Hemp in Animal Diets—Cannabidiol
Abstract
:Simple Summary
Abstract
1. Introduction
- Hemp classification, laws and regulations on its use;
- CBD structure, extraction, and the mechanism of action in the body;
- CBD anti-inflammatory, hepatic and antioxidative effects;
- Hemp in livestock feeding.
2. Description of Cannabis
2.1. Categorization and Botanical Features
2.2. Laws and Legal Restrictions
2.3. Nutrients
3. CBD Structure
3.1. Chemical Structure
- (1)
- In the cyclohexene ring at C-1 with a methyl group,
- (2)
- In the phenolic ring at C-1ʹ and C-5ʹ with a hydroxyl group, and
- (3)
- In the phenolic ring at C-3ʹ with the pentyl chain.
3.2. Biosynthesis
4. Methods of Extraction
4.1. Soxhlet Method
4.2. Immersion Method (Maceration)
4.3. Supercritical Fluids Extraction (SFE)
4.4. Supercritical Hot Water Extraction
4.5. High-Performance Liquid Chromatography (HPLC)
5. Mechanism of Action
Endocannabinoid System (ECS)
6. Analgesic and Anti-Inflammatory Effects of CBD
7. Hepatotoxicity and Tolerability
8. CBD Health Benefits
8.1. Direct Antioxidant Activity
8.2. Indirect Antioxidant Activity
9. Hemp Use in Livestock Diet
10. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Species | Varieties | |
---|---|---|
Domesticated | Wild | |
Cannabis sativa | sativa | spontanea |
Cannabis indica | indica | kafiristanica |
Main units | Description | Functions | Compounds |
---|---|---|---|
Endocannabinoids | Lipid compounds metabolized in multiple enzymatic pathways | Binds to the receptors, recovers homeostasis after cellular stress, interacts with the human endocannabinoid system [75,76] | Neurotransmitters: anandamide-N-arachidonylethanolamine (AEA) and 2-arachidonylglycerol (2-AG) |
Cannabinoid receptors | Able to stimulate receptors, produces physiological responses | G protein-coupled receptors (GPCRs), also known as 7-transmembrane receptors (7-TM receptors) and their endogenous ligands [3] | |
CB1 receptors | Found in the central nervous system, e.g., brain and spinal cord, some cells in the immune system, muscles, liver, kidney, lungs, reproductive system, and adipose tissues | Mediates the release of neurotransmitters: acetylcholine, noradrenaline, dopamine, gamma-aminobutyric acid (GABA), and glutamate Increases reactive oxygen species (ROS) production and pro-inflammatory responses such as tumor necrosis factor-alpha synthesis (TNF-α) [77] | |
CB2 receptors | Active receptors in the peripheral nervous system, e.g., immune system, liver, kidney, adipose tissues, and spleen | Releases cytokines, adjusts immune cell migration [78,79,80] without psychoactive functions [53], decreases ROS, (TNF-α) levels, oxidative stress, and inflammation [77] | |
Enzymes | Involved in synthesis and catabolism [81] | Fatty acid amide hydrolase (FAAH), monoacylglycerol lipase |
Species | Type of Pain or Disorder | CBD Amount and Duration | Results | Reference |
---|---|---|---|---|
Dogs (16) | OA a pain and lameness | CBD oil b 2 mg/kg every 12 h, 4 weeks | Significant reduction in pain, no significant difference in lameness degree | [91] |
Dogs (37) | Chronic maladaptive pain | CBD oil c 0.25 mg/kg once a day for 3 days, then every 12 hrs | Significant reduction in pain, increase in mobility and quality of life | [92] |
Dogs (20) | OA pain | 20 mg/day (0.5 mg/kg) naked CBD d, 50 mg/day (1.2 mg/kg) naked CBD, 20 mg/day liposomal CBD e | Significant reduction in pain, increase in mobility | [93] |
Rats | RA f pain | CBD gels g (0.6, 3.1, 6.2 or 62.3 mg/day) for 4 days after arthritis | Significant decrease in joint swelling, inflammation biomarkers, pain scores, and synovial membrane thickness | [94] |
Rats | Spared nerve injury | Repeated CBD injections h (0.1–1.0 mg/kg) | Declined mechanical allodynia, anxiety-like behavior | [95] |
Rats | Exposed to pain (paw pressure and tail-flick test) | Intra-ventrolateral periaqueductul grey (PAG) microinjections of CBD (1.5, 3 and 6 nmol) | Reduction in activity of ON and OFF neurons, anti-nociceptive responses in the tail-flick test | [96] |
Mice | Sciatic nerve injury (neuropathic pain i) | CBD-containing gelatine j, orally ad libitum | Significant reduction in pain after 3 weeks of surgery | [97] |
Mice | Type 1 diabetes | 5 mg/kg CBD k, 5 times weekly for 10 weeks | Significant reduction in leukocyte activation, increase in pancreatic microcirculation | [98] |
Mice | Spinal cord injury | Intraperitoneal injections of CBD l 1.5 mg/kg, for 10 weeks following injury | Reduction in pro-inflammatory cytokine, prevented thermal sensitivity development | [99] |
Human | Peripheral neuropathic pain | Transdermal CBD (250 mg CBD/3 fl. Oz) | Significant reduction in severe pain, cold and itchy sensations | [100] |
Human (72 children, 60 adults) | Treatment-resistant epilepsy | 5 mg/kg/day CBD m, titrated up to 50 mg/kg/day | Reduction in seizure frequency and severity | [101] |
Human | Dravet syndrome n | 100 mg/mL CBD o, oral solution at 2–10 mg/kg/day, titrated up to 25–50 mg/kg/day. Evaluating seizures at 12-week intervals through 96 weeks CBD p 20 mg/kg of body weight per day + standard antiepileptic treatment | Decrease in motor seizures and improved patients conditions | [102,103] |
Species | Experiment Duration | Hemp Type and Amount | Results | Reference |
---|---|---|---|---|
19-week-old Bovan White | 12 weeks | HS a: 10, 20% HSO b: 4, 8, 12% | Significant decrease in the expression of hepatic fatty acid desaturase 1 and 2 (genes for the desaturation of polyunsaturated fatty acids) | [107] |
19-week-old Lohmann LSL- Classic White | 12 weeks | HS: 10, 20, 30% HSO: 4.5, 9.0% | No significant effects on proteins, glucose, uric acid, and cholesterol plasma levels HS 10, 20% and HSO 4.5%: The significant lowest level of the gamma-glutamyl transferase, reduction in liver damage HS: Significant decrease in AST c levels, possible protective effect of HS (10, 20%) and HSO (4.5%) on liver damage | [108] |
1-day-old male Ross 308 | 35 days | EF d: 6% HS: 3, 4, 5% HS + EF: (3% and 6%, 4% and 6%, 5% and 6%) | HS + EF (5 and 6%): Positive increase in the vitamin E level in the liver | [109] |
1-day-old Caribro-Vishal | 42 days | HS: 0.2% HS + DS: e (0.2% and 0.3) HS: 0.3% HS + DS: (0.3% and 0.3) BMD f: 0.025% | Significant reduction in triglyceride, LDL g and total cholesterol levels, significant decrease in AST and ALT h, improvement in serum lipid and liver enzyme levels | [110] |
Species | Health Status | CBD Amount and Duration | Results | Reference |
---|---|---|---|---|
Dogs | OA pain and lameness | CBD oil: 2, 8 mg/kg every 12 h 4 weeks | A significant increase in serum ALP a No observable side effects | [91] |
Dogs | Idiopathic epilepsy | CBD-infused oil: 2.5 mg/kg twice daily 12 weeks | A significant increase in serum ALP | [117] |
Dogs and cats | Healthy | CBD chews: 2 mg/kg orally twice daily 12 weeks | No significant changes in serum chemistry Safe in dogs Adverse effects of excessive licking and head shaking for cats | [118] |
8-week-old mice | Healthy | CBD extract: (acute toxicity, 24 h) 246, 738, or 2460 mg/kg (sub-acute toxicity, daily doses) 61.5, 184.5, or 615 mg/kg for 10 days | 2460 mg/kg: A significant increase in LBW b, plasma ALT c, AST d, and total bilirubin, evidence of hepatotoxicity 615 mg/kg: A moderate increase in LBW, ALT, AST, and total bilirubin | [119] |
Laying Hens | Experiment Duration | Hemp Type and Amount | Results | Reference |
---|---|---|---|---|
19-week-old Lohmann white | 6 weeks | HO a or HΩ b: 4 or 8% | Significant increase in total n-3 PUFAs c and a significant reduction in MUFAs d (both in egg yolks) in all groups No effect on performance and egg yolk n-6 PUFAs | [140] |
19-week-old Bovan white | 12 weeks | HO: 4, 8, 12% HS e: 10, 20% | 20% HS: Significantly increased egg weight Significant increase in the total egg yolk n-3 fatty acid content No effect on average hen-day egg production | [107] |
30-week-old Bovan white | 19 weeks | HSC f: 10, 20, 30% | Significant reduction in body weight in all treatments No effect on performance | [141] |
30-week-old Bovan white | 3-week acclimation phase + 16 weeks | HSC: 10, 20, 30% | Significant increase in egg PUFAs No detectable cannabinoid residue level in eggs, blood, breast meat, body fat, liver, kidneys and spleen | [142] |
Lohmann Brown | 12 weeks | HS: 3, 6, 9% | 3% HS: Significantly increased egg production and mass 9% HS: Significantly decreased egg shell thickness Positive effect on tibia Ca g concentration Significant decrease in egg yolk cholesterol Significant increase in breaking strength of tibia in all groups | [143] |
Broilers | Experiment Duration | Hemp Type and Amount | Results | Reference |
---|---|---|---|---|
1-day-old male Ross 308 | From days 9 to 35 (challenge with Clostridium perfringens) | HE a: 15 g/kg (12% CBD) | Upregulation in gene expression involved in gut barrier function Increase in the activity of gut bacterial enzyme | [144] |
150-day-old mixed-sex Ross 308 | 21 days | HO or HΩ: 3 or 6% | Significant increase in total n-3 PUFAs in thighs and breasts Significant reduction in MUFAs in thighs No effect on performance and meat n-6 PUFAs | [140] |
1-day-old male Ross 308 | 35 days | EF b: 6% HS: 3, 4, 5% HS + EF: (3% and 6%, 4% and 6%, 5% and 6%) | HS + EF (4% and 6%): Significantly increased body weight, decreased n-6/n-3 fatty acid ratio in breast meat HS, HS + EF (40 and 60 g/kg), HS + EF (50 and 60 g/kg): Positive effect on bone strength | [109] |
1-day-old male Ross 308 | 6 weeks | HS: 2.5, 5, 7.5% DOS c: 0.1% | HS 2.5%: Significant reduction in average daily feed intake and ADG d HS and DOS: No significant effect on complete blood count, antibody production and relative weight of bursa and spleen | [145] |
1-day-old Caribro-Vishal | 42 days | HS: 0.2%, HS + DS e: (0.2% and 0.3) HS: 0.3% HS + DS: (0.3% and 0.3) BMD f:0.025% | Significant reduction in Coliform count in caecum and jejunum No effect on performance, jejunal villus height and crypt depth | [110] |
Other Species | Experiment Duration | Hemp Type and Amount | Results | Reference |
---|---|---|---|---|
7-day-old Japanese quails | 5 weeks | HS: 5%, 10%, 20% | 20% HS: Significant decrease in breast meat cooking loss Significant reduction in palmitoleic and oleic FAs in breast meat Significant increase in meat linoleic and linolenic acid | [146] |
8-week-old laying quails | 6 weeks | HS: 5%, 10%, 20% | Significant linear increase in egg linoleic and linolenic FAs Significant decrease in egg palmitoleic and oleic FAs | [146] |
Swedish red dairy cows | 5 weeks, 1 week (pre-experimental period) | HSC: 14.3, 23.3, 31.8% (dry matter) | 14.3% HSC: Higher milk yield 23.3 or 31.8% HSC: No benefits in milk performance | [147] |
Steers | 166 days | Full-fat HS: 9 or 14% | Significant increase in CLA a level, also trans and saturated fats in tissues No effect on DMI b, ADG, carcass traits | [148] |
Male Holstein cattle | 14 days | IH c: 25 g mixed in 200 g of grain (target daily dose of 5.5 mg/kg CBDA d) | Significant increase in lying behavior Significant decrease in cortisol level and PGE2 e | [149] |
Male Holstein calves | Single oral dose, 4 days | IH: 35 g (target dose of 5.4 mg/kg CBDA) | No significant changes in serum parameters | [150] |
Carpathian goats | 31 days | HSO f: 93 g/day | Higher milk fat content, increase in conjugated fatty acid and PUFAs No effect on milk yield | [151] |
Pregnant sows | 10 days (before farrowing), 21 days (lactation period) | HS: 2% (10 days) 5% (21 days) | Significant improvement in sows oxidative status during lactation Positive effect on antioxidant enzyme activities (TAC g, NO h) Significant decrease in plasma lipid peroxidation until weaning | [152] |
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Fallahi, S.; Bobak, Ł.; Opaliński, S. Hemp in Animal Diets—Cannabidiol. Animals 2022, 12, 2541. https://doi.org/10.3390/ani12192541
Fallahi S, Bobak Ł, Opaliński S. Hemp in Animal Diets—Cannabidiol. Animals. 2022; 12(19):2541. https://doi.org/10.3390/ani12192541
Chicago/Turabian StyleFallahi, Sepideh, Łukasz Bobak, and Sebastian Opaliński. 2022. "Hemp in Animal Diets—Cannabidiol" Animals 12, no. 19: 2541. https://doi.org/10.3390/ani12192541