Location: Food Animal Metabolism Research
Project Number: 3060-32420-003-002-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Sep 1, 2020
End Date: Aug 31, 2024
Objective:
Industrial hemp is grown commercially as a fiber source and as a source of cannabidiol (CBD), a compound which is commonly used for its purported beneficial effects on human health. Historically, hemp has served as a feed source for livestock, especially cattle. We anticipate that as the acreage of industrial hemp increases in the U.S., hemp seed cake, baled hemp, hemp forage, and other hemp byproducts will increasingly become available to livestock producers as feed ingredients. For CBD producers, hemp byproducts (i.e., hemp seed cake) represents a costly byproduct for disposal even though hemp products are -in theory- viable, nutritious animal feeds. By statute, unprocessed industrial hemp can contain a maximum of 0.3% tetrahydrocannabinol (THC; dry matter basis) but there are no limitations to the amount of CBD that the plant may contain. Remarkably, extant varieties of hemp are reported to contain as much as 8% CBD. The current trend in industrial hemp production is to maximize the concentration of CBD without infringing on the 0.3% regulatory threshold for THC. Although CBD is not considered psychotropic, it cannot be considered physiologically inactive as it has demonstrated anti-seizure properties, is commonly used in the treatment of epileptic patients, and is thought to have beneficial effects on gastrointestinal health and as a cancer therapy. Through the interaction with the endocannabinoid system, CBD is thought to have orexigenic, anorexigenic, and anti-inflammatory properties. The CBD content of hemp is of sufficient concern that the Association of American Feed Control Officials has categorized CBD as a "drug" and does not recommend feeding hemp products to livestock.
While the pharmacologic, toxicologic, and metabolic effects of CBD have been extensively studied in non-ruminant species, there has been essentially no research describing physiologic endpoints or the fate of either THC or CBD in food animals. The use of industrial hemp or its byproducts as ‘value added’ animal feeds cannot be realized until production and physiologic effects of dietary hemp are understood in target animal species. Further, the fate and/or clearance of pharmacologically active phytochemicals such as CBD and THC must be described before animals on hemp feeding regimens can be marketed.
Objectives of the collaborative research projects are to determine: 1) performance endpoints, 2) immune function endpoints, 3) stress hormone endpoints, 4) cannabinoid concentration endpoints 5) gastrointestinal health and function endpoints, and 6) ovary/uterine function in feedlot cattle fed hemp seed cake during the finishing period.
Approach:
A feedlot study will be conducted in cooperation with the USDA ARS Northern Plains Research Laboratory (NPRL; Mandan, ND) and North Dakota State University (NSDU). Twenty feedlot steers or heifers will be purchased, housed at the NDSU Beef Cattle Research Center, and stepped-up to a final finishing ration by increasing the percentage of corn in the ration by approximately 10% each week until a final finishing ration energy level is reached. Steers will then be sorted into 5 groups of pens of 4 animals each on what will be considered study day 0. Cattle will be fed with a Calan gate feeding or other system that allows for individual feed intake data to be collected. Control cattle (n=4) will receive a hemp-free finishing diet. The hemp group (n = 16) will receive pressed hemp seed cake (or other suitable hemp product) as replacement for a portion of the fiber in the control diet. Cattle will be grown for an approximate 112-day (16 week) feeding period. Feed intakes will be measured as appropriate for the rearing facility. Feed samples will be collected bi-weekly to determine CBD content and THC contents. Blood serum and plasma samples will be taken daily from the jugular on study days 0, 1, 2, 4, and 6 and then weekly or biweekly thereafter for CBD, THC, and/or metabolite/hormone analyses. Cattle will be weighed at weekly or bi-weekly blood collection times. Urine will be collected at mutually agreed upon intervals. After 16 weeks, the hemp-containing finishing ration will be replaced with a control finishing ration (withdrawl day 0) and urine and tissue samples will be collected after 0, 1, 4, and 8 day withdrawl periods. Urine and tissue CBD and THC (or appropriate metabolite) content will be measured and each matrix will be used for the development and validation of rapid screening assays (field or laboratory based). Physiologic endpoints will include tissue weights and mRNA abundance of endocannabinoid receptors 1 and 2 (CB1 and CB2) will be determined in rumen, small intestine, uterus, ovary, and hypothalamus. Tissues also will be fixed and histological and immunocytochemistry approaches will be used to examine tissue structure and localization of CB1 and CB2. In vitro oxygen consumption and mitochondrial function also will be assessed in rumen and small intestine using Oroboros O2k respirometry. Hepatic and renal Cytochrome P450 activities in control and treated animal tissues will be measured using standard substrates.