ThePineapple - Journal Club #49: CBD | β-Caryophyllene | Metabolism | Intestinal permeability

Journal Club #49: CBD, β-Caryophyllene,Metabolism,Intestinal permeability

Week of 07-10-22

This week the world will witness science history in the making. NASA is going to present the first full color images of the James Webb Space Telescope on the 12th of July. This is very exciting and yet has absolutely nothing to do with cannabis. But it does mean that legions of science enthusiasts are going to be glued to their screens when that happens, possibly lighting up a blunt and most definitely having a snack. Speaking of snacks, this week’s journal club will bring you a number of articles on obesity, metabolism and intestinal permeability. So that is kind of related. And makes sense seeing how you will likely be snacking on free pizza while discussing these papers in your respective seminars. Enjoy.

Note: This is a post for cannabis scientists. A weekly curation of fresh papers that help advance our understanding of cannabis and the endocannabinoid system. 

β-Caryophyllene, a Dietary Cannabinoid, Protects Against Metabolic and Immune Dysregulation in a Diet-Induced Obesity Mouse Model.

Franco-Arroyo NN, Viveros-Paredes JM, Zepeda-Morales ASM, Roldán E, Márquez-Aguirre AL, Zepeda-Nuño JS, Velázquez-Juárez G, Fafutis-Morris M, López-Roa RI. 

J Med Food. 2022 Jul 6. 

Obesity is an abnormal or excessive accumulation of fat in the body that exacerbates metabolic and inflammatory processes, and impairs the health of afflicted individuals. β-caryophyllene is a natural sesquiterpene that is a dietary cannabinoid with anti-inflammatory properties and potential activity against metabolic diseases. In the present study, we evaluated the effect of β-caryophyllene on C57BL/6 mice using a diet-induced obesity model. Male mice were randomly assigned to the following groups over a 16-week period: (1) standard diet as lean control, (2) high-fat diet (HFD) as obese control, and (3) HFD + β-caryophyllene with β-caryophyllene at 50 mg/kg. Treatment with β-caryophyllene improved various metabolic parameters including increased total body weight, fasting glucose levels, oral-glucose tolerance, insulin tolerance, fasting triglycerides, adipocyte hypertrophy, and liver macrovesicular steatosis. β-caryophyllene also modulated the levels and expression of immune response factors including adiponectin, leptin, insulin, interleukin-6, tumor necrosis factor-a, and Toll-like receptor-4. Our data indicate that chronic supplementation with β-caryophyllene can improve relevant metabolic and immunological processes in obese mice. This protocol was approved by the Institutional Committee for Care and Use of Laboratory Animals from the University of Guadalajara with protocol code CUCEI/CINV/CICUAL-01/2022.

doi: 10.1089/jmf.2021.0166. Epub ahead of print. PMID: 35792574.

The effect of β-caryophyllene on food addiction and its related behaviors: A randomized, double-blind, placebo-controlled trial.

Alizadeh S, Djafarian K, Mofidi Nejad M, Yekaninejad MS, Javanbakht MH. 

Appetite 2022 Jul 6:106160. 

Food addiction (FA) is a psychological construct that may be involved in the etiology of obesity. The cannabinoid system is involved in the addictive-like food preferences by acting on the dopaminergic pathway of the brain. β-caryophyllene is a dietary cannabinoid that is a cannabinoid type 2 (CB2) receptor agonist. This study explored the impacts of β-caryophyllene supplementation on eating behavior, appetite, mental health, anthropometric parameters, body composition, and some hormones related to appetite in women with obesity diagnosed with FA. Women with obesity and FA, diagnosed by the Yale Food Addiction Scale Score (YFAS-S) ≥3, were randomly allocated to receive a β-caryophyllene softgel (n = 26) (100 mg/daily with meal) or placebo (n = 26) for 8 weeks. Anthropometric measurements, body composition, eating behavior, biochemical markers, dietary intake, appetite, stress, anxiety, and depression were evaluated during the study period. β-caryophyllene administration significantly reduced YFAS-S compared to the placebo group (changes in FA score: 1.5 ± 0.9 vs. - 0.7 ± 1.4; corrected P = 0.05). Serum levels of orexin-A significantly decreased in the β-caryophyllene group (p = 0.02); however, no significant difference was observed compared to the placebo group (corrected P = 0.09). β-caryophyllene supplementation had no significant effect on body composition, anthropometric indices, appetite, eating behavior, dietary intake, physical activity level, mental health, and levels of oxytocin and neuropeptide Y (NPY), compared to the placebo. β-caryophyllene supplementation may have beneficial effects on improving YFAS-S in women with obesity diagnosed with FA. TRIAL REGISTRATION: Iranian Registry of Clinical Trials identifier: IRCT20200914048712N1.

doi: 10.1016/j.appet.2022.106160. Epub ahead of print. PMID: 35809704.

Role of CB1 receptors in the acute regulation of small intestinal permeability: Effects of high-fat diet.

Cuddihey H, Cavin JB, Keenan CM, Wallace LE, Vemuri K, Makriyannis A, MacNaughton WK, Sharkey KA. 

Am J Physiol Gastrointest Liver Physiol. 2022 Jul 5.

The endocannabinoid system of the gastrointestinal tract is involved in the control of intestinal barrier function. Whether the cannabinoid 1 (CB1) receptor is expressed on the intestinal epithelium and acutely regulates barrier function has not been determined. Here we tested the hypothesis that ligands of the CB1 receptor acutely modulate small intestinal permeability and that this is associated with altered distribution of tight junction proteins. We examined the acute effects of CB1 receptor ligands on small intestinal permeability both in chow fed and 2-week high-fat diet (HFD) fed mice using Ussing chambers. We assessed the distribution of CB1 receptor and tight junction proteins using immunofluorescence and the expression of CB1 receptor using PCR. A low level of CB1 expression was found on the intestinal epithelium. CB1 receptor was highly expressed on enteric nerves in the lamina propria. Neither the CB1/CB2 agonist CP55,940 nor the CB1 neutral antagonist AM6545 altered the flux of 4Kda FITC dextran (FD4) across the jejunum or ileum of chow-fed mice. Remarkably, both CP55,940 and AM6545 reduced FD4 flux across the jejunum and ileum in HFD-fed mice that have elevated baseline intestinal permeability. These effects were absent in CB1 knockout mice. CP55,940 reduced the expression of claudin-2, while AM6545 had little effect on claudin-2 expression. Neither ligand altered the expression of ZO-1. Our data suggest that CB1 receptor on the intestinal epithelium regulates tight junction protein expression and restores barrier function when it is increased following exposure to a HFD for 2 weeks.

doi: 10.1152/ajpgi.00341.2021. Epub ahead of print. PMID: 35787179.

Effects of chronic cannabidiol in a mouse model of naturally occurring neuroinflammation, neurodegeneration, and spontaneous seizures. 

Dearborn JT, Nelvagal HR, Rensing NR, Takahashi K, Hughes SM, Wishart TM, Cooper JD, Wong M, Sands MS. 

Sci Rep. 2022 Jul 4;12(1):11286. 

Cannabidiol (CBD) has gained attention as a therapeutic agent and is purported to have immunomodulatory, neuroprotective, and anti-seizure effects. Here, we determined the effects of chronic CBD administration in a mouse model of CLN1 disease (Cln1-/-) that simultaneously exhibits neuroinflammation, neurodegeneration, and spontaneous seizures. Proteomic analysis showed that putative CBD receptors are expressed at similar levels in the brains of Cln1-/- mice compared to normal animals. Cln1-/- mice received an oral dose (100 mg/kg/day) of CBD for six months and were evaluated for changes in pathological markers of disease and seizures. Chronic cannabidiol administration was well-tolerated, high levels of CBD were detected in the brain, and markers of astrocytosis and microgliosis were reduced. However, CBD had no apparent effect on seizure frequency or neuron survival. These data are consistent with CBD having immunomodulatory effects. It is possible that a higher dose of CBD could also reduce neurodegeneration and seizure frequency.

doi: 10.1038/s41598-022-15134-5. PMID: 35789177; PMCID: PMC9253004.