Hemp Growing

Governments have imposed widespread restrictions on public life to cope with the pandemic worldwide. The resulting “social distancing” policies and other measures to contain the incidence of COVID-19 infections led to isolation and solitude for many individuals. Men are disproportionately affected by severe COVID-19 disease progression and show a higher mortality due to COVID-19. However, there is evidence from the scientific literature that women may be more affected by the economic, social and psychological consequences of the pandemic. Sectors with a high share of female employees  were disproportionately affected by lockdown related closures, short-time work and job losses. Women are also more likely to work in atypical jobs with lower social security coverage or part-time, which contributes to lower financial security. In the pandemic, at least in families with “traditional” gender roles, the main burden of child care at home was on women because of closed schools and child care . In addition, employees in health care and other essential services  are also mostly female and have been exposed to stress, high workload levels and an increased risk of infection during the pandemic. Additionally, in a student population, perceived stress with regard to COVID-19 was shown to be higher in female than in male individuals. Since the beginning of the pandemic, the impact of the COVID-19 situation on mental health in the population has been discussed. At the beginning of the pandemic, researchers drew attention to the necessity to address the public mental health consequences. Some authors argued that a “psychiatric pandemic” was co-occurring with COVID-19. In the meantime, numerous studies in various countries showed that the COVID-19 situation has negatively affected mental health. Population-based studies in Germany found evidence that depressive symptoms, anxiety, sleep disturbances and psychological distress increased as a response to COVID-19.

Research with repeated cross-sectional designs indicated that the implementation of contact restrictions was associated with increased levels of depression and anxiety that seem to have persisted even during the easing of those restrictions. Women experienced higher levels of depression and anxiety than men during the first COVID-19 wave. This corresponds to previous research demonstrating gender differences regarding depression, anxiety and insomnia because of the pandemic . Psychological distress and mental health problems are well-described risk factors for increases in the use of alcohol and other substances. Besides the potential negative effects for individuals,cannabis grow equipment significant increases in alcohol use are also a public health concern. In the German general population, per capita alcohol consumption is high by global standards. In the group of women in Germany, 13.1% drink alcohol in a hazardous pattern, defined for women as more than 10 g pure alcohol per day on average . Among women, alcohol consumption increases with higher socioeconomic status. Women with a higher socioeconomic status are twice as likely to drink hazardously than women with a middle or low socioeconomic status . A number of publications document changes in alcohol consumption under COVID-19 pandemic conditions for different countries, e.g., for the United States, the United Kingdom, Poland, Australia and France. These studies have shown that between one fifth and one quarter of adults increased their alcohol use after the pandemic started. Corresponding to those results, retailers in various countries have reported an increase in the sale of alcoholic beverages since the beginning of contact restrictions or lockdowns. In contrast, a very recent study in 21 EU countries showed that in most countries, with the exception of Ireland and the United Kingdom, there was a decrease in alcohol consumption. However, a reduction in alcohol consumption was less common among people who were particularly stressed by the pandemic. Other studies also found significant associations between higher levels of psychological distress, or depressive or anxiety symptoms and an increase in alcohol use. Among women, psychological distress related to COVID-19 has been significantly associated with the quantity of alcohol use, such as the number of drinks had at the last heaviest drinking event and the number of drinks on a typical occasion. For women, social distancing policies and the resulting loss of social support has been associated with an increase in hazardous drinking during the first lockdown in the USA. Those increases in alcohol consumption under pandemic conditions were interpreted as a dysfunctional coping mechanism for distress caused by the pandemic.

The analysis refers exclusively to the female part of a population-based German sample as it is hypothesized that women have been psychologically burdened by the COVID-19 pandemic differently to men due to their professional, family and social situation. In addition, women and men are known to differ in the extent and pattern of their drinking behavior. The objective of this analysis is to examine whether alcohol consumption changed in a German population-based sample of women under conditions of the COVID- 19 pandemic. In addition, the extent of depressive symptoms, anxiety and COVID-19 specific fears and their influence on alcohol, nicotine and illicit substance consumption are analyzed.A population-based and cross-sectional online survey with a self-selected convenience sample was conducted from October until December 2020. The survey covers the period of the “second wave” of the COVID-19 pandemic in Germany. During this phase, government mandated contact restrictions to contain the pandemic in Germany were relatively strict. Schools remained closed, public life was significantly restricted and people’s daily lives changed significantly. Inclusion criteria were at least 18 years of age and German language capabilities, since the survey was only available in German. Participants were recruited via social media, institutional newsletters and online press releases. Participation was anonymous and there were no financial compensations or other incentives for participation. Electronic informed consent was obtained prior to the start of the survey. Participation was voluntary and anonymous, and participants could withdraw from the study at any time. The study was conducted in accordance with the Declaration of Helsinki, and the Ethics Committee of the University Hospitals Essen has approved the study . The Foundation of University Medicine Essen  funded the study. The Open Access Fund of the University of Duisburg-Essen funded the publication of the study.In this population-based sample of women in Germany, nearly one quarter of those who use alcohol increased their alcohol use.

Nearly one third of smokers increased their nicotine use and more than forty percent who used other substances increased their sub-stance use during the COVID-19 pandemic. One in five women reported major depressive symptoms and nearly one quarter at least mild symptoms of generalized anxiety.Depressive symptoms and specific COVID-19-related fears did not contribute significantly to an increase in alcohol or nicotine use. The proportion of approximately one quarter of the participants who reported an increase in their alcohol corresponds with the results of previous studies, which found similar rates of alcohol use during the first wave of COVID-19. The most significant increase in alcohol consumption in the 35–55 year old group may be explained by the fact that in this group the stress of childcare, homeschooling or caring for elderly relatives may have been more prevalent. Due to the ongoing social distancing policies, the opportunity to drink alcohol at parties, bars, restaurants or events decreased markedly. This may explain the decrease in alcohol consumption in the youngest age group, in which almost the same number of women reduced as increased their alcohol consumption. Due to the social distancing measures, it is likely that the increased alcohol consumption primarily occurred in private settings with family members, closest friends or alone. Social distancing and self-isolation came along with the disruption of daily routines, boredom, loss of daily structure and lack of social contacts, which were identified as motives for a rise in alcohol consumption during the pandemic. A US study also found that the longer people spent time at home, the higher the risk of binge drinking at home. The relief of negative emotions and stress caused by the pandemic might have been a further motivator to drink more alcohol. Increases in alcohol consumption can negatively affect physical health in various ways; it is a leading risk factor for global disease burden and causes substantial health loss. Alcohol use is an important cause of traffic accidents and self-harm among young people and promotes various types of cancer. Alcohol use also adversely affects cardiovascular diseases such as hypertension in a dose-dependent manner. In the context of COVID-19, the negative health impacts of alcohol use are important to consider as both cardiovascular diseases and cancer increase the risk for severe COVID-19 disease progression or mortality. With regard to nicotine, its use is also highly correlated with mental stress in women. In addition, external reasons may also have led to an increase in nicotine consumption. Contact restrictions and working from home meant that many people stayed mainly in their home environment. For smokers, this may mean that the smoking bans in public and reduced social control  disappeared and may have led to an increase in cigarette consumption. Active smoking is a well-studied risk factor for the development and worsening of COPD, asthma and chronic respiratory diseases. Non-smokers in households with smokers may also have been more exposed to secondhand smoke during the pandemic and associated “stay at home” policies. Passive smoking increases the risk of asthma,mobile grow system reduced lung function and respiratory tract infections in children.

Tobacco use has a special role in the context of COVID-19 because of its negative impact on several preexisting conditions that promote the risk of severe COVID-19 disease progression. In the small subgroup of participants who use any illicit substances, predominantly cannabis, consumption increased considerably more than for alcohol and nicotine. These results were contrary to a Belgian sample that found no changes in cannabis use. However, the results are consistent with a longitudinal Dutch study that also found an increase in cannabis use during COVID-19, but no increase in the severity of cannabis use disorder  in daily consumers. In this study, mental well being was reduced and contributed significantly to changes in cannabis use. In Canada, self-isolation was associated with an increase in consumption in male cannabis users; coping with depression motivated the use of more cannabis than pre-pandemic, and an increase in cannabis use was associated with financial concerns and lower education.Symptoms of generalized anxiety were the only mental health factor that predicted an increase in alcohol and nicotine use in this sample. Previous studies have shown diverse findings regarding alcohol use and anxiety under COVID-19 conditions. An Australian study found an association between anxiety and alcohol use, whereas another study in the United Kingdom found no correlation between alcohol use and anxiety in an adult sample who were in self-isolation. In general, the association of alcohol use and symptoms of anxiety and anxiety disorders are well documented. Although the COVID-19 pandemic is a novel situation, research on other collective stressful events such as SARS 1 in 2003 or the economic crisis in 2008 demonstrated that those events were associated with an increase in alcohol use, partly mediated by depression and anxiety symptoms. Evidence of specific COVID-19-related anxiety as an influencing factor is less clear. In contrast to generalized anxiety, specific fear of COVID-19 did not contribute significantly to explain changes in substance use in our study. This corresponds to findings from a US study, which also found that the subjective fear of virus infection was not associated with an increase in substance use. Another international study group found, however, a significant association between COVID-19-related fear and increases in substance use among Russian, Belarusian and Israeli students during the first wave of COVID-19. The finding that depressive symptoms do not significantly contribute to the increase in alcohol consumption is rather unexpected since previous studies showed the opposite effect. In general, an increase in depressive symptoms is a risk factor for alcohol use and vice versa. Major depression and alcohol use disorder  are closely associated. The presence of either disorder doubles the risk of the second disorder. Co-occurrence of AUD and depressive disorders is associated with greater severity and worse prognosis for both disorde. In our female sample, one in five reported depressive symptoms above the cut-off in the PHQ, indicating that COVID-19 negatively affects mood and mental well being, but drinking alcohol to cope with depression does not seem to be the preferred option.

The head-motion estimates calculated in the correction step were also placed within the corresponding confounds file. All resampling can be performed with a single interpolation step by composing all the pertinent transformations . Gridded resampling was performed using ants Apply Transforms , configured with Lanczos interpolation to minimize the smoothing effects of other kernels . Non-gridded  resampling was performed using mri_vol2surf . Many internal operations of fMRIPrep use Nilearn 0.5.0, mostly within the functional processing workflow. For more details of the pipeline, see the section corresponding to workflows in fMRIP rep’s documentation. Data analysis was conducted in AFNI Version AFNI_20.0.18 ’Galba’ . The first level general linear model was conducted via 3dDeconvolve to generate contrast maps for each individual participant, including a regressor-of interest for each of the 4 task conditions . Six motion parameters  were included as regressors of nointerest, as were the six a CompCor parameters.This generated beta-weight values at each voxel location for each of the four task conditions to carry forward to group analysis . Following first-level analysis, data were smoothed using a 6 mm gaussian kernel , for a final average smoothing level of 8.18 mm. For each of the following analyses, a whole-brain mask excluding the cerebellum was used. All analyses were performed using the AFNI function 3dLME , a group analysis program that performs linear mixed effects  analysis on data with multiple measurements per participant. The primary analysis tested the effects of cannabis use and MDD diagnosis on emotion regulation. The model was specified as follows: task condition , cannabis use , MDD diagnosis , including two- and three-way interaction terms, were included as variables of interest. Medication use , age, and number of alcoholic drinks consumed in the last 28 days as regressors. Sex was not included as a regressor due to high collinearity with cannabis use. Numeric variables  in this analysis and all subsequent analyses were mean-centered. A random effect of participant was included in the model, and a marginal sum of squares was used. Three secondary analyses were then conducted. First, we examined the interaction between emotion regulation style and task-condition in the full sample. Similar to the main analysis, an LME model was specified with a condition × ERQ score interaction term, and age, alcohol, and medication use included as regressors. The ERQ score involved subtracting the maladaptive emotional style  from the adaptive style . Thus, higher ERQ scores indicated more adaptive emotion regulation than lower scores.

Two participants were excluded from this analysis due to missing ERQ score data. Next, we examined the relationship between HAM-D score and BOLD-signal activation during the emotion regulation task. Here, only individuals with an active MDD diagnosis were included . The LME model was specified with a condition × HAM-D score interaction, and age, alcohol, and medication were included as regressors. Finally, the effects of early-onset cannabis use on task-related BOLD signal activation were examined. Here, we only included individuals who actively used cannabis . We tested our hypothesis that early-onset cannabis use would have pronounced negative effects by grouping subjects into early-onset  versus late onset . LME analysis is well-suited for such unbalanced groups . We then identified where early-onset cannabis users had greater or lower activation than late-onset users. The LME model was specified with a condition × age of onset interaction,vertical grow system and age, alcohol, and medication were included as regressors. For second-level analyses, the minimum cluster-size threshold was determined in two steps. First, we estimated the smoothness of the residuals for each subject output by 3dDeconvolve using the autocorrelation function  option , and the mean smoothness level was calculated. Next, minimum cluster size was determined using a 10,000 iteration Monte Carlo simulation  at a voxelwise alpha level of p = 0.05. Correction for multiple comparisons at p = 0.05 was achieved by setting a minimum cluster size of 64 voxels. Posthoc contrasts were FDR corrected. The current study used an fMRI paradigm of positively- and negatively-valenced emotional scenes to investigate the individual and combined effects of MDD and frequent cannabis use on emotion regulation. We also conducted several secondary analyses to explore how the various characteristics of emotion regulation, MDD, cannabis use and age of onset of cannabis use further contribute to emotion processing in the brain. Although we did not see a three-way interaction, both MDD and cannabis use showed a complete reversal of activity levels relative to their controls in response to the different conditions of the emotion regulation task. Specifically, while participants without MDD showed higher activation to the positive attend condition vs. the other three, those with MDD showed low activation to this condition, with the other three showing higher levels . Similarly, participants who did not use cannabis showed higher activation levels in response to the negatively vs. positively valenced conditions, while the opposite was true for cannabis users . The fact that we saw this reversal in all four conditions strongly suggests that both MDD and cannabis use affect several aspects of emotion processing. That is, we observed a change in both positive and negative, and effortful and passive emotion processing. Prior research has shown the effects of MDD and cannabis use on specific types of emotion processing, such as dysfunctional activity during active emotional reappraisal . The present results indicate that both MDD and cannabis use may have a more global effect than previously thought. Both of these effects were observed in the left temporal lobe. While these results were not predicted and are in need of replication, both theleft MTG and STG have frequently been associated with emotion processing , and have previously shown decreases in activity levels in individuals with MDD during emotion processing . Both regions are also involved in multisensory association . Given that the present stimuli were complex emotional scenes, it is possible that the interactions with MDD and cannabis use in each area reflect differences in multisensory representation. Individuals with MDD showed a reduced representation of positive stimuli during the attend condition, a difference that was eliminated with effortful emotion regulation. Thus, it is possible that individuals with MDD may be successfully augmenting positive representations, while being less successful in their attempt to regulate negative representations. In contrast, cannabis users showed an increased representation of positive stimuli and suppression of negative stimuli, and these mood-altering effects may reflect some of the participants’ motivation for ongoing cannabis use.

The difference between the observed effects, namely regulation versus representation of valence, could be why the specific area of temporal lobe differs. Finally, although both MDD and cannabis use affected emotional processing within the temporal lobe, the difference in specific regions may account for why we did not observe a threeway interaction. Although several regions of the frontal cortex showed activation differences among emotion regulation task conditions, there were no interactions with MDD or cannabis use. Models of both depression and of cannabis use predict the under-activation of frontal regions, specifically the vlPFC, dlPFC, and dmPFC. During healthy emotion regulation, we also observe suppression of these areas . Because the individuals with MDD are already experiencing suppression in these regions, it is possible that the amount of change during the emotion regulation task was not enough to appear different from non-depressed participants. We also found that higher ERQ scores, which represent a greater ability to adaptively control one’s emotions, correlated with less activity in the right frontal lobe. This was observed across all task conditions, indicating that better emotional control leads to less effortful emotion processing overall. While this may seem intuitive,mobile grow systems it may be surprising that there was no interaction with condition; for example, Greening and colleagues  found suppressed BOLD activity in individuals with MDD during negative regulation compared to healthy controls, but no difference in positive regulation. However, here, even in the ‘attend’ conditions, individuals with low ERQ scores showed more effortful processing than those with high scores. This consistency may reflect that emotion processing occurs even when passively viewing emotionally laden images . Poorer emotional regulation has been linked to MDD , and correlates with increases in activity in frontal regions when viewing emotional images . Thus, these results fit well with previous literature, and suggest that even passive emotional processing is more effortful for those with poorer regulation, which may be a neural representation of less adaptive emotion regulation strategies . The relationship in the left MTG between HAM-D and task condition in individuals with MDD was driven by the steep increase in activity in response to the ‘negative reduce’ condition with increasing score. This relationship echoes the results found when comparing individuals with and without MDD , which showed a similar increase in activity in this condition. Notably, a similar relationship was not found in the other three conditions, highlighting the fact that even within a group of persons with MDD, there are individual differences in levels of depressive symptoms that affect different aspects of emotion regulation. Finally, our emotion regulation task showed activation within the expected network of regions involved in emotion processing, specifically the left inferior parietal lobe, the left middle frontal gyrus, the right insula, and the left inferior frontal gyrus. In both the left inferior parietal lobe and left inferior frontal gyrus, the ‘negative attend’ condition had significantly lower levels of activation than the other conditions. The left middle frontal gyrus showed lower activity to negative versus positive conditions, and the insula showed increased activation in the ‘negative reduce’ condition relative to the others. All four regions have shown differential activation during viewing of emotionally negative stimuli compared to neutral stimuli , and are thought to belong to a larger network of regions involved in the initial appraisal , regulation , and the final generation of regulated emotional states. However, although the regions showing an effect of task condition were part of the well-studied emotion processing network, the areas we found to be modulated by MDD, cannabis use, or characteristics of these two factors  were outside of this network. The fact that these effects extended beyond typical emotion processing areas during the present task indicates that both MDD and cannabis use have far-reaching consequences for the brain, perhaps affecting domain-general processes .

One limitation of the present study is that our analysis of early-onset cannabis use did not identify any significant effects of age of onset, with only a main effect of condition, implying these results were similar across age groups. This was surprising, as early-onset cannabis use was previously associated with increased connectivity between the default mode network and reward-processing areas in the same sample , though the early age of onset group was defined differently. Additionally, a recent review paper reported that adolescent exposure to cannabinoids can lead to dysregulation of emotion and reward processing in rats . One possible explanation for the lack of effects in this area is the low number of participants in this analysis; only 12 individuals were considered “early” cannabis users, which may not have been a large enough sample to detect differences between early and late cannabis use. A second limitation is that we did not study the effects of comorbidity with other psychiatric illnesses. Data on comorbidities were collected and reported; as can be seen in Table S1, there was a large range of psychiatric comorbidities within the sample of individuals with MDD. Because of the large variation in the type of comorbidities observedwithin the sample, we do not have reason to believe that any one diagnosis could be driving the results observed here. However, comorbidity of MDD with other psychopathologies can impact emotion regulation and should be considered in future work. Tobacco and cannabis are among the most commonly used substances by adolescents worldwide. In 2019, 27.1% U.S. high school students and 22.3% of U.S. high school seniors reported past-30-days use of tobacco products and cannabis, respectively, with 2.4% and 6.4% of U.S. high school seniors using cigarettes and cannabis on a daily basis, respectively . Cannabis is often used in combination with combustible tobacco by young people. Approximately 14% of young adults in the U.S. report combustible tobacco and cannabis co-use within the past month .

To assess the statistical heterogeneity between studies, we used the I2 statistic, which provides an estimate of the percentage of variability due to heterogeneity rather than chance alone . The chi-squared test was used for significance testing. A visual inspection of the funnel plots was used to detect publication bias . The robustness of the conducted analyses was examined by conducting sensitivity analyses including only highquality studies. Furthermore, meta-regressions for potential moderators were planned . To our knowledge, this is the first meta-analysis of observational studies that focuses on the link between negative symptoms, cannabis and nicotine. Novel results are revealed based on a pool of more than ten thousand patients. Current non-abstinent cannabis users were not different from nonusers with regard to negative symptoms.Since nicotine was consumed by all participants in all cannabis studies, it is important to note that no association was found between nicotine use and negative symptoms. Thus, our findings support a specific effect of cannabis abstinence on negative symptoms. Regarding positive symptoms, we observed borderline significant results with a very small effect size, suggesting a possible association with current cannabis use; however, this effect became nonsignificant when including only high-quality studies. In addition, we found that nicotine users reported higher levels of positive symptoms than nonusers, a result that had a very small effect size and was essentially driven by the ‘nicotine as main drug of choice’ group. For cannabis, the overall results revealed the absence of a specific association between current cannabis use and the severity of negative symptoms. No difference was found between the subgroup using only cannabis and nicotine and the subgroup using cannabis as a main drug of choice. These findings are consistent with the meta-analysis by Large and colleagues  that also reported no significant differences between current cannabis users and nonusers. The similarity of the results is of note because there were considerable differences in the methods and included studies. Overall, we included a larger set of studies, but we restricted the included groups to patients with schizophrenia and excluded patients with broad first-episode psychosis. An earlier meta-analysis by Potvin and colleagues  also restricted the inclusion criteria to patients with schizophrenia and suggested that cannabis users would show less negative symptoms than nonusers. However, only three cannabis studies could be included in that meta-analysis, and in one study, subjects had to be abstinent for at least three weeks.

Overall, our study does not confirm Potvin and colleagues findings and shows that for patients with schizophrenia, there does not seem to be a significant difference in the severity of negative symptoms between current cannabis users and nonusers. A key finding of the present study is the observation that patients with schizophrenia and chronic cannabis use who have recently stopped using cannabis show less severe negative symptoms than patients with schizophrenia who do not use cannabis grow racks. To the best of our knowledge, this finding has not yet been reported in a meta-analysis of cross-sectional data. Some evidence comes from a meta-analysis of longitudinal studies that showed a small trend-level effect, suggesting that cannabis discontinuers show less severe negative symptoms than continuous users and nonusers . A recent poster by Ihler and colleagues reported that experiential negative symptoms related to amotivation improved after 12 months of follow-up in the group who discontinued cannabis compared to continued use . The findings for recent cannabis abstainers have to be considered with caution, because most studies had small sample size and the only large study reported a small effect size . However, the study was rated as having a high risk of bias and the low effect size in this study can be explained by less restrictive criteria for abstinence, in particular the lack of urine drug screening to verify abstinence. Importantly, all of the abovementioned results remained largely unchanged when restricting the analyses to high-quality studies. An important limitation of our results concerns the fact that it was not possible to conduct a meta-regression with the amount of cannabis used as an independent variable because only a few studies reported the grams of cannabis used per day, and only one study estimated the THC content. However, the dose dependence of cannabis effects remains of major importance and needs further evaluation with respect to negative symptoms .Our results suggest that patients with schizophrenia who use nicotine do not report different levels of negative symptoms than nonusers, with the effect size being close to zero. This finding is consistent with a recent meta-analysis by Huang and colleagues that also found no association between nicotine and negative symptoms . Here, we expand the findings by Huang et al. by using a larger sample of studies to show that this absence of an association occurs in studies including patients using nicotine only as well as in studies including patients using nicotine as a main drug of choice. The available data did not allow us to perform a meta-analysis of nicotine abstainers compared to nonsmokers. Boggs and colleagues report a small nonsignificant decrease in negative symptoms following one week of nicotine abstinence , indicating that further research is needed. Here, we report that patients with schizophrenia who current use cannabis do not differ from nonusers regarding the severity of negative symptoms. One interpretation of the absence of an association in the current users would be that cannabis simply does not exert any effects on negative symptoms. While this interpretation would not be in line with the hypothesis concerning the amotivational effects of cannabis use, it must be considered that the evidence for the negative effects of cannabis on motivation remains heterogeneous .

It may also be difficult to detect the effects of cannabis consumption on negative symptoms because patients with schizophrenia will often suffer from a combination of primary and secondary negative symptoms. Thus, the potential amotivational effects of cannabis as a secondary symptom may account for only a part of the overall negative symptomatology shown by the individual patient. Alternatively, it is conceivable that in chronic cannabis users with schizophrenia, the stimulating and blocking effects of cannabis on the reward system offset each other and result in the absence of an effect on negative symptoms . However, these considerations cannot account for the second important finding reported here, i.e., that recent cannabis abstainers show less severe negative symptoms than nonusers. This finding is consistent with the reduced susceptibility of developing negative symptoms among patients with schizophrenia who use cannabis grow system. Previous reports have suggested that cannabis-using patients with schizophrenia have better cognitive functioning than nonusers, particularly with respect to premorbid cognitive functioning . Furthermore, a recent study conducted by Mallet and colleagues has found that patients with heavy cannabis use before the onset of psychosis showed significantly less neurological soft signs, less negative symptoms and better cognitive functioning in different domains than their non-heavy user counterparts . It has therefore been hypothesized that cannabis-using patients constitute a subgroup that has lower biological vulnerability, which also results in a reduced susceptibility to developing negative symptoms. Another explanation suggests that cannabis-using patients might more easily access cannabis due to better premorbid social functioning, which could also be related to a reduced susceptibility to developing negative symptoms . Thus, cannabis-using patients with schizophrenia have less severe negative symptoms when they abstain from the drug. When using the drug, this difference may be obscured by the amotivational effects of cannabis . Importantly, the abstinence duration of at least three weeks required in the abstinence studies seems to be sufficient to alleviate the negative effects of cannabis on motivation. This timeframe is consistent with positron emission tomography studies in healthy cannabis users that show reduced dopamine release in the associative striatum in current users . Interestingly, in earlier studies with the same minimum duration of abstinence as in our abstainer studies, dopamine release in the striatum was not different from nonusing controls . Therefore, the time period of abstinence required in our recent abstainer group is consistent the normalization of dopamine release in the striatum.

We found a borderline significant association of current cannabis use with positive symptoms without significant subgroup differences between cannabis and nicotine groups and cannabis as the main drug of choice groups. However, the effect size was very small and might be of questionable clinical significance. These results differ to some extent from those reported by Large and colleagues, who found a medium effect size for the association of current cannabis use with positive symptoms . Several differences between the two meta-analyses must be noted. First, we included a larger number of studies than Large, but we did not include studies with patients experiencing broad first-episode psychosis, which may lead to stronger effects of cannabis on positive symptoms. Second, in the first-episode studies included in the Large meta-analysis, not all patients were receiving antipsychotics. The fact that we were focusing on stabilized populations treated with antipsychotic medication might have led to a weaker association of cannabis with positive symptoms. Third, our analysis allowed us to differentiate the groups ‘cannabis and nicotine’ from cannabis as the main drug of choice, but this differentiation did not have an impact on effect size. Furthermore, we were able to specifically address the recent cannabis abstainer group. In contrast to the findings for negative symptoms, this group did not significantly differ from the nonuser group. Overall, our results show only a very limited cross-sectional association between cannabis use and positive symptoms. Our results show that overall nicotine use is associated with more severe positive symptoms, although the effect size was very small. In the subgroup analysis, the effect was significant only for the ‘nicotine as a main drug of choice’ group. Importantly, this subgroup effect remained significant when considering only high-quality studies, while the overall effect became nonsignificant. Huang and colleagues reported a somewhat larger effect size for the association of nicotine use with positive symptoms . Our meta-analysis included a larger number of important studies and allowed a clear distinction of ‘nicotine only’ and ‘nicotine as a main drug of choice’ subgroups. Our subgroup analysis suggests that the observed association with positive symptoms might be more strongly related to the concomitant use of other drugs along with nicotine. However, we cannot exclude the possibility that nicotine use alone could increase the severity of positive symptoms to some extent. Our results only suggest a very limited cross-sectional association of continued cannabis use with positive symptoms. The acute psychosisinducing effects of THC have been well documented and seem to at least be partially related to increased dopamine release in the striatum . However, the long-term effects seem to depend on a large number of parameters, including the duration and intensity of the exposition as well as the proportion of THC and cannabidiol .

Our data suggest that the effects of ongoing cannabis consumption are to some extent offset by ongoing antipsychotic drug treatment. Although our data provide little evidence for a specific association of nicotine use with positive symptoms, it has to be noted that there is some evidence that psychotic-like experience have been associated with the smokers’ status in the general population after adjustment for confounding factors . Moreover nicotine has been suggested to increase positive symptoms via increased dopamine release and the increased metabolism of antipsychotic drugs . There was a small but highly significant association in the nicotine as the main drug of choice group. A mechanistic interpretation of the finding is difficult because substance use in this subgroup was very heterogeneous across the different studies. The main limitation of our meta-analysis is the nature of the included studies, which employed heterogeneous methods. It should be noted that the number of patients included was much higher in the nicotine groups than for the cannabis groups. Therefore, future studies with large sample size could change the results for cannabis users and recent abstainers. Nevertheless, this is the largest meta-analysis on the topic so far, and we were able to conduct sensitivity analyses including only high-quality studies that confirmed the main findings. Several limitations concern the case and control definition, such as differences in population, inclusion criteria and methodology across the included studies.

Catatonia may also present as part of a primary psychotic disorder, general medical condition, or relating to substance abuse.This case describes a catatonic state associated with psychosis and mania postulated to be induced by vaping cannabis oil. We acknowledge that it is difficult torule out an underlying BPD in this case and that his cannabis use could have induced a mood episode or was simply incidental to the presentation, especially given that catatonia is seen most commonly in BPD mood episodes. In addition, it is more likely for patients experiencing a manic episode to engage in risky behavior such as substance use, and the patient may not have noticed the onset of mania when he began to engage in cannabis use. However, we still fifind his case to be compelling in that he never experienced psychosis, mania, or catatonia outside of episodes of high-potency THC use, which the patient reported preceded the start of his acute psychiatric symptoms. In addition, it is atypical for a patient with BPD to have never experienced a depressive episode or not have a family history of mood disorders. Ultimately, it would be difficult to diagnose BPD in this patient unless he has future mood episodes in the absence of precipitating substance use. There were no general medical conditions found that we could contribute to the development of catatonia. He also had no residual symptoms of psychosis that would be expected of a primary psychotic disorder in the periods between his two admissions. Lastly, the patient denied that he had used any illicit substances other than cannabis before either hospital admission that could have contributed to the development of catatonia. Regarding cases of cannabis-induced catatonia, the literature draws from scattered case reports only. One case was found involving a 17-year-old patient with cannabis dependence and catatonia who eventually was diagnosed with schizophrenia.11 Another case published in 2011 touts itself as the “only report of cannabis-induced catatonia” found at that time in the literature. This case involved a 30-year-old patient with increased use of pot for growing marijuana for three weeks before admission for catatonia. This patient had a history of five prior episodes of catatonia with no interepisode psychiatric symptoms, several of which were associated with increased cannabis use.

Catatonia has also been associated with abrupt withdrawal of heavy cannabis use in one case report. In this case, a 32- year-old man who reportedly smoked approximately 20 g of cannabis daily for many years was incarcerated. Three weeks later, he was admitted for catatonia after he had ceased talking and eating and had a Bush-Francis catatonia rating scale score of 30. He required six weeks of treatment before his symptoms fully resolved.13 Although cannabis use is common in patients with BPD, the association between cannabis use and bipolar symptomology remains equivocal. This is also a point of interest given that individuals with BPD have increased rates of cannabis use compared with patients with other psychiatric disorders and the general population. Cannabis use disorder prevalence is also higher in patients with BPD, specifically 7.2% in patients with BPD compared with 1.2% in the general population.14 Authors of a 2018 review on cannabis use and mood disorders concluded that there is moderate evidence to support earlier onset and increased exacerbations of BPD symptoms in patients with problematic cannabis use.15 However, a more recent review from 2020 concluded that some studies found a significant association between cannabis use and BPD onset and progression, whereas other studies did not, highlighting the need for more longitudinal research in this area.16 While the general body of literature regarding the effects of high potency cannabis remains limited, we do have a possible model in the form of synthetic cannabinoids . One recent case report links the use of SCs to the development of catatonia in two patients.17 Similar to our patient, these two patients also experienced psychosis and related catatonic symptoms. These compounds, commonly called K2 or spice, bind as full agonists to CB1 and CB2 and elicit cannabimimetic effects similar to those of THC. However, SCs have been shown to bind to cannabinoid receptors with potencies 2–100 times greater than traditional herbal cannabinoids and are associated with greater risks of adverse psychiatric symptoms such as agitation and psychosis.

Moreover, SCs do not contain any psychoprotective CBD, which is also similar to high-potency THC products. One could postulate that despite the difference in binding potentials, receptor saturation through high-potency herbal THC products may result in similar symptoms experienced with SCs. It would follow that higher rates of psychosis and catatonia seen in SC users may also be seen in those vaping highpotency cannabis oil.Our review of published literature found five case reports  of hospitalizations associated with cannabis oil vaping. Of particular interest, one patient also developed catatonia and was treated with lorazepam similar to our case. However, this patient had been administered antipsychotics, which itself can be a risk factor for the development of catatonia. Four cases reported prominent symptoms of psychosis, includingcommand auditory hallucinations, persecutory and paranoid delusions, incoherent speech, and poor selfcare. In four of the cases, clinicians attempted treatment with risperidone. Interestingly, two cases reported cardiotoxicity with diaphoresis, hypertension, and tachycardia. In one case, the patient required sedation becuase of seizures. Psychiatric disorders are cited as one of the most common reasons for using medicinal cannabinoids. However, a recent systematic review and meta-analysis found that there is insuffificient evidence to suggest that cannabinoids improve depression, anxiety, or psychosis. In fact, it is well established that cannabis use, especially of products with highly concentrated THC, increases the likelihood of developing psychotic disorders in individuals at risk and predicts higher psychosis relapse rates.A recently published large multicenter case-control study of patients with first-episode psychosis found that the greatest risk factors for psychosis were daily use of cannabis and use of high-potency cannabis .

The odds of developing psychosis among daily low-potency cannabis users  were 2.2 times higher than for never users. The odds of psychosis among users of daily high-potency cannabis users were 4.8 times higher than for never users. Assuming cannabis use caused these patients’ psychosis, the study investigators estimated that 20% of new cases of psychotic disorders could have been prevented if daily cannabis use were abolished.24 Furthermore, there is ample evidence that initiation of cannabis use in adolescence is associated in a dose-dependent fashion with the emergence andseverity of psychotic symptoms. Those adolescents who initiate use earlier and use at higher frequencies show more significant symptoms of psychosis and poorer treatment outcomes. These associations are more robust for those patients with a strong family history of psychotic disorders.25 One concern highlighted extensively by the media is the rise in vaping-related lung injuries. National and state data from patient reports and product sample testing show THC-containing e-cigarette or vaping products are linked to most e-cigarette or vaping product use– associated lung injury cases. As of February 4, 2020, a total of 2758 hospitalized e-cigarette or vaping product use–associated lung injury cases and 64 deaths had been reported to the US Centers for Disease Control and Prevention. Among these cases reported to the Centers for Disease Control and Prevention , 82% reported using THC-containing products with 33% using THC-containing products exclusively. Of these cases, 52% were younger than the age of 24 years.Owing to this large rise in vaping product use among adolescents,container for growing weed the US Food and Drug Administration  issued an enforcement policy in January 2020, which prohibits the production, distribution, and sale of all flflavored cartridge-based e-cigarettes with the exception of menthol and tobacco flflavors. In accordance with the FDA, the change is an attempt to limit the alarming rise in the use of e-cigarettes by teens, who overwhelmingly prefer flflavors. However, to date, the FDA’s efforts to improve the safety of vaping devices has focused only on the regulation of nicotine vaping products.

Our case raises concerns about the potential for increased psychiatric toxicity from vaping highly concentrated THC products. Numerous studies continue to show the relationship between cannabis use and the development of psychosis; however, there is currently no clear relationship between the onset and progression of BPD owing to cannabis use or the development of catatonia. Based on our case, one could hypothesize that the use of highly concentrated THC products could result not only in psychosis but also episodes of mania and catatonia that may have not been seen in the past when lower-potency THC use was more the norm. High-potency cannabis use may result in more severe psychiatric side effects, similar to SCs in which several cases of catatonia have been documented. There is currently no available research to guide the public about what level of THC is benefificial for any medical condition or what level may result in medical and psychiatric toxicity, though it is apparent that daily use and high-potency THC use  result in higher psychosis risk.This is alarming in light of recent data showing increasing numbers of adolescents and adults initiating and using cannabis products daily.8 The vaping of concentrated cannabis oils is also growing, especially among adolescents, further increasing exposure to high-potency THC. Current evidence suggests that this trend will likely lead to more cases of psychosis and need for acute psychiatric treatment.4 More education about these risks should be made available to the public and legislators should consider regulations to limit the concentrations of THC and types of cannabis products offered in dispensaries until more research is available regarding their safety. Our case also highlights the need for more research into the potential medical and psychiatric complications from the use of newer, highly concentrated THC products. More attention should also be given to the possible negative medical consequences of vaping THC products such as e-cigarette or vaping product use– associated lung injury. We propose based on our case that high-potency cannabis products may have signififi- cantly more psychiatric toxicity than traditional lower potency products, and future research should be aimed at clarifying this potential association.Modern civilization has extensive utilization of multiple pharmaceutical drugs such as Non-steroidal anti-inflflammatory drugs  for the reprieve of pain, as analgesics and antipyretics, sex hormones, antiepileptic , blood lipid-lowering and b-blocker agents.

NSAIDs are the class of drugs that are used more abundantly because these are over the counter drugs and can be easily purchased from the market without specific prescription. More common drugs in this class are acetylsalicylic acid, paracetamol, ibuprofen, naproxen and diclofenac.Moreover, many common pharmaceuticals are available with extensive utilization in medical care having paracetamol as a base ingredient and are used with different formulations and considered safe, except for high dosage. The structural formula is given in Scheme 1. As the use of these drugs is unavoidable and these pharmaceutical compounds are excreted in urine and other biological wastes as active metabolites, either directly or indirectly, in high fractions. These wastes are constantly being discharged into municipal wastewaters which results in contaminated aquatic surroundings, surface and ground waters, and finally into the drinking water supplies. Despite their very low concentrations, these are hazardous for human beings especially for infants, and cannot be removed employing conventional water treatment techniques such as chlorination. Advanced oxidations, reverse and forward osmosis can be used to remove these contaminants but these processes are expensive; hence, large scale application for municipal water treatment is uneconomical. Up to now, membrane fifiltration, UV-degradation, ultrasonic degradation and electrochemical degradation are the reported processes for the removal of NSAIDs from surface or drinking water. The combination of catalytic decomposition along with ultrasonic degradation was studied by Soltani et al.,.Results elucidated that the dispersion of stonewaste  improved the pore volume and specific surface area of ZnO catalyst which significantly improved the paracetamol degradation effificiency up to 98.1%. Mirzaee et al., investigated the electrochemical decomposition of paracetamol in an ultrasound environment. Using Iron anode improved the degradation potential of the modified hybrid process  as compared to individual processes.

Most respondents had either a university degree or a trade/vocational certificate  and were engaged in either full time or part time employment . The most frequently reported primary condition being treated with cannabis was pain , followed by mental health conditions  and sleep-related conditions . Inhalation  was the most common route of administration . Only a small number of respondents  accessed legal medical cannabis with a prescription, with most respondents sourcing their medical cannabis from an illicit dealer , from friends or family  or by growing their own . With regard to the type of cannabis  mainly used, 21.5% reported THC-dominant or THC only, 18% reported approximately equal amounts of THC and CBD, 12.5% reported CBD-dominant or CBD only, and 48% indicated that it varied between batches or that they did not know. The mean  duration of time until respondents felt no effect after using medical cannabis was 219  min , 253  min , 294  min  and 210  min . Fig. 1 shows responses to several statements regarding driving related behaviours. Most respondents  agreed or strongly agreed that they felt confident in their capacity to accurately assess their driving ability after consuming medical cannabis. A similar percentage  agreed or strongly agreed that their medical cannabis use does not impair their driving. A majority  felt they tended to drive more carefully following use of medical cannabis and most denied that cannabis affected reaction time, focus, speeding, drifting out of lane or risk taking. Just under half  agreed or strongly agreed that they tended to leave a larger gap between them and the car ahead after using medical cannabis. There was less certainty from respondents around whether they felt more in control of their vehicle . Fig. 2a shows the duration of time that respondents typically wait before driving after using medical cannabis relative to primary route of administration. Overall, more than a third of respondents  reported driving within 3 hours of using medical cannabis; 11.9% waited 4-6 hours and 25.9% waited 7-12 hours, while 27.5% waited at least 12 hours. Fig. 2b shows the length of time until respondents feel no effects after using medical cannabis. Most said 1-3 hours ; 27.8% said 4-6 hours while 8.8% said 4-6 hours and 0.9% said 13-24 hours.

Patients using oral products tended to report a longer duration of action when compared with smoked or vaporized cannabis. From the above, most respondents  were estimated to be unlikely to drive while under the influence of cannabis; this proportion was slightly higher for inhaled routes of administration  than for oral routes . This proportion was also higher for THC-dominant products  and THC/CBD-equivalent products  than for CBD-dominant products . Only a minority of respondents had been subjected to roadside drug testing , with very few respondents having ever been convicted of DUIC . Most respondents  indicated that the presence of roadside drug testing deterred them from driving after using medical cannabis. Table 2 shows the results of two binary logistic regression models that assessed the relationship between respondent characteristics and DUIC behaviours. In the first model, there was a strong association between frequency of cannabis use  and respondents’ belief in whether medical cannabis impairs their driving. Specifically,trimming tray respondents were 3.1% more likely to think that their cannabis use does not impair their driving for each additional day of cannabis use . Respondents’ confidence in their capacity to assess their own driving ability after using medical cannabis was strongly related to their belief in whether medical cannabis impairs their driving, with those who were confident  being far more likely than those who were not confident  to report that their medical cannabis use does not impair their driving . Respondents who were not deterred by the presence of roadside drug testing were also more likely to think that cannabis does not impair their driving  In the second model, estimated likelihood of DUIC was strongly associated with employment status, with those who unemployed being significantly more likely to engage in DUIC relative to those who were engaged in full time or part time work . Frequency of use was also related to likelihood of meeting criteria for DUIC, with a 2.7% increase in odds for each additional day of cannabis use . There was a marginal decrease in DUIC likelihood for each percentage increase in proportion of total cannabis use that was medical . Respondents who were confident they could accurately assess their driving ability were far more likely to engage in DUIC  than those who were not confident. Respondents who were not deterred by the presence of roadside drug testing were almost 3 times as likely to engage in DUIC relative to those who were deterred .The present study was designed to assess driving-related behaviours and attitudes among a convenience sample of Australian medical cannabis users recruited as part of our larger CAMS-18 survey. The term ‘medical cannabis’ was used to refer to any use of a cannabinoid product to treat or alleviate symptoms arising from a self-reported medical condition. These were in some ways an unusual medical cannabis patient group by international standards: the relatively slow roll out of official legal medical cannabis in Australia meant that the vast majority of respondents were still self-medicating with illegal products using inhaled routes of administration.

This user profile is likely to change as the official access scheme, which is dominated by orally delivered THC and CBD containing products, converts more patients from illegal to legal access. A key finding of the current study is that a substantial proportion of medical cannabis users are driving shortly after using cannabis, with some driving during the time of peak effects when impairment tends to be greatest. More than 19.0% of users reporting driving within one hour of consuming cannabis and 34.6% of all users within 3 hours of use . By comparison, 56.4% of medical cannabis users in Michigan with chronic pain drove within 2 hours of consuming cannabis. In other surveys, 9.3% of older drivers in Colorado reported driving within one hour of cannabis use, and 13.2% of Canadian non-medical cannabis users reported driving within two hours of use. While it is important to note that most respondents in the present survey reported waiting at least 7 hours before driving, with 25.9% waiting 7-12 hours, and 27.5% waiting at least 12 hours, the relatively high incidence of driving shortly after using cannabis is concerning. This suggests a need for public information campaigns that educate medical cannabis users around the risks associated with DUIC. Existing public health guidelines, such as Canada’s Lower Risk Cannabis Use Guidelines , recommend that medical cannabis patients wait at least 6 hours before driving after using cannabis. However, as other jurisdictions consider establishing similar guidelines, it is important to consider that the duration and magnitude of cannabis effects may vary with factors such as gender, body mass and consumption of alcohol and may in some cases exceed 6 hours. For example, alcohol and cannabis produce additive effects that may exacerbate and prolong driving impairment. Conversely, the magnitude and duration of cannabis effects may be decreased with increased frequency of cannabis use, most likely due to tolerance, and with use of CBD-dominant or low THC products. Further research is needed to elucidate the extent to which these factors impact the driving impairment produced by cannabis and to guide public policy in this area. It is somewhat surprising that more than 1 in 3 respondents drove within 3 hours of cannabis use given that Australia is one of the few jurisdictions in the world to have extensive, random roadside drug testing for THC in oral fluid. In our recent study, most participants tested positive for oral fluid THC at 10 min after vaporization of cannabis containing predominantly THC or equivalent amounts of THC and CBD, with some testing positive at 3 hours . Despite the relatively high prevalence of driving shortly after cannabis use, a large proportion of respondents  did say that the presence of roadside drug testing deterred them from driving after using medical cannabis. Only a small minority of the overall cohort  had been subjected to such testing at the time of the survey, however, with an even smaller proportion  indicating they had ever been convicted of DUIC. It is interesting to note that those who were not deterred from driving after using cannabis by the presence of roadside drug testing were more likely to think that cannabis does not impair their driving and more likely to engage in DUIC. The finding that 71.9% of respondents felt that their medical cannabis use does not impair their driving is consistent with previous reports showing that cannabis users tend to perceive DUIC as relatively low risk, especially when compared with alcohol . This may support the idea that cannabis users tend to show a comparative optimism bias toward thinking that that their own driving is less impaired and their accident risk lower after using cannabis relative to other cannabis users .

Indeed, in a random survey of weekend night-time drivers in California, only 1 out of 21 drivers who reported using cannabis in the past 2 hours and tested positive for THC agreed that they had taken a drug that impaired their driving. Most respondents in the current study reported that they drive more carefully and take fewer risks after consuming cannabis. Respondents did not agree that cannabis impaired their focus, reaction time or ability to stick to the speed limit. While experimental studies with non-medical cannabis users often find that respondents drive more slowly and leave a larger gap to the vehicle ahead after consuming cannabis, less than half of respondents in the present study said they tended to leave larger gap between them and the car ahead. Similarly, while studies with healthy volunteers show that cannabis can impair lateral control and increase lane weaving, particularly in the first hour and up to 3.5 hours after vaporising or smoking cannabis, most respondents denied drifting out of their lane more frequently after using medical cannabis. It is unclear whether these disparities reflect a high degree of tolerance among respondents in the present study or a lack of awareness of actual driving impairment. Logistic regression showed that respondents who were confident they could assess their driving ability after using medical cannabis were far more likely to deny impairment and to engage in DUIC relative to those who were not confident, irrespective of age or gender. Some evidence shows a poor relation between perceived and actual driving ability in both older and younger drivers and in occasional cannabis users, implying that over-confidence in driving ability after using cannabis grow racks is likely to be a risk factor for DUIC behaviours. Employment status was also strongly related to estimated likelihood of DUIC, with respondents who were unemployed being more than four times as likely to engage in DUIC relative to those who were employed.

While this may reflect greater daytime use of cannabis in this population which in turn may be due to the severity of the underlying condition for which medical cannabis is being used, it is important to note that only a small proportion of respondents  were unemployed. This possible explanation should therefore be treated with caution. Frequency of cannabis use was also strongly related to likelihood of DUIC; while the increase in odds was relatively small, a recent study likewise found that frequency of cannabis use was positively associated with the incidence of DUIC, as was the level of intoxication that respondents deemed safe for driving. This is perhaps unsurprising, as those individuals who are using cannabis more frequently  will be inherently more likely to drive when having recently using cannabis. Despite the growing use of cannabis for medical purposes, there have been no studies to date that have investigated the acute and/or chronic effects of medical cannabis use on driving. In a recent review, Celius et al. found that most patients with multiple sclerosis-related spasticity who were being treated with nabiximols actually showed an improvement in driving ability, most likely due to a reduction in spasticity and/or improved cognitive function. This finding lends support to the idea that treating medical conditions that might otherwise impair driving  with medical cannabis could conceivably have a positive, or at least neutral, effect on driving performance.

Given the similar chemical composition to tobacco smoke, the negative health effects of marijuana smoke exposure may be similar. Pediatricians are encouraged to ask about and counsel parents about tobacco use, with one goal of decreasing secondhand smoke exposure in children. In our cohort, 11% of caregivers admitted to regularly smoking or vaping marijuana, yet only a small percentage of marijuana-using caregivers  had been asked by their child’s pediatrician about marijuana use. The results of this study suggests health care providers are not starting the conversation or engaging caregivers about marijuana smoking, and the consequent secondhand smoke exposure for children. A potential limitation of the study is the under-reporting of substance use given the nature of a survey study. Many of our respondents  did not indicate any substance use, while this number may actually be lower. However, even if tobacco or marijuana-using caregivers did not accurately indicate their use, the overall impact on the results is likely very low. Another potential limitation is the single geographic location from which the study population was derived. The results may not beindicative of marijuana users and/or pediatricians across the country. Given the study population residing in a state with legalized marijuana use, it is reasonable to assume the pediatricians in this state are more likely than others to be familiar with marijuana use among parents and more comfortable with asking about marijuana.We did not measure biochemical validation in the children, which would have provided a precise measure of tobacco smoke exposure or marijuana smoke exposure. Prior studies have evaluated tobacco exposure in children by proxy of parental report, and we used a similar method. In the state where we conducted the survey, recreational use of marijuana is legal, yet it remains illegal to use marijuana on public property, raising the likelihood of caregivers using marijuana on their private property.

The survey did not ask the participants to clarify the exact location of use. Medical marijuana  has attracted a great deal of attention as an adjunct to conventional pharmacologic approaches to symptom management for patients with cancer. Gynecologic cancer patients commonly experience nausea, vomiting, pain, anorexia, and fatigue related to cancer-directed therapy or to their cancer itself, that may be treated with MM or synthetic cannabinoids. A meta-analysis by Whiting et al found a trend towards benefit for cannabinoids compared to either placebo or anti-emetics for nausea and vomiting due to chemotherapy, but no statistically significant improvement across studies . In the United States, both dronabinol and nabilone are FDA-approved for the treatment of chemotherapy-induced nausea/vomiting that has not responded to conventional antiemetics. Several small randomized trials have compared dronabinol or nabilone in combination with or versus standard anti-emetics in preventing chemotherapy-induced nausea/vomiting . Dronabinol was found to be equivalent to ondansetron with no benefit for combined therapy . The National Comprehensive Cancer Network includes dronabinol and nabilone as therapeutic options for breakthrough nausea/vomiting . The American Society of Clinical Oncology considers the evidence insufficient to recommend cannabis grow equipment for prevention of nausea/ vomiting or as an alternative to dronabinol and nabilone for chemotherapy-induced nausea/vomiting . There is limited evidence regarding the effectiveness of MM or synthetic cannabinoids for pain management compared to multimodality symptom management with conventional medications. In cancer patients with inadequately controlled pain on opioids, the addition of THC: CBD containing compounds and nabiximols improves pain scores compared to placebo in some, but not all studies . In preclinical and pilot studies investigating the modulation of the cannabinoid pathway for the treatment of cancer-associated neuropathic pain, preliminary data suggest a benefit . Improved pain control, however, may come at the cost of side effects associated with cannabinoids, including somnolence, dizziness, confusion, and nausea . Medical marijuana use is common among patients with cancer. Among respondents to the U.S. National Health and Nutrition Examination Survey between 2005 and 2014 with cancer, 40% had used marijuana within the past year and the likelihood of marijuana use increased over time . Among 290 gynecologic cancer patients in California and Colorado surveyed by Blake et al, 27% reported using cannabis products following their diagnosis and an additional 36% were interested in doing so if facilitated by their treating physician . A survey of 36 patients in Connecticut with gynecologic cancer who were prescribed MM found 83% experienced relief of at least one cancer or treatment-related symptom . As of November 10, 2020, 40 states and territories have approved medical marijuana/cannabis programs .

Medical marijuana was legalized for patients with cancer and other serious medical conditions in New York in 2016; New Jersey legalized cannabis for recreational use in 2020. Gynecologic cancer patients commonly report nausea, vomitinand pain associated with both thei cancer itself and cancer-directed treatments. The Society of Gynecologic Oncology recently published a clinical practice statement summarizing the evidence for MM for chemotherapy-induced nausea/vomiting, prevention of neuropathy secondary to taxanes, and cancer-related pain . Despite this guidance, relatively little is known about the utilization and efficacy of MM in this population. We evaluated the effect of MM for symptom management in gynecologic cancer patients at our institution. Women with gynecologic cancer who used MM between May 2016 and February 2019 were identified through our institution’s electronic medical record. Medical marijuana was prescribed by one gynecologic oncologist at our institution  or an authorized palliative care physician. Clinicopathologic and demographic data, including age, race/ ethnicity, insurance status, cancer diagnosis, and treatment information were collected. Detailed information regarding dosage form, including the ratio of THC to CBD, quantity prescribed, self-reported usage, and length of treatment were collected from the electronic medical record. Prior to MM prescription, patients were asked what symptoms they hoped to alleviate with cannabinoids. Follow-up questions to assess efficacy and tolerance in clinic were routinely implemented with the use of a standardized EPIC smart phase after starting MM. This queried if patients had used MM, how long they used it for, efficacy for specific symptoms, and any side effects experienced. For patients where information on efficacy and tolerance was not obtained, follow-up data was not considered to be available. This study was approved by the institutional review board at our institution and the requirement for obtaining informed consent was waived. Descriptive statistics were calculated. Categorical variables were compared using Fisher’s exact test and a p-value of <0.05 was considered statistically significant. From May 2016 to February 2019, 45 gynecologic cancer patients at our institution were prescribed MM. Table 1 shows the baseline clinicopathologic and demographic characteristics of the study cohort. Patients were a median of 60 years old  when MM was first prescribed. The majority of patients  were non-Hispanic White; 9% each were non-Hispanic Black or Asian, and 7% of patients were Hispanic and White. Just over half of patients  had Medicare insurance, with 33% insured privately and 16% insured by Medicaid. Those with ovarian, fallopian tube, or primary peritoneal cancer  made up the majority of the patient population, with the remainder split between cervical and uterine cancer. Almost all patients  were receiving chemotherapy when prescribed MM and just over half were undergoing primary treatment . There was significant heterogeneity in the formulation and THC:CBD ratio prescribed, as shown in Table 2.

The majority of patients  were prescribed formulations with a 1:1 THC:CBD ratio, but this data was missing for almost a quarter of patients. Administration route also varied: while inhaled and sublingual formulations were most commonly prescribed , free form, edible, and oil preparations were also utilized. Many patients were prescribed more than one formulation, either initially, or following a trial period of another formulation. Among 41 patients with follow-up information available, MM was used for a median of 5.2  months. The most common indications for MM in patients were: pain, 25 ; nausea/vomiting, 21 ; anorexia, 15 ; and insomnia, 12 . Fig. 1 illustrates commonly prescribed indications and self-reported effectiveness by symptom. More than 70% of patients reported that use of marijuanaimproved nausea/vomiting, while only 36% of patients using MM for pain reported symptom improvement . Among the 41 patients with follow-up information, 29  reported medical marijuana improved at least one symptom. The most common reasons for discontinuation were death from disease progression  and no improvement in symptoms . Only one patient specifically cited side effects  as a reason for stopping use of MM. Other reported side effects included: euphoria, dizziness, feeling ‘high’, nausea, headache, and fatigue. Four patients were still using MM at the time of last follow-up. The reason for discontinuation was missing for 17 patients . Among gynecologic cancer patients prescribed MM for symptom management, follow-up indicated symptom relief for the majority of patients and minimal therapy-related side effects. Almost 90% of patients were receiving chemotherapy when first prescribed MM, most of whom were undergoing primary treatment. Patients used MM for a median of almost six months, vertical grow system with significant variation in length of use; some patients had continued to use it for more than two years at time of last follow-up. Although MM use is legal in a majority of states and commonly utilized by cancer patients, few oncology providers feel comfortable prescribing it. Braun and colleagues surveyed a nationally representative population of medical oncologists; only 29% felt sufficiently knowledgeable to prescribe MM. Of providers surveyed, 56% recommended MM to their patients . A follow-up survey by Braun and colleagues found the most perceived benefit for patients at the end of life  compared to those with early stage disease  and cancer survivors. Given the prevalence of MM use among cancer patients, improved education of both patients and providers may help increase its utilization for symptom management throughout the disease continuum. This data provides one of the initial reports of the symptom relief profile of MM among patients on cancer-directed therapy in women with gynecologic malignancy. In this limited cohort of gynecologic oncology patients, MM was effective for the relief of nausea/vomiting, anorexia, and insomnia in a majority of patients but was less helpful for pain management. This is consistent with the findings of Webster et al, where the majority of patients reported symptom relief with medical cannabis use, but details were not provided on efficacy for specific symptoms.

Patients were not, however, queried on the adjunctive use of other medications or interventions for cancer-associated symptoms while using MM. Although patients reported MM provided symptom relief, this could have been affected by recall bias and we did not assess for the relative efficacy of any other approaches  compared to MM. Patients were also not queried on the specific type or location of pain they hoped to improve with MM use. Additionally, there was no standardized collection of the type and frequency with which other pain medications were used concurrent with MM. The use of cannabis products as an adjunct has been shown to improve pain control in patients with severe cancer-associated pain, but has not been associated with a decrease in opioid use . While there is preclinical data and studies in other diseases associated with neuropathic pain , we did not specifically query patients on the use of MM for the prevention or treatment of taxane-induced neuropathy. The heterogeneity of preparations and administration methods prescribed, with many patients being prescribed more than one formulation, limits our ability to comment on the effectiveness of specific THC: CBD ratios or preparations for specific symptoms. For patients prescribed more than one formulation, we did not assess whether or not they were used simultaneously or query why an alternate preparation was not effective. We also did not explicitly exclude patients who used marijuana recreationally. Larger, prospective, and more standardized studies in gynecologic cancer patients will hopefully provide further clarity on this question. Prior studies have found that many of the undesirable side effects of MM are related to high amounts of THC and optimizing the ratio between THC and CBD may maximize symptom relief while minimizing side effects . Among a small cohort of gynecologic cancer patients prescribed MM for symptom management, the majority reported improvement in at least one disease or treatment-related symptom and reported minimal side effects.

The psychoactive drug use was measured using a blunt measure, which asked the participants if they had used any psychoactive drug in the past year and this might have hindered the detection of an association with RTIs. Additionally, this study may lack the statistical power to detect a potential association between marijuana use and RTIs, considering confounders. In spite of these limitations, the strength of our study lies in the ability to use population-based controls rather than hospitalbased controls. Population-based controls are preferred due to their representativeness of the source population as compared with control selected from hospital- which may share similar essential exposures with cases and hence leading to overmatching . Additionally, we have used a validated AUDIT questionnaire, which has been pre-tested in Tanzania among trauma patients and has shown an acceptable validity and reliability . Face-to-face structured questionnaire were used in data collection, which provides an advantage of making clarifications of difficult questions if needed and ideal in population with low literacy. A further strength is that our study was able to adjust for risky driving behaviour as well as important workrelated factors, which has been shown to be common among commercial motorcyclists . Based on individual-level self-concept theory  and previous research , identification as a substance user is a risk factor for deleterious substance use. A drinking/marijuana identity, for example, reflects the extent to which alcohol/marijuana use is an integral part of how one sees one’s self. Identity is viewed in the current study from the perspective of one’s personal identity which emphasizes aspects of the selfthat are independent of group or role identities .

Less clearly understood are factors that might mediate the relationship between identity and alcohol/marijuana-related outcomes . Given that past research has examined protective behavioral strategies  and their use as a harm reduction strategy with PBS defined as “strategies employed before, during, or after drinking [or marijuana use] that reduce alcohol [marijuana] use, intoxication, and/or alcohol [marijuana] related harm”.PBS more broadly may be a mediator of the relationship between identity and outcomes. The current study focuses on the extent that PBS mediate the relationship between drinking/marijuana identity and alcohol/marijuana-related outcomes. Research indicates that drinking identity is positively associated with past-month alcohol frequency , typical quantity , and alcohol-related consequences . Studies have evaluated and confirmed a similar relationship between identity and alcohol-related outcomes in more diverse populations . Studies have also reported that marijuana identity is positively associated with marijuana use-related outcomes .Elucidating mediators of the identity-outcome association has the potential to identify factors that could be targeted in future interventions. Alcohol PBS have generally been negatively associated with alcoholrelated outcomes . Further, specific alcohol PBS  have been found to be negatively associated with quantity  and consequences . With respect to cannabis grow system, marijuana PBS have generally been found to be negatively associated with marijuana frequency , quantity  and consequences . Less well understood is whether an association between identity and PBS exists, as well as whether PBS are a mediator of identity-outcome association in college student and community-based samples. Individuals may be using PBS in order to maximize the perceived benefits of substance use  while also mitigating the risk associated with substance use . However, individuals with a high level of drinking/marijuana identity may be less inclined to use strategies that would limit their engagement in identity-consistent behavior. Therefore, identity may be negatively associated with PBS. In terms of clinical implications of the examination of PBS as a mediator of the identity-outcome relationship, identity-based and PBS-based interventions that attempt to decrease an individual’s level of drinking/marijuana identification or increase an individual’s use of PBS may help to reduce/attenuate the identity-outcome association.

In the current study, PBS were hypothesized to mediate the relationship between drinking/marijuana identity and alcohol/marijuana-related outcomes . In the cross-sectional studies, PBS were found to mediate the relationship between identity and outcomes. With respect to alcohol, mediation findings were limited to MOD PBS and specific to two  alcohol-related outcomes  evaluated. In the longitudinal study, across the three models, limited support for PBS as mediator was observed. With respect to marijuana, marijuana PBS were found to mediate the relationship between marijuana identity and all three of the marijuana-related outcomes evaluated . These findings represent an important scientific contribution to the existing substance use identity and PBS literature because they support the existence of a relationship between identity and PBS, a relationship that could be targeted in prevention/intervention work. First, to our knowledge, no published studies have reported on the relationship between drinking identity and alcohol PBS. In the current study, drinking identity was consistently found to be negatively associated with MOD PBS, followed to a lesser extent by LSD PBS and SHR PBS. In addition, drinking identity was found to be predictive of change in MOD and SHR PBS although the change in PBS from baseline to 3- months in Study 1 was not found to be statistically significant . Second, similar to past PBS mediation investigations, MOD PBS was a statistically significant mediator. For example, MOD PBS have been found to mediate the relationship between college-related alcohol beliefs and alcohol-related outcomes , preparty-specific motives and event-level preparty drinking , and in the current study, drinking identity and alcohol-related outcomes. MOD PBS include drinking slowly and the avoidance of drinking games, shots of liquor, and mixing different types of alcohol. Although speculative, research indicates that individuals drink to have a good time with friends , and individuals with a higher level identification as a drinker may be reluctant to use MOD PBS because these strategies may reduce engagement in activities  that facilitate having a good time. Another explanation for the MOD PBS mediation findings is that an individual whose identity is strongly linked with using alcohol may be less inclined to use MOD PBS because these strategies may limit the ability to convey important identity-related information to others when drinking . Taken together, these findings indicate that an individual with a high level of drinking identity is likely to not use strategies that limit participation in drinking games or the consumption of shots and that the lack of use of these strategies may lead to the consumption of higher quantities of alcohol and the experiencing of alcohol-related consequences.

Future research in this area is needed to identify why individuals who report a high level of identification as a drinker may report not using specific alcohol PBS. Third, MOD PBS were found to be a statistically significant mediator in both the college and community-based samples, findings that tentatively support the generalizability of these mediation effects beyond college student populations. Across all studies, LSD PBS and SHR PBS did not mediate the relationship between drinking identity and outcomes. From a conceptual standpoint, it is unclear why drinking identity is differentially related to different forms of PBS and mixed method research is needed to elucidate these findings. However, as an example, it has been argued that some LSD PBS may not serve a protective function that helps individuals reduce alcohol use and consequences . Thus, lack of support for mediation could be a function of a weak association between specific PBS and outcomes. When alcohol quantity and consequences served as the alcohol-related outcome in the mediation models, the statistically significant cross-sectional mediation effect with MOD PBS was replicated longitudinally in Study 1  data. However, mediation effects were not replicated in the other two longitudinal models. The lack of statistical mediation in the other two models were likely due to the intervention not specifically targeting drinking identity or PBS directly. Identity and MOD PBS were not found to have significantly changed in either the control or intervention group between baseline and 3-month follow-up; thus, controlling for baseline PBS use potentially left little variability for identity to explain in MOD PBS at 3 months. Future identity-based interventions are needed to examine whether reductions in identification as a drinker are associated with greater PBS use. Future PBS-based interventions would also benefit from examining whether increased PBS use is associated with decreased identification as a drinker. Similar intervention approaches are needed to better test whether PBS mediate the association between marijuana identity and outcomes. Participants with a high level of identification as a marijuana user reported the use of fewer marijuana PBS, findings that add to the emergent literature on the relationship between marijuana identity and marijuana PBS . Similar to reasons for alcohol use, research indicates that individuals use marijuana to have a good time with friends , and it may be that the use of marijuana PBS that limit an individual’s ability to have a good time may be strategies infrequently used by individuals with a high level of cannabis grow lights identity . Additional research is needed to clarify the role marijuana PBS play as a mediator in non-college populations.Based on these findings, there may be two potential targets to reduce alcohol quantity and consequences:  increase an individual’s use of MOD PBS and/or  decrease an individual’s level of identification as a drinker. For the first, although the evidence base for PBS interventions is mixed , recent adaptions of PBS interventions have been found to be more efficacious, particularly when targeting MOD PBS . These new PBS interventions may be particularly well-suited to reduce the influence that identity has on alcohol/marijuana-related outcomes given that the message framing of PBS normative feedback within these interventions is tailored based on how common others are perceived to be using PBS. Based on findings from the current study, it would appear that an alcohol PBS intervention that attempts to increase a participant’s level of MOD PBS may help to reduce the effect that identifying as drinker may have on both the quantity of alcohol consumed and the number of alcohol-related consequences experienced.

With respect to marijuana PBS interventions, there is less specificity in terms of which specificmarijuana PBS to target. Additional research is needed to identify marijuana PBS that individuals are willing to use and which are effective at reducing marijuana use-related outcomes. It is unclear the extent to which interventions can directly target drinking identity, and relatedly, marijuana identity. Given the difficulty inherent in experimentally manipulating an individual’s level of substance use identity, it may be more feasible to target specific PBS  at the current time. Research is needed to evaluate novel approaches that may be effective at changing an individual’s level of identity as well as their PBS use, particularly for individuals who strongly identify as an alcohol/marijuana user. Findings from the current study should be considered within the context of certain study limitations. For example, the questions as well as the time frame for reporting retrospective PBS use and outcomes sometimes varied across studies. Although this is a limitation in the current study, demonstrating that MOD PBS were a statistically significant mediator and that this finding was observed despite different assessment approaches is also a notable strength. In addition, low levels of internal consistency were observed in the measurement of PBS in Study 1 thus limiting confidence in the extent that subscale items reflected different forms of PBS. Although PBS mediation effects were examined cross-sectionally/ longitudinally, the analytic approach was still correlational. Additional experimental studies are needed to disentangle the causal sequencing of the relationship between identity, PBS, and the outcomes. In Study 3, there were a sizable number of participants who were currently attending college. Caution should be exercised about the extent to which findings from Study 3 truly reflect data from non-college attending adult populations. Global health experts have raised substantial concern regarding the impact of the COVID-19 pandemic on substance use due to increased social isolation and elevated stress . Yet, the impact of the pandemic is unclear given the reduction in social gatherings where substances are commonly consumed and the potential difficulty physically obtaining or financially affording substances . The pandemic may also impact the severity of substance use disorders due to changes in frequency of substance use and the disruption of substance use treatment .

Most patients support insurance coverage of MC,suggesting that in the future insuracne coverage could potentially offset the cost barrier to MC use. Further studies are necessary to evaluate the effectiveness of MC for the treatment of common hand conditions, as well as to better define the long-term safety and side effects of MC in this patient population. Under suppressive antiretroviral therapies , infection with Human Immunodeficiency Virus  remains a challenge, both due to the maintenance of cellular reservoirs and to chronic inflammation driven by low viral replication and dysregulated immune mechanisms. In end organs such as the brain, where the majority of theHIV-1 targets and reservoirs are of myeloid origin , the remaining inflammatory environment contributes to comorbidities,including neurological and cognitive problems , particularly if ART is not introduced sufficiently early . Substance use disorders are frequent among the HIV-infected population, further contributing to cognitive impairment . Nonetheless, the mechanisms by which addictive substances and HIV interact are multi-factorial and poorly understood.Drugs of abuse impact the brain reward system, by modifying levels and balance of neurotransmitters . The HIV target cells, macrophages and microglia, as well as CD4 T cells, express receptors to neurotransmitters, so SUDs are likely to impact mechanisms of immune and inflammatory, and anti-viral responses. Biomarkers that detect the effect of SUDs, and distinguish HIV in that context, may clarify how drugs affect HIV and inflammation.Cannabis is one of the most prevalent substances among HIVt subjects,compared to the non-infected population ,either prescribed for ameliorating symptoms associated with the virus or with ART , or used recreationally, as well as a component of poly substance use , which in itself is a risk factor for HIV infection.

The effects of cannabis may drastically differ from the effects of stimulant drugs such as Methamphetamine, particularly in the context of HIV infection . Yet, similar to other drugs of abuse, cannabis drying racks may be a confoundershifting the expression of biomarkers of inflammation and cognition,masking our ability to clearly measure the impact of virus, ART or other treatments in the immune status and brain pathogenesis, or may be altogether beneficial.In terms of cognition, cannabis exposure has been linked to lower odds of impairment in people living with HIV. On the other hand, impaired verbal learning and memory, may be negatively impacted by cannabis use.Other studies report no-differences, or detrimental effects in HIV-negative populations, suggesting that the observed effects of cannabis, including its benefits, may be largely domain and context-dependent.It has been reported that cannabis use improves biomarkers of inflammation in the CSF and plasma of HIVt subjects and decreases the number of circulating inflammatory cells.We have tested the value of a large panel of transcripts associated with inflammation and neurological disorders, digitally multiplexed and detectable in peripheral blood cells from HIV-positive  and HIV-negative  subjects, users of cannabis  or not .The differences between groups were analyzed using a systems biology approach that identified associated gene networks based on pathways and molecular interfaces, for identifying and visualizing orchestrated transcriptional patterns consistent with HIV infection, CAN exposure,and their interactions. Trends in the behaviors of gene clusters and their predicted regulators revealed that effects of cannabis differ between HIV and HIVt groups. Moreover, mixed statistical models have pinpointed genes that are further influenced by cannabis in the context of poly substanceuse. These context-dependent effects of cannabis indicate the complexity of its molecular actions and properties, and the challenges of biomarker discovery in the context of SUDs. At the same time, the results suggest that cannabis in the context of HIV infection may drive benefits by promoting a decrease of pro-inflammatory and neurotoxic transcriptional patterns, changes and changes in gene clusters associated with leukocyte transmigration and neurological disorders. The impact of HIV, cannabis and their interaction on peripheral markers of cell subset, cellular function and activation was estimate dusing a combination of cell surface protein detection by flow cytometry and a targeted digital multiplex transcriptomic analysis.

The specimens were from males, with homogeneous age and education, and the same race distribution, as shown in Table 1. The examination of clinical data revealed that in HIVt individuals, cannabis did not significantly affectCD4 nadir, CD4/CD8 ratio, plasma or CSF viral load. Cannabis users were significantly more likely to engage in poly substance use, or use other drugs, including alcohol, cocaine and METH. HIV status significantly increased the incidence of lifetime major depressive disorders, which was not affected by cannabis use . Neuropsychological data indicated that cannabis had a marginal effect on Global T scores .By flow cytometry, we verified that the specimen freezing process did not impact subset distribution . For instance, HIVt subjects had significantly lower percentage of CD11btCD14t monocytes compared to HIV- subjects, particularly the ones exhibiting the inflammatory marker CD16t, regardless of cannabis use . The percentage of CD4t T cells was also decreased in HIVt specimens when compared to HIV, with no effect of cannabis . The percentage ofCD8t cells, on the other hand, was significantly increased in HIVtnon-cannabis users, but not in cannabis users, compared to respective controls . Molecular markers of neuro inflammation, activation and leukocytetransmigration were measured in the peripheral blood cells under the hypothesis that cannabis use has an effect by itself and on modulating the effects of HIV. A panel of 784 markers relevant to neurological disorders and inflammation were tested by Nanostring. Of these 381 did not produce any signal in any of the specimens and were excluded from the analysis. The expression of genes with significant signal over noise in more than arbitrarily 10% of the samples was normalized by an average of 8 housekeeping genes. Hierarchical clustering performed using average normalization method applied to digital gene expression data has revealed similarities between HIV-/CANt, HIVt/CAN- and HIVt/CANt, but all these groups were distinct from HIV-/CAN-. Clustering also allowed to identify individual specimens that showed patterns distinct from the majority within groups .Systems biology strategies were used to identify defining expression patterns in transcriptional data, and gene clusters exhibiting orchestrated behaviors perturbed by HIV infection, by the use of cannabis, or by their interaction.

We have identified significant trends in a number of gene clusters functionally annotated to biological processes and pathways of relevance to the neuropathogenesis of HIV. Overall, the analysis indicates context-dependent effects of cannabis.The majority of the digitally multiplexed genes  exhibited detectable and overlapping interactions based on pathway, as indicated in Fig. 4. The effects of HIV alone were estimated by the ratio comparison between HIVt/CAN- versus  HIV-/CAN-. The effects of cannabis alone were estimated by the ratio between HIV-/CANt vs. HIV-/CAN-.The overall combined effects were estimated by the ratio between HIVt/CANt vs. HIV-/CAN-. The effects of HIV in the context of cannabis were measured by the ratio between HIV-/CANt vs. HIVt/CANt. The effects of cannabis in the context of HIV were detected by the ratio between HIVt/CAN- vs. HIVt/CANt. The visual inspection of the cluster in Fig. 4 shows that both HIV and cannabis alone increase the expression of a number of genes indicated by nodes with orange color . In cells from HIVt/CANt individuals, a number of genes showed decreased expression compared to HIV-/CAN- . HIV infection in the context of cannabis, revealed by the comparison of HIVt/CANt and HIV-/CANt , was characterized by strong erupregulation of genes, but also several genes with decreased expression.The effects of cannabis in the context of HIV  measured by the ratio between HIVt/CANt and HIVt/CAN-, were characterized by a higher number of down regulated genes, and a more modest upregulation,as suggested by overall lighter orange shades. A complete list of the genes in this network and T ratio in indicated comparisons can be found in Supplementary Materials 1.Pathway-based interactions were subdivided for identification of embedded functional annotations impacted by HIV and/or cannabis grow tray,identified by DAVID Bio informatics Resources with a gene list input.Individual functional annotations were then assembled in Gene Mania forvisualization of effects. A complete list of significant pathways and functional annotations can be found in Supplementary Materials 1. The pathways selected for visualization were curated based on the expression of inflammatory genes, significance to neurological disorders in the context of HIV, viral infection, pathogenesis and networks with interventional value. For instance, a gene network functionally annotated to viral host interactions was identified , where the ratio between HIVt/CAN- and HIV-/CAN-  indicated that HIV increased a number of genes annotated to that function. The ratio between HIV-/CANt and HIV-/CAN- , as well as between HIVt/CANt subjects were compared to HIV-/CANt,indicated that both cannabis alone and HIV in the context of cannabis use increased a largenumber of genes in this cluster, but several genes were also decreased in both conditions, including the Ras homolog gene family GTPase RhoA,the Proteasome 20S Subunit Beta 8 , the intracellular cholesterol transporter , the E1A Binding Protein P300  and the histone deacetylase Sirtuin 1 . The ratio between HIVt/CANt and HIVt/CAN- indicated that cannabis in the context of HIV was associated with a mild increase of genes in viral host interaction function, and a decrease in the general transcription factor IIB  and the ubiquitin protein ligase 3A  were characteristic of this comparison.Apoptosis was also identified as a relevant functional annotation, showing differential effects of HIV and/or cannabis.

HIV alone decreased Caspase 7 CASP7, but increased CASP9 and the apoptosis regulator BCL2. The effect of cannabis, on the other hand , indicated decrease in BCL2. Likewise, HIV in the context of cannabis  had a decrease in BCL2 . On the other hand, the ratio between HIVt/CANt and HIVt/CAN- indicated that cannabis decreased or had mild effects on the expression of genes associated with apoptotic functions detectable in peripheral leukocytes.Given the large degree of overlap between these networks , we applied a merge network function in Cytoscape,which is shown in Fig. 7. The visualization of this gene network indicates that both HIV and cannabis increase genes with functions inneurode generation and inflammation,but cannabis decreased key contributors to the inflammatory process such asIL1b, TLR2, MyD88 and PARK7, as well as RASGRP1 . HIV infection in the context of cannabis  indicated patterns that were similar to cannabis alone, with decreased expression in the same genes.Moreover, cannabis in the context of HIV elevated TLR2, TLR4 andMyD88, but had no or mild effects, or decreased a number of genes in this network . Functional annotations associated with leukocyte-vascular adhesion and transmigration capacity were also sorted from pathway interactions.These functions were affected by HIV and cannabis . A large number of genes in this network were differentially increased by HIV and by cannabis . Yet cannabis lowered the expression of a large number of genes with cytoskeleton and signaling properties, including RHOA, AKT3, RAC1, BRAF and BCL2 . HIV in the context of cannabis had also lower MAPK1 and CTNNB1 compared to uninfected cannabis users . HIVt cannabis users had a high number of genes that were lower or mildly changed compared to HIV non-cannabis users .Inflammation is highly regulated by a kinases. HIV and cannabis affected the expression of a number of kinases and genes involved inkinase regulation. The effects were differential and context-dependent.All the conditions showed decrease in CAMK4, in comparison to respective controls . HIV alone decreased mTOR, CSF1R, EPHA4,PDPK1 and DGKE . Cannabis alone, as well as HIV in the context of cannabis , decreased ATK3 andMAPKPK2. Cannabis alone decreased CALM1 . HIV in the context of cannabis decreased the expression of PGK1 and RAF1. Cannabis in the context of HIV decreased several genes in this network that were either not modified or increased by the other conditions. These included MAP2K1, MAPK9, MAPK3, PRKCA andPDPK1 . The screening of a large number of transcripts associated with neurological disorders has shown that the effects of cannabis differed drastically between HIV- and HIVt groups, particularly in gene networks playing a role in inflammation, neurodegeneration,apoptosis and leukocyte adhesion and transmigration. The results indicate that cannabis in the context of HIV may have beneficial effects. However, in individual genes, we identified detrimental effects that were associated with polysubstance use as a covariate, particularly methamphetamine.

GLCM texture parameters such as contrast, homogeneity, energy, variance, and correlation have been proven to be successful in increasing classification accuracies by providing important textural characteristics that help in discriminating land cover . Additionally, GLCM texture metrics have been used in combination with SAR S1 data for crop discrimination . When classifying different crop types in an agricultural field, extracting information from neighboring pixels could be of great importance in improving classification accuracy. Texture features involve this information and help in identifying the intensity variations in an image which can further contribute to improving overall accuracy. We further observe that the addition of texture features can decrease the accuracy of a classifier, similar to what happened when using a CART classifier. Although RF and CART are tree-based machine learning algorithms, this decrease in accuracy was not observed using the RF classifier. This is because RF is an ensemble machine learning algorithm which makes it more robust and stable compared to a single decision tree classifier. In terms of comparing classifiers, the highest overall accuracy was observed using the SVM classifier, followed by GBT, RF, and finally CART. Similar findings were observed in a study that compares machine learning algorithms  by Mustak et al. , where authors report SVM classifier achieving better accuracy in crop discrimination compared to RF and CART. Moreover, Sonobe et al.  evaluated the potential of Terra-SAR-X data for crop mapping by comparing the performance of CART, RF, and SVM. Authors arrive at similar findings, with SVM being the optimum algorithm used. RF and GBT yielded similar results which have been observed earlier by Freeman et al.  when predicting tree canopy cover in four study regions. We further assess the average accuracy in classifying cannabis by computing the F1-measure, which Yang et al.  defined as the harmonic mean of the user’s accuracy and producer’s accuracy. In the 2016 classification, the average F1-measure achieved by RF, GBT, and SVM is 0.88. Thus, we assume that the three classifiers achieve similar results in identifying cannabis fields. In 2018, classification SVM and GBT achieve a similar average F1-measure , and RF achieves a slightly lower value . Since the classification models in 2016 achieved promising results in identifying cannabis, we use them to classify cannabis in 2017.

The models classify cannabis vertical farming with an average accuracy of 83% for SVM, 73% for RF, and 52% for GBT. Therefore, it is possible to detect illegal cannabis fields early in the season since it is usually harvested end of September – early October, and the classification period ends in August. The novelty of our study lies in classifying a non-dominant crop type  with high accuracy as well as in the comparative analysis of the four most used machine-learning classifiers in Google Earth Engine. Previous crop classification research classifies crops that are dominantly present in study areas. To our knowledge, there has been no similar work carried out on cannabis classification.  The Agricultural Improvement Act of 2018 permits the cultivation and legal trade of industrial hemp in the United States. This act defines hemp as Cannabis sativa and any part or derivative of the plant including seeds, extracts, cannabinoids, isomers, acids, salts, and salts of isomers with a total delta-9 tetrahydrocannabinol  concentration below 0.3 %  on a dry weight basis . This statute removed hemp-cannabis from its schedule I classification by using this definition to separate it from marijuana-type cannabis. Currently, there are no standardized methods to distinguish hemp from marijuana. Most forensic laboratories use chromatographic methods such as Gas Chromatography  or High-Performance Liquid Chromatography  methods coupled to mass spectrometry to quantitate the THC in suspicious plant materials. Furthermore, colorimetric tests that were once used to presumptively identify cannabis are not able to differentiate between hemp and marijuana, creating the need for an effective field test that can differentiate between hemp-type cannabis and marijuana-type cannabis. Hemp and marijuana are two different strains of the Cannabis plant with the main difference between the two being the concentration of cannabinoids contained in them. The two most important cannabinoids in these plants are THC and cannabidiol . THC is the cannabinoid that causes a psychoactive response in the body giving the person a “high”. It also has anti-inflammatory and analgesic properties, which make it desirable for medical use . CBD is also known for these beneficial properties but is non-psychoactive, so it does not give a person a “high” when used . Typically, hemp is CBD-rich containing low concentrations of THC causing its THC:CBD ratio to be below 1. Cannabis is considered marijuana when it has a concertation of total Δ9- THC ≥ 0.3% , but usually has a THC:CBD ratio above 1 . Elsohly et. al. reported that from 2009 to 2019 marijuana in the U.S. increased in THC potency across the decade from an average of 10% THC in 2009 to 14% THC in 2019. In 2019, the average CBD concentration in marijuana was found to be 0.6% , and that the THC:CBD ratio was above 20 across the decade . This difference in THC:CBD ratios can be used in the design of an effective field test for the identification of marijuana-type cannabis.

These tests are considered presumptive as they only indicate the possibility of the analyte being present in the substance . Until the Agricultural Improvement Act of 2018, the modified Duquenois-Levine  test was the color test used to presumptively identify a suspicious plant material as cannabis. Although used for many years, the D-L test is known to produce false positives with reaction of molecules containing a resorcinol backbone and an aliphatic chain . Therefore, the D-L test is to produce false positive results from plants such as patchouli, spearmint, and eucalyptus. Furthermore, THC, CBD, and many other cannabinoids contain both a resorcinol group and an aliphatic chain, resulting in a D-L test that is not selective enough to differentiate between the cannabinoids. This shortcoming is the reason that the D-L test is no longer a suitable field test for the identification of marijuana-type cannabis. There is now an urgent need for color tests that can differentiate between hemp  and marijuana . One colorimetric test that is currently being used to differentiate between hemp and marijuana is the 4-aminophenol  test developed by the Swiss Forensic Institute in Zurich . A recent validation study has shown that a pink color forms when the THC:CBD ratio is below 0.3  and a blue color forms when the plant has a THC: CBD ratio above 3  . A confirmatory chemical test such as GC-FID or GC–MS is still required after a positive 4-AP test. The test requires the use of at least 1 mL of one of its reagents, 4-aminophenol, to produce a color result. Although the 4-AP test has demonstrated capability as a presumptive test for cannabis, it has also been reported that it may not be selective for THC. False positive results have been obtained with sage, oregano, and several cannabinoids, such as cannabinol.A more selective and smaller-scale alternative presumptive test could improve the presumptive confirmation for marijuana in the field. A colorimetric reagent that has been used for many years as a visualization reagent for cannabinoids when analyzing cannabis extracts through thin layer chromatography  is the Fast Blue BB  reagent . The FBBB test is selective among major cannabinoids, providing a red color for THC, an orange color for CBD, and a purple color for CBN. Ultraviolet-Visible Spectroscopy has shown that the FBBB + THC chromophore has an absorption band at 471 nm, which is responsible for its red color. The Almirall lab previously reported the structure of the FBBB + THC chromophore using results from high-resolution mass spectrometry  and Hydrogen Nuclear Magnetic Resonance . It was determined that, in basic conditions THC becomes a phenolate anion and that this anion attacks the diazo group in FBBB at the para position to form the chromophore  . A bathochromic  shift results from the extended conjugation in the chromophore and the n→π* transition caused by the electrons in the diazo group of FBBB . In addition to characterizing the chromophore, the previous study evaluated the selectivity of FBBB for THC detection. Eight different types of tea, 3 hop products, and 3 authentic hemp buds were extracted and tested using FBBB. This test was performed by adding 10 μL of the extract to a filter paper, followed by 10 μL of 0.1% FBBB and 0.1 N NaOH. Extracts that were made from methylene chloride produced only 1 false positive with one of the teas . Of note, none of the hemp samples produced a false positive result, displaying an orange color indicative of CBD . These results support the selective nature of the FBBB test for use as a presumptive field test to distinguish between hemp, marijuana, and other plant materials. In the previous study, filter paper, a Capillary Microextraction of Volatiles  device, and CMV strips were used as possible substrates to perform the FBBB test.

A CMV device is an open-ended 2 cm glass capillary tube that contains seven 2 cm by 2 mm glass filter strips have been coated with vinyl-terminated polydimethylsiloxane that was developed by the Almirall lab as an alternative to Solid Phase Microextraction. The modified glass filters that make up the CMV, known as Planar SPME , have excellent absorption/ adsorption capabilities and can withstand high temperatures. It was found that when the FBBB test is performed on one of the PSPME strips the LOD for THC was 100 ng, which is significantly lower than the known LOD for the D-L test, 5000 ng of THC . Using PSPME as a substrate is advantageous over regular filter paper since it can withstand high temperatures allowing the chromophores formed to be detected using DART-MS with very little background . In this current study, the capabilities of using FBBB as a presumptive field test to differentiate between hemp and marijuana are presented. We also report a fast and easy extraction method for plant material that can be used in the field. A previously reported substrate  known as PSPME support  was used for the FBBB reaction . Six cannabinoids, 5 retail hemp samples, vertical grow system 20 authentic cannabis samples, tobacco, hops, herbs, and essential oils were tested with the FBBB reagent. RGB  numerical codes were obtained for each color result to confirm the color produced by the reaction in an objective manner. The fluorescence results of the FBBB + THC fluorophore is reported for the first time. The fluorescence spectra of the FBBB + THC product are distinguishable from the spectra of FBBB + CBD chromophores. The RGB score combined with the fluorescence of the FBBB + THC chromophore/fluorophore enhances the selectivity of the FBBB test for marijuana. Linear Discriminant Analysis was performed to determine whether FBBB could be used to classify cannabis correctly as hemp-type and marijuana type. The FBBB test was used to evaluate 6 different cannabinoids, 5 commercial hemp strains, 20 cannabis samples, and various herbs and spices. It was determined that when FBBB reacts with THC, it forms a red chromophore that fluoresces under 480 nm light. Conversely, when reacted with CBD or CBD-rich products, such as hemp, an orange chromophore is formed, and this chromophore does not fluoresce. This is the first time, to the author’s knowledge, that the fluorescence of the FBBB + THC chromophore/fluorophore is reported for a colorimetric test. This fluorescence is easily visualized using a portable Dino-Lite microscope and its spectra obtained with a VSC2000 spectrometer. The intensity and wavelength of the fluorescence for the chromophore combined with the distinct red color it displays makes for a more selective and sensitive test to differentiate between marijuana and hemp. The structure for FBBB + THC has been previously determined by the Almirall lab, as shown in Fig. 1 . The chromophore results from an extended conjugation of π-bonds decreasing the distance between energy transitions between the ground state and excited state. This extended conjugation causes a “red shift” of the FBBB chromophore, which is responsible for the red color and the fluorescence that is observed when THC reacts with FBBB. One theory for CBD + FBBB lacking fluorescence intensity is that CBD has a less rigid structure than THC. It is known that structure rigidity and a fused ring structure increases the quantum efficiency, and therefore fluorescence of a molecule. Since CBD is less rigid than THC and does not have a fused ring structure, it is prone to relaxation through internal conversion rather than through radiative means . Therefore, FBBB + CBD likely relaxes through nonradiative mechanisms, which decreases overall fluorescence. The difference in both color and fluorescence that is observed for FBBB + THC and FBBB + CBD is an advantage that the FBBB test has compared to other tests for presumptive analysis of cannabis, which only use color.

Whether they used cannabis or not, results showed that students who had the lowest executive and memory scores were more addicted to tobacco and had higher trait anxiety. An association with tobacco use has been shown to be prevalent in both BD and cannabis users . In another context, chronic tobacco smoking was found to be related to neuropsychological impairment, notably for memory and flexibility . Like tobacco, anxiety can represent a risk factor for neuropsychological impairments, above all by affecting executive functioning . In the present study, college students who exhibited cognitive impairments tended to be more anxious. Students used alcohol to cope, especially those with higher levels of anxiety . The relationship between BD, cannabis use, and anxiety remains unclear, especially in college students . Tobacco and a high anxiety level, added to BD and/or cannabis use, may worsen the cognitive impairments highlighted in our study, as they seem to impair the same cognitive areas. Although the nature of our study did not allow us to establish any causal relationship between these variables, our results do suggest that they should be taken into account in prevention. The circularity of the possible risk factors for developing cognitive impairments between substance use, anxiety, and substance use to cope with anxiety is alarming, especially so regarding the current health context. With the SARS-CoV-2 pandemic, students have had to contend with high levels of anxiety . Regardless of context, these findings highlight the importance of prevention, so that students can be identified and psychologically supported at an early stage-even before they indulge in BD or substance use, or develop anxiety. Complementary analyses suggested that students with neuropsychological impairments spent more money on cannabis than those with preserved performance .

Even if this result has yet to be properly analyzed, it highlights the problem of how to measure cannabis intake. Unlike alcohol, with its standard drink units, cannabis lacks a precise measure that would reflect the actual amount consumed, and this issue needs to be further explored. One limitation of this study is that some patterns of students’ consumption were not represented in our sample, and consumption was self-reported. We chose to divide participants into three groups, based on available data, mobile grow system in order to examine the impact of co-occurring BD and cannabis use on neuropsychological profiles. However, the study sample did not encompass students who consumed cannabis without BD, as this profile is scarce in college students, and was particularly lacking in our sample. Future studies will therefore have to be conducted among cannabis users without BD to further focus on the aggravating effects of combined BD and cannabis use. Moreover, the three groups in our sample differed in size, which may have influenced statistical power and Type I errors. Furthermore, the neuropsychological assessment we used in this study was a screening test  with multicomponent tasks that rely on executive and memory abilities. This tool was designed to screen alcohol-related neuropsychological impairments and was not initially intended to assess cannabis consumption. However, the fact that alcohol and cannabis share the same cognitive impairment spectrum encouraged researchers to extend its use. The present study nonetheless represents a first step in understanding the neuropsychological consequences of BD and cannabis co-use. Further research is required to perform more detailed and extended neuropsychological assessments to overcome the above-mentioned limitations. This could be the opportunity to adapt the BEARNI’s cut-offs and psychometrics to educated young people. The assessment of neuropsychological impairment among college students engaging in BD associated with cannabis use demonstrated that these two practices have an additive effect, especially for memory and executive impairments.

They seem to have specific harmful effects on students’ cognition and consumption patterns. As BD and cannabis co-use can lead to cognitive impairments, it may partly explain the reduced academic success reported in the literature . Clinical practice could greatly benefit from this information, as it emphasizes the need to better characterize the different consumption and psychological profiles, especially in young students. As we know that neuropsychological impairments can hinder the motivation to quit or reduce consumption  and may also diminish the efficiency of prevention protocols, asking BD if they also use cannabis could be highly beneficial in clinical practice, for both prevention and research. Furthermore, it could allow prevention and care strategies to be adapted to each person’s neuropsychological profile. This study suggests that future prevention programs should take memory and executive impairments into account, as well as consumption profiles and anxiety levels, in order to improve the impact and efficiency of these programs in college students.  In 2018, Canada became the second country in the world to legalize adult recreational cannabis use , following its legalization for medical use in 2001 . Canada’s Cannabis Act dictates that cannabis policies should “keep cannabis out of the hands of youth”, “keep profits out of the pockets of criminals” and “protect public health and safety by allowing adults access to legal cannabis” . Canada’s emphasis on youth cannabis prevention or delayed initiation is evidence-based. Earlier and more frequent adolescent cannabis use is associated with greater risk of harm to the developing brain  and multiple adverse outcomes including impaired neurocognitive functioning,affective problems,suicidality,psychosis, cannabis dependence syndrome, and cannabis-related morbidity in later years.With the legalization of adult recreational cannabis use, however, adolescents may experience increased cannabis availability, increased social acceptance of cannabis, and confusing messages about whether cannabis use is safe . Evidence regarding the effects of adult cannabis legalization on adolescents is mixed.Although research surrounding the impact of recreational cannabis legalization on youth in Canada is scarce, national survey data show a gradual increase in cannabis use among youth coinciding with increased public discourse on the topic . The extent to which Canada’s shift towards more liberal cannabis policies, practices and culture will impact youth cannabis attitudes, intentions, and use are largely unknown. A key influence on youth cannabis attitudes, beliefs, expectancies, and intentions to use, is cannabis-related marketing . Though it is illegal to market cannabis products to youth in Canada, recent studies , and a long history of research on other age-restricted substances with abuse potential , demonstrate that companies ignore these laws and intentionally target their products to youth .

Research on alcohol and tobacco marketing shows strong correlations between youth exposure to marketing and earlier initiation, and higher consumption among those already using . All told, exposure to cannabis marketing could similarly spur youth cannabis use . While emerging research suggests that cannabis marketing puts Canadian youth at risk , preliminary studies are limited because they use inexact measures such as general awareness of marketing and receptivity to marketing that rely on retrospective recall, which are subject to participant recall error and bias . Existing studies also describe marketing exposures in aggregate, obfuscating the context of individual exposures,mobile vertical rack such as when and where exposures occur, and other psychosocial factors which could influence their effects . In particular, existing research does not describe the channels through which cannabis marketing exposures occur, nor the ways in which federal marketing prohibitions are violated. Policymakers also need research that shows whether cannabis marketing of different types and through different channels has varying impacts on youth. Real-time, real-world assessment techniques such as Ecological Momentary Assessment may be used to reduce bias and increase the reliability, accuracy, and acuity of information about adolescents’ exposures to cannabis marketing. In EMA protocols, participants use smartphone technology – that they already use throughout the day in multiple settings  – to track a range of phenomena as they occur in participants’ natural environments. Previously, we created an EMA protocol for tracking youth exposure to alcohol and tobacco marketing . Middle- and high-school participants made electronic time-stamped recordings of tobacco and alcohol marketing exposures, demonstrating that exposures primarily occurred in the afternoon, at point-of-sale locations, and on days leading up to the weekend . To our knowledge, no research has similarly documented Canadian adolescent cannabis marketing exposures using an EMA approach. The goal of this pilot study was to assess the feasibility of a 9-day, smartphone-based EMA protocol to obtain a preliminary understanding of the frequency of Canadian adolescents’ exposures to cannabis marketing, their reactions to such exposures, and the context in which exposures occur in the real-world and in real-time. The intent of this research was not to provide a definitive description of how and how often Canadian adolescents are exposed to cannabis marketing, but to provide and test a tool that could facilitate such future research.

With this tool, we also aim to provide preliminary data demonstrating the existence and potential impacts of cannabis advertising on youth. Historical research on other legalized, recreational drugs  suggests that Canadian youth are likely cannabis marketing targets, but to date,almost no data exists regarding the scope and impact of cannabis marketing on Canadian youth in a post-legalization context . This study presents some of the very first data that demonstrate that cannabis marketing to youth is actively occurring in Canada, and that researchers and policymakers must begin to take action on the issue in order to protect youth and public health. To our knowledge, this is the very first study to use EMA to capture adolescent cannabis marketing exposures, in Canada or elsewhere. A particular strength of the EMA approach is that it enables detailed data collection about each exposure , and its immediate impacts, that are otherwise obscured or blurred in retrospective self-report. . Thus, the current study provides novel evidence for a powerful tool that researchers and policymakers can use to obtain detailed information about cannabis marketing exposure characteristics , and strategies for assessing their subsequent effect on adolescents’ cannabis-related expectancies and intentions. We recognize that EMA methods overall are not new, and that Shiffman  and others have been advancing the science of EMA for more than 30 years. The newness of cannabis legalization in Canada and the associated taboo of cannabis in some communities , however, necessitated this extensive pilot work, not only to demonstrate the concept of the work , but also that our recruitment procedures, messaging, and protections were acceptable to adolescents and their guardians, as all of these components of the study are essential to effectively conduct the research. Overall, our results show that the protocol is feasible. Although overall rates of compliance  were slightly lower than previous EMA studies of adolescents, rates among the participants whose app was working well were directly in-line with other work . Unexpectedly, a major task of this pilot research was to resolve software compatibility issues between the Expiwell app and older versions of Android platforms, including identifying device setting issues such as “do not disturb” or “battery saver” mode on individuals’ phones that interfered with participants receiving notifications from the study app. Participant compliance rates were much better among those with newer phones whose platforms were more compatible with the app. Researchers replicating or extending this research will need to consider the pros and cons of allowing participants to use their own devices for data capture  as compared to using a study-issued device  . Despite it’s feasibility design, this study also provides new, albeit very preliminary knowledge regarding the quantity and characteristics of cannabis marketing currently reaching Canadian adolescents; information that has previously only been described in aggregate, retrospectively, and by self-report. Overall, data showed that nearly all participating adolescents had cannabis marketing exposures during the study period. This included an average of about two cannabis-related marketing exposures per week, substantiating previous research . This finding demonstrates cannabis companies’ success in skirting current cannabis-related marketing laws which categorically prohibit marketing of cannabis products to youth. Our data also showed that most cannabis-related exposures occurred through promotion by public figures and through ads on the internet. This finding is likely influenced by the COVID-19 context  in which data were collected, and it is consistent with a significant increase among youth in the use of social media, streaming services, gaming sites and apps . At the same time, previous research has demonstrated that cannabis has an established and sophisticated presence specific to the internet based on creative advertisements designed for social media platforms , regardless of legality or media company policies . Indeed, while alcohol and tobacco industries developed their original marketing campaigns decades ago using traditional media channels , Canada’s sale and legalization of cannabis began in the digital age, and as a result, cannabis companies rely mostly on social media to market their products .