Review: Nutritional aspects of hemp-based products and their effects on health and performance of monogastric animals

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“Sustainable agriculture aims to produce food and feed that ensure food security and play a key role in environmental protection. For this, producers, supported by scientific research, are investigating new protein alternatives for animals that guarantee high performance and preserve their health.

Among these, hemp (Cannabis sativa L.) is gaining great success, both for its active role in environmental conservation and for the high nutritional profile of the seeds (20-30% carbohydrates, 25-30% proteins easy to digest and rich in essential amino acids, and 25-35% lipids with a balanced fatty acid composition), also ensured by the co-products, particularly seed cakes (30-34% proteins and 10-12% lipids).

However, the last scientific report by the European Food Safety Authority for the use of hemp-based products in the feed sector now dates back to 2011. For this reason, the objective of this review, in addition to outlining the nutritional profile of hempseeds (HSs) and co-products, aims to investigate their use in the monogastric sector, particularly in the diets of pigs, broilers, and laying hens, by summarising the main works in the literature up to 2023, investigating the effects on animal health and performances.

The reported results showed that the addition of 50 g/kg of HSs and HS oil improved the nutritional profile of milk and colostrum in lactating sows, particularly the lipid profile, positively affecting the health of piglets. For broilers, the inclusion of HSs (20 g/kg) resulted in better values on growth performance. This was not matched by the addition of HS oil (up to 60 g/kg). In particular, although a better polyunsaturated fatty acid profile was observed, the results on growth performance were contradictory. The same trend was observed for HSs cakes with 50, 150, and 200 g/kg inclusion. For laying hens, the inclusion of HSs (up to 250 g/kg), HS oil (up to 300 g/kg), and HSs cake (up to 150 g/kg) increased the nutritional and functional profile of the eggs, safeguarding performance and animal welfare. However, despite the promising results, the function of hemp-based products in the diet of monogastric animals needs to be further investigated to identify the optimal level of inclusion and timing of administration, necessary to ensure high performance and health of the animals.”

https://pubmed.ncbi.nlm.nih.gov/38211413/

“Hempseeds and hemp-based products are characterised by a high nutritional aspect.”

https://www.sciencedirect.com/science/article/pii/S1751731123003750?via%3Dihub

Chemical Analysis of the Antihyperglycemic, and Pancreatic α-Amylase, Lipase, and Intestinal α-Glucosidase Inhibitory Activities of Cannabis sativa L. Seed Extracts

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“Cannabis is considered (Cannabis sativa L.) a sacred herb in many countries and is vastly employed in traditional medicine to remedy numerous diseases, such as diabetes.

This research investigates the chemical composition of the aqueous extracts from Cannabis sativa L. seeds. Furthermore, the impact of these extracts on pancreatic α-amylase and lipase, and intestinal α-glucosidase enzymes is evaluated, as well as their antihyperglycemic effect. Analysis of the chemical composition of the aqueous extract was conducted using high-performance liquid chromatography with a photodiode array detector (HPLC-DAD). In contrast, the ethanol, hexanic, dichloromethane, and aqueous extract compositions have been established. Additionally, the inhibitory effects of ethanolic, dichloromethane, and aqueous extracts on pancreatic α-amylase and lipase, and intestinal α-glucosidase activities were evaluated in vitro and in vivo.

The results of HPLC analysis indicate that the most abundant phenolic compound in the aqueous cannabis seed extract is 3-hydroxycinnamic acid, followed by 4-hydroxybenzoic acid and rutin acid. Moreover, administration of ethanolic and aqueous extracts at a dose of 150 mg/Kg significantly suppressed postprandial hyperglycemia compared to the control group; the ethanolic, dichloromethane, and aqueous extracts significantly inhibit pancreatic α-amylase and lipase, and intestinal α-glucosidase in vitro. The pancreatic α-amylase test exhibited an inhibition with IC50 values of 16.36 ± 1.24 µg/mL, 19.33 ± 1.40 µg/mL, 23.53 ± 1.70 µg/mL, and 17.06 ± 9.91 µg/mL for EAq, EDm, EET, and EHx, respectively. EET has the highest inhibitory capacity for intestinal α-glucosidase activity, with an IC50 of 32.23 ± 3.26 µg/mL. The extracts inhibit porcine pancreatic lipase activity, demonstrating their potential as lipase inhibitors. Specifically, at a concentration of 1 mg/mL, the highest inhibition rate (77%) was observed for EDm. To confirm these results, the inhibitory effect of these extracts on enzymes was tested in vivo. The oral intake of aqueous extract markedly reduced starch- and sucrose-induced hyperglycemia in healthy rats. Administration of the ethanolic extract at a specific dose of 150 mg/kg significantly reduced postprandial glycemia compared with the control group.

It is, therefore, undeniable that cannabis extracts represent a promising option as a potentially effective treatment for type 2 diabetes.”

https://pubmed.ncbi.nlm.nih.gov/38202676/

“The cultivation of cannabis seeds in Morocco has sparked interest in exploring their potential applications. Our research has revealed their ability, both in vitro and in vivo, to inhibit the activity of ⍺-amylase, pancreatic lipase, and intestinal ⍺-glucosidase. These enzymes play a crucial role in sugar digestion, and the observed hypoglycemic effects suggest the potential of our hemp seed extract in diabetes prevention. This effect can be explained by the presence of phenolic compounds as well as the notable antioxidant potency of the extracts, as substantiated by our prior investigations.The results of this study show interesting anti-diabetic activity, suggesting its application in the medical field and food industry. “

https://www.mdpi.com/1420-3049/29/1/93

Medical Cannabis Increases Appetite but Not Body Weight in Patients with Inflammatory Bowel Diseases

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“We aimed to elucidate the effect of Medical Cannabis (MC) on appetite and nutritional status among patients with inflammatory bowel disease (IBD). A case series of patients with IBD were initiating treatment with MC for disease-related symptoms, at the IBD clinic of a tertiary referral medical center. Patients’ demographics, anthropometrics, medical history and treatment and MC use were systematically recorded. An appetite and food frequency questionnaire (SNAQ and FFQ) were filled before, and at 3 and 6 months of treatment. Patients with IBD initiating MC were enrolled (n = 149, age 39.0 ± 14.1 years, 42.3% female), and 33.6% (n = 50) were treated for improvement of nutritional status. A modest increase in appetite after 3 months was detected among all patients enrolled (Pv = 0.08), but there were no significant differences in energy or macronutrient intake, and in patients’ body mass index (BMI). A significant appetite improvement after 3 months was detected among 34.0% (n = 17) of patients, but this was not associated with increased caloric intake or BMI at 3 or 6 months. Among patients without increased appetite after 3 months of MC therapy, BMI decreased at 6 months (24.1 ± 3.7 vs. 23.4 ± 3.6, Pv = 0.010). MC may be a potential strategy to improve appetite among some patients with IBD, but not caloric intake or BMI.”

https://pubmed.ncbi.nlm.nih.gov/38201908/

“MC may be a potential strategy to increase appetite among some patients with IBD, which may prevent further weight loss, but is not associated with a significant increase in caloric intake or in BMI.”

https://www.mdpi.com/2072-6643/16/1/78

Cannabinoids and the Endocannabinoid System in Early SARS-CoV-2 Infection and Long COVID-19-A Scoping Review

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“Coronavirus disease-19 (COVID-19) is a highly contagious illness caused by the SARS-CoV-2 virus.

The clinical presentation of COVID-19 is variable, often including symptoms such as fever, cough, headache, fatigue, and an altered sense of smell and taste. Recently, post-acute “long” COVID-19 has emerged as a concern, with symptoms persisting beyond the acute infection. Vaccinations remain one of the most effective preventative methods against severe COVID-19 outcomes and the development of long-term COVID-19. However, individuals with underlying health conditions may not mount an adequate protective response to COVID-19 vaccines, increasing the likelihood of severe symptoms, hospitalization, and the development of long-term COVID-19 in high-risk populations.

This review explores the potential therapeutic role of cannabinoids in limiting the susceptibility and severity of infection, both pre- and post-SARS-CoV-19 infection.

Early in the SARS-CoV-19 infection, cannabinoids have been shown to prevent viral entry, mitigate oxidative stress, and alleviate the associated cytokine storm.

Post-SARS-CoV-2 infection, cannabinoids have shown promise in treating symptoms associated with post-acute long COVID-19, including depression, anxiety, post-traumatic stress injury, insomnia, pain, and decreased appetite.

While current research primarily focuses on potential treatments for the acute phase of COVID-19, there is a gap in research addressing therapeutics for the early and post-infectious phases. This review highlights the potential for future research to bridge this gap by investigating cannabinoids and the endocannabinoid system as a potential treatment strategy for both early and post-SARS-CoV-19 infection.”

https://pubmed.ncbi.nlm.nih.gov/38202234/

https://www.mdpi.com/2077-0383/13/1/227

Cannabinoids in Treating Chemotherapy-Induced Nausea and Vomiting, Cancer-Associated Pain, and Tumor Growth

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“Cannabis has been used as an herbal remedy for thousands of years, and recent research indicates promising new uses in medicine. So far, some studies have shown cannabinoids to be safe in helping mitigate some cancer-associated complications, including chemotherapy-induced nausea and vomiting, cancer-associated pain, and tumor growth.

Researchers have been particularly interested in the potential uses of cannabinoids in treating cancer due to their ability to regulate cancer-related cell cycle pathways, prompting many beneficial effects, such as tumor growth prevention, cell cycle obstruction, and cell death.

Cannabinoids have been found to affect tumors of the brain, prostate, colon and rectum, breast, uterus, cervix, thyroid, skin, pancreas, and lymph. However, the full potential of cannabinoids is yet to be understood.

This review discusses current knowledge on the promising applications of cannabinoids in treating three different side effects of cancer-chemotherapy-induced nausea and vomiting, cancer-associated pain, and tumor development.

The findings suggest that cannabinoids can be used to address some side effects of cancer and to limit the growth of tumors, though a lack of supporting clinical trials presents a challenge for use on actual patients. An additional challenge will be examining whether any of the over one hundred naturally occurring cannabinoids or dozens of synthetic compounds also exhibit useful clinical properties.

Currently, clinical trials are underway; however, no regulatory agencies have approved cannabinoid use for any cancer symptoms beyond antinausea.”

https://pubmed.ncbi.nlm.nih.gov/38203245/

https://www.mdpi.com/1422-0067/25/1/74

Cannabinoids in the treatment of cancer anorexia and cachexia: Where have we been, where are we going?

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“Cachexia-anorexia cancer syndrome remains an unmet clinical need with a dearth of treatment and no standard of care.

Acting through the endocannabinoid system, cannabinoids are one potential cancer cachexia treatment.

Herein, the potential mechanisms for cannabinoids for cancer cachexia are discussed as are previous and ongoing clinical trials.”

https://pubmed.ncbi.nlm.nih.gov/38197037/

https://linkinghub.elsevier.com/retrieve/pii/S2347562523001105

Overview: Chronic Pain and Cannabis-Based Medicines

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“Chronic pain is primarily conceptualized as a disease in its own right when it is associated with emotional distress and functional impairment. Pathophysiologically, dysfunction of the cortico-mesolimbic connectome is of major importance, with overlapping signals in the nociceptive and stress systems.

The endocannabinoid system plays an important role in the central processing of nociceptive signals and regulates the central stress response. Clinically, there is moderate evidence that cannabis-based medicines (CBM) can contribute to a significant reduction in pain, especially the associated pain effect, and improvement in physical function and sleep quality in a proportion of patients with chronic pain.

The analgesic effect appears to be largely independent of the cause of pain. In this context, CBM preferentially regulates stress-associated pain processing.”

https://pubmed.ncbi.nlm.nih.gov/38198809/

https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-2231-6630

The NLRP3 inflammasome: a vital player in inflammation and mediating the anti-inflammatory effect of CBD

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“Background: The NLRP3 inflammasome is a vital player in the emergence of inflammation. The priming and activation of the NLRP3 inflammasome is a major trigger for inflammation which is a defense response against adverse stimuli. However, the excessive activation of the NLRP3 inflammasome can lead to the development of various inflammatory diseases. Cannabidiol, as the second-most abundant component in cannabis, has a variety of pharmacological properties, particularly anti-inflammation. Unlike tetrahydrocannabinol, cannabidiol has a lower affinity for cannabinoid receptors, which may be the reason why it is not psychoactive. Notably, the mechanism by which cannabidiol exerts its anti-inflammatory effect is still unclear.

Methods: We have performed a literature review based on published original and review articles encompassing the NLRP3 inflammasome and cannabidiol in inflammation from central databases, including PubMed and Web of Science.

Results and conclusions: In this review, we first summarize the composition and activation process of the NLRP3 inflammasome. Then, we list possible molecular mechanisms of action of cannabidiol. Next, we explain the role of the NLRP3 inflammasome and the anti-inflammatory effect of cannabidiol in inflammatory disorders. Finally, we emphasize the capacity of cannabidiol to suppress inflammation by blocking the NLRP3 signaling pathway, which indicates that cannabidiol is a quite promising anti-inflammatory compound.”

https://pubmed.ncbi.nlm.nih.gov/38191853/

https://link.springer.com/article/10.1007/s00011-023-01831-y

How Does CBG Administration Affect Sphingolipid Deposition in the Liver of Insulin-Resistant Rats?

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“Background: Cannabigerol (CBG), a non-psychotropic phytocannabinoid found in Cannabis sativa plants, has been the focus of recent studies due to its potential therapeutic properties. We proposed that by focusing on sphingolipid metabolism, which plays a critical role in insulin signaling and the development of insulin resistance, CBG may provide a novel therapeutic approach for metabolic disorders, particularly insulin resistance.

Methods: In a rat model of insulin resistance induced by a high-fat, high-sucrose diet (HFHS), we aimed to elucidate the effect of intragastrically administered CBG on hepatic sphingolipid deposition and metabolism. Moreover, we also elucidated the expression of sphingolipid transporters and changes in the sphingolipid concentration in the plasma.

Results: The results, surprisingly, showed a lack of changes in de novo ceramide synthesis pathway enzymes and significant enhancement in the expression of enzymes involved in ceramide catabolism, which was confirmed by changes in hepatic sphingomyelin, sphinganine, sphingosine-1-phosphate, and sphinganine-1-phosphate concentrations.

Conclusions: The results suggest that CBG treatment may modulate sphingolipid metabolism in the liver and plasma, potentially protecting the liver against the development of metabolic disorders such as insulin resistance.”

https://pubmed.ncbi.nlm.nih.gov/37892425/

https://www.mdpi.com/2072-6643/15/20/4350

Sila-CBD Derivatives as Inhibitors of Heme-Induced NLRP3 Inflammasome: Application in Hemolytic Diseases

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“Synthesis and biological evaluation of silicon-incorporated phytocannabinoids with improved pharmacological properties toward inflammatory diseases are described. The synthesized sila-analogues 15a, 15b, and 15c displayed potent inhibition of pro-inflammatory cytokines, including IL-1β, TNF-α, and IL-6 at 10 μM. Further, the release of heme during the lysis of red blood cells in hemolytic diseases is one of the major reasons for inflammation associated with the pathophysiology of these diseases. Due to scanty literature related to inhibitors of heme-mediated induction of the NLRP3 inflammasome, we decided to test these compounds against it. Compounds 15a and 15c significantly inhibited the heme-mediated induction of the NLRP3 inflammasome at a concentration of 0.1 μM. Interestingly, the sila-CBD derivatives also showed higher metabolic stability in contrast to their carbon analogues. Anti-NLRP3 inflammasome activity of compounds 15a and 15c were further validated in vivo against heme-mediated peritoneal inflammation. The anti-inflammatory activity of these compounds could be useful in treating diseases such as sickle cell anemia and thalassemia involving the hemolysis-mediated activation of the NLRP3 inflammasome.”

https://pubmed.ncbi.nlm.nih.gov/38116428/

https://pubs.acs.org/doi/10.1021/acsmedchemlett.3c00352