to indicate how many hits of marijuana or drinks of alcohol they consumed . “Drinks” were defined as one can of beer, one glass of wine or one shot of hard liquor to clarify amount of alcohol consumed. If asked, a “hit” of marijuana was defined as a puff from a pipe, bong, joint or vaporizer since smoking is the most common method of use. State Scales. The Beck Depression Inventory and the Spiel berger State Trait Anxiety Inventory measured mood prior to the time of scanning. The Stanford Sleepiness Scale determined alertness immediately before and after scanning with self-report ratings .Psychopathological Syndromes. Parents were interviewed about the child’s internalizing and externalizing behaviors via the Child Behavior Checklist . Spatial Working MemoryTask. This task consisted of 18 21-second blocks that alternated between resting fixation, vigilance, and working memory conditions . Each block began by showing a one-second word cue that prompted the upcoming block. The resting fixation block began with the cue “LOOK” and subjects were asked to look at the fixation cross. Each vigilance block was prompted by the cue “DOTS” and subjects were asked to respond with a button press to figures that had a dot above them . Before each working memory block, the cue “WHERE” appeared on the screen. During these blocks, abstract figures were individually shown in one of eight spatial locations, and subjects were instructed to respond with a button press every time a figure appeared in the same location as a previous figure had been within that block. Unknown to the subject, repeat location stimuli were 2-back, and composed 30% of stimuli. For both the vigilance and working memory conditions, stimuli were presented for 1000 ms, with an interstimulus interval of 1000 ms . All subjects were given practice with the task prior to entering the scanner and were monitored to ensure they understood the task instructions. Performance data were collected for accuracy and reaction time with a fiber optic response box. Procedures Toxicology. The toxicology procedure was designed to ensure that participants would not use substances in the 28 days prior to the fMRI scan. Cannabis metabolites can reliably remain detectible in urine for at least four days . Subjects were required to give a urine sample every three to four days each week during the 28 days prior to the fMRI session to make sure there was no recent use of cannabis, amphetamines, methamphetamines, benzodiazepines, cocaine, barbiturates, codeine, morphine, phencyclidine, and ethanol. Samples were collected and analyzed at the VA Medical Center using CEDIA DAU assays. Collections were observed to minimize the risk of participant tampering. Quantitative indices were tracked to determine if tetrahydrocannabinol metabolite levels decreased during the 28-day period. Participants who initially screened positive for cannabis were accepted and retained, as long as THC metabolite indices decreased continually throughout the 28 days. If participant’s levels increased or if a positive screen was obtained after a negative screen, the participant was given the option to restart the 28-day abstinence period or was dropped from the study. All participants produced negative urine toxicology screens at the time of scanning. Breathalyzers checked for recent alcohol use prior to the fMRI scan. Imaging. Anatomical and functional imaging data were acquired with a 1.5 Tesla General Electric Signa LX scanner . The high-resolution structural scan was collected in the sagittal plane using an inversion recovery prepared T1-weighted 3D spiral fast spin echo sequence . The functional scan was acquired in the axial plane using T2*-weighted spiral gradient recall echo imaging . Task Performance.

College students often drink alcohol and use drugs simultaneously during parties and other social events

It may also be possible that some SMW are turning to accessible coping outlets to deal with minority stress—including both spirituality and substance use. Findings from tests of interaction between religious attendance and sexual identity approached but did not reach statistical significance in relation to past year AUD or any marijuana use in the past year. Lack of significant differences may be related to the markedly lower levels of religious service attendance reported by SMW relative to heterosexual women, which may have reduced our ability to detect differential risk by sexual identity. These findings underscore the importance of future research considering religious behavior, such as attending religious services, in addition to religiosity or spirituality, given the potential of each to contribute to disparately negative behavioral health outcomes for SMW. We also explored potential differences in outcomes among participants based on religious environment—specifically, whether the study outcomes differed for participants involved in religious environments that were unwelcoming to LGBT people. Differences by sexual identity in interaction models were attenuated and no longer significant when we added this variable. Our ability to explore this question in greater depth was limited by the relatively small number of SMW participants who reported that they attended services in unwelcoming religious environments . Although the percentage of participants reporting attendance at LGBT welcoming environments was similar across sexual identity groups , over 80 % of SMW,marijuana grow system compared with 48.5 % of heterosexual women, described themselves as not affiliated with or attending services. These demographic differences are consistent with literature suggesting that sexual minorities are more likely than heterosexuals to dissociate from religious institutions entirely or seek alternatives to disaffirming religions .

Studies with larger samples of SMW who attend religious services that are both welcoming and unwelcoming of LGBT people are needed to explore the potential impact of the immediate religious environment on substance use outcomes. Findings should be interpreted in the context of study limitations. Although the SMW participants were drawn from two large national panel samples of SMW, they were not recruited using probability sampling methods, which may limit generalizability. As noted above, the great majority of SMW did not participate in religious services, which limited our ability to explore the impact of religious environment on substance use outcomes. There were also some limitations related to measurement. We assessed importance of religion, religious attendance, and importance of spirituality each with a single item. Although the use of single items are common in survey research, there are other measures that capture different dimensions of religiosity not captured in the current study, such as organizational, nonorganizational, and subjective religiosity ; daily spiritual experiences such as awe, inner peace, gratitude, transcendent experiences ; or facets of religiosity that may be particularly salient to health such as religious coping and religious social support . It is possible that a measure of religious coping or a multi-dimensional measure of spirituality would have yielded different results. Furthermore, it was not possible to assess the degree to which participants conflated religiosity and spirituality; multidimensional measures may have allowed for a more nuanced exploration of the impact of spirituality independent of religiosity.

Measures of religious environment also differed between the SMW and heterosexual women, which may have contributed to the different distributions of “non-affirming” attendance by sexual identity. Given research suggesting differences in perceived importance of religion and religious affiliation by race and ethnicity among SMW , future studies might examine possible subgroup differences in the associations of religiosity and spirituality to substance use outcomes. Finally, differences between the two panel samples may have influenced the findings in the current study. Although research suggests that substance use is typically greater among SMW relative to heterosexual women regardless of the sample or measures used , LGBT specific panels may reach individuals whose characteristics differ than LGBT peers recruited from general samples . Marijuana is a commonly used drug during pregnancy, and its use has increased among pregnant women in recent years . While more research is needed , there are significant concerns about the potential risks of prenatal marijuana use, and national guidelines strongly recommend that clinicians screen for and advise against marijuana use in pregnancy . Marijuana has antiemetic properties, and prenatal marijuana use is most prevalent in the first trimester of pregnancy when nausea and vomiting in pregnancy peaks . Available data from a small number of studies suggest that pregnant women may use marijuana to self-medicate their NVP symptoms. Cross-sectional data from 2009-2011 from the Hawaii Pregnancy Risk Assessment Monitoring System indicated that self-reported prenatal marijuana use was higher among those with versus without severe self-reported NVP . Similarly, our study of California women screened for prenatal marijuana use by self-report and urine toxicology tests using combined data from 2009-2016 found that first trimester marijuana use was elevated among those with severe and mild versus no NVP .

Results from two smaller surveys indicated that most pregnant women with ongoing prenatal marijuana use reported using marijuana to self-medicate nausea , and a majority of those who used it for this purpose rated it as effective in treating NVP . As public acceptance and availability of marijuana increase overall , pregnant women may be increasingly using marijuana for a variety of reasons unrelated to NVP . Understanding whether prenatal marijuana use has remained elevated among pregnant women with NVP in recent years is critical and of growing importance, as this information can be used by clinicians to better tailor discussions with pregnant patients and to inform interventions and education programs to reduce prenatal marijuana use. The current study extended our previous work using data from a large California healthcare system with universal screening for prenatal marijuana use via self-report and urine toxicology from 2009-2016 and is the first study to examine trends in prenatal marijuana use separately for women with and without clinical NVP diagnoses. We modeled the prevalence of prenatal marijuana use annually by NVP status using Poisson regression with a log link function controlling for age, race/ethnicity, median neighborhood household income,cannabis vertical farming prenatal marijuana use screening year, and parity. We estimated the covariate-adjusted prevalence using the direct method, standardized to the total study sample population across all years. We modeled linear trends of marijuana use and NVP by including a linear term for calendar year in the Poisson regression model, and we tested for statistical significance using a Wald test. We modeled marijuana use trends by NVP status by including cross product terms for year by NVP status in the Poisson regression model, and we tested for significance of trend differences using a Wald test. We repeated these analyses for self-report and toxicology results separately. Next, we additionally adjusted for self-reported marijuana use during the year before pregnancy to examine how results were affected by pre-pregnancy marijuana use. In a large diverse sample of pregnant women in California with universal screening for marijuana use via self-report and urine toxicology testing as part of standard prenatal care, women with NVP had a higher prevalence of marijuana use than those without NVP each year from 2009 to 2016. The adjusted prevalence of marijuana use increased at a similar rate regardless of NVP status, increasing from 6.5% to 11.1% among women with NVP and from 3.4% to 5.8% among those without NVP. The elevated prevalence of marijuana use across years among pregnant women with NVP is notable. Although national clinical management guidelines indicate that NVP can be successfully treated with dietary and lifestyle modifications and safe medically recommended interventions , pregnant women may instead choose to use marijuana to self-medicate NVP symptoms. Despite potential risks and national guidelines that advise strongly against marijuana use in pregnancy , pregnant women perceive a lack of evidence about the harms of prenatal marijuana use , and some believe there is little-to-no harm in using marijuana during pregnancy .

Women report searching online and seeking advice about prenatal marijuana use from friends, describing stories of others who used marijuana throughout pregnancy without apparent negative effects . Further, online media and marijuana dispensaries are touting marijuana as a harmless and effective treatment for NVP, which may contribute to elevated use among women with NVP. For example, a systematic content analysis of online media items about prenatal and postpartum marijuana use identified using Google Alerts between 2015 and 2017 indicated that more than one-quarter of online media items mentioned the treatment of NVP as a health benefit of marijuana use . Further, in a recent study of marijuana dispensaries in Colorado, 69% of dispensaries recommended marijuana products to treat NVP in the first trimester of pregnancy, and 36% of dispensaries endorsed the safety of marijuana use in pregnancy . In the current study and in the Hawaii PRAMS , women with NVP were also more likely than those without NVP to self-report marijuana use in the year before pregnancy. Thus, it is possible that marijuana use before pregnancy is related to increased risk of NVP. For example, withdrawal from marijuana among women who stop using it when they learn they are pregnant might lead to or worsen NVP symptoms, increasing the likelihood of an NVP diagnosis. However, we found a similar pattern of results after adjusting for marijuana use in the year prior to pregnancy, suggesting that pre-pregnancy use does not fully account for the elevated prenatal marijuana use associated with NVP. Additional research is needed to understand whether the relationship between marijuana use and NVP is bidirectional. Importantly, although the prevalence of prenatal marijuana use was higher each year among women with NVP, use also increased significantly over time among women without a diagnosis of NVP. This suggests that milder NVP symptoms that do not come to the attention of the healthcare system or factors other than NVP are also likely contributing to rising use of marijuana in pregnancy. With legalization of marijuana for recreational use in California in 2018, rates of prenatal marijuana use may increase even more rapidly in the future. Our sample included KPNC women who were screened for marijuana use in the first trimester of pregnancy. Findings may not generalize to women without healthcare or to those who enter prenatal care late. Provider diagnoses of NVP may not capture mild NVP. Further, our self-reported measure of marijuana use in pregnancy does not differentiate prenatal use before versus after women realized they were pregnant. While cannabis metabolites are detectable in urine for ~30 days, this varies with marijuana potency and heaviness of use, and toxicology tests may have picked up pre-pregnancy use in a small number of cases. Finally, our study did not examine whether frequency of marijuana use varies with NVP status, which is an important question for future studies. Dual marijuana and alcohol use is especially prevalent, with 47% of marijuana users reporting simultaneous use of alcohol . Furthermore, individuals who have a cannabis use disorder are at increased likelihood for the development of an alcohol use disorder , and rates of substance use disorders and treatment admissions are highest among individuals that use marijuana or alcohol compared to other substances . Approximately 68% of individuals with current CUD and over 86% of those with a history of CUD meet criteria for an AUD . Cannabis dependence doubles the risk for long-term persistent alcohol consequences and dual marijuana and alcohol users consume higher levels of alcohol and experience more alcohol-related consequences than only drinkers . Despite these additional risks, 60% of college students do not perceive regular marijuana use to be harmful .The combination of low perceived risk, policy changes surrounding marijuana legalization, and the rise in marijuana use over the past 10 years heightens the importance of effective interventions for alcohol and marijuana use. In the adult substance use treatment literature, it is relatively well-established that alcohol use negatively impacts treatment of other substances . In contrast, literature examining the impact of marijuana use on the treatment of other substances is mixed. With the exception of a few studies that do not show marijuana use to negatively influence alcohol or smoking cessation outcomes , many studies have demonstrated that using marijuana before or during alcohol treatment is associated with higher levels of drinking at follow-up . For example, among alcohol dependent individuals, those who used marijuana during alcohol treatment reported fewer days abstinent from alcohol one year following treatment than those who did not use marijuana . Thus, marijuana use seems to have a negative impact on alcohol treatment outcomes.

Marijuana is the most used illicit drug in the world and third most commonly used drug of abuse in the nation

Several studies show that the several facets of the UPPS-P model of impulsivity are highly intercorrelated. Including all five traits in a single model can create statistical suppression and make it difficult to interpret each unique effect. In order to address this issue, we first examined the correlations between each trait to guide decisions for which traits to examine for mediation. Specifically, we examined Negative Urgency [NU], Positive Urgency [PU], and Lack of Perseverance [PS] because, as reported below, they were significantly associated with both MDD and marijuana outcomes in this sample. A total of eight mediational models were tested. First, we tested separate models for each of the marijuana outcomes , for each of the mediators , which resulted in a total of six models. Then, we tested two models with all mediators entered simultaneously in order to examine whether any significant associations remained. Finally, given the cross-sectional nature of the data, followup mediation analyses with reverse directionality were tested, where marijuana use and problems were specified as the predictor, or independent variable; MDD was specified as the outcome, with impulsivity measures remaining as mediators of interest. The primary data analyses were a structural equation model with maximum likelihood estimation to using AMOS 24.0 . All models regressed the dependent variable onto covariates . Covariates were allowed to correlate with each other in single and multiple mediator models. In order to estimate mediation effects, bootstrapped and bias-corrected 95% confidence intervals were estimated for the indirect effects. Mediation is tested by examining the direct, indirect, and total effects. Significant mediation effects are apparent when indirect effects are significant and total effects are reduced in the presence of the mediator. To assess the degree to which the structural models fit the sample variance-covariance data,vertical grow rack system two criteria of model fit were relied upon: the Comparative Fit Index , and the root-mean- square error of residual approximation .

Although guidelines for good fit vary, values above for CFI and below .05 for RMSEA are considered acceptable.The goal of the present study was to better understand mechanisms associated with high rates of co-occurring MDD and problematic marijuana use by examining the role of specific facets of the UPPS-P model of impulsive personality in this comorbidity. To our knowledge, the current study is the first to systematically examine the role of these personality traits between MDD and marijuana use and problems. As hypothesized, we found that NU partially accounted for the relationship between MDD and marijuana problems, but this was not true of the other impulsivity traits. Consistent with previous research, we found that MDD was associated with marijuana use and problems. Although this is not the first study to examine the relationship between MDD and marijuana use and problems, it is the first to examine how individual dispositions to impulsive/rash action may help explain the association between these two clinical problems. We were also able to replicate previous research suggesting an association between MDD and NU. The current study expands this literature by suggesting that individuals with MDD and high levels of NU are in turn more likely to have greater number of marijuana problems. Importantly, our results also suggest that NU is the only trait in the UPPS model that accounted for the association between MDD and marijuana problems. This is consistent with theory suggesting the increased negative affect experienced by those with mood disorder, such as MDD, may lead to increased substance-related problems. This high rate of negative affect may be particularly problematic for individuals also high in NU, who may in turn be more likely to act impulsively when experiencing negative mood states, and thus be more likely to experience problems related to substance use.

Although results in support of this mediational pathway are compelling, remaining variance in our models suggest alternative pathways may exist to explain this comorbidity. For example, marijuana coping motives have also been shown to mediate the relationship between MDD or other affective vulnerabilities, such as anxiety and distress tolerance, and marijuana use and problems in general and veteran populations. Contrary to our hypothesis, this mediational pathway was not present for marijuana use, indicating that NU is specifically implicated in the experience of problematic marijuana use. This is consistent with work suggesting that NU is a robust predictor of both marijuana problems and alcohol problems, although the relationship between NU and marijuana problems has received far less attention. Previous studies have used similar methods to explain the relationship between MDD and alcohol use and problems. In one study of young adult drinkers, NU significantly mediated the relationship between depressive symptoms and alcohol problems when controlling for alcohol use. Similarly, King and colleagues examined which of the UPPS-P model traits might moderate the relationship between depressive symptoms and alcohol problems among college student drinkers. They found that although NU was the strongest predictor of alcohol problems, lack of premeditation was the only moderator of depressive symptoms and alcohol problems. Although this study examined impulsivity traits as moderators, it is important to mention as they found unique associations between NU and depressive symptoms when examining alcohol problems, which is consistent with our findings with marijuana problems. The present study expands this knowledge by not only showing that the relationship between MDD and marijuana problems may be partially explained by NU, but also in a population of military veterans. Veterans often have higher rates of MDD and substance use disorders including CUD compared to the general population, and thus an important target population for intervention. The present research has important treatment and prevention implications for individuals with MDD and marijuana problems.

Given the emerging evidence of an association between NU and marijuana problems in a number of different populations,vertical grow system it may be important for clinicians to assess for NU to be aware of the additional risk for those with MDD and high levels of NU. Although we focused on the directional pathway of MDD predicting marijuana-related behvaiors, it is also important to acknowledge that longitudinal evidence also exists to suggest that marijuana use is prospectively associated with depressive symptoms and other mood disorders [see review: 16]. Therefore, individuals at risk for depression and those with MDD should consider avoiding using marijuana, as it could in turn exacerbate the severity of depressive symptoms.Alcohol, tobacco, and marijuana are the three most commonly used drugs of abuse in the US , and cross-sectional, epidemiological findings suggest that it is common for individuals to report concurrently using these substances . The prevalence of, problems arising from, and motives underlying the co-use of alcohol and tobacco have been well documented . Approximately 20% of regular tobacco smokers are also heavy-drinkers , and those who use both substances tend to regularly do so simultaneously . The chronic, simultaneous use of cigarettes and alcohol yields adverse consequences. First, heavy-drinking tobacco smokers experience more frequent and severe negative health consequences as compared to those who use either drug alone . Second, this simultaneous co-use creates substantial impediments to smoking cessation among this sub group. Alcohol use is associated with substantially poorer smoking cessation rates and, at a more fine-grained level of analysis, a smoking lapse is four times more likely to occur in the context of a drinking episode as compared to a non-drinking episode . The understanding of the daily, event-level patterns of simultaneous cigarette and alcohol co-use, for example how use of one drug can acutely increase craving for and drive use of the other , contributed to line of research focused on developing pharmacological and behavioral treatments that are specifically tailored for individuals who are dependent on both substances . Thus, characterizing patterns of drug co-use at the individual rather than population level may be beneficial in identifying the behavioral mechanisms that drive problematic, simultaneous substance use in order to leverage that knowledge into targeted treatments for co-abusing populations. While marijuana is the most commonly used illicit drug in the world and is becoming increasingly legal in the USA, relatively little is known about event-level patterns of marijuana co-use with alcohol and/or tobacco. In the US, past year marijuana use more than doubled between 2001– 2002 and 2012–2013 with a near parallel magnitude of increase in the prevalence of cannabis use disorder . While there is still some debate on this topic , the national rise in the prevalence of marijuana use, particularly in adults, appears to be related to the increasing number of states that fully legalized or legalized medicinal use over this same time . As more states legalize or decriminalize marijuana use and its use becomes more tacitly accepted across the country, it is expected that prevalence of marijuana use and CUD will continue to rise .

Although marijuana is considered less harmful to self and others compared with alcohol and tobacco , acute and chronic marijuana use is indeed associated with a wide variety of health risks , and treatment outcomes for CUD are generally poor across various intervention types . These adverse consequences from marijuana use and poor treatment outcomes are thought to be exacerbated by the commonality of marijuana being used concurrently with other substances . Given the rising prevalence of marijuana use, CUD, and their related health and treatment problems, it is critical to characterize situations and patterns in which marijuana is concurrently and simultaneously used with other drugs of abuse. At the population level, concurrent alcohol and marijuana use is quite common, with over 75% of marijuana users reporting alcohol use . Large scale, longitudinal survey data suggest that most who report concurrently using alcohol and marijuana also use both drugs simultaneously, and simultaneous use is associated with heightened heavy-drinking behavior, drunk driving, adverse social consequences, and harm to self and others . As alcohol consumption across youth to adulthood is substantially higher in marijuana users than non-users , it is not surprising that marijuana use and CUD are each associated with the development and maintenance of AUD . Simultaneous marijuana and alcohol use is increasing in younger populations, and in states that have recently legalized marijuana use, there have been early indications of increases in impaired driving stemming from simultaneous co-use . Lastly, concurrent alcohol and marijuana use has consequences for treatment as well: using marijuana during alcohol treatment is associated with poorer alcohol treatment outcomes , and when attempting to reduce their marijuana use, drinkers with and without AUD have reported increased alcohol craving and consumption . As observed with the co-use of alcohol and tobacco, alcohol and marijuana appear to regularly be coad ministered in a pattern that escalates severity of use of each drug and creates impediments in reduction of drug use. Similar to findings with alcohol, epidemiological studies suggest concurrent marijuana and cigarette use is highly prevalent and problematic. Recent findings indicate that more than two-thirds of current marijuana users concurrently use tobacco , and up to 53% of current tobacco users also use marijuana . The co-use of these substances is increasing, particularly in individuals who were initially tobacco only users and/or live in states where marijuana use is legal . Relatedly, there is bidirectional evidence that tobacco or marijuana use precedes and increases the likelihood of future use of the other substance . Concurrent marijuana and tobacco use, vs. use of either substance alone, is associated with increased risk of CUD, more psychosocial and mental health problems, more severe nicotine dependence, heavier alcohol consumption, and poorer treatment outcomes for both substances . As with alcohol co-use, simultaneous use of marijuana and tobacco is common among youths and adults and associated with more severe drug use and worse health outcomes than concurrent use . For example, individuals who simultaneously use marijuana and tobacco are at heightened risk for escalating consumption to hazardous levels, development of dependence, and poor cessation outcomes for each substance . In summary, epidemiological studies indicate that marijuana and tobacco or alcohol are commonly co-used in a concurrent and simultaneous fashion, and the co-use of these substances, particularly when used simultaneously, is related to greater quantity and frequency of use, development of dependence, and health problems above and beyond the use of each substance alone.

Research assistants explained detailed information regarding this study and confirmed study eligibility

Study inclusion criteria were currently or formerly in treatment for marijuana use or, alternatively, having used marijuana heavily in the past year and reduced the marijuana use since then, and able to provide informed consent. To reduce recall bias and selection bias, we excluded participants who received any treatment for substances other than marijuana, had used marijuana heavily more than one year ago, and had been decreasing marijuana use for less than a month. Given the lack of a standard definition for heavy cannabis use , in part due to variability in amount, frequency, and methods of cannabis use, heavy use and reduction were self-defined by the participant. Participants were recruited through flyers and advertisements in local substance use treatment clinics and other sources . A total of 123 interested individuals answered open-ended questions that required them to self-identify as eligible to participate the study. All respondents were eligible to participate. After prospective participants gave informed consent, small groups of approximately 10 eligible participants were provided instructions on how to complete questionnaires regarding marijuana use patterns and other functional outcomes. Research assistants provided assistance to the groups to facilitate self-administration of assessments. The group sessions lasted about two hours, and participants were compensated for their time. All responses were anonymous. The study was approved by the Institutional Review Boards at the University of California, Los Angeles.Relationships between marijuana use frequency,flood tray severity of marijuana-related problems. and HRQoL were analyzed, controlling for mental health symptoms and physical health conditions for the respective outcome measures. Multiple imputations were used due to missing data.

We used the structural equation model for the analyses. SEM is a multivariate method that combines factor analysis and path analysis, which allows relationships among multiple measures or constructs to be tested simultaneously . A latent construct is a factor indicated by multiple indicators and therefore is free of random error. A path analysis allows the evaluation of causal relationships in which an independent variable produces both direct and indirect effects on a dependent variable , in our case, we are testing if marijuana use produces direct effects on HRQoL and indirect effects on HRQoL via the marijuana-related problems as a mediator. The analysis was conducted in three steps. First, a preliminary analysis and Pearson’s r correlation coefficients for all variables were computed and reported. Second, confirmatory factor analysis was conducted to assess the associations between latent variables and factors to support the subsequent assessment of the SEM. There are three latent variables in the model. One was marijuana use frequency with two indicators: number of days of marijuana use and number of times marijuana was used per day. The second was mental health symptoms . The third construct was physical health conditions, with indicators including sleep disturbance, respiratory function, pain intensity, and appetite. Finally, SEM was performed with SAS version 9.4 PROC PATH by the maximum likelihood estimation. Model fit was assessed by the chi-square test statistic and the values in the following goodness-of-fit indices: comparative fit index of equal to or greater than 0.95, root mean square error of approximation of less than or equal to 0.08, standardized root mean square residual of < 0.09, and Adjusted Goodness of Fit Index of equal to or greater than 0.90, in accordance with the recommendations . The study findings are mostly consistent with our hypotheses. Using SEM to examine the relationships between marijuana use frequency, severity of marijuana-related problems, and the physical and mental HRQoL domains, separately, we found that marijuana use frequency was positively associated with severity of marijuana-related problems, which in turn had negative effects on mental HRQoL but non-significant relationship with physical HRQoL.

The relationship between marijuana use frequency and either mental or physical HRQoL domains was not significant. Overall, the hypothesized model explained 48% of the variance on the mental HRQoL measure, while it explained only 11% of the variance on the physical HRQoL. A prior study reported an effect of marijuana use frequency on mental HRQoL but not physical HRQoL . However, our study did not support the direct association between marijuana use frequency and either mental HRQoL or physical HRQoL. Instead, we found that marijuana use frequency was associated with severity of marijuana related problems, which affected mental HRQoL. This finding suggests that individuals who frequently use marijuana subsequently had more marijuana-related problems, and this relationship further affected their mental HRQoL. The present study results suggest a new insight that reducing problems associated with marijuana use may be an important clinical target for patients to improve their HRQoL and attain better treatment outcomes. Our findings suggest that reductions in marijuana use alone may not affect mental health-related quality of life if perceived problems are still active. Based on the participants’ responses, the most common marijuana-related problems included financial difficulties, procrastination, and poor relationships with family or partner. These problems may more directly affect mental health and have less impact on physical health related quality of life. The primary problems reported in this study were similar to those observed in prior studies among college students . Marijuana-related problems may be diverse among adolescent and adult populations, warranting more research to clarify their relationships with HRQoL. The hypothesis that mental health symptoms was negatively associated with mental HRQoL was supported by the present study. Prior research demonstrated similar findings that marijuana use was associated with poorer mental HRQoL among patients with anxiety and depression who were already at risk for low mental HRQoL .

Our study has found that anxiety and depression were significant mental health symptoms affecting mental HRQoL. Additionally,ebb and flow tray our study findings suggest that stress and paranoia are also important mental health symptoms among marijuana users, but these symptoms have not been well examined in prior marijuana-focused studies. More research regarding stress and paranoia as well as other mental health symptoms are needed to further examine their relationship to mental HRQoL among marijuana users. It is not surprising that the study also showed that severity of physical health conditions was negatively associated with physical HRQoL. A positive relationship between marijuana use and poor physical health conditions was found in this study, which is consistent with prior studies . In the past, there has been limited research to evaluate the relationship between physical health problems and physical HRQoL among marijuana users. In the present study, we found that marijuana users who reported these physical symptoms or conditions had poor HRQoL for physical domain. It is worth noting that sleep disturbance and respiratory function were two of the greatest health problem contributors to physical HRQoL as indicated by high factor loadings on physical health conditions. Nevertheless, our study findings reveal that neither the marijuana use frequency nor the marijuana-related problems were significantly associated with physical HRQoL domain. A prior longitudinal study of stimulant users reported similar results, suggesting that reductions in use over time contributed to only minor improvements in physical HRQoL . Still, given the limited research examining marijuana use and physical HRQoL, additional research efforts are needed to shed light on relevant physical health problems in relation to marijuana use and HRQoL. There were several limitations in the present study. First, the causal relationships between marijuana use frequency, severity of marijuana-related problems, and mental and physical HRQoL cannot be determined because the study is based on data from a cross-sectional survey. Longitudinal studies would be needed to reveal temporal relationships between marijuana use frequency and mental health problems and to confirm the findings. Second, selection biases might exist because this study involved a cross-sectional survey of participants who were recruited by flyers and advertisements. Third, functional assessments were collected by self-report, without verification by objective measurements. However, scales used had been tested in other studies with good validity and reliability. Also, past month marijuana use patterns were based on participants’ self-report, which may be influenced by recall bias. Finally, the sample size was too small to investigate more complex relationships between variables using additional potential constructs and covariates .

Despite these limitations, this study provides better understanding of the relationships between marijuana use frequency, severity of problems related to marijuana use, and HRQoL, controlling for mental and physical symptoms. Our findings suggest that to improve marijuana users’ HRQoL, treatment should incorporate interventions that address not only marijuana use reduction but also problems caused by marijuana use that may take additional time to address even after use levels have been reduced. For example, interventions could be designed to enhance and optimize skills related to time management, coping with stress, and improving family relationships. Also, severity of marijuana-related problems could be used as an indicator for efficacy of treatments , as individuals with more severe problems related to marijuana use are generally more likely to seek treatment for marijuana use . Additionally, our findings show that more frequent marijuana users have concurrent mental health symptoms and worse physical health conditions that may negatively impact their HRQoL. Integrated treatment models simultaneously addressing marijuana use and mental health symptoms have been recommended . In conclusion, this study extends previous research and improves the understanding of the relationships among marijuana use, marijuana-related problems, and HRQoL.Marijuana legalization and the rising popularity of new delivery systems for psychoactive substances or vaporizers are changing the landscape of substance use. Uruguay legalized non-medical marijuana in 2013 and Canada will propose similar legislation in 2017. Eight US states and the District of Columbia have passed ballot initiatives legalizing adult possession and use, and 28 states have legalized medical marijuana. Marijuana and tobacco are consumed similarly: rolled in paper, smoked in pipes, or electronic vaporizers . Tobacco and marijuana can also be consumed together through “blunts” or “spliffs” . Tobacco is the leading cause of preventable disease and premature death in the United States and the second major cause of mortality worldwide. US Federal prohibition of marijuana impeded studies quantifying the effects of marijuana use on population health. Many drug experts agreed that marijuana carries less personal and societal harm than drugs like alcohol, tobacco, heroin, and cocaine. Emerging evidence, however, has linked marijuana use with negative physiological and psychological outcomes. Compared to non-smokers, chronic, heavy marijuana smokers have been found to have impaired lung function. Though marijuana smoke contains known carcinogens, light and moderate use does not seem to be linked to lung cancer, with mixed evidence linking heavy use to lung cancer. Marijuana use, however, has been associated with increased cardiovascular disease including stroke and myocardial infarction. Exposure to THC increases risk for depression, anxiety, and psychosis. Long-term and heavy use likely results in persistent cognitive impairments especially if use begins during adolescence. Often, marijuana users also consume tobacco products, posing a challenge to determine effects solely of marijuana use not confounded by concomitant tobacco use. Administering nicotine and THC without combustion is arguably safer, but not harmless. Policy and product transformations may affect comparative harm and benefit perceptions of various products and administration routes. Research on comparative perceptions of tobacco and marijuana has been limited to a few quantitative surveys: US college students rated marijuana as safer than tobacco products; a convenience sample of US marijuana users believed marijuana flower was less harmful than marijuana concentrates; and an Australian population survey found a majority believed marijuana use can cause health, behavioral, and social problems. In one qualitative study, California adolescents identified acute and chronic negative health outcomes for cigarettes, but were less certain about negative effects of e-cigarettes or marijuana. The effect of changing delivery and potency of marijuana products, and the shifting legal landscape on perceptions of comparative harm or benefit remains largely unexplored. To begin filling these gaps, we conducted a qualitative study with young adults in Colorado to understand comparative perceptions of tobacco and marijuana products. We chose Colorado as the case study because it was the first state to legalize retail marijuana sales and distribution in 2014, five years after introducing a state licensing system for medical marijuana dispensaries in 2009. We focused on young adults because they have the highest rates of marijuana and tobacco use in the US compared to other age groups, and had legal access to at least the medical marijuana market. Thirty-two young adults were recruited based on current use of at least one of three products .

Univariate odds ratio and adjusted odds ratios and 95% confidence intervals were reported

Although we did use propensity scoring to control for preexisting differences between marijuana use groups on variables that were thought to differentiate the groups, we did not account for other important variables that likely differ between marijuana users and nonusers that may have been related to tobacco use and thoughts about use.HIV infected individuals experience a wide range of medical and psychiatric co-morbidities such as neuropathy, anxiety and depression, as well as adverse side effects associated with antiretroviral treatment.Users of effective antiretroviral therapy experience a range of symptoms including neuropathic pain, nausea, diarrhea, loss of appetite, disturbed sleep, depression and anxiety, and physical sickness; these factors are cited as a common reason for delaying, missing, and discontinuing doses of ART.Despite the major benefits of ART on HIV-related survival, there is an ongoing need to help alleviate medication side effects in order to ensure the long term adherence to antiretroviral treatments that is necessary for optimal health outcomes. Initial randomized controlled studies of HIV-infected individuals with peripheral neuropathy suggest significant reduction of pain with daily marijuana use compared to placebo.The substance in marijuana thought to produce these beneficial effects is delta-9-THC. Several pharmaceutical oral formulations of delta-9-THC are currently FDA approved for treatment of loss of appetite in AIDS as well as chemotherapy-induced nausea and vomiting,ebb and flow bench including Marinol and Dronabinol.

Although Marinol and Dronabinol have been approved for use in AIDS since 1992, frequency of medical marijuana use among HIV-infected individuals has not been well studied. Observation studies of HIV-infected individuals in the U.S. have reported both that current marijuana use is relatively common and that its use may reduce HIV-related symptoms.Prevalence of marijuana use in the general U.S. population, by contrast, is between 3–7%. In a Canadian study, where cannabis has been legal for medicinal use in HIV since 2001, 61% of HIV-infected individuals classified themselves as current medical cannabis users .The demand for medical marijuana appears to be significant, but given that medicinal use is illegal in the majority of U.S. states, this presents a challenge to U.S. drug policy.A previous study in the Women’s Interagency HIV Study , a multisite longitudinal observational study of HIV infection among U.S. women, reported a high prevalence of lifetime marijuana use.Furthermore, a substantial subgroup currently used marijuana at least weekly, and 13% of the 2,308 WIHS women who were not weekly marijuana users at study baseline initiated weekly use between 1994 and 2000.We now extend this previous study to evaluate longitudinal patterns of marijuana use, as well as predictors and motivators of use over a 16-year period during which effective ART came into common use. Since the use of marijuana among chronically ill persons seems to be frequent and ongoing in the U.S., it is important to understand factors that influence use as well as the outcomes related to marijuana use.Interviewer-administered questionnaires are administered twice annually in WIHS, and data are routinely collected on the use of recreational and therapeutic drugs, alcohol, and cigarettes over the past six months .

Questions assess the prevalence and frequency of current marijuana use. Recent marijuana use was assessed by asking participants: “Since your last visit have you used marijuana or hash?” Frequency of use was assessed by asking, “On average, how often did you use marijuana or hash since your last visit?” Validity of self-reported drug use has been shown in multiple studies,although some studies suggest higher reporting of drug use using computer assisted self interview.Between 2004–2008 additional questions on reasons for marijuana use were added to the WIHS interview. Four specific reasons for marijuana use were queried at each visit 2004– 08: to relax, for social situations, to reduce HIV symptoms, and to increase appetite . Respondents reporting marijuana use for other reasons were also asked to describe those reasons with open text responses that were then grouped into meaningful categories. The range of reasons for use was similar at each visit and therefore only the cumulative prevalence of each reason are reported. Marijuana users on ART were also asked whether their marijuana affected how they took their ART medication . In 2009 a question on medicinal marijuana use was added for all women reporting recent marijuana use; this question asked women whether their use of marijuana was “medical, meaning prescribed by a doctor, or recreational, or both.” Each study visit also included collection of demographic, psychosocial, and biological variables as well as a physical examination and labs which include CD4 T-cell count and HIV viral load. The definition of ART was guided by the DHHS/Kaiser Panel 23 and is defined as: the reported use of three or more antiretroviral medications, one of which has to be a protease inhibitor , a non-nucleoside reverse transcriptase inhibitor , an integrase inhibitor, or an entry inhibitor, with one of the nucleoside reverse transcriptase inhibitors abacavir or tenofovir.

Covariates of interest included the following HIV-related variables: CD4 cell count tested at every visit , antiretroviral therapy use in the past six months ; and, among those on ART, adherence to the regimen defined as a self-report of taking antiretroviral drugs as prescribed ≥95% of the time. In addition, we evaluated co-morbidities including self-reported peripheral neuropathy defined as “since your last visit have you experienced numbness, tingling or burning sensations in your arms, legs, hands or feet that lasted for more than two weeks”; self-reported asthma; symptoms of depression assessed via Center for Epidemiologic Studies Depression Scale where a CESD≥16 is defined as a high level of symptoms; diabetes defined by self-report, taking diabetes medication or having serum glucose >125; and self-reported quality of life rated using a shortened Medical Outcome Study-HIV Health Survey with scores ranging from 0 to 10, where 6 or higher was defined as good perceived health. In addition we asked about any use in the past six months of: tobacco, cocaine, and injection drug use, as well as the number of sexual partners in the past six months and condom use during the past six months as measures of sexual risk taking; and age. Race and ethnicity were categorized as White non-Hispanic, Black non-Hispanic, other race nonHispanic, and Hispanic any race. As results were similar for Hispanics of any race and White non-Hispanics they were grouped together in the final analyses. IRB approval was obtained at each study site and informed consent obtained from each participant.We describe participant characteristics at study baseline and in 2010. Prevalence of current marijuana use was plotted over calendar time. Univariate and multivariate logistic regression models clustered by person using GEE were used to evaluate risk factors for current marijuana use at semi-annual visits between 1994 and 2010. Three separate models considered i) any current marijuana use , ii) current daily marijuana use current marijuana use among marijuana users as outcomes. Heavy marijuana use was defined as daily marijuana use in the past six months.We were especially interested in the association between ART use/adherence and marijuana use,4x8ft rolling benches as marijuana use has been reported to help alleviate some ART related side effects and might therefore increase adherence. At each visit, covariates of interest at the same visit were compared to marijuana use at that visit. These models included the following time updated variables: age, CD4 cell count, HIV-status, ART use in the past six months, ART adherence, current peripheral neuropathy, asthma, depression symptoms, diabetes, quality of life, current tobacco, cocaine, and injection drug use, recent number of sexual partners and recent condom use. Race/ethnicity, study site and enrollment wave into study were also included in these models.

All variables significant in univariate analysis and variables of a-priori interest were included in the multivariate models and removed in a stepwise fashion. Final multivariate models for each outcome retained all statistically significant variables as well as those variables of interest from previous research as well as variables significant in the other outcome models, for comparison. The association of current marijuana use on increased odds of ART adherence was similarly modeled. All analysis was done using Stata 11. In 2009–10, marijuana users were asked whether their use was recreational or medicinal . The majority of marijuana users reported some medicinal marijuana use, including 26% of users reporting purely medicinal use and another 29% of users reporting both medicinal and recreational usage,Table 2. Medicinal marijuana use was even more common among heavy marijuana users; among daily marijuana users, more than two-thirds reported some medicinal marijuana use, Table 2. While medicinal marijuana use was common among HIV-infected marijuana users, it remained rare in the study population overall, with 7.1% of women at the 2010 study visit reporting current medicinal marijuana use. More general reasons for marijuana use were asked between 2004 and 2008, with participants asked to indicate all reasons that applied to their marijuana use. The most common reasons reported for marijuana use were: relaxation , appetite stimulation , for social situations , and for reduction of HIV symptoms . Less common reasons reported for use included recreational use, physical pain relief, for mental health reasons, and as a sleep aid . Among those using marijuana daily, use for relaxation and social situations were also common,Table 2. However, daily marijuana users were more likely than less frequent marijuana users to report use for appetite stimulation or for reduction of HIV symptoms . Marijuana users consistently reported that their marijuana use did not affect how they took their HIV medications.This cohort study evaluated marijuana use and related reasons for use every six months over 16 years in a large multi-site study of HIV-infected women in the United States. The study demonstrates that marijuana use is common among HIV-infected women in the U.S., including both recreational and medicinal marijuana use. While the prevalence of marijuana use decreased during study follow-up as participants aged, an increasing proportion of HIV infected women using marijuana in the study also began using marijuana daily. These heavy users reported using marijuana primarily for medicinal purposes, suggesting the rationale for marijuana use among HIV-infected women in this HAART era study may have changed from purely recreational to a combination of recreational and medicinal usage. The prevalence of current marijuana use in this multi-center cohort of HIV-infected women in the U.S. was similar to that reported in several other U.S. studies, although it was lower than a Canadian study which reported 43% of HIV-infected participants used marijuana recently.A previous study of marijuana use in this same WIHS cohort had a lower prevalence of current marijuana use than this study because they had excluded women with an history of daily marijuana use before study baseline.The increasing use of medical marijuana among HIV-infected women in this study is consistent with previous studies showing medicinal use in the majority of HIV-infected marijuana users.In the most recent data in this study, some medicinal marijuana use was reported by 55% of current marijuana users, similar to other U.S. studies which reported medical use in 45–67% of HIV-infected marijuana users.Despite high rates of recreational marijuana use, current rates of medically-prescribed marijuana use remained uncommon overall, reported by 7.1% of HIV-infected women in 2010 in the current study; other studies reported a higher prevalence of current medicinal marijuana use among HIV-infected individuals, but this may in part be explained by our definition of medicinal marijuana use as being prescribed by a doctor. Many women who reporting using marijuana that was not medically prescribed, indicated relief of HIV-related symptoms or increasing appetite as a motivator for use . There was substantial variation in marijuana use between the six U.S. study sites. These differences may reflect differing state laws and availability of any marijuana and medically prescribed marijuana. In California, which had the highest prevalence and increase in medicinal marijuana use during the study, medical marijuana became legal in 1996. Medicinal marijuana was not legalized in the other states in this study during the study period, although in D.C. medicinal marijuana did become legal in 2010. A recent study suggested that states with legal medical marijuana use have a higher prevalence of marijuana use, but that the percent of marijuana users with marijuana dependence/abuse was similar in states with and without laws allowing medical marijuana use.

All of these community engagement tools will be created to cull qualitative research methods

An example of a community organization that resides in South Los Angeles and propounds development of universal services for marginalized residents impacted by substance misuse is South Central Prevention Coalition. SCPC fosters educational development and primary prevention strategies to inform youth/ marginalized adults on the risks and dangers related to substance misuse as well as encourage individuals to be cognizant of educational programming which can provide them resources for scouting out and advocating for recovery/prevention programs in their area of residence. Community-engaged research tools devised would align with South Prevention Coalition Prevention partnership efforts to decrease marijuana use among youth, decreasing meth use among youth and adults, and decreasing drug misuse among youth/adults by reducing unlawful and lawful access to opioid drugs. Types of community-engagement tools cultivated to address the research inquiry as described above would be developing educational curricula on marijuana/opioid misuse awareness for faith-based organizations as well as low-income communities housing middle schools, gleaning a focus group cohort who will relay their experiences with their community’s current state of substance mis-use programming/whether they know of adverse community indicators that contribute to the patterns of drug-misuse behavior that they observe, and creating program evaluations for a Drug Take Back event in efforts to understand the African American/Latinx current perceptions of substance mis-use as well as promote means to safely dispose prescription drugs to further educate public about substance mis-use. Qualitative data within this research approach aligning with this research inquiry is collected by learning from the faith-based African American and Latinx participants sampled from the focus group,hydroponic trays rather than imposing the researcher’s standpoint onto participants through questionnaires and interview sessions.

While, quantitative data is collected from the advancement of the research question stated above through development of surveys and post-event evaluations measuring participant agreement with written statements regarding their current experiences with substance mis-use prevention programs. The topic of exploration that is situated in this proposal is investigating how marginalized communities of color, specifically African American and Latinx communities are more susceptible to drug misuse which can be attributed to maladaptive community indicators such as implicit bias, “drug-misuse labeling,” as well as lack of community programming/tools cultivated to bring awareness to drug mis-use/spur advocacy towards substance mis-use prevention endeavors. A community engaged research approach alongside SCPC’s collaboration will be utilized to address the inquiry of whether program evaluation, and focus group interviews can unravel current community organizational awareness of substance misuse disorders as well as whether educational curricula development can curb the progression of unstable community indicators that lead to elevated substance mis-use. Specific community engagement research strategies that align with SCPC’s methodological approaches of primary prevention strategies and collaborative learning strategies, include the development of substance mis-use educational curricula, focus group interviews involving faith-based community members that presentations were delivered to, and program evaluation surveys administered after the completion of Drug Take Back day. The importance of this work resiles in that contributing factors to substance mis-use disorders affecting adolescents and adults of color will be clarified as well as the relationship between faltering community stability indicators and substance mis-use disorders will be substantiated through qualitative data collection.The focus of this community engagement research project was to investigate the contribution of community indicators and risk factors on marginalized youth’s development of marijuana misuse.

Additionally, the sub-focus of this project was to measure the effectiveness of organized community indicators such as marijuana mis-use prevention program creation, perceptions of implicit bias permeated by hegemonic power structures, and educational resources as well as its propensity to mitigate instances of marijuana mis-use. These focuses were investigated through a community engagement research approach in which I devised and presented substance mis-use educational curricula for faith based communities as well as high schools in low-income areas within SPA-6. Upon presentation of these materials, a focus group interview qualitative data tool was utilized to record participant positive or negative perceptions of healthcare disparity educational material and programming disseminated by their community. Post presentation surveys were created for participants to evaluate presentation effectiveness in addressing current substance mis-use substances, advocacy for substance mis-use prevention, as well as whether these resources should be implemented in their community to actively resist substance mis-use. In alignment with SCPC SLAM Coalition, I participated in Drug Take Back Day by creating post event surveys which measured participant perceptions on the effectiveness of Drug Take Back Day in disseminating safe prescription disposal practices as well as promoting substance mis-use treatment resources.Program evaluations are defined as a form of documentation and assessment of program implementation. In the form of google form survey, I utilized SCPC’s post Drug Take Back Day program evaluation which prompted me to develop questions about participant viewpoints on program milestones and to analyze participant responses with a logical model framework in a report. The logical model framework reflected on relationship building between implementation of the program and desired outcome, but SCPC’s program evaluation design evaluated the desired program outcomes through the collection of participant views on the effectiveness of the program in disseminating awareness for substance mis-use. Participants who attended this Drug Take Back day event were given a choice to complete these program evaluations in the form of surveys.

Simplified question language encompassed rhetoric familiar to all age level participants and biased language was not applied to the survey questions. To retain authenticity of participant answers, falsifying or fabricating participant answers was prohibited. Factors that may jeopardize validity and generalizability were considered. As survey questions were devised in the form of a post event survey,mobile grow system privacy and confidentiality of participant responses will be enforced. Qualitative data in the form of focus group interviews and program evaluation was measured using self-reported health status which allowed participants to provide their own perceptions of a health condition. However, the data that I collected will further utilize the SRHS framework in that participants will be asked to self-report their perceptions on the effectiveness of programming for Drug Take Back day, describe the effectiveness of substance mis-use education programming that they were exposed to, as well as their current views on substance mis-use affecting them as a marginalized person of color. Program evaluation data analysis was conducted through describing and summarizing Drug Take Back Day attendee responses. These descriptions were written in the style of an evaluation report which includes a summary of findings. Upon completion of the focus group interview, responses were compiled and transcribed utilizing qualitative data coding. In alignment with Charmaz’s framework into qualitative data coding, the following initial questions were considered: “What is going on? What is this person saying?” Subsequently, analysis was performed to “produce a detailed and systematic recording of themes” as well as socioeconomic indicators that were touched upon during the focus group interview. Connecting with this analytical framework, an “exhaustive category system” was created to ascertain common themes and viewpoints during the interview. General themes within the transcripts that coalesce with Burnard’s Stage Two analysis and that were gleaned from open coding practices included reactions when comprehending marijuana mis-use statistics amongst youth knowing that the pattern of alcohol outlet development is translatable to marijuana outlet development, discussions on marijuana mis-use due to unstable community indicators, unanimous agreement on the absence of marijuana mis-use prevention educational measures, as well as common realizations that marijuana mis-use education is missing from youth concentrated communities in South Central LA. The term mis-use was defined by participants as frequent and over-use of marijuana due to the increased presence of marijuana outlets. Upon performing data analysis as mentioned above, the major themes extricated were general reactions on marijuana mis-use presentation materials, marijuana mis-use due to unstable community indicators, perceptions on current marijuana mis-use prevention educational measures, marijuana promotion, and lacking education on this issue which can be mitigated by community development tools which can steer users to marijuana mis-use recovery. Subheadings for each theme included the following respectively: shocked and not shocked reactions upon reacting to marijuana outlet concentrations, increased accessibility to marijuana due to marijuana outlet increase, participants have never heard of recovery programs through education/visuals, commercialization of marijuana, as well as ideas for community programming development towards elementary/middle school students.

Utilizing interview transcript analysis and open coding principles, it was found that four individuals elicited a shocking reaction through their reflections when visualizing higher marijuana mis-use rates amongst high school individuals, while the remaining 4 individuals elicited an unsurprised reaction through their reflections on the overly concentration distributions of marijuana outlets. Additionally, all 8 individuals deduced the contributing causes of marijuana mis-use to be attributed to the increase in dispensaries in urban areas and high schools as well as increased marijuana accessibility due to legalization of marijuana. All of the participants in this focus group interview stated that they have not heard of or seen visual marijuana mis-use prevention posters within their respective communities which posed as unnerving concern to them. Four out of eight participants stated that they had/have lived in a community where there is/was an abundance of marijuana outlets, including Crenshaw, Melrose, and the Redlands. Participants also agreed that the commercialization of marijuana accounted for youth of color as well as adults of color to go into dispensaries. Lastly, all eight participants proposed that restoring education that is lacking in their communities would be key to reducing prevalence of marijuana mis-use rates alongside steering mis-users to seek out recovery programs. These findings that were extricated, substantiated the topic of focus: a discussion surrounding the prevalence of marijuana mis-use amongst youth and adults of color in South Central LA due to lacking community educational interventions as well as whether the implementation of organized community indicators such as marijuana mis-use prevention program creation within their community/increased educational resources has the potential to curb instances of marijuana mis-use amongst high schoolers. After participants were asked to listen to the marijuana mis-use presentation prior to the conduct of the focus group interview, they were asked to reflect on the strengths and weaknesses of the presentation as well as the effectiveness of this resource as a proxy for audiences to unpack the contributing causes of elevated marijuana mis-use disorder rates. As responses were transcribed for a question concerning their reflections on the presentation material and comprehensibility, a major theme emerged which was that participants felt mixed emotions when internalizing the statistical content of the marijuana mis-use presentation. In devising this theme, an open coding process was applied in this following sequence, aligning with Burnard’s method of interview transcript analysis. Burnard’s first 10 stages of analysis were prompted during the open coding process of this theme. After Stage 2 of Burnard’s analysis was applied in determination of this theme, transcripts were thoroughly re-read and transcriptions that aligned with the theme were further placed into a table. In deciphering this theme, the open coding process involved delving into the participant’s words to unravel common sentiments that they stated regarding marijuana mis-use presentation content as well as platforming these sentiments as a “freely generated category.” Continuing Burnard’s stages up until Stage 10, it was imperative that I utilized the “dross” process to cut down “unnecessary fillers” as well as retain the main subject matter of participant statistical perceptions upon registering the impact of the presentation. As more data was added to this theme, I created the subheadings of “Participants were shocked seeing these statistics reflect the youth accessibility of marijuana and subsequent mis-use” and “participants were not shocked seeing these statistics reflect the youth accessibility of marijuana and subsequent mis-use” to fit both the surprising and not surprising sentiments that were stated by the participants. As stated by 29 year old participant Janice, “So the numbers in the stats were pretty shocking to me, especially for the age of the eighth graders.” Another participant named Monica stated “I see the effects of the increased marijuana use some, especially among young people. And I’ve seen how marijuana has changed over the years. So what is going on with it now, kind of alarmed me.” These interview quotes serve as evidence that participants elicited shocked or alarmed reactions to the presentation statistics which highlighted the emerging prevalence of marjuana mis-use amongst 7th and 8th graders. On the other hand, a participant named Rhoda stated that “Unfortunately, the statistics, it’s not surprising, but it’s very sad.” Along similar lines, a participant named Arthur seconded that “I wasn’t surprised when I looked at the statistics.” Another participant named Soriyah stated that “I’m not surprised by the statistics.” These responses corroborate the development sub-heading in that participants elicited sentiments of not being startled by the presence of alarming statistics as they realized that deficits in educational programming tailored to the youth and dispensary production increases underlie the creation of these statistics. These shocking and non-shocking sentiments were important to note because it demonstrated how educational content within the presentation allowed them to grasp salient statistics as well as all of the participants to comment on the context behind these statistics.

We identified numerous methylation markers associated with recent and cumulative marijuana use

Adolescents that reported higher than average exposure to MM ads also tended to report greater marijuana use, stronger intentions to use marijuana in the future, stronger positive expectancies about marijuana use, and more negative consequences from use. In addition, adolescents who reported increased exposure to MM ads over the seven-year period also reported increases in their marijuana use, intentions to use, positive expectancies, and negative consequences. This association was particularly strong for exposure to MM ads and marijuana use. Overall, results suggest that exposure to MM advertising may not only play a significant role in shaping attitudes about marijuana, but may also contribute to increased marijuana use and related negative consequences throughout adolescence. The association between exposure to MM ads and past year consequences likely occurred because youth who were exposed to MM ads were then more likely to use marijuana more heavily and therefore experience more negative consequences. Future work should begin to explore mechanisms for these associations. Overall, our findings mirror those from the alcohol and tobacco fields, which have shown that increased exposure to advertising for these products is associated with increased use among adolescents . This highlights the importance of beginning to think about regulations for marijuana advertising , similar to regulations that are in place for tobacco and alcohol . Findings must be understood in the context of the changing legal landscape of marijuana in the United States. For example, it is important to note that marijuana use and consequences may be viewed differently than alcohol use and consequences,trimming cannabis as teens tend to associate marijuana use with fewer negative consequences than alcohol use .

For example, nearly one in five teens report driving under the influence of marijuana, one third of whom believed their driving ability was improved after marijuana use , and younger drivers are especially likely to believe that driving under the influence of marijuana is socially acceptable and safe . Given the health claims that are made for marijuana use , and the effects of advertising we found over this seven-year period, it is crucial to address perceptions about marijuana effects and the potential consequences from use as part of our prevention and intervention efforts with adolescents. One recent study found, for example, that when adults communicated with youth about information in anti-marijuana ads using moderate, non-directive language, this was more effective in decreasing adolescents’ intentions to use marijuana than when adults used more extreme, directive language . Teachers, parents, and community leaders need to be ready to provide teens with up-to-date information on both medical and recreational marijuana to help youth better understand that although there may be some benefits medically for adults , marijuana use during adolescence can affect functioning during the teen years as the brain is still developing , and is also associated with impairment in young adulthood and adulthood . Findings from this study are an important first step in understanding the long-term effects of MM advertising; however, there are limitations to our work. As the data indicated, there is a great degree of variability in exposure to MM ads, use, cognitions, and consequences, which is likely due to the fact that other factors are associated with these constructs, such as parental monitoring, peer use, or where an adolescent may live. Future work could begin to examine how these factors, along with advertising, may affect these associations over time. In addition, we cannot draw conclusions from this study about the reciprocal associations of exposure to MM ads with marijuana use and related cognitions.

Our previous longitudinal work examined these associations using cross-lagged analyses over one year and found a reciprocal association such that teens exposed to MM ads reported greater marijuana use, and teens who reported greater marijuana use were also more likely to report exposure to MM ads . In this study, we were more interested in capturing interindividual differences in intra-individual growth, as well as modeling the functional form of growth. The parallel process LGMs used in current analyses allow us to do that by focusing on conjoint longitudinal change in MM advertising and adolescents’ marijuana use, intentions, positive expectancies and negative consequences. It is also important to note that we only had one item measuring exposure to MM advertising. Future work could ask more detailed questions about where exposure to ads occurred to rule out recall bias. Another limitation is that we relied exclusively on self-reported marijuana use. However, the limits of self-report are often exaggerated , and recent work with young adults 18–21 has shown that self-reported alcohol use can be corroborated by biomarkers . In addition, our sample’s marijuana use rates match those seen for national samples . Finally, this sample was limited geographically to adolescents living in southern California, thus, generalizability may be restricted. Marijuana is one of the most commonly used psychoactive substances in the US, with an estimated 49% of adults having ever used marijuana, including 19% within the past year, and 12% within the past month. The prevalence of marijuana use has risen over the past several decades and its use is expected to increase as more states legalize marijuana. Medically, marijuana may help treat chemotherapy induced nausea and vomiting, chronic neuropathic pain, inflammatory conditions, Parkinson’s disease symptoms, and epilepsy. Despite these therapeutic benefits, marijuana use may have adverse effects on health including short-term and long-term use. Additionally, marijuana use has been associated with increased risk of psychiatric disorders.

Due to the expected rise in use coinciding with legalization, studies investigating the association between marijuana use and molecular or epigenetic mechanisms may provide novel insights into the short- and long-term impacts of marijuana on health-related outcomes. DNA methylation, one of the most-studied epigenetic modifications, is a regulatory process that affects gene expression through the addition or removal of methyl groups. These modifications can be induced by environmental and lifestyle factors, which may serve as blood-based biomarkers for recent and cumulative exposures. Additionally, the modifiable nature of DNA methylation allows for the investigation of exposure-induced changes to the epigenome and its variability across time, potentially leading to the identification of dynamic and/or stable biomarkers.These methylation changes may serve as biomarkers for recent and cumulative marijuana use, and subsequently,drying and curing cannabis may further our understanding of the acute and additive influences of marijuana on molecular and biological processes influencing downstream health conditions. Despite the growing use of marijuana, a limited number of studies have examined epigenome wide biomarkers associated with marijuana use. Previous studies have identified differentially methylated DNA signatures associated with marijuana, including markers located in AHRR, ALPG, CEMIP, and MYO1G. These biomarkers, however, were limited to a single time point and did not examine both recent and cumulative marijuana use. Studies examining the relationship between recent and cumulative marijuana use and epigenetic factors in a diverse population across time with repeated measurements may provide novel insights. Therefore, the purpose of this study was to investigate the association between recent and cumulative marijuana use and repeated genome-wide DNA methylation patterns measured in middle aged adults.Details of blood sample collection and DNA processing have previously been described. Briefly, a random sample of 1200 participants with available whole blood at both Y15 and Y20 underwent DNA methylation profiling using the Illumina MethylationEPIC BeadChip. Data process and quality control of the DNA methylation datasets were performed using the default settings in the R package Enmix. Low quality methylation measurements were defined as markers with a detection P < 1E−06 or less than 3 beads. A total of 6209 markers with a detection rate <95% and 87 samples with methylation measurements of low-quality >5% or extremely low intensity of bisulfite conversion probes were removed from further analysis. Additionally, 95 samples were identified as extreme outliers as determined by the average total intensity value [intensity of unmethylated signals + intensity of methylated signals ] or β value [M/] across all markers and Tukey’s method. Model-based correction was applied using ENmix and dye bias correction was conducted using RELIC . M or U intensities for Infinium I or II probes underwent quantile normalization separately, respectively. Low-quality methylation markers and β value outliers, as defined by Tukey’s method, were set to missing. After applying these criteria, 1042 and 957 samples at Y15 and Y20 remained for downstream analysis, respectively.In this multiple time point epigenome-wide association study of middle-aged adults, we observed 201 methylation markers associated with recent and cumulative marijuana use across time. We replicated 8 previously reported methylation markers associated with marijuana use.

We also observed 638 cis-meQTLs associated with several marijuana-methylation markers, as well as 198 differentially methylated regions. During pathway and disease analyses, marijuana-associated genes were statistically over represented in numerous pathways and diseases. While replication of these findings in independent cohorts is warranted, our results provide novel insights into the association between recent and cumulative marijuana use and the epigenome and related biological processes, which may serve as a mechanism of earlystage disease associated with marijuana use.Of these, cg05575921 in AHRR was associated with recent and cumulative marijuana use at both time points, including the single most-associated methylation marker for two of the four analyses. This methylation marker has previously been associated with heavy cannabis use among tobacco users, tobacco use, and is 1 of 172 CpGs included in the estimation of a DNA methylation surrogate for pack-years of smoking for GrimAge, a measure of biological age associated with lifespan. The association of this epigenetic marker with both tobacco and marijuana use may suggest common modulating effects on DNA methylation and may represent a nondiscriminatory smoke related biomarker, irrespective of tobacco or marijuana use. Additionally, cg05575921 has been associated with psychiatric disorders.The top methylation marker associated with recent marijuana use at Y15, cg18110140, is located on chromosome 15 in an ‘open sea’ region of the epigenome. This marker was recently found to be associated with smoking status. Several top epigenomic loci have also previously been associated with tobacco smoking, including BMF and MYO1B, and may provide additional measurable biomarkers for tobacco and marijuana exposure. Moreover, numerous epigenomic loci have been reported to have potential therapeutic benefits via the endocannabinoid system. NOX4 is a member of the NADPH oxidase family and an enzyme that synthesizes reactive oxygen species and cannabidiol , one of the most common cannabinoids, has been reported to attenuate ROS formation and enhance expression of NOX4. Similarly, TFEB is associated with the autophagy-lysosomal pathway and may aid in reducing inflammation and cognitive impairment via the cannabinoid receptor type II . Although the effect estimates for the observed associations are relatively small, the magnitude of the beta coefficients are consistent with previous EWAS studies and further studies investigating the cumulative effect of these individual CpGs may yield greater biological, and potentially clinical, relevance. We also replicated several previously reported marijuana loci, i.e., AHRR, ALPG, F2RL3, and MYO1G, in this mixed sex and self-reported race study sample, although additional studies in more diverse populations are needed to further evaluate previously associated epigenetic markers. Additionally, we observed differential DNA methylation levels by self-reported race and tobacco smoking status. While regression coefficients were highly correlated during stratified analyses, these findings provide insight into the interactive roles of self-reported race and tobacco smoking on marijuana associated methylation markers. For example, recent and cumulative marijuana use tended to exhibit greater hypomethylation of cg05575921 among Black participants and nonsmokers compared to White participants and former and current smokers, respectively. For the latter finding, the hypomethylation of cg05575921 during pooled and stratified analyses by tobacco smoking status suggests marijuana’s association with methylation may be consistent and independent of tobacco smoking. Our results highlight the interactive influences of biological and environmental factors on methylation signatures and provide insight into the differing impact of marijuana on the epigenome by population strata. These findings may serve as potential biomarkers to identify recent and long term marijuana use and molecular targets for further investigation. The epigenome is dynamic and responsive to environmental and lifestyle factors throughout the lifespan. Due to the ever changing nature of the epigenome, evaluating differences in methylation patterns across time not only enables the temporal assessment of a phenotype and epigenetic changes in the context of the natural history of a disease, but also permits examination of intra- and inter-individual variability and trajectories in methylation patterns over time.

Such variables make research about adolescent social cognition both challenging and compelling

Nucci and Turiel explain that, during this period of life, individuals expand their ability to recognize and incorporate multiple, and at times conflicting, aspects of a single issue to form their judgments and conclusions. In order to illustrate this complexity of thought and offer insight into how adolescents conceptualize the issue, this study examined adolescents’ judgments and justifications about marijuana use. This study was based on the proposition that unveiling the factors adolescents use in their thinking and the coordination process involved in this process can provide insight into their judgments about specific issues. Given the instability of public knowledge, perceptions, and attitudes toward the issue of marijuana use and its prevalence among the adolescent population in general , this issue was selected as the topic of research for this project. Specifically, this study was an investigation of adolescents’ judgments and justifications about marijuana use through the lens of social domain theory. Through the use of open-ended questions asking respondents to evaluate the act and their reasons for the evaluations, the study was intended to illuminate how adolescents conceptualize marijuana use. Marijuana use was also compared to other more clear-cut social issues in order to demonstrate its more ambiguous nature. It was intended that the results of this investigation contribute to the social domain theory body of research,how to trim cannabis and provide insight into adolescents’ judgments about a complex social issue that is relevant to this period of development.

The data partially confirmed the hypothesis that adolescents would show inconsistent judgments of marijuana use. Though they did show a mix of evaluations, respondents indicated more favorable views of the act overall. When asked about the act generally, only 8% of the respondents reported negative evaluations of the act . Not surprisingly, positive act evaluations of marijuana were negatively correlated with responses that there should be a law prohibiting use. Significantly more respondents disagreed that there should be a law prohibiting marijuana use than those who agreed with such a law. Likewise, most respondents reported positive evaluations of marijuana use in the case that it was common practice to engage in the act. When stating their reasons for their evaluations to these questions, respondents most frequently referenced conventional, prudential, and personal domain justifications. Specifically, the Custom/Tradition, Social Coordination, Safety, and Personal Choice categories were most frequently referenced. Respondents also frequently referenced the medical use of marijuana. Justifications to item 1 were considered most representative of the considerations that respondents found to be most relevant to the issue. Based on their responses to this item, considerations about the medical use of marijuana, the safety of marijuana, and personal choice to engage in the act were most salient to respondents’ reasoning. The other items in the marijuana use item set asked respondents to reason about specific conditions such as legality and common practices, and justifications to these items often referenced such considerations. For example, justifications for item 2 frequently referenced the Authority category, justifications for item 3 frequently referenced the Authority and Age Contingency, and justifications to item 4 frequently referenced the Custom/Tradition category.

Notably, however, the Safety and Personal Choice categories were consistently the next most frequently referenced justifications for each of these items. This finding as well as findings regarding justifications provided for item 1 suggest that safety and personal choice considerations were paramount to this sample’s reasoning about marijuana use. This proposition is supported by results that likewise suggested that prudential reasons were most frequently referenced; this justification was significantly more likely to be used than personal or moral justifications, and the personal domain was significantly more likely to be referenced than the moral domain. Results confirmed the hypothesis that adolescents reason about marijuana use by adults differently from how they reason about marijuana use by adolescents. Respondents were significantly more likely to provide positive evaluations of marijuana use under the age contingency condition than when generally asked about marijuana use. There was a 23% increase in respondents’ positive evaluations of the act under the age contingency condition than in their general evaluations of the act. Furthermore, respondents who initially had uncertain evaluations or negative evaluations of marijuana use seemed to be influenced by the added age contingency placed on the act: respectively 75% and 77% of respondents who had initially provided uncertain/mixed evaluations and negative evaluations of marijuana use shifted to positive evaluations of the act under the age contingency condition. These results suggest that an age law for marijuana was impactful to their evaluations about the acceptability of use. Justifications to this item supported this assertion, as respondents often stated that individuals 21 and older are “mature” and “more responsible” and thereby better able to make decisions about engagement in these types of activities. Respondents also frequently compared marijuana to alcohol when responding to this item and stated that the two substances are similar and should therefore treated in a similar fashion.

These findings are interesting to consider in the context of timing of data collection for this study: The administration of the study took place nine months prior to the November 2016 election in California , which resulted in the legalization of the recreational use of marijuana for individuals age 21 and over . The timing of data collection may have played an influential role in respondents’ judgments about marijuana use. For example, it is possible that respondents were not only exposed to political advertisements regarding the legalization of recreational marijuana use. Respondents may have even participated in classroom or social discussions about the issue of recreational legalization. It is not possible to know whether and to what extent such factors impacted these respondents’ judgments about marijuana curing use in the present study. However, such potential influences are important factors to bear in mind when considering the present study results . It is noteworthy that, as mentioned, the age contingency condition yielded the most positive evaluations of marijuana use in this item set. These mostly positive evaluations of marijuana use under this condition suggest that the age of the user is indeed an important factor in respondents’ judgments of the act. Moreover, given that this legal age condition has components of both conventional and prudential considerations, these findings have implications for the social domains that the respondents seemed to find most relevant to marijuana use; that respondents were significantly swayed toward positive evaluations of the act under this condition indicates that respondents find the conventional and prudential domains particularly relevant to their evaluations. Domain reference results suggesting that respondents provided significantly more prudential and conventional domain justifications in their responses to the marijuana item set provides further evidence that these considerations were particularly impactful to this sample’s reasoning about marijuana use.Respondents’ conceptualization of marijuana use regarding criterion judgments was determined through an assessment of their general act evaluations of marijuana use and through questions asking about marijuana use given specific conditional factors . Response patterns suggested that criterion judgments associated with the moral domain were not applicable, as the vast majority of respondents did not generally evaluate the act as wrong, nor did their evaluations necessarily indicate that they think of the issue as independent of law/rules/authority or common practice .

These results contrast with results from the studies conducted by Abide et al. , Amonini and Donovan , and Kuther and Higgins-D’Alessandro , which suggested that participants frequently or primarily evaluated marijuana or drug use as a moral issue. However, as was discussed in the review of the literature, these studies did not distinguish prudential considerations from moral, conventional, and otherwise personal ones when asking participants to make their evaluations; participants were asked to classify issues within the moral, personal, and/or conventional domains only. The lack of prudential domain differentiation may have confused their findings, as participants may have been thinking in terms of safety and harm when evaluating substance or marijuana use as “wrong regardless of existing laws” or as “morally wrong” . Separating the prudential domain from the others allowed for more accurate inferences to be made from the findings of the present study than those of such previous research. The response patterns from this study further suggest that conventional criterion judgments were less relevant to marijuana use evaluations than other considerations may have been. Respondents provided similarly mixed responses when asked about the acceptability of use in the presence or in the absence of a law prohibiting use. This suggests that the condition of rules or laws against marijuana were not significantly influential to their evaluations . Context specificity also seemed uninfluential to their judgments. This was evidenced by results showing no significant shifts in respondents’ evaluations of marijuana use under the common practice condition proposed; a statistically significant majority of respondents who were asked to consider this condition maintained that use would be all right even if was not commonly practiced or accepted . Taken together, these results suggest that marijuana use does not seem to meet the criterion judgments found to be associated with the moral and conventional domains. The lack of applicability of the moral and conventional criterion judgments is in turn suggestive that the personal domain is most closely characteristic of the marijuana use issue. Findings suggesting that personal domain criterion judgments were prominent in respondents’ reasoning about marijuana are consistent with previous research likewise suggesting that adolescents primarily evaluated substance use within the personal domain .Informational assumptions are the reasons or evidence that individuals point to when justifying their evaluations of an issue . In other words, individuals’ understandings of an issue are based on the informational assumptions that they have come to associate with the matter, and such understandings are utilized when reasoning about it. It is often the uncertainties of the informational assumptions associated with non-prototypical social issues that give them their ambiguous character, and in turn result in inconsistent judgments of these issues. Results from this study provide evidence suggesting that informational assumptions about the harm involved in marijuana use were related to respondents’ evaluations of the act. Results indicated that the significant majority of respondents held informational assumptions that frequent marijuana use causes physical or psychological harm to the user. The hypothesis that informational assumptions about the harm of using marijuana would be associated with responses to general marijuana act evaluations was supported. Though small in number , all individuals who reported that marijuana use was not all right were more likely to report that use causes harm, implying that the harmfulness of marijuana use contributed their negative initial evaluation of the act. The impact of informational assumptions about marijuana use harm on respondents’ judgments is further supported by the finding that 74% of those who provided uncertain evaluations of marijuana use when generally evaluating the act also reported that frequent marijuana use causes harm. This finding implies that beliefs about the harm involved in marijuana use may have contributed to these respondents’ negative general evaluations about the acceptability of use. The reverse finding likewise suggested that informational assumptions about harm play a role in evaluation judgments about marijuana use: Beliefs about the lack of harm involved in use also had an impact on evaluations, as those who reported positive evaluations of marijuana use were less likely to report that marijuana use causes harm. Specifically, of those who said that marijuana use is all right, only 38% reported thinking that use causes harm. This is in contrast to the 74% and 100% of the respective uncertain and negative evaluators of marijuana use who reported that use causes harm. The impact of beliefs about harm on evaluations about marijuana use was further assessed through the manipulation conditions that followed the general question about marijuana use. It was hypothesized that, when asked about the acceptability of use under the condition that it is not harmful, respondents would be more likely to evaluate the use of marijuana positively. Conversely, it was hypothesized that, when asked about the acceptability of use under the condition that marijuana use is harmful, participants would be expected to provide negative act evaluations. Results partially supported these hypotheses. Respondents who reported that frequent marijuana use harms the user were significantly more likely to evaluate use as all right under the condition that it was conclusively determined to be safe for the user. However, the condition of harmfulness did not seem to have a significant impact on the evaluations of the acceptability of marijuana use by those respondents who originally reported that frequent marijuana use is not harmful.

The items on the survey were designed to address participants’ reasoning about marijuana use

Additional research evidence for adolescents’ multi-faceted reasoning about ambiguous social issues such as substance use was conducted by Shaw, Amsel and Schillo . They investigated late adolescents’ domain reasoning when presented with hypothetical scenarios involving risk-taking behaviors and by asking respondents to justify engagement or lack thereof in the behavior/activity. It was found that 84% of the respondents’ justifications referred to at least one social domain of reasoning. Moreover, 88% of the justifications respondents provided when evaluating each of the risktaking behaviors made reference to a combination of prudential, conventional, and moral considerations as reasons for not engaging in the behavior/activity. This and other studies have thereby shown the multiple lines of reasoning adolescents employ when reasoning about such ambiguous social issues and behaviors. Such variability in adolescents’ domains of reasoning in the above studies suggests that they are accounting for various contextual factors when judging these issues. As adolescents develop, they are more able to consider multiple facets of an issue rather than thinking about the issue in a unilateral way. Thus, as they become more able to integrate the various features of an issue as well as their informational assumptions,cure cannabis their thinking about these ambiguous issues becomes more complex and their evaluations more multi-dimensional . The above review of the literature indicates that the findings about which social domain of reasoning is most prominent in adolescents’ thinking about an issue like substance use have been inconsistent.

Results also suggest that teens may draw upon a multitude of factors across social domains when reasoning about such issues. Moreover, problems with the methodology and/or analysis of some of these studies suggest that a forced-choice approach to data collection in this line of research limits the clarity and interpretability of results, and therefore the ability to draw conclusions from the findings. As related more specifically to the issue that is the focus of the present research, previous research has suggested that marijuana use is a social matter that involves different and at times conflicting considerations. The array of relevant facets involved in marijuana use make it an ambiguous social issue as opposed to prototypical moral, conventional, or personal issues. Thus far, the following points have been discussed: 1) marijuana use is an important yet vaguely understood social issue that warrants further research, 2) marijuana use is an ambiguous issue that is often comprised of various relevant facets that merit consideration, 3) the salience of these various considerations are associated with the informational assumptions held by an individual, and 4) understanding the various informational assumptions that become salient in adolescents’ reasoning about marijuana use can help elucidate the basis for their judgments and related justifications. In the present investigation, the patterns of adolescents’ judgments and justifications regarding marijuana use were explored through open-ended questions about their evaluations of marijuana use in general and under the consideration of certain hypothetical conditions. These patterns of reasoning were then compared to the patterns of judgments regarding unambiguous issues. In addition to questions about marijuana use, respondents were asked to evaluate a prototypical moral issue and a prototypical personal issue . Adolescents’ judgments and justifications about the prototypical moral or personal issues were expected to be judged within the respective moral or personal domains.

However, judgments and justifications about marijuana use were expected to reflect a different pattern ; evaluations of marijuana use were expected to be inconsistent and to reference various domains of reasoning depending on the informational assumptions held. This study, which assessed adolescents’ evaluations and judgments about marijuana use is modeled on previous social domain research that has investigated individuals’ reasoning about ambiguous social issues, such as pornography, homosexuality, and abortion . The present study used a similar research methodology as the Turiel et al. studies. Some of the questions that were used in the Turiel et al. studies have likewise been adapted for the aims of the present study. The present study employed a short-answer response format to data collection, which allowed for a larger sample size , while retaining the value that qualitative data collection methodology offers. By allowing respondents to provide justifications for their evaluations rather than only expressions of agreement or disagreement, it was expected that the present study would yield greater depth in understanding how respondents evaluate issues. Data were gathered through the administration of surveys that asked participants whether and why/why not 1) marijuana use is all right or not all right, 2) there should be a law in the U.S. prohibiting the use of marijuana, 3) marijuana use by individuals of certain ages is all right, and 4) marijuana use would be all right if was common practice for people in the U.S. to engage in it. Based on the participant’s responses to these items, he/she was asked follow-up questions about his/her evaluation of the issue in the case of certain hypothetical situations.

The survey items addressed whether and how adolescents use informational assumptions when justifying their judgments of marijuana use. This was accomplished by 1) obtaining the participants’ reasons for their evaluations, followed by 2) specific items asking participants whether they think frequent marijuana use causes physical or psychological harm to the user. The participants were also asked follow-up questions based on their response to the item regarding their thoughts on whether or not marijuana use causes harm to the user. If the participant responded that he/she does not think frequent marijuana use causes harm to the user,curing drying he/she was asked to suppose that scientists conclusively determined that marijuana use was in fact harmful to the user and to judge whether marijuana use would be all right or not all right in this case. If the participant responded that he/she does think frequent marijuana use causes harm to the user, he/she was asked to suppose that scientists conclusively determined that marijuana use was not harmful to the user and to judge whether marijuana use would be all right or not all right in this case. Research aims and intended contributions of the present study. Though there have been some studies aimed at understanding adolescent reasoning about marijuana use through a social domain framework , much of the research in this field has been based on a forced-choice, survey format for data collection. While such methods can be useful for amassing large amounts of data by presenting a number of multiple-choice items to participants, they are limited in the capacity to extract the participants’ thinking; the forced choice format fails to reveal the complexity of thinking and the informational assumptions individuals draw upon to reach their judgments. This study adopts an open-ended written response format of data collection. In this way, the study expanded upon findings from previous research by assessing the ways criterion judgments, justifications, and informational assumptions are brought to bear during adolescents’ evaluations of use of marijuana. Specifically, the questions were designed to assess participants’ evaluations and justifications about the acceptability of marijuana use as related to age, rules/laws/authority contingency, and common practice. These questions, as well as specific questions regarding participants’ beliefs and understandings about the presence and degree of harm associated with use, are designed to assess the informational assumptions adolescents maintain regarding marijuana use. There are three hypotheses for the expected results of this study. The first is that marijuana use is regarded as an ambiguous social issue that elicits multi-domain considerations, resulting in positive and negative evaluations that may be inconsistent across- and even within- individuals depending upon the specific criterion judgments and justifications employed. Variation in response types and patterns are expected between participants, as are inconsistent patterns of criterion judgments within participants’ responses . Likewise, variations within and between participants are expected with regard to the justifications and domains that participants reference in their responses.

The second hypothesis is that individual evaluations will be associated with the informational assumptions held regarding the extent of harm in marijuana use. When asked about the acceptability of use under the condition that it is not harmful, participants are expected to evaluate the use of marijuana positively if prudential concerns were part of the basis for their initially negative evaluation of marijuana use. On the other hand, when asked about the acceptability of use under the condition that marijuana use is harmful, participants are expected to provide negative act evaluations in response to this follow-up question if prudential considerations were part of the basis for their initially positive evaluation of use. The third hypothesis for this study is that, whereas evaluations in criterion judgments of marijuana use will be variable within and between subjects, evaluations of prototypical issues will be consistent . In other words, results from the questions addressing marijuana use issue were expected to contrast with results of prototypical moral and prototypical personal issues in that the prototypical moral issue is expected to be consistently evaluated negatively with justifications referencing the Welfare, Justice and Rights, and Moral Obligation categories and the prototypical personal issue are expected to be consistently evaluated positively with justifications referencing the Personal Choice category. To summarize, results from this portion of the study are expected to show the following: 1) consistently negative judgments regarding the acceptability of stealing, 2) consistently positive judgments about the acceptability of using one’s allowance money to purchase music, and, respectively, 3) morally-based criterion judgments and justifications in response to the stealing issue and 4) personal domain-based criterion judgments and justifications in response to the purchasing music issue. Participants for this study were 100 adolescents aged sixteen to eighteen years of age and in their junior and senior years of high school. Participants were composed of 35 males and 65 females. Seven of the participants were age 16, sixty-three participants were age 17, and thirty were 18 years of age. The majority of the participants were in the 12th grade. Fourteen of the participants were in the 11th grade. The racial/ethnic composition of the participants was primarily White and Hispanic , but there were also a small number of participants who identified as ‘Mixed’ , Asian , or ‘Other’ . Participants were recruited from a high school in a mid-sized rural city in the northern San Francisco Bay Area that is primarily composed of middle class households . Participation in the study was optional and based on students’ interest in participating in the research. The surveys were administered to students in the four class periods of the Psychology course offered at the high school. Study administration took place during typical school day hours. The classroom teacher explained to students that they would have the opportunity to participate in a research study being conducted by a graduate student for the purposes of a doctoral dissertation. Students were asked to review Student Consent/Assent forms as well as Parent Permission Form and to return signed forms if choosing to participate in the study . Completion and submission of the Student Consent/Assent and the Parent Permission Form were mandatory prerequisites for being given the choice to participate in the study on the day of administration. The Graduate Student Investigator reviewed three guidelines for the surveys that would be handed out. The following instructions, which had been written on the front board prior to the students’ arrival, were reviewed and further explained with the participants: 1) State “all right,” “not all right,” or “depends” in response to each question, 2) always make sure to state your reason for your response , and 3) for items that have a part and part , answer either part or –the survey provides directions about whether to answer part or based on the previous response given. After reviewing these guidelines, participants were asked if they had any questions. Participants’ questions were answered and the surveys were distributed. Participants were asked about their judgments of marijuana use in general , whether there should be a law that prohibits marijuana use, and whether marijuana use would be all right if there was not a law prohibiting use , or if there was law prohibiting use . Respondents were then asked to evaluate marijuana in the case that the majority of the people in the United States decided that marijuana use should be allowed for individuals ages 21 and over, and in the case that it was common practice for individuals to engage in marijuana use.

The report of higher levels of support in our survey could be explained by several factors

As research continues, it will be important to include underrepresented populations as patterns of use for medical purposes may differ by socioeconomic status, race, and access to medical care. Despite the lack of evidence on the efficacy of marijuana use for health conditions, nearly half of those who disclosed medical marijuana use to their doctors reported they were supportive and only 8% of patients felt their doctors were not supportive. The overall high perception of support in our survey contrasts several prior physician surveys describing low approval rates of medical marijuana. In 2005, a survey of 960 physicians nationwide found that only 36% supported legalization of medical marijuana and 26% were neutral.A 2013 survey of 520 family physicians in Colorado found that, despite medical marijuana being legal, only 19% of physicians believed they should be able to recommend it and most agreed it posed serious mental and physical health risks.We did not query healthcare providers directly but instead asked participants their perception of their healthcare providers’ level of support. As such, participants who reported marijuana use to their doctor may have already known they would be supportive. Our data is also more recent compared to the prior surveys, and physicians’ attitudes may parallel the decreased perception of harm that has been documented in surveys of the general population.Indeed,curing weed a more recent survey of 400 medical oncologists found that 46% would recommend medical marijuana to their patients and 67% viewed it as a helpful adjunct to pain management.We also found that 26% of those who used marijuana for medical purposes did not inform their doctor and that this rate was higher in states where medical marijuana was illegal.

Potential reasons for non-disclosure include mistrust, fear of disapproval or bias, and legal consequences in states where marijuana is illegal. Additionally, it is possible patients did not disclose their use because their doctor did not directly ask them. Given the lack of evidence, training, and guidelines on the use of marijuana for medical purposes, some healthcare providers may feel uncomfortable discussing this with patients. Regardless of the reasons why marijuana use was not disclosed, this demonstrates a concerning lack of communication and missed opportunity for providers to counsel patients about the risks and benefits of marijuana use. Additionally, we found that 21% of participants using medical marijuana did not have a doctor. The majority were between ages 18 and 34 and only 22% had a total household income of more than $75,000. Therefore, while their insurance status is unknown, their young age and lower income may have impacted their decision or ability to see a provider. Despite the limitations of the evidence, several healthcare institutions and societies have created policies and guidelines for their healthcare workers to have these important conversations. For example, while Veterans Health Administration providers are unable to complete forms referring patients to State-approved marijuana programs, 2017 VA guidelines encourage physicians to discuss marijuana use with patients and explore how its use may be affecting their health.Though our study benefits from a nationally representative sample, it has several limitations. First, the ordering of the list was not randomized across participants. Also, our results may be more reflective of individuals who are willing to participate in online surveys. However, demographics of our survey respondents were similar to those from prior national studies and there was no evidence of non-response bias on key demographics.Another limitation is that our survey did not directly address perceived efficacy of marijuana use for medical conditions. It would be helpful to know if patients and their healthcare providers believe marijuana is improving their symptoms. Also, we asked about chronic pain as a general category and not specific sub-types of pain.

Finally, we did not survey providers directly, rather, respondents reported their perception of their doctors’ views on marijuana and we did not ask about disclosure to other types of healthcare providers. Despite these limitations, our results demonstrate that US adults are using marijuana to treat conditions where it has not been convincingly shown to provide benefit and highlight the urgent need for higher quality studies on the effectiveness of medical marijuana. They also underscore the need for clinical guidelines to support more complete and informed discussions between patients and providers about medical marijuana use.Marijuana use is common, particularly in people living with HIV . Prior studies suggest that the prevalence of current marijuana use in PLWH ranges from 20% to 60%. In the general population, this number is 8%8 . Discussions with patients about marijuana have taken on more urgency in HIV primary care over the past several years as over half of states have moved to legalize medical marijuana, which is likely to increase use. Furthermore, at least 27 states have designated HIV seropositivity as a qualifying diagnosis for medical marijuana certification. Although experimental trials that substantiate specific benefits are lacking, commonly reported reasons for marijuana use in PLWH include pain relief, as well as other symptoms such as nausea and anorexia. Additionally, chronic pain is common in PLWH, with prevalence estimates ranging from 25% to 85% depending on the cohort studied, and is the most common reason why people seek treatment with medical marijuana. However, recent systematic reviews have highlighted the limited evidence base for medical marijuana in treating pain and other symptoms in the general population, and specifically in PLWH. Another common perception includes a belief that marijuana may allow patients prescribed long-term opioid therapy for chronic pain to reduce their opioid use. Ecological studies in the general population and one study in PLWH support this possibility. With this background, HIV clinicians need empirically based findings to guide patients regarding marijuana use. Additionally, clinicians are faced with the tension between state laws naming HIV as a qualifying diagnosis for medical marijuana and the limited evidence base.

Recent studies suggest that the lay public has generally positive views of the benefits of medical marijuana and views risks as minimal. Given the limited evidence base, providers may be influenced by the layperson’s view of marijuana. Since clinical trials studying the effects of medical marijuana are hampered by federal classification of marijuana as a schedule I substance,weed curing observational data must be relied on to advance our understanding of the impact of marijuana on health outcomes. We investigated whether recreational marijuana use among PLWH who have chronic pain is associated with two clinically important chronic pain-related outcomes: changes in pain severity and prescribed opioid use . We first asked whether a change in marijuana use over time predicted a change in pain severity, hypothesizing that an increase in marijuana use would be associated with decreased pain and a decrease in marijuana use would be associated with an increase in pain severity. We then asked whether baseline marijuana use would be associated with lower opioid prescribing. We hypothesized that baseline marijuana use would be associated with lower rates of initiation and higher rates of discontinuation of prescribed opioids. This study is an analysis of data from a large, ongoing national prospective cohort study of chronic pain and HIV outcomes embedded within the Centers for AIDS Research Network of Integrated Clinical Systems. CNICS sites are patient-centered medical homes for PLWH, meaning that they provide primary and specialty care for PLWH including mental health treatment and social services. The majority of patients from CNICS sites are enrolled in the cohort. CNICS collects demographic and clinical data at routine clinic visits, including laboratory tests, visit data, and prescribed medications from the electronic medical record. Additionally, as part of routine clinical care appointments, participants complete in-person Patient Reported Outcome measures on a computer or tablet on a variety of social and behavioral domains approximately every 4 to 6 months. The CNICS clinical assessment of PROs includes the Alcohol, Smoking, and Substance Involvement Screening Test , which collects self-report of “non-medical” marijuana use over the past 3 months.

The possible categories are no current use, use 1–2 times in the past 3 months, monthly, weekly, or daily. Pain instruments were added to the CNICS clinical assessment between July 2015 and July 2016, providing 12 months of data from which to study chronic pain in this cohort. The following five CNICS sites included the Pain instruments and contributed data to this analysis: Fenway Health in Boston, the University of Alabama at Birmingham , University of California, San Diego , University of North Carolina , and University of Washington . At the time of this study, marijuana was legal recreationally in Washington , medically in Washington and California , and illegal in all other sites. Pain instruments included the Brief Chronic Pain Questionnaire . The BCPQ asks whether participants have pain that has lasted for more than 3 months, and the severity of their pain. Participants who reported at least “moderate” pain for at least 3 months were classified as “chronic pain” and also received the three-item PEG to assess pain severity. This instrument assesses pain intensity , interference with enjoyment of life , and interference with general activity on a scale of 0–10 for each item. Participants with at least moderate chronic pain were also asked to complete the following question: “Check everywhere you have had pain for at least 3 months: numbness or tingling in hands and/or feet; headache; abdominal pain; low back pain; hip pain; shoulder pain; knee pain; pain everywhere in your body.” This study was approved by the Institutional Review Board of the University of Alabama at Birmingham . The date participants completed their first pain PRO instrument was defined as their “index visit.” The study period was defined as the 1-year period following the index visit. Criteria for inclusion in this analysis were age ≥18 years, participation in CNICS for at least one year prior to the index visit to allow for assessment of prescribed opioids during this period and to prevent inclusion of participants new to HIV care, and chronic pain. We also required participants to have two marijuana and two pain PRO measurements during the study period so that changes in these variables could be assessed. Marijuana use—Marijuana use was assessed at the PRO assessments during the study period. Among participants who reported no current use, use monthly, use 1–2 times per month, or use weekly, we defined an increase in marijuana use as any change to a category of more frequent use during the study period. Participants who reported daily use were not able to increase their use and therefore were not included in this analysis. Among participants who reported use 1–2 times in the past 3 months, monthly, weekly, or daily, we defined a decrease in marijuana use as any change to a category of less frequent use during the study period. Participants who reported no current use were not able to decrease their use and therefore were not included in this analysis. For analysis of marijuana use at the index visit, levels were combined to improve interpretations such that three groups were considered; daily/weekly use, monthly/1–2 times in past 3 months, and no current use.The PEG score was calculated as the mean of the 3 items in the questionnaire. We defined long-term opioid therapy as opioid therapy for 90 consecutive days based on medical record data. Prescribed opioid discontinuation was defined as being prescribed LTOT at any point during the year prior to the index visit, and not being prescribed LTOT during the follow-up period. Prescribed opioid initiation was defined as not being prescribed LTOT for one year prior to the index visit and having LTOT initiated during the study period. While it may be of interest to examine longitudinal relationships using all potential visits, only 12% of patients have more than two visits during the follow-up period and it is not clear how having less than the maximum number of observations would be considered statistically significant as this is a clinical cohort without a formal protocol. Change in pain severity outcome: For the relationship between marijuana use and change in pain severity, we considered whether an individual’s marijuana use increased or decreased during the study period.