Activation of PPAR-a in vivo causes an upregulation of the mRNA and protein levels of a number of peroxisome- and nonperoxisome-associated enzymes and structural proteins, including the antioxidant enzymes catalase, superperoxide-dismutase and mediators of the glutathione pathway. In this context, pretreatment with fenofibrate reduces cerebral infarct volume in apolipoprotein E-deficient mice. The neuroprotective effect of fenofibrate is completely absent in PPAR-a-deficient mice, suggesting that PPAR-a activation is involved as a protective mechanism against cerebral injury . We failed to confirm the initially hypothesized increase of anandamide after sleep deprivation questioning its proposed role in sleep induction in humans . This is in line with findings on cannabinoid CB1- receptor gene expression, which is suggested to be modulated by sleep. While sleep rebound significantly increased CB1-receptor protein and decreased respective mRNA, no effects were found following sleep deprivation . Interestingly, according to the product information, the CB1-receptor antagonist rimonabant induces sleep disturbances frequently but also sedation in clinical trials. Several shortcomings might have influenced our somehow preliminary data; first, a randomized, balanced crossover design would have been the ideal design for the trial. Second, EEG recordings might have provided more detailed information on sleep quality instead of an actigraphy for control of sleep deprivation only.More high school students smoked little cigars and cigarillos than cigarettes in 33 US states in 2015. Concern is growing about co-use of tobacco and marijuana among youth,rolling benches hydroponics particularly among African-American youth.In a 2015 survey, for example, one in four Florida high school students reported ever using cigars or cigar wraps to smoke marijuana. One colloquial term for this is a “blunt.”
Adolescent cigar smokers were almost ten times more likely than adults to report that their usual brand offers a flavored variety. Since the US ban on flavored cigarettes , the number of unique LCC flavors more than doubled.Anticipating further regulation, the industry increasingly markets flavored LCCs with sensory and other descriptors that are not recognizable tastes. For example, after New York City prohibited the sale of flavored cigars, blueberry and strawberry cigarillos were marketed as blue and pink, but contained the same flavor ingredients as prohibited products.Among the proliferation of such “concept” flavors , anecdotal evidence suggests that references to marijuana are evident.Cigar marketing includes the colloquial term, “blunt”, in brand names and product labels . Other marketing techniques imply that some brands of cigarillos make it easier for users to replace the contents with marijuana.For example, the image of a zipper on the packaging for Splitarillos and claims about “EZ roll” suggest that products are easily manipulated for making blunts. We use the term “marijuana co-marketing” to refer to such tobacco industry marketing that may promote dual use of tobacco and marijuana and concurrent use . In addition to flavoring, low prices for LCCs also likely increase their appeal to youth. 10 In California, 74% of licensed tobacco retailers sold cigarillos for less than $1 in 2013. Before Boston regulated cigar pack size and price in 2012, the median price for a popular brand of grape-flavored cigars was $1.19. In 2012, 78% of US tobacco retailers sold single cigarillos, which suggests that the problem of cheap, combustible tobacco is widespread. Additionally, the magnitude of the problem is worse in some neighborhoods than others. Popular brands of flavored cigarillos cost significantly less in Washington DC block groups with a higher proportion of African Americans and in California census tracts with lower median household income.For the first time, this study examines neighborhood variation in the maximum pack size of cigarillos priced at $1 or less and assesses the prevalence of marijuana co-marketing in the retail environment for tobacco.
School neighborhoods are the focus of this research because 78% of USA teens attend school within walking distance of a tobacco retailer. In addition, emerging research suggests that adolescents’ exposure to retail marketing is associated with greater curiosity about smoking cigars and higher odds of ever smoking blunts. In California, 79% of licensed tobacco retailers near public schools sold LCCs and approximately 6 in 10 of these LCC retailers sold cigar products labeled as blunts or blunt wraps or sold cigar products with a marijuana-related flavor descriptor. A greater presence of marijuana co-marketing in neighborhoods with a higher proportion of school-age youth and lower median household income raises concerns about how industry marketing tactics may contribute to disparities in LCC use. The study results also suggest that $1 buys significantly more cigarillos in California school neighborhoods with lower median household income. Policies to establish minimum pack sizes and prices could reduce the widespread availability of cheap cigar products and address disparities in disadvantaged areas.After Boston’s 2012 cigar regulation, the mean price for a grape-flavored cigar was $1.35 higher than in comparison communities.The industry circumvented sales restrictions in some cities by marketing even larger packs of cigarillos at the same low price, 2and the industry’s tipping point on supersized cigarillo packs for less than $1 is not yet known. The retail availability of 5- and 6-packs of LCCs for less than $1 observed near California schools underscores policy recommendations to establish minimum prices for multipacks .A novel measure of marijuana co-marketing and a representative sample of retailers near schools are strengths of the current study. A limitation is that the study assessed the presence of marijuana co-marketing, but not the quantity. The protocol likely underestimates the prevalence of marijuana co-marketing near schools because we lacked a comprehensive list of LCC brands and flavor varieties. Indeed, state and local tobacco control policy research and enforcement would be greatly enhanced by access to a comprehensive list of tobacco products from the US Food and Drug Administration, including product name, category, identification number and flavor. Both a routinely updated list and product repository would be useful for tobacco control research, particularly for further identifying how packaging and product design reference marijuana use. This first assessment of marijuana co-marketing focused on brand and flavor names because of their appeal to youth.However, the narrow focus is a limitation that also likely underestimates the prevalence of marijuana co-marketing. Other elements of packaging and product design should be considered in future assessments. Examples are pack imagery that refers to blunt making, such as the zipper on Splitarillos, as well as re-sealable packaging for cigarillos and blunt wraps, which is convenient for tobacco users who want to store marijuana. Coding for brands that are perforated to facilitate blunt making and marketing that refers to “EZ roll” should also be considered.
Future research could assess marijuana co-marketing across a larger scope of tobacco/nicotine products. The same devices can be used for vaping both nicotine and marijuana. Advertising for vaping products also features compatibility with “herbs” and otherwise associates nicotine with words or images that refer to marijuana . Conducted before California legalized recreational marijuana use, the current study represents a baseline for understanding how retail marketing responds to a policy environment where restrictions on marijuana and tobacco are changing, albeit in opposite directions.The prevalence of marijuana co-marketing near schools makes it imperative to understand how tobacco marketing capitalizes on the appeal of marijuana to youth and other priority populations. How marijuana co-marketing contributes to dual and concurrent use of marijuana and tobacco warrants study,hydro tray particularly for youth and young adults. In previous research, the prevalence of adult marijuana use in 50 California cities was positively correlated with the retail availability of blunts. Whether this is correlated with blunt use by adolescents is not yet known. Consumer perception studies are necessary to assess whether marijuana co-marketing increases the appeal of cigar smoking or contributes to false beliefs about product ingredients. Research is also needed to understand how the tobacco industry exploits opportunities for marijuana co-marketing in response to policies that restrict sales of flavored tobacco products and to policies that legalize recreational marijuana use. Such assessments are essential to understand young people’s use patterns and to inform current policy concerns about how expanding retail environments for recreational marijuana will impact tobacco marketing and use.Oleoylethanolamide is a fatty acid ethanolamide and a natural analog of the endogenous cannabinoid anandamide. There is no detailed research on the role of endocannabinoids in sleep in humans. Anandamide is known to engross slow-wave sleep by increasing adenosin levels in the forebrain of rodents . This is blocked by the cannabinoid CB1-receptor antagonist rimonabant. Oleamide is an endogenous sleepinducing lipid with putative cannabinomimetic properties . Murillo-Rodriguez et al. supposed oleoylethanolamide, which—unlike oleamide— activates the nuclear peroxisome proliferator-activated receptor-a to increase alertness and to participate in the regulation of waking. Up to now, elevated levels of oleoylethanolamide and anandamide were found in human microdialysates within the first day of ischemia as well as following neural injuryor other stressors associated with necrosis. Furthermore, massive increases in FAEs and their precursor phospholipids have been found during the acute phase of stroke in the adult rat brain . Thereby it was suggested that increases of brain FAE levels serve a neuroprotective function mediated by CB1-receptors. Oleoylethanolamide does not bind to cannabinoid CBreceptors but to PPAR-a, thereby activating a different neuroprotective mechanism. Sleep deprivation has been hypothesized to represent an oxidative challenge for the brain and that sleep may have a protective role against oxidative damage. While Gopalakrishnan et al. found no change in antioxidant enzymatic activities or increased oxidant production in the brain or in peripheral tissues after prolonged sleep deprivation, other studies suppose that sleep deprivation may result in a condition of oxidative stress including a reduction in glutathione levels in whole brains of rats . Ramanathan et al. showed that prolonged sleep deprivation results in significant decreases in the activity of superperoxide-dismutase in rat hippocampus and brainstem. This effect may be due to the degradation of antioxidative enzymes after prolonged activation during wakefulness, which suggests an alteration in the metabolism resulting in oxidative stress. Even if sleep deprivation might not show extensive effects comparable to cerebral injury or tissue necrosis, FAEs have been shown previously to be elevated during situations of cellular stress and oxidative stress factors are elevated following sleep deprivation . Therefore, in this study, we investigated whether the levels of the endogenous PPAR-a agonist oleoylethanolamide and the endocannabinoid anandamide were elevated in CSF and serum of healthy individuals after acute sleep deprivation.The Ethics Committee of the Medical Faculty of the University of Cologne reviewed and approved the protocol of this study and the procedures for sample collection and analysis. All volunteers gave written informed consent twice at least 1 day prior to each lumbar puncture after extensive introduction into the procedures and goal of this study. The healthy subjects received an allowance for the participation in this trial. All investigations were conducted in accordance with the Declaration of Helsinki. This study was integral to a larger project on endocannabinoid levels in CSF and serum of healthy volunteers and patients suffering psychiatric disorders. As part of that, volunteers were investigated to establish baseline levels of endocannabinoids in a healthy control population . Twenty healthy volunteers with no family history and no clinical indication for any relevant medical, psychiatric or neurological disturbances were included in our study to investigate effects of sleep withdrawal on endocannabinoid levels. Necessary criteria for inclusion were absence of cannabis use within the last year and lifetime cannabis use not exceeding five times.Living circumstances for those volunteers selected did not change substantially during this period. Subjects were lumbar-punctured twice during the course of our study using a nontraumatic LP procedure. The first LP was done under regular sleep condition. The second LP took place after 24 h of sleep deprivation about 1 year later to avoid seasonal influences and artificial alterations in cerebrospinal fluid due to a previous LP in the near past. All subjects spent the nights before both LPs at home; sleep quality before the first lumbar puncture was assessed by the self-rating questionnaire for fatigue and for sleep and awakening quality . The night of sleep deprivation was spent in the habitual environment of the volunteers. Alertness was monitored by wrist actigraphy, using the ‘‘Actiwatch2000,’’ a piezoelectric transductor recording a maximum of 240 wrist motions per minute. Actiwatch was given to the volunteers 24 h before the second lumbar puncture. Volunteers showing a mosaic of inactivation at the actiwatch-scan of more than 5 min during the 24-h period were excluded from the experiment. This approach allowed us to continuously monitor the subjects during the night of sleep withdrawal .