The Information on this website and training provided is for informational purposes only. It should not be used or construed as medical advice or used or relied upon for any diagnostic or treatment purposes. The information is provided as a resource and not used for patient education. There is no patient physician relationship and should not be used as a substitute for a professional diagnosis or treatment. By using this website you waive all claims which might arise from the use of this website or any information contained on this website or links provided and you release any person or entity connected with this website from any liabilities.
Cannabidiol (CBD) and tetrahydrocannabinol (THC) are both naturally occurring compounds found in Cannabis. 1 Delta-9-tetrahydrocannabinol (∆9-THC) was the first cannabinoid to be discovered and studied and is well known for its psychoactive effects. 2 Cannabidiol (CBD), like ∆9-THC is a major phytocannabinoid and is non-psychotropic.3 The endocannabinoid system (ECS) consists of two types of endogenous G-protein coupled cannabinoid receptors, CB1 and CB2. The CB1 receptor is located primarily in the central and peripheral nervous system and found abundantly in the brain. CB2 receptors are distributed widely in the tissues of the immune system. 3
Obesity is a major public health concern increasing the risk of diabetes, cancer, and cardiovascular disease. Worldwide nearly 1.9 billion adults are overweight and 600 million are obese. 4 The development of obesity involves a complex interaction between genetics, diet, and environmental factors but there are differences in the bacterial composition of the microbiome in individuals who are overweight or obese. The microbiome is the genetic material of all the microbes including bacteria, fungi, protozoa, and viruses that live on and inside the human body(microbiota).5 The majority live in our gut, particularly in the large intestine. The gut microbiota can alter host body weight and plays a role in the development of diet-induced obesity. Several studies are looking at alterations in the microbiome leading to obesity. 6
“It is well established that the endocannabinoid system is involved in both the regulation of energy balance and the development of obesity. Gut microbiota regulates adipogenesis through endocannabinoid signaling”. 7 The endocannabinoid system interacts with several neuropeptides that modulate hunger and satiety including ghrelin 8 and leptin. 4 Leptin reduces food intake by upregulating anorexigenic (appetite-reducing) neuropeptides and ghrelin is a potent orexigenic (appetite-stimulating) brain-gut peptide with lipogenic and diabetogenic effects 4,8
Microbial DNA sequencing has demonstrated that the mammalian gut microbiota is predominantly composed of four bacterial phyla: Gram-negative Bacteroidetes and Proteobacteria and Gram-positive Actinobacteria and Firmicutes. Studies investigating the possible relationship between gut microbiota composition and obesity were in a leptin-deficient ob/ob mouse model. This model revealed a reduction in the abundance of Bacteroidetes and a proportional increase in Firmicutes.9 A study conducted by Ley et al. 10 observed analogous differences in the distal gut microbiota in human obesity. The authors suggest that Firmicutes produce more complete metabolism of a given energy source than do Bacteroidetes, promoting more efficient absorption of calories and subsequent weight gain.
In a recent study chronic administration of THC prevented weight gain in diet-induced obesity in mice and the investigators suggest that these actions may be mediated in part by modifications of the gut microbiota. The same study found that in diet-induced obesity in mice chronic THC administration increased Akkermansia mucinphilia levels. Akkermansia mucinphilia has been shown to regulate fat storage and adipose tissue metabolism leading to weight loss. 7
“Traditionally, adipose tissues have been divided into subcategories of white adipose tissue (WAT) and brown adipose tissue (BAT) according to their function and morphology. Brown adipose tissue is characterized by small lipid droplets and a high density of mitochondria which leads to the brown appearance. White adipose tissue stores and releases fatty acids and these fatty acids are stored in a large unilocular lipid droplet giving it a white appearance. Brown adipose tissue is involved in thermogenesis and caloric expenditure during rest and exercise”. 11 White adipose tissue is involved in fat storage and endocrine secretion of hormones. In response to various types of stimuli white adipose tissue can become beige adipose tissue (browning of white fat,). “Recruitment of the brown-like phenotype in white adipocytes and activation of existing brown adipocytes are currently being investigated as a potential treatment for obesity and recent studies suggest that CBD may play a role in the browning of adipocytes and thus may be a potentially promising therapeutic agent in the prevention of obesity.”12
Therefore, I am proposing a research study to determine if CBD has the same effect on the gut microbiota profile as THC and whether CBD can halt the progression of obesity. This study could address the research gap that exists since previous studies investigating CBD’s effect on food intake, food preferences, and weight gain in rats have shown contradictory results some demonstrate CBD induced a decrease in weight gain while other studies have shown no significant impact on food intake or body weight in mice and rats. 13
References
1. Rudd, J. CBD vs THC-What are the Main Differences? https://www.analyticalcannabis.com/articles/cbd-vs-thc-what-are-the-main-differences-297486. Published Feb 20, 2018. Accessed March 21, 2021.
2. Pisanti, S et al. Cannabidiol: State of the art and new challenges for therapeutic applications. Pharmacology & Therapeutics 2017.http://dx.doi.org/10.1016/j.pharmthera.2017.02.041
3. Maroon J, Bost J. Review of the neurological benefits of phytocannabinoids. Surg Neurol Int. 2018;9:91. Published 2018 Apr 26. doi:10.4103/sni.sni_45_18
4. Rossi F, Punzo F, Umano GR, Argenziano M, Miraglia Del Giudice E. Role of Cannabinoids in Obesity. Int J Mol Sci. 2018 Sep 10;19(9):2690. doi: 10.3390/ijms19092690. PMID: 30201891; PMCID: PMC6163475.
5. Ferranti EP, Dunbar SB, Dunlop AL, Corwin EJ. 20 things you didn't know about the human gut microbiome. J Cardiovasc Nurs. 2014;29(6):479-481. doi:10.1097/JCN.0000000000000166
6. Castaner O, Goday A, Park YM, et al. The Gut Microbiome Profile in Obesity: A Systematic Review. Int J Endocrinol. 2018;2018:4095789. Published 2018 Mar 22. doi:10.1155/2018/4095789
7. Cluny NL, Keenan CM, Reimer RA, Le Foll B, Sharkey KA. Prevention of Diet-Induced Obesity Effects on Body Weight and Gut Microbiota in Mice Treated Chronically with Δ9-Tetrahydrocannabinol. PLoS One. 2015 Dec 3;10(12):e0144270. doi: 10.1371/journal.pone.0144270. PMID: 26633823; PMCID: PMC4669115.
8. Lim CT, Kola B, Feltrin D, et al. Ghrelin and cannabinoids require the ghrelin receptor to affect cellular energy metabolism. Mol Cell Endocrinol. 2013;365(2):303-308. doi:10.1016/j.mce.2012.11.007
9. Clarke SF, Murphy EF, Nilaweera K, Ross PR, Shanahan F, O'Toole PW, Cotter PD. The gut microbiota and its relationship to diet and obesity: new insights. Gut Microbes. 2012 May-Jun;3(3):186-202. doi: 10.4161/gmic.20168. Epub 2012 May 1. PMID: 22572830; PMCID: PMC3427212.
10. Ley, R., Turnbaugh, P., Klein, S. et al. Human gut microbes associated with obesity. Nature 444, 1022–1023 (2006). https://doi.org/10.1038/4441022a
11. Kaisanlahti A, Glumoff T. Browning of white fat: agents and implications for beige adipose tissue to type 2 diabetes. J Physiol Biochem. 2019;75(1):1-10. doi:10.1007/s13105-018-0658-5
12. Parray HA, Yun JW. Cannabidiol promotes browning in 3T3-L1 adipocytes. Mol Cell Biochem. 2016 May;416(1-2):131-9. doi: 10.1007/s11010-016-2702-5. Epub 2016 Apr 11. PMID: 27067870.
13. Bielawiec P, Harasim-Symbor E, Chabowski A. Phytocannabinoids: Useful Drugs for the Treatment of Obesity? Special Focus on Cannabidiol. Front Endocrinol (Lausanne). 2020;11:114. Published 2020 Mar 4. doi:10.3389/fendo.2020.00114
The onset and duration of cannabis is different based on the mode of administration. The main difference between ingestion and inhalation of cannabis is the delayed onset of action with ingestion. When ingesting cannabis the delayed onset may result in the consumption of a greater than intended amount often resulting in adverse effects but for medicinal cannabis users with chronic conditions, one of the advantages of edibles may be the longer duration of action. Even in states where medicinal cannabis is legal smoking cannabis in public is often still prohibited.1
The route of administration determines a drug’s pharmacokinetics, Pharmacokinetics is defined as the time and process through which a chemical such as Δ9 -THC, enters the body, travels to various tissues and organs, and is metabolized before elimination. After consuming an edible cannabis product Δ9 -THC is absorbed into the bloodstream and travels via the portal vein to the liver, where it undergoes first-pass metabolism. Liver enzymes (primarily the cytochrome P450 system) hydroxylates Δ9 -THC to form 11-hydroxytetrahydrocannabinol (11-OH-THC). 11-OH-THC is more potent than Δ9 -THC. When cannabis is inhaled through smoking or vaping, Δ9 -THC reaches the brain, takes initial effect within minutes, and shows peak effect in about 20 to 30 minutes, with the psychoactive effects tapering off within 2 to 3 hours.1
It takes longer for the initial psychoactive effect of edibles (30 to 90 minutes) to be felt, the resulting “high” is longer-lasting, with a peak occurring at 2 to 4 hours after ingestion. The amount of Δ9 -THC in edibles can vary across a single product and across batches formulated at different times, making it difficult for users to estimate how much Δ9 -THC they have consumed
Another challenge related to edibles is the cannabis extracts used to produce edibles can be quite different from the actual plant material. There is considerable variation in the amount and homogeneity of cannabinoids in the final product.
Since there are no national standards for cannabis labeling. Consumers should receive information about the products they are purchasing that have been tested by a third-party lab. This can help to verify the product's potency, purity, and safety. Consumers should be advised to request the product's certificate of analysis which will provide the consumer with information regarding cannabinoids and terpenes present. their potency in addition to any residual solvents, pesticides, microbial pathogens, and heavy metals present in the product. 2
1. Barrus DG, Capogrossi KL, Cates SC, et al. Tasty THC: Promises and Challenges of Cannabis Edibles. Methods Rep RTI Press. 2016; 2016:10.3768/rtipress.2016. op.0035.1611. doi:10.3768/rtipress.2016. op.0035.1611
2. O’Driscoll A. Why you should read the label on your cannabis product. https://www.leafly.com/news/cannabis-101/how-to-read-cannabis-product-label Published April 30, 2020. Accessed February 27, 2021New Paragraph
