Alcohol use correlated with brain response in the right thalamus and pulvinar in the current study, but results remained significant even when accounting for alcohol use, and alcohol use did not correlate to activation in any other significant regions. Our previous research identified brain response abnormalities among marijuana users above and beyond those demonstrated by users of alcohol alone , supporting the hypothesis of marijuana-specific differences in brain response, even among teens who are heavy drinkers. Future studies should attempt to clarify the differential and interactive impact of concomitant alcohol and marijuana use on brain functioning on adolescents. Furthermore, lifetime marijuana use episodes were associated with activation in the right uncus and superior temporal gyrus. Future analyses could further investigate the associations of other brain regions, as well as neuropsychological performance, with lifetime use episodes. These subtle differenced among users may provide additional insight into the mechanisms involved with prolonged abstinence from marijuana. Future studies should also focus on investigating the nature of interactions in other domains of cognition to test if other types of tasks show these patterns. A more complex task should be an aim for future studies because it may elicit a difference in task performance. If a user’s neural differences are actually a compensatory tool,cannabis drainage system then a more difficult task may overcome their compensation abilities, therefore resulting in performance deficits.

In addition, a parametric manipulation of working memory load could help specify degree of compensatory activation in marijuana users compared to controls, as marijuana users may reach a limit earlier than controls. Further studies could also explore which mechanisms and strategies subjects utilize during the tasks through qualitative data investigation. Human immunodefificiency virus is widely prevalent in the U.S., with approximately 1.1 million individuals estimated as infected with the virus . Antiretroviral medication, the ‘‘gold standard’’ for treating HIV, has progressively improved and, if taken correctly, significantly extends lives and reduces mortality rates, transforming HIV into a chronic illness . Here, earlier research indicated that medication adherence of at least 95 % was required to achieve HIV viral suppression, lower hospitalization rates, as well as decreased burden of the infection and risk of virus transmission . While advances in pharmacotherapy have made antiretroviral medication regimens more manageable and may allow for positive outcomes with imperfect adherence in some patients , low adherence is associated with medication resistance, increased HIV viral load, risk of developing acquired immune defificiency syndrome , and increased mortality . Despite the medical advances in HIV care, sub-optimal adherence to antiretroviral therapy remains commonwith the average adherence rate across studies and groups hovering around 70 % . Studies that have assessed adherence rates among individuals with HIV have found that between 14 and 35 % of individuals with HIV have trouble maintaining at least 80 % adherence to ART , with viral suppression not achieved among 30–70 % of HIV positive individuals . The primary contributors to poor adherence among individuals with HIV include medication side effects , regimen complexity , substance use , and emotional factors . There is growing recognition that individuals with HIV report greater cannabis use than the general population. Studies examining rates of cannabis use among individuals with HIV suggest that between 23 % and 56 % of HIV + individuals have used cannabis in the past month .

For comparison, only 6.9 % of the general U.S. population over age 12 reported past month cannabis use in 2010 . These rates are particularly noteworthy as, even in places where the use of cannabis for medicinal purposes is sanctioned, the large majority of cannabis using individuals with HIV obtain their cannabis from illegal sources . Though some studies examining the negative effects of cannabis on individuals with HIV have been conducted, the literature pertaining to the use of cannabis among individuals with HIV has primarily focused on its positive effects . Here, studies have shown that approximately 25–33 % of individuals with HIV report using cannabis to alleviate HIV-related symptoms and medication side effects . specifically, HIV + individuals report the primary benefits of cannabis use to be the alleviation of anxiety and depression, stimulation of appetite and resulting weight gain, and relief of pain . Though there are many empirical studies on the effects of cannabis use on HIV symptoms/ART side effects, there is a general dearth of literature examining the effects of cannabis use on HIV treatment adherence. Because of the preliminary nature of these studies, there is no agreement as to the extent to which cannabis is benefificial or detrimental to adherence. As an illustrative example, cannabis use for the purpose of alleviating nausea was found to improve HIV treatment adherence , while heavy cannabis use has been associated with non-adherence . Other studies have found similar negative effects of cannabis use, more broadly, in terms of treatment adherence . specifically, in a study of a representative U.S. sample of 1,910 HIV + patients who self-reported on their antiretroviral adherence, Tucker et al., found patients with past-month cannabis use to be at increased odds of non-adherence to antiretroviral medication than non-users. Similarly, in a study by Corless et al., among 775 individuals with HIV from Africa, Puerto Rico, and the contiguous U.S., individuals who used cannabis had significantly poorer adherence than individuals who did not. A study of 200 Australians with HIV by Wilson et al., found that using cannabis more than 4 times per week was associated with increased odds of selfreported non-adherence .

These data collectively indicate that the interrelations between cannabis use and treatment adherence are complex, with differences in adherence likely involving functionally distinct cannabis use patterns. Though there has been some empirical study of the effects of cannabis use on HIV treatment adherence, there has been no consistency in findings. Additionally, of the existing studies of the relations between cannabis use and HIV treatment adherence, none have classifified cannabis use by diagnostic criteria , a more accurate method of identifying problematic use patterns. Indeed, as quantity of use as well as problems associated with use are central to understanding cannabis use patterns as well as intervention targets, the examination of frequency of use provides a poor metric of those severely impacted by cannabis use . This lack of research focused expressly on the association between cannabis use patterns and antiretroviral treatment adherence, is particularly noteworthy. Such research is central for understanding risk for low treatment adherence among individuals with HIV. The present study aimed to fill these clinically significant gaps in the HIV literature by exploring associations between cannabis use and ART adherence and HIV symptoms/ART side effects. The primary purpose of this project was to evaluate the extent to which non-cannabis use and dependent use was associated with sub-optimal HIV treatment adherence and a heightened experience of HIV symptoms/ART side effects, as compared with non-dependent cannabis use . Indeed, we predicted a non-linear relation between cannabis use patterns and ART adherence and HIV symptoms/ART side effects, based on previous literature reporting benefits of cannabis for side-effect management. Consistent with the HIV treatment adherence literature, we posited that non-cannabis using individuals would experience negative effects of HIV symptoms,indoor cannabis grow system including ART side effects, and that these symptoms would contribute to decreased treatment adherence . This prediction was primarily based on the results of recent work, among mostly non-cannabis using HIV populations, showing generally poor adherence to HIV treatment . On the other end of the continuum, we expected similarly low HIV treatment adherence and a heightened experience of HIV symptoms/ART side effects among individuals who were cannabis dependent. This prediction was based on prior literature indicating an association between heavy cannabis use and sub-optimal treatment adherence , as well as the literature pointing to the detrimental psychological and health-related effects of dependent cannabis use . Finally, based on prior work showing that cannabis use for specific symptom alleviation is beneficial in terms of adherence , we hypothesized that non-dependent cannabis users may actually exhibit greater ART adherence and fewer and less severe HIV symptoms/ART side effects than the other two groups. So as to provide a rigorous test of the association between cannabis use status and anti-retroviral medication adherence, a multi-method approach was employed, with both objective and subjective measures of adherence. Additionally, both alcohol and tobacco use were assessed and considered as covariates as they have been shown to be associated with both cannabis use and ART adherence .The present study aimed to determine the association between cannabis use status and antiretroviral medication adherence, as well as HIV symptoms/ ART side effects, among a sample of HIV-positive individuals. Partially consistent with hypothesis, those in the CD group generally reported lower adherence and greater HIV symptoms/ART side effects than the other two groups.

In terms of pill count, those in the CD group reported significantly lower adherence than those in the C group, and the CD group tended to report lower self-reported adherence than those in the NC group. With regard to viral load, again, those in the CD group had higher viral load than those in the NC group, while those in the CD group reported more frequent and severe HIV symptoms/ ART side effects than those in either of the other two groups. These findings are consistent with prior work that has shown heavy cannabis use to be associated with non-adherence as well as work showing cannabis dependence to be related to a variety of negative psychological and health-related factors . Here, it is also noteworthy that the observed findings for pill count and HIV symptoms/ART side effects remained after accounting for the effects of age, highest level of education, and alcohol consumption, which were shown to differ between cannabis groups. Though it was hypothesized that both the CD and NC groups would report lower adherence and more frequent and severe HIV symptoms/ART side effects than the C group, there were in fact no differences observed between NC and C groups in any of the analyses; differences were only observed between the CD group and either or both of the other two groups, depending on the outcome. This lack of differences between C and NC groups was not expected given that those in the NC group do not use a coping mechanism that has been shown to reduce HIV symptoms and ART side effects and thus improve adherence . Indeed, our findings suggest that moderate cannabis use , as compared with non-use, may not be meaningfully associated with symptom relief or medication adherence. Further examination of these group differences is needed to ascertain the functions of cannabis use among individuals with HIV who use cannabis moderately . It is also noteworthy that viral load, but not absolute CD4 count, was shown to differ between groups.It is possible that no effect was observed for absolute CD4 count because viral load may be a more reliable marker of responsiveness to ART as CD4 count changes are sometimes delayed in relation to changes in viral load and, for some patients, do not stably increase even with durable undetectable viral load . Additionally, in terms of self-reported ART adherence, it is noteworthy that group differences were observed for 4-day, but not 2-week, self-reported adherence. Though it is possible that 4-day data are more accurate , future work would benefit from further examining concordance or discordance between different windows of self-reported ART adherence among HIV+ individuals with varying degrees of cannabis use. There are many potential clinical implications from the present findings, however, it is important to note that the cross-sectional nature of the study does not allow for the interpretation of directionality of findings and thus clinical implications must be interpreted with some caution. Indeed, it is just as likely that cannabis dependence led to poor adherence as it is that poor adherence was associated with more severe HIV symptoms which led individuals to use cannabis for coping-oriented reasons, leading to dependence. In either case, cannabis dependence appears to be an indicator of increased risk of poor adherence and more severe HIV symptoms/ART side effects.