Industrial Hemp ( Cannabis sativa subsp. sativa) as an Emerging Source for Value-Added Functional Food Ingredients and Nutraceuticals

molecules-logo“Industrial hemp (Cannabis sativa L., Cannabaceae) is an ancient cultivated plant originating from Central Asia and historically has been a multi-use crop valued for its fiber, food, and medicinal uses. Various oriental and Asian cultures kept records of its production and numerous uses.

Due to the similarities between industrial hemp (fiber and grain) and the narcotic/medical type of Cannabis, the production of industrial hemp was prohibited in most countries, wiping out centuries of learning and genetic resources. In the past two decades, most countries have legalized industrial hemp production, prompting a significant amount of research on the health benefits of hemp and hemp products.

Current research is yet to verify the various health claims of the numerous commercially available hemp products. Hence, this review aims to compile recent advances in the science of industrial hemp, with respect to its use as value-added functional food ingredients/nutraceuticals and health benefits, while also highlighting gaps in our current knowledge and avenues of future research on this high-value multi-use plant for the global food chain.”

https://pubmed.ncbi.nlm.nih.gov/32906622/

https://www.mdpi.com/1420-3049/25/18/4078

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It Is Our Turn to Get Cannabis High: Put Cannabinoids in Food and Health Baskets

molecules-logo“Cannabis is an annual plant with a long history of use as food, feed, fiber, oil, medicine, and narcotics. Despite realizing its true value, it has not yet found its true place. Cannabis has had a long history with many ups and downs, and now it is our turn to promote it.

Cannabis contains approximately 600 identified and many yet unidentified potentially useful compounds. Cannabinoids, phenolic compounds, terpenoids, and alkaloids are some of the secondary metabolites present in cannabis. However, among a plethora of unique chemical compounds found in this plant, the most important ones are phytocannabinoids (PCs).

Over hundreds of 21-22-carbon compounds exclusively produce in cannabis glandular hairs through either polyketide and or deoxyxylulose phosphate/methylerythritol phosphate (DOXP/MEP) pathways. Trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) are those that first come to mind while talking about cannabis. Nevertheless, despite the low concentration, cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabinodiol (CBND), and cannabinidiol (CBDL) may have potentially some medical effects.

PCs and endocannabinoids (ECs) mediate their effects mainly through CB1 and CB2 receptors. Despite all concerns regarding cannabis, nobody can ignore the use of cannabinoids as promising tonic, analgesic, antipyretic, antiemetic, anti-inflammatory, anti-epileptic, anticancer agents, which are effective for pain relief, depression, anxiety, sleep disorders, nausea and vomiting, multiple sclerosis, cardiovascular disorders, and appetite stimulation.

The scientific community and public society have now increasingly accepted cannabis specifically hemp as much more than a recreational drug. There are growing demands for cannabinoids, mainly CBD, with many diverse therapeutic and nutritional properties in veterinary or human medicine. The main objective of this review article is to historically summarize findings concerning cannabinoids, mainly THC and CBD, towards putting these valuable compounds into food, feed and health baskets and current and future trends in the consumption of products derived from cannabis.”

https://pubmed.ncbi.nlm.nih.gov/32899626/

https://www.mdpi.com/1420-3049/25/18/4036

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Hemp in Veterinary Medicine: From Feed to Drug

 See the source image“Hemp (Cannabis sativa) is an angiosperm plant belonging to the Cannabaceae family. Its cultivation dates back to centuries. It has always been cultivated due to the possibility of exploiting almost all the parts of the plant: paper, fabrics, ropes, bio-compounds with excellent insulating capacity, fuel, biodegradable plastic, antibacterial detergents, and food products, such as flour, oils, seeds, herbal teas, and beer, are indeed obtained from hemp.

Hemp flowers have also always been used for their curative effects, as well as for recreational purposes due to their psychotropic effects. Cannabis contains almost 500 chemical compounds, such as phytocannabinoids, terpenes, flavonoids, amino acids, fatty acids, vitamins, and macro-, and micro-elements, among others.

When utilized as a food source, hemp shows excellent nutritional and health-promoting (nutraceutical) properties, mainly due to the high content in polyunsaturated fatty acids (especially those belonging to the ω-3 series), as well as in phenolic compounds, which seem effective in the prevention of common diseases such as gastrointestinal disorders, neurodegenerative diseases, cancer, and others.

Moreover, hemp oil and other oils (i.e., olive oil and medium-chain triglyceride-MCT-oil) enriched in CBD, as well as extracts from hemp dried flowers (Cannabis extracts), are authorized in some countries for therapeutic purposes as a second-choice approach (when conventional therapies have failed) for a certain number of clinical conditions such as pain and inflammation, epilepsy, anxiety disorders, nausea, emesis, and anorexia, among others.

The present review will synthetize the beneficial properties of hemp and hemp derivatives in animal nutrition and therapeutics.”

https://pubmed.ncbi.nlm.nih.gov/32850997/

C. sativa has been an important source of food in the Old World, as hempseeds and seed meal are excellent sources of dietary oil, fiber, and protein. Many of the constituents of C. sativa can be classified as either nutrients, nutraceuticals, or pharmaceutical ingredients.”

https://www.frontiersin.org/articles/10.3389/fvets.2020.00387/full

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The Seed of Industrial Hemp ( Cannabis sativa L.): Nutritional Quality and Potential Functionality for Human Health and Nutrition

nutrients-logo“Hempseeds, the edible fruits of the Cannabis sativa L. plant, were initially considered a by-product of the hemp technical fibre industry. Nowadays, following the restorationing of the cultivation of C. sativa L. plants containing an amount of delta-9-tetrahydrocannabinol (THC) <0.3% or 0.2% (industrial hemp) there is a growing interest for the hempseeds production due to their high nutritional value and functional features.

The goal of this review is to examine the scientific literature concerning the nutritional and functional properties of hempseeds. Furthermore, we revised the scientific literature regarding the potential use of hempseeds and their derivatives as a dietary supplement for the prevention and treatment of inflammatory and chronic-degenerative diseases on animal models and humans too.

In the first part of the work, we provide information regarding the genetic, biochemical, and legislative aspects of this plant that are, in our opinion essential to understand the difference between “industrial” and “drug-type” hemp. In the final part of the review, the employment of hempseeds by the food industry as livestock feed supplement and as ingredient to enrich or fortify daily foods has also revised.

Overall, this review intends to encourage further and comprehensive investigations about the adoption of hempseeds in the functional foods field.”

https://pubmed.ncbi.nlm.nih.gov/32610691/

https://www.mdpi.com/2072-6643/12/7/1935

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The Cannabis Spread Throughout the Continents and Its Therapeutic Use in History

“Historical relevance: Cannabis sativa L. (C. sativa) is a plant whose use as a therapeutic agent shares its origins with the first Far East’s human societies. Cannabis has been used not only for recreational purposes, but as a food to obtain textile fibers, to produce hemp paper, to treat many physical and mental disorders.

This review aims to provide a complete assessment of the deep knowledge of the cannabis psychoactive effects and medicinal properties in the course of history covering i.) the empirical use of the seeds and the inflorescences to treat many physical ailments by the ancient Oriental physicians ii.) the current use of cannabis as a therapeutic agent after the discovery of its key psychoactive constituent and the human endogenous endocannabinoid system.

Results and conclusion: Through a detailed analysis of the available resources about the origins of C. sativa we found that its use by ancient civilizations as a source of food and textile fibers dates back over 10,000 years, while its therapeutic applications have been improved over the centuries, from the ancient East medicine of the 2nd and 1st millennium B.C. to the more recent introduction in the Western world after the 1st century A.D. In the 20th and 21th centuries, Cannabis and its derivatives have been considered as a menace and banned throughout the world, but nowadays they are still the most widely consumed illicit drugs all over the world. Its legalization in some jurisdictions has been accompanied by new lines of research to investigate its possible applications for medical and therapeutic purposes.”

https://pubmed.ncbi.nlm.nih.gov/32433013/?from_term=cannabinoid&from_sort=date&from_size=200&from_pos=6

http://www.eurekaselect.com/182145/article

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Cannabidiol and Other Non-Psychoactive Cannabinoids for Prevention and Treatment of Gastrointestinal Disorders: Useful Nutraceuticals?

ijms-logo“Cannabis sativa is an aromatic annual flowering plant with several botanical varieties, used for different purposes, like the production of fibers, the production of oil from the seeds, and especially for recreational or medical purposes.

Phytocannabinoids (terpenophenolic compounds derived from the plant), include the well-known psychoactive cannabinoid Δ9-tetrahydrocannabinol, and many non-psychoactive cannabinoids, like cannabidiol.

The endocannabinoid system (ECS) comprises of endocannabinoid ligands, enzymes for synthesis and degradation of such ligands, and receptors. This system is widely distributed in the gastrointestinal tract, where phytocannabinoids exert potent effects, particularly under pathological (i.e., inflammatory) conditions.

Herein, we will first look at the hemp plant as a possible source of new functional food ingredients and nutraceuticals that might be eventually useful to treat or even prevent gastrointestinal conditions.

Subsequently, we will briefly describe the ECS and the general pharmacology of phytocannabinoids. Finally, we will revise the available data showing that non-psychoactive phytocannabinoids, particularly cannabidiol, may be useful to treat different disorders and diseases of the gastrointestinal tract.

With the increasing interest in the development of functional foods for a healthy life, the non-psychoactive phytocannabinoids are hoped to find a place as nutraceuticals and food ingredients also for a healthy gastrointestinal tract function.”

https://www.ncbi.nlm.nih.gov/pubmed/32357565

https://www.mdpi.com/1422-0067/21/9/3067

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Effect οf Genotype and Growing Year on the Nutritional, Phytochemical, and Antioxidant Properties of Industrial Hemp (Cannabis sativa L.) Seeds.

antioxidants-logo “Cannabis sativa L. seeds have been an important source of protein, oil, and dietary fiber for human and animals. Currently, there is a growing interest in the commercial products of these seeds, which are recognized as a legitimate source of medicaments, cosmeceuticals, and nutraceuticals.

The objective of this study was to investigate the nutritional, phytochemical composition, and antioxidant properties of seeds from seven hemp cultivars grown in Greece for three consecutive years.

All the measured parameters strongly varied under the influence of growing year and genotype. In particular, protein, oil, and carbohydrates’ content of hemp seeds as well as fatty acids’ composition were mainly affected by genotype, whereas the growing year had a major effect on phytochemical components and antioxidant activity, which was determined by the 2,2′-azino-bis (3-ethylbenzthiazoline sulfonate) (ABTS) and ferric-reducing antioxidant power (FRAP) assays. Moreover, a predominant effect of the year was observed for phenolic profiles as determined by high-performance liquid chromatography and total carotenoids’ content.

This study suggests that hemp seeds could be a promising food crop as a result of their high nutritive traits and antioxidant potential. A comparison of the studied cultivars, showed that Finola seeds had the highest oil and protein contents and, thus, appeared to be the most promising cultivar for cultivation in Greece.”

https://www.ncbi.nlm.nih.gov/pubmed/31627349

https://www.mdpi.com/2076-3921/8/10/491

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The cannabinoid receptor 2 agonist, β-caryophyllene, improves working memory and reduces circulating levels of specific proinflammatory cytokines in aged male mice.

Behavioural Brain Research“Age-related cognitive decline has been associated with proinflammatory cytokines, yet the precise relationship between cognitive decline and cytokine load remains to be elucidated. β-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist with established anti-inflammatory effects that is known to improve memory and increase lifespan. It is of interest to explore the potential of BCP to reduce age-related cognitive decline and proinflammatory cytokine load. In this study, we assessed changes in circulating cytokines across the lifespan, memory performance in young and aged mice, and the effects of BCP on memory function and cytokine load. The plasma levels of 12 cytokines were assessed in male Swiss-Webster mice at 3, 12, and 18 months of age using multiplexed flow cytometry. Working memory was compared in 3 and 12 month-old mice using spontaneous alternations. A dose-response function (100-300 mg/kg, subchronic administration) for BCP-induced memory restoration was determined in 3 and 12 month-old mice. Finally, the effects on cytokine levels of the peak memory enhancing dose of BCP was assessed in 18 month-old mice. Circulating levels of several cytokines significantly increased with age. Multilinear regression analysis showed that IL-23 levels were most strongly associated with age. Aged mice showed deficits in working memory and higher levels of IL-23, both of which were reversed by BCP treatment. BCP appears to reverse age-associated impairments in memory and modulates cytokine production. IL-23 may play a significant role in the aging process, and future research should determine whether it has utility as a biomarker for novel anti-aging therapeutics.”

https://www.ncbi.nlm.nih.gov/pubmed/31173795

https://www.sciencedirect.com/science/article/pii/S0166432819304516?via%3Dihub

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

“Beta-caryophyllene is a dietary cannabinoid.”   https://www.ncbi.nlm.nih.gov/pubmed/18574142

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β-Caryophyllene, a Natural Sesquiterpene, Attenuates Neuropathic Pain and Depressive-Like Behavior in Experimental Diabetic Mice.

 View details for Journal of Medicinal Food cover image“Neuropathic pain (NP) is associated with chronic hyperglycemia and emotional disorders such as depression in diabetic patients, complicating the course of treatment. Drugs currently used to treat NP have undesirable side effects, so research on other natural sources has been required.

β-caryophyllene (BCP), a natural sesquiterpene found in some food condiments and considered an agonist to cannabinoid receptor type 2, could have potential therapeutic effects to treat conditions such as NP and emotional disorders. For this reason, we assessed whether BCP modulates nociception, anxiety, and depressive-like behavior in streptozotocin (STZ)-induced experimental diabetic BALB/c female mice.

BCP was orally chronic administrated (10 mg/kg/60 μL). Pain developed with STZ was evaluated with von Frey filament test, SMALGO®, and hot plate test. Anxiety and depression-like behavior were assessed by marbles test, forced swim test, and tail suspension test. BCP significantly reduced glycemia in experimental diabetic mice. The pain was also mitigated by BCP administration. Depression-like behavior assessed with tail suspension test was attenuated with orally chronic BCP administration. Substance P and cytokines such as interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) were also attenuated with BCP administration. NP was positively correlated with substance P and IL-6 and IL-1β release.

Our data using an orally chronic BCP administration in the STZ challenged mice to suggest that glycemia, diabetes-related NP, and depressive-like behavior could be prevented/reduced by dietary BCP.”

https://www.ncbi.nlm.nih.gov/pubmed/30864870

https://www.liebertpub.com/doi/10.1089/jmf.2018.0157

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

“Beta-caryophyllene is a dietary cannabinoid.”   https://www.ncbi.nlm.nih.gov/pubmed/18574142

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The protective effects of β-caryophyllene on LPS-induced primary microglia M1/M2 imbalance: A mechanistic evaluation.

Life Sciences

“Neuroinflammation is observed as a routine characterization of neurodegenerative disorders such as dementia, multiple sclerosis (MS) and Alzheimer’s diseases (AD). Scientific evidence propounds both of the neuromodulatory and immunomodulatory effects of CB2 in the immune system. β-Caryophyllene (BCP) is a dietary selective CB2 agonist, which deserves the anti-inflammatory and antioxidant effects at both low and high doses through activation of the CB2 receptor.

METHODS:

In this study, we investigated the protective effects of a broad range concentration of BCP against LPS-induced primary microglia cells inflammation and M1/M2 imbalance and identifying the portion of the involvement of related signaling pathways on BCP effects using pharmacological antagonists of CB2, PPAR-γ, and sphingomyelinase (SMase).

KEY FINDINGS:

The protective effects of BCP on LPS-induced microglia imbalance is provided by the M2 healing phenotype of microglia, releasing the anti-inflammatory (IL-10, Arg-1, and urea) and anti-oxidant (GSH) parameters and reducing the inflammatory (IL-1β, TNF-α, PGE2, iNOS and NO) and oxidative (ROS) biomarkers. Moreover, we showed that BCP exerts its effects through CB2receptors which overproduction of ceramides by SMase at middle to higher concentrations of BCP reduce the protective activity of BCP and results in the activation of the PPAR-γ pathway.

SIGNIFICANCE:

In conclusion, the low concentration of BCP has higher selective anti-inflammatory effects rather than high levels. On this occasion, BCP by modulating the microglia is able to have potential therapeutic effects in neuro-inflammation conditions and microglia cells such as MS and AD.”

https://www.ncbi.nlm.nih.gov/pubmed/30620895

https://www.sciencedirect.com/science/article/abs/pii/S0024320518308610?via%3Dihub

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

“Beta-caryophyllene is a dietary cannabinoid.”  https://www.ncbi.nlm.nih.gov/pubmed/18574142

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