Metabolic Effects of Chronic Cannabis Smoking

Muniyappa, Ranganath; Sable, Sara; Ouwerkerk, Ronald; Mari, Andrea; Gharib, Ahmed M.; Walter, Mary; Courville, Amber B.; Hall, G. E.; Chen, Kong Y.; Volkow, Nora D.; Kunos, George; Huestis, Marilyn A.; Skarulis, Monica C.

doi:10.2337/dc12-2303

Cited by 127 publications

(121 citation statements)

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“…Contrary to the CB 1 -mediated insulin resistance and abdominal obesity (39), which can be mimicked by short-term exposure to marijuana (40), chronic marijuana use has not been associated with increased cardiometabolic risk, either in terms of being overweight or in the form of insulin resistance (41,42). Down-regulation of CB 1 Rs in chronic marijuana smokers (43), and/or inhibition of endocannabinoid action at CB 1 R by the partial agonist Δ 9 -tetrahydrocannabinol, may account for these differences.…”

Section: Discussionmentioning

confidence: 99%

Monounsaturated fatty acids generated via stearoyl CoA desaturase-1 are endogenous inhibitors of fatty acid amide hydrolase

Liu

Çınar²,

Xiong³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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High-fat diet (HFD)-induced obesity and insulin resistance are associated with increased activity of the endocannabinoid/CB 1 receptor (CB 1 R) system that promotes the hepatic expression of lipogenic genes, including stearoyl-CoA desaturase-1 (SCD1). Mice deficient in CB 1 R or SCD1 remain lean and insulin-sensitive on an HFD, suggesting a functional link between the two systems. The HFD-induced increase in the hepatic levels of the endocannabinoid anandamide [i.e., arachidonoylethanolamide (AEA)] has been attributed to reduced activity of the AEA-degrading enzyme fatty acid amide hydrolase (FAAH). Here we show that HFD-induced increased hepatic AEA levels and decreased FAAH activity are absent in SCD1 −/− mice, and the monounsaturated fatty acid (MUFA) products of SCD1, palmitoleic and oleic acid, inhibit FAAH activity in vitro at low micromolar concentrations. HFD markedly increases hepatic SCD1 activity in WT mice as well as in CB 1 R −/− mice with transgenic reexpression of CB 1 R in hepatocytes, but not in global CB 1 R −/− mice. Treatment of HFD-fed mice with the SCD1 inhibitor A939572 prevents the diet-induced reduction of hepatic FAAH activity, normalizes hepatic AEA levels, and improves insulin sensitivity. SCD1 −/− mice on an HFD remain insulin-sensitive, but develop glucose intolerance and insulin resistance in response to chronic treatment with the FAAH inhibitor URB597. An HFD rich in MUFA or feeding mice pure oleic acid fail to inhibit hepatic FAAH activity. We conclude that MUFAs generated via SCD1 activity, but not dietderived MUFAs, function as endogenous FAAH inhibitors mediating the HFD-induced increase in hepatic AEA, which then activates hepatic CB 1 R to induce insulin resistance.T he endocannabinoid system includes cannabinoid receptors, endogenous ligands that activate them-with arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG) being the two most widely investigated-and mechanisms for endocannabinoid biosynthesis and inactivation (1, 2). The latter occurs through cellular reuptake facilitated by a putative membrane transporter and is followed by enzymatic degradation by hydrolytic enzymes, including fatty acid amide hydrolase (FAAH) (3) and monoacylglycerol lipase (MAGL) (4, 5). FAAH was the first enzyme responsible for endocannabinoid hydrolysis to be purified and characterized. It exists as a dimer in its membrane-associated form, and possesses an unusual binding site and mechanism of catalytic action using a Ser-Ser-Lys triad (6, 7). Several endogenous compounds have been identified as good substrates for FAAH, including AEA and related fatty acid amides such as oleoylethanolamide (OEA) and palmitoylethanolamide, the tissue levels of which increase following genetic ablation or pharmacological inhibition of FAAH. Although FAAH can also degrade 2-AG in vitro (7), the enzyme that most specifically controls the levels of 2-AG is MAGL (4, 5), and 2-AG tissue levels remain unchanged in the absence of FAAH or FAAH activity in vivo (8).Endocannabinoids produce a broad range of...

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Section: Discussionmentioning

confidence: 99%

Monounsaturated fatty acids generated via stearoyl CoA desaturase-1 are endogenous inhibitors of fatty acid amide hydrolase

Liu

Çınar²,

Xiong³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

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“…4 For YCMC, marijuana use carries risks for disease exacerbation from poor diet associated with heavy use, 11,12 airway inflammation, 13 and treatment/medication nonadherence from being impaired or sleep deprived. 7,[14][15][16][17] Emerging evidence suggests antiinflammatory effects from cannabinoids, the active ingredients in marijuana 18,19 ; however, no studies have established their therapeutic value for youth, and the American Academy of Pediatrics opposes all use of marijuana for children and adolescents, including for "medical use."…”

Section: What This Study Addsmentioning

confidence: 99%

Alcohol and Marijuana Use and Treatment Nonadherence Among Medically Vulnerable Youth

et al. 2015

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BACKGROUND AND OBJECTIVE: Adolescents face peak risks for onset and intensification of alcohol and marijuana use. However, we know little about these behaviors and their associations with knowledge or treatment adherence among chronically ill youth, a medically vulnerable group.METHODS: Cross-sectional assessment of consented youth ages 9 to 18 years receiving care for asthma/cystic fibrosis, type 1 diabetes, arthritis, or inflammatory bowel disease (IBD) by using a self-administered online tool. Prevalence and correlates of risk behaviors and associations with knowledge and treatment adherence were estimated using descriptive statistics and logistic regression, controlling for demographics, mental health, and the multiclinic sampling frame.RESULTS: Of 403 consented youth (75.8% response), 51.6% were girls, 75.1% were white, and average age was 15.6 years. Of high school youth, 36.5% and 12.7% reported past-year alcohol use and binge drinking, respectively; 20% reported past-year marijuana use. Among high school youth, 53.1% and 37.2% answered correctly that alcohol can interfere with their medications and laboratory tests; youth answering incorrectly were 8.53 and 4.46 times more likely to drink and binge drink, respectively (P values , .001). Thirty-two percent and 8.3% of high school youth reported regularly forgetting or skipping their medications in the past 30 days; compared with past-year nondrinking youth, drinkers were 1.79 and 1.61 times as likely to report regularly missing or skipping medications (P values , .05).CONCLUSIONS: Alcohol and marijuana use are common among youth with chronic medical conditions. Alcohol use is associated with treatment nonadherence. Education and preventive interventions are warranted to ameliorate risk. WHAT'S KNOWN ON THIS SUBJECT:Increasing percentages of youth are living with chronic medical conditions. Although adolescents face peak risks for onset and intensification of alcohol and marijuana use, we know little about these behaviors and their associations with treatment adherence among chronically ill youth. WHAT THIS STUDY ADDS:This study quantifies alcohol and marijuana use behaviors among a heterogeneous sample of chronically ill youth in aggregate and by condition, and measures associations between alcohol use/binge drinking and knowledge about alcohol interactions with medications/laboratory tests and also treatment nonadherence.

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“…One large-sample, retrospective analysis found an association between marijuana use and higher caloric and alcohol consumption but did not find an association between current use and BMI or cardiovascular risk factors [6]. In a case-control study matched for age, sex, ethnicity, and BMI, marijuana use was associated with higher abdominal visceral fat, lower HDL-C, and lower adipocyte insulin resistance; however, there were no differences in total body fat, hepatic steatosis, insulin insensitivity, measures of beta-cell function, or glucose intolerance [7]. A study that used two large U.S. data sets found no significant difference in the multivariate-adjusted odds of obesity in marijuana users compared with abstainers, with the exception of users who smoked marijuana more than three times a week [8].…”

Section: Introductionmentioning

confidence: 52%

Estimating the association between metabolic risk factors and marijuana use in U.S. adults using data from the continuous National Health and Nutrition Examination Survey

Thompson

Hay

2015

Annals of Epidemiology

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Metabolic Effects of Chronic Cannabis Smoking

Cited by 127 publications

References 50 publications

Monounsaturated fatty acids generated via stearoyl CoA desaturase-1 are endogenous inhibitors of fatty acid amide hydrolase

Monounsaturated fatty acids generated via stearoyl CoA desaturase-1 are endogenous inhibitors of fatty acid amide hydrolase

Alcohol and Marijuana Use and Treatment Nonadherence Among Medically Vulnerable Youth

Estimating the association between metabolic risk factors and marijuana use in U.S. adults using data from the continuous National Health and Nutrition Examination Survey

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