research paper on hemp

• Open access
• Published: 29 July 2022

Industrial hemp seed: from the field to value-added food ingredients

• Rachel A. Burton   ORCID: orcid.org/0000-0002-0638-4709 1 , 2 ,
• Mike Andres 3 ,
• Martin Cole 1 , 4 ,
• James M. Cowley   ORCID: orcid.org/0000-0002-9030-7190 1 &
• Mary Ann Augustin   ORCID: orcid.org/0000-0001-9001-8164 5  

Journal of Cannabis Research volume  4 , Article number:  45 ( 2022 ) Cite this article

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Industrial hemp, with low levels of the intoxicating cannabinoid tetrahydrocannabinol (THC), is grown for fibre and seeds. The industrial hemp industry is poised for expansion. The legalisation of industrial hemp as an agricultural commodity and the inclusion of hemp seed in foods is helping to drive the expansion of the hemp food ingredients industry. This paper discusses the opportunity to build an industrial hemp industry, with a focus on the prospects of hemp seed and its components in food applications. The market opportunities for industrial hemp products are examined. Various aspects of the science that underpins the development of an industrial hemp industry through the food supply chain are presented. This includes a discussion on the agronomy, on-farm and post-harvest considerations and the various types of food ingredients that can be made from hemp seed. The characteristics of hemp seed meal, hemp seed protein and hemp seed oil are reviewed. Different processes for production of value-added ingredients from hemp seed, hemp seed oil and hemp seed protein, are examined. The applicability of hemp seed ingredients in food applications is reviewed. The design of hemp seed ingredients that are fit-for-purpose for target food applications, through the selection of varieties and processing methods for production of various hemp seed ingredients, needs to consider market-led opportunities. This will require an integrated through chain approach, combined with the development of on-farm and post-farm strategies, to ensure that the hemp seed ingredients and foods containing hemp seed are acceptable to the consumer.

Cannabis sativa, native to Eastern Asia, was probably first cultivated in China ( circa 2700 BC) for its medicinal properties. It is a potentially profitable, multi-use crop that has good sustainability credentials due to its low environmental impact (Ranalli and Venturi 2004 ). Hemp seed is highly nutritious, containing around 25% protein, 35% oil, and high levels of antioxidants (Callaway 2004 ; Farinon et al. 2020 ). The vegetative biomass from hemp has applications as building materials and in biofuel production, and its stem fibres can be used to produce textiles (Farinon et al. 2020 ). Hemp has deep tap roots which enables efficient water acquisition and the storage of carbon and which are also effective at improving soil structure (Farinon et al. 2020 ).

Of particular importance is the wide range of phytochemicals found in hemp inflorescences that have wide applications in food, pharmaceutical and cosmetic industries. The two major and better-known phytochemicals in hemp are cannabinoids, (–)- trans -Δ 9 -tetrahydrocannabinol (THC) which has an intoxicating effect, and (-)-cannabidiol (CBD), which is non-intoxicating but has potential medicinal benefits. As such, CBD supplements are currently highly sought after by the nutritional supplement industry (Cerino et al. 2021 ).

Industrial hemp— Cannabis varieties with low tetrahydrocannabinol (THC) levels—are grown primarily for the production of fibre and/or seeds. The impetus for the budding global industrial hemp industry is the result of key changes to legislation, namely the 2014 and 2018 Farm Bills in the USA. The 2014 Farm Bill defined hemp as plants with a THC threshold of 0.3% or less on a dry weight basis (compared with c. 15% for illicit drug-type Cannabis (ElSohly et al. 2021 )) and allowed its production under specific conditions. The 2018 Farm Bill built on this by legalising the production of hemp as an agricultural commodity and removed it from the list of controlled substances (American Farm Bureau Federation 2019 ). Australia legalised hemp foods in November 2017 after a ban that had been in place since 1937 (The Farmer Magazine 2020 ).

The aim of this paper is to review the opportunity for designing a whole supply chain for industrial hemp, with a focus on the prospects of hemp seed for the food industry. For decades, hemp seed has been an under-valued co-product from industrial hemp production, primarily grown for its fibre. Subsequently, most varieties have not been optimised for the production of seed or high-quality oil and protein. Industrial hemp is an exciting alternative in a landscape where we traditionally grow a limited number of crops, where it provides an opportunity to widen our agribiodiversity. The potential of industrial hemp seed remains underdeveloped and so to highlight its promise and emerging role as a valuable source of protein and oil for the food industry, in this review, we will cover the market opportunities for industrial hemp products, discuss the growth, harvesting and storage requirements of industrial hemp seed, and describe the nutritional attributes of hemp seed and the processing/fractionation it requires to produce value-added food ingredients. Finally, recommendations will be made for future research which we anticipate will enable the development of sustainable industrial hemp supply chains, stimulating a call to action for the industrial hemp industry.

Market opportunity

Globally, it is estimated that at least 47 countries grow hemp for commercial or research purposes (Cannabis Business Plan 2021 ). In 2019, Brightfield Group estimated that the top 10 producing nations alone had 864,000 acres of industrial hemp under cultivation (S&P Global Market Intelligence 2019 ). However, as of September 2021, there are no official estimates available that reliably and comprehensively track worldwide industrial hemp under cultivation. FAO Statistics, for example, do not capture five of the top 10 producing nations, even though Canadian figures, which are not captured by FAO, are available directly from the Canadian Government (FAOSTAT 2020 ; Government of Canada 2020 ). Due to the recency of legislative changes, the Australian industrial hemp industry is still in its infancy, with an estimated 6180 acres under cultivation, of which 64% are in Tasmania (Gordon and Brodrick 2020 ).

The global market size estimates for industrial hemp for 2025 vary greatly, with some estimates as high as USD 26.6 billion (MarketsandMarkets 2019 ). There are three key reasons for this. Firstly, the lack of official estimates for hemp under cultivation severely limits forecasting. Secondly, the crash in wholesale prices for nearly all hemp products in the USA during the second half of 2019 led to around 60% of growers struggling to find buyers due to massive oversupply (ACS Laboratory 2020 ). During this time prices for hemp seeds and crude hemp oil fell 18% and 68% respectively (ACS Laboratory 2020 ). Thirdly, there are thousands of applications for hemp, with food and beverage, fibre (textiles and paper), and beauty and personal care standing out as the three largest market opportunities (Whitney Economics 2019 ). Given that each of these opportunities plays into a global billion-dollar market, with 2019 market size estimates for packaged food and beverage at USD 4837 billion (Euromonitor International 2020a ), textiles at USD 1587 billion (Technavio 2019 ), and beauty and personal care at USD 503 billion (Euromonitor International 2020b ), even a small change in the size of the estimated captured market can lead to huge differences in market size estimates. Given the still nascent state of the global industrial hemp market, more conservative market size estimates, such as those from Magna Intelligence seem more reliable. Magna expects the global industrial hemp market to grow from USD 4.6 billion in 2019 to USD 9.4 billion by 2025, at an annual growth rate of 12.8% (Magna Intelligence 2020 ).

Although hemp can be grown as a dual-purpose crop, production systems are usually geared to producing either fibre or seed, and generally not both (AgriFutures Australia 2017 ). While a production system geared towards seed will not yield the long bast fibres desired in textile production, it will still yield some shorter fibres (bast and hurd or pulp) after seed harvesting, that could be used in hemp paper production (Industrial Hemp Western Australia Association Inc 2021 ). Hence, a seed production operation could potentially play into three key segments of the global industrial hemp market—food and beverage, personal care products, and paper. Together, these three segments represent a USD 5.1 billion opportunity comprising 53.9% of the global industrial hemp market by 2025 (Magna Intelligence 2020 ).

Aside from regulatory hurdles, there are currently two main obstacles that hold back the industrial hemp industry. The first is the risk of a hemp crop “going hot” (exceeding the legislated THC limit), requiring the entire crop to be destroyed. Current cultivars, even when grown successfully in previous years, may produce THC levels above the legal threshold in the following year due to varying growing conditions (ABC News 2021 ). The second challenge is the lack of proper planting and harvesting equipment. For example, current air-seeders used in planting can only be operated with low air volumes due to the fragility of hemp seeds (MarketsandMarkets 2019 ). Machinery currently used in the hemp harvest, especially smaller equipment such as sickle-bar mowers and hay swathers, struggle with frequent clogging and blunting of blades (AgriFutures Australia 2017 ). As planting increases, mechanised planting and harvesting needs to be refined for efficiency alongside commercial-scale processing facilities.

Despite these challenges, the plant-based protein products market is ripe for new protein sources. The two main protein sources in 2020 were soy and wheat, contributing 57.6% and 36.8% to the overall market, respectively (Technavio 2021 ). However, both soy and wheat are among the top eight major food allergens, which account for 90% of all food allergy reactions (Messina and Venter 2020 ). Wheat is also problematic for about 109 million people worldwide, or 1.4% of the global population in 2020, who suffer from coeliac disease (Singh et al. 2018 ; United Nations 2019 ). Furthermore, while meat consumption is extensive around the globe (an average of 86% of people in 39 countries surveyed saying that their diet includes meat (Statista 2020 )), consumer health concerns and the desire for more sustainable and ethical products is driving the global demand for non-meat protein alternatives such as plant-based meats and dairy (Euromonitor International 2020c ). Many consumers are continuing to move towards flexitarian or plant-based diets, with 23% of all consumers indicating that they try to limit their intake of meat (Euromonitor International 2020c ). Novel plant-protein sources such as hemp, not known to cause food allergies or affecting coeliac sufferers, therefore are well-positioned to meet the growing global demand for plant-based proteins.

Industrial hemp—cultivation, harvesting and storage

Hemp is a fast-growing productive crop that is regarded as sustainable, despite the fact that in many areas of the world it requires irrigation (Tang et al. 2018 ). For a productive crop, hemp might require more water than dryland cereals (Schultz et al. 2020 ), but substantially less than other fibre crops such as cotton (Andre et al. 2016 ). There is still a lack of accurate studies into best practice water use (Adesina et al. 2020 ; Amaducci et al. 2000 ) but a recent study reported that hemp can survive and reproduce under extreme water deficit (Gill et al. 2022 ). Under ideal conditions hemp can grow very rapidly and at high sowing rates will achieve canopy closure quickly, suppressing weed growth (Struik et al. 2000 ). It has been shown to have a positive effect on the soil and can also be used for phytoremediation, particularly for the removal of heavy metals such as lead (Burczyk et al. 2008 ). Although frequently touted as requiring low inputs, hemp requires large amounts of nitrogen input for good plant establishment and there are few studies into the impact that plant nutrition has on subsequent seed and fibre quality (Herppich et al. 2020 ). There is sparse information on salinity tolerance of hemp across all growth stages (Cheng et al. 2016 ; Hu et al. 2018 ). Given that a successful hemp crop is dependent on irrigation, and that irrigation water and soils are becoming increasingly salinised around the world (Brady et al. 2008 ), hemp’s salinity tolerance will be important to define and incorporate into breeding programs.

There are established hemp breeding programs for fibre and seed with many of these in the commercial sector, with a general lack of knowledge across the industry about the type of germplasm available. There is limited information about the availability of elite breeding lines for improved seed size and quality (Small 2018 ). Quality factors of hemp seed including total oil content, fatty acid ratios, total protein content and beneficial phytochemicals are known to be highly variable among genotypes, as well as contents of anti-nutrients like phytate (Schultz et al. 2020 ). There is a strong need for a core germplasm resource to be set up for industrial hemp to support genomic efforts to unravel many key traits including those related to seed (Small 2018 ; Hurgobin et al. 2021 ; Welling et al. 2016 ). It is likely that a wide range of cultivars will be needed to meet the needs of different growing regions, not just around the world, but even within the same country (Schluttenhofer and Yuan 2017 ). Australia is a prime example of this since the northern states have hot, wet summers and cooler, drier winters ideal for hemp cultivation, however the day length requirements of hemp to trigger flowering are not ideal at these latitudes. In contrast, the southern states grow industrial hemp in the dry, hot summer months where the crop is dependent on irrigation but flowering can be more confidently predicted. Cultivars that can push the seasonal envelope, establishing well in the colder and wetter spring months of southern Australia and thus need far less irrigation, will further extend the sustainability credentials of this crop.

There is a huge range of phenotypic variety displayed by the hemp cultivars currently available. This bodes well for future breeding efforts and is further augmented by the large amount of genetic variation present in germplasm collections that are not well described and therefore remain relatively untouched to date (Welling et al. 2016 ). There will need to be synergy between the crop types grown for seed and the development of efficient harvesters. Fibre crops are tall and densely planted and will require different harvesting specifications to shorter and bushier seed crops, planted at lower density (Huang et al. 2017 ). Where crops are grown for dual purpose, with the seed heads harvested first and then the remaining stalks collected for fibre, harvesting considerations will be more complex. Efficient separation of seed from biomass during on-field harvesting is ideal and potentially this can be achieved by the use of modified cereal combines (Pahole et al. 2018 ). However, there are currently only a few bespoke hemp harvesters available for commercial use. The HempTrain TM is an advance on traditional post-harvest processing methods for decortication and separation and production of high value products. It enables separation of baled hemp straw and may be used for processing of fresh/green feedstock and dry feedstock (Canadian Greenfield Technologies Corp 2021 ).

The timing of harvest is also likely to have an impact on seed quality, particularly with regard to the lipid profiles. The content of linoleic, α-linolenic, oleic, and palmitic fatty acids varied with harvesting times, as did the polyunsaturated to saturated ratio, and could be correlated with seed ripeness (Marzocchi and Caboni 2020 ). A recent survey of hemp cultivars grown in Italy demonstrates that multiple properties, including phenolic and sterolic contents of hemp seeds, can be affected by both terroir and harvest method (Calzolari et al. 2021 ). Lastly, there is little known about the influence of harvesting times, and storage, on the anti-nutritional contents of hemp seeds, including phytate and lignanamide (Mattila et al. 2018 ) which will also influence downstream food uses.

Postharvest segregation and storage

Both post-harvest segregation and correct storage of hemp seed will be essential. The high oil content of hemp seed means that seed quality is likely to be influenced by storage conditions, in turn dictating downstream use that is impacted by oil oxidation and rancidity (Suriyong et al. 2015 ). The protective compounds in hemp seeds which can help to stabilise the lipid profile during storage, can vary widely by cultivar, and thus shelf life will also vary (Izzo et al. 2020 ). A better understanding of factors that delay or prevent rancidity will be essential to ensure a supply of consistently high-quality seed. The effects of storage regimes on hemp seed protein profiles are little known and given that hemp protein is likely to become an important alternative plant protein resource (Shen et al. 2021 ), this will need further attention.

Segregation of seed types during storage and downstream processing will also be important to maintain the status of hemp seed as a credible gluten-free ingredient. Contamination from common cereals such as wheat and barley, for example via the use of shared harvesters and/or storage facilities, could occur, as has been seen for other gluten-free grains such as buckwheat (Atasoy et al. 2020 ).

Food ingredients from hemp seed

There is a range of hemp seed products in the market including whole hemp seed and dehulled hemp seed, hemp seed oil, hemp seed cake (the by-product after mechanical oil pressing), hemp seed meal (the by-product after solvent-based protein extraction of pressed cake), hemp hulls and hemp protein concentrates/isolates (Fig. 1 ). Hemp seed oleosomes, which are in-tact oil bodies, are an emerging ingredient that may be isolated from hemp seed.

Food-grade hemp seed is harvested from industrial hemp plants with less than 1% (–)- trans -Δ 9 -tetrahydrocannabinol (THC). The hemp seed is comprised of an outer hull which is high in dietary fibre and the heart (seed embryo) which is rich in protein and fats. Whole hemp seeds are milled into hemp flour which is sequentially extracted to produce hemp oil and hemp protein concentrates/isolates which are used for food formulation. Residues from these extractions, hemp seed cake and hemp seed meal, can also be used to fortify foods with antioxidants and dietary fibre. Residue hemp plant biomass may also be a source of antioxidant compounds and short fibres for materials.

Knowing the composition, nutritional properties and techno-functionality of hemp-based food ingredients is of fundamental importance for determining their fitness-for-purpose in formulated food. In addition, understanding of the manufacturing processes for hemp seed-based ingredients is also relevant as the composition, quality, and functional properties of the ingredient are influenced by the post-harvest handling and processing. The properties of the ingredients are also influenced by the cultivar, seasonality and growing conditions of the plant.

Composition of hemp seed

The variety and agronomic conditions affect the composition of the hemp seed as detailed in Section 3 above and composition of major and minor components show significant variation. Hemp seed is a good source of macronutrients (proteins, fat and fibre), minerals (P, K, Mg, Ca, Na, Fe, Mn, Zn, Cu) and phytonutrients (tocopherols, carotenoids, sterols) but also contains a number of anti-nutritional components (phytic acid, condensed tannins, trypsin inhibitors, cyanogenic glycosides and saponins) (Callaway 2004 ; Leonard et al. 2020 ).

Whole hemp seed, dehulled hemp seed and hulls

Typically, whole hemp seeds contain 25–35% fat, 20–25% protein, and 20–30% carbohydrates which is mainly insoluble dietary fibre. However, the variability reported is highly dependent on cultivar and agronomic conditions (Farinon et al. 2020 ). Hemp seed sampled from commercial sources were found to be comprised of 90.8–96.0% dry matter, 25.4–33.0% fat, 21.3–27.3% protein, 21.8–26.1% acid detergent fibre, 27.8–36.2% neutral detergent fibre and 3.7–5.9% ash (House et al. 2010 ). An Italian study of 20 non-drug hemp cultivars and wild hemp accessions reported oil content to range from 28.5–36% dry matter for oil and protein ranging from 31.6–35.6% dry matter(Galasso et al. 2016 ). The seed composition of ten industrial hemp cultivars (Alyssa, Anka, CanMa, CFX1, CFX2, CRS1, Delores, Finola, Jutta, Yvonne) grown in Canada were reported to be 26.9–30.6% oil, 23.8–28.0% protein, 25.9–29.8% acid detergent fibre, 32.7–38.8% neutral detergent fibre and 5.1–5.8% ash (Vonapartis et al. 2015 ). A compositional analysis of seven hemp cultivars (Bialobrzeskie, Felina 32, Tygra, Futura 75, Santhica 27, Fedora 17, Finola) grown in Greece over 3 years indicated that contents ranged from 8.5-29.2% for oil, 12.2-25.4% for protein, 40.8–74.5% for carbohydrates and 4.4-5.3% ash, with cv. Finola having the highest protein and oil content and lowest carbohydrate content (Irakli et al. 2019 ).

A comparison of the composition of dehulled hemp seed and hulls indicates how the individual components are distributed in the fractions. This would also be dependent on the method used in the dehulling operations. An analysis of six commercial dehulled hemp seed samples found that they contained 93.7–97.0% dry matter, 37.6–52.3% fat, 30.3–38.7% protein, 0.6–12.0% acid detergent fibre, 4.6–18.1% neutral detergent fibre and 5.4–7.1% ash (House et al. 2010 ). By contrast, the hulls of three commercial samples contained (on an as is basis) 93.4–97.0% dry matter, 4.3–15.8% fat, 8.8–16.3% protein, 44.9–56.9% acid detergent fibre, 55.7–74.2 % neutral detergent fibre and 3.1–4.4% ash (House et al. 2010 ). Distribution of components between the heart and hull reported by House et al. (House et al. 2010 ) are consistent with a recent microscopic study which found high levels of xylan, an important human dietary fibre, located within the hull, while the embryo contained numerous protein bodies (Schultz et al. 2020 ).

Hemp seed oil

Hemp seed oil is a rich source of polyunsaturated fatty acids (> 70%), particularly the essential fatty acids linoleic acid (18:2 n-6) and α-linolenic acid (18:3 n-3) with a good n-6 to n-3 ratio (2.5–5.5) for human health. Various levels of linoleic acid (51.6–59.0% fatty acids in oil), α-linolenic acid (10.5–22.0% fatty acids in oil), total tocopherols (56–97 mg/100 g of oil), phytosterols (279 mg/100 g of oil) have been reported showing the wide variability in oil composition (Callaway 2004 ; Farinon et al. 2020 ; Irakli et al. 2019 ). Virgin hemp seed oil produced by screw-pressing only is a green colour because of the chlorophyll co-extracted with the oil (Matthäus and Brühl 2008 ).

Hemp seed protein

Hemp seeds have protein content in a similar range to that of other oilseeds. They have a higher protein level than sunflower seeds or canola seeds but are lower in protein compared to soybean (Potin and Saurel 2020 ). Hemp seed proteins contain all the essential amino acids for human health and the protein fraction of hemp is highly digestible (Farinon et al. 2020 ; Mattila et al. 2018 ; House et al. 2010 ).

Globulins account for 60–80% of the total protein while albumins constitute the majority of the rest. Hemp globulins are mainly comprised of the 11S edestins, which is a hexameric legumin with a MW of ~ 320 kDa. Each monomer of the hexamer is ~ 54 kDa and composed of an acid α subunit and a heterogenous basic β subunit. The minority proteins in the globulin fraction are 7S globulins consisting of a subunit of ~ 48 kDa. The albumin fraction has a less compact structure than the globulin fraction and comprises seven polypeptides of 6–35 kDa. The protein fraction also contains other minor proteins (Potin and Saurel 2020 ; Pihlanto et al. 2020 ; Tang et al. 2006 ).

Minor components

Hemp seeds contain a range of phytochemicals, with the presence of phenolic compounds and tocopherols contributing to their antioxidant activity. Agronomic conditions can affect the levels of phenolic compounds in the hemp seed. For example, growing hemp seed at high density without pre-seeding fertilisation led to an accumulation of phenolic compounds; a typical stress response (Faugno et al. 2019 ). Hemp seeds also contain some antinutritional factors like trypsin inhibitors that affect protein digestibility and bioavailability, along with phytate/phytic acid that chelates minerals like iron and zinc, reducing their bioavailability. In one study, the concentration of phytic acid in hemp seed meal was found to range from 43.8–75.5 g/kg dry matter, while trypsin inhibitors ranged from 10.8 to 27.8 unit/mg (Galasso et al. 2016 ). Levels of these anti-nutrients are comparable or lower than other oilseeds (Galasso et al. 2016 ). Condensed tannins, cyanogenic glycosides and saponins are present at levels of 1.75, 0.23 and 69 mg/kg dry matter respectively (Russo and Reggiani 2013 ). Further details on the mineral composition, unsaponifiable components (e.g. tocopherols, phytosterols, carotenoids) and anti-nutritional factors and their effects on nutritional quality of hemp ingredients are available in several reviews (Callaway 2004 ; Farinon et al. 2020 ; House et al. 2010 ; Galasso et al. 2016 ; Vonapartis et al. 2015 ).

Cannabinoids are reported to exist in very low levels in hemp seed (Jang et al. 2020 ) even in seed from drug-type varieties where cannabinoid contents of flower tissues can be very high (Ross et al. 2000 ). One study has reported that cannabinoid contents in hemp seed might be underestimated by typical analyses and, in some instances, might exceed ten times the legal limit by weight (Yang et al. 2017 ). As cannabinoid synthesis occurs in glandular trichomes not present in seeds, this discrepancy in content may be due to differences in contamination from vegetative materials. Further work should be done to determine if cannabinoid contents of hemp seeds are indeed this variable or a function of contamination.

Processing of value-added hemp seed ingredients

There is a range of products that can be derived from hemp seed. Apart from the milling of whole or dehulled hemp seed into flour, value-added oil- and protein-enriched fractions may be isolated. Additionally, phytochemical extracts are becoming of increasing interest as their role and application in health and nutrition are increasingly being recognised (Rupasinghe et al. 2020 ).

Oil extraction

Hemp seed oil may be extracted from whole or dehulled hemp seed (House et al. 2010 ). Conventional processing techniques are primarily aimed at extracting oil efficiently and to obtain an oil of good quality. Opportunities for improvements in processing for hemp seed and production of fractions from hemp seed oil will be similar to that for the processing of more established oil seeds such as soybean, rapeseed/canola seed, sunflower seed, safflower seeds, flax seeds and palm kernels. The various methods for extraction of oil from oilseeds that have been applied to hemp seed include mechanical pressing, solvent extraction, use of supercritical CO 2 , and microwave or ultrasound assisted processing (Devi and Khanam 2019 ; Oomah et al. 2002 ; Da Porto et al. 2012 ). The oil may then be further purified and refined.

Pressing is one of the oldest methods used for extraction of hemp oil, with seed pre-treatment and processing variables affecting the efficiency of oil extraction and quality of the oil. Seed pre-treatment (50°C/1 h), a higher temperature of extraction (70 °C compared to 50 °C) and slow rotational screw speed (22 rpm versus 32 rpm) increased the oil yield (Crimaldi et al. 2017 ). The conditions used for cold-pressing can also affect the content of phenols and polyphenols in hemp seed oil (Faugno et al. 2019 ). Enzyme-assisted cold pressing has been found to increase the oil extraction efficiency without compromising oil quality (Latif and Anwar 2009 ). A comparison of solvent extracted oil from untreated hemp seed or hemp seed that were previously subject to a microwave treatment showed that microwave treatment improved oil yield, carotenoid and tocopherol contents but did not alter fatty acid composition and increased the resistance to oxidation (Oomah et al. 2002 ). Extraction of oil from hemp seed using supercritical CO 2 , cold pressing or solvent extraction resulted in oils with similar fatty acid composition, however oil extracted using supercritical CO 2 had higher tocopherol content, but reduced pigment compared to cold pressed oil. Solvent-extracted hemp seed oil did not contain tocopherols due to the high temperatures used during extraction and had intermediate levels of pigments compared to oils extracted by the other two methods (Aladić et al. 2015 ). Due to high levels of polyunsaturated fatty acids, hemp seed oil is very susceptible to oxidation with virgin oil being especially sensitive. This is due to high contents of chlorophyll that acts as a photosensitiser (Matthäus and Brühl 2008 ).

Oil was traditionally considered the more valuable component of oilseed processing and the pressed cake and meal were considered to be by-products, initially used in the animal feed industry. With the recognition that oilseeds were also good sources of protein, a range of protein concentrates and isolates have been produced from the solvent-extracted oil seed, the mechanically pressed cake or seed meal produced after solvent extraction of the pressed cake (Shen et al. 2021 ). There appears to be some confusion around the labelling of hemp seed cake and hemp seed meal in the literature and market as sometimes these terms are used interchangeably. However, to be consistent with other oilseed literature, hemp seed cake should refer to product obtained after mechanical pressing of oil while hemp seed meal is obtained after solvent extraction of the pressed cake. After expelling the oil using a screw press, the oil content in the residue obtained has 8.4–15.5% oil (Callaway 2004 ; House et al. 2010 ) while the oil content in the de-lipidated hemp meal after solvent extraction is expected to be much lower (~ 1% oil) (Potin and Saurel 2020 ).

Oil in oilseeds is present as oil bodies which are covered by oleosin proteins. A method for simultaneous aqueous separation of oleosomes and protein from oilseed has been reported. Using this process intact oleosomes are recovered and may be used as a natural oil-in-water emulsion with high physical and chemical stability (Ntone et al. 2020 ). Methods for non-destructively manufacturing oleosomes have been patented (Gray 2014 ). These methods are expected to be applicable to other oilseed including hemp.

Protein extraction

Methods used for protein isolation from oilseeds (Arrutia et al. 2020 ) may be applied to isolation of hemp seed protein fractions from hemp seed (Potin and Saurel 2020 ; Pihlanto et al. 2020 ). Understanding the source used for protein extraction and the prehistory of the starting ingredient for protein extraction is important as pre-processing can impact the protein extraction efficiency and protein quality. As the protein was originally considered a secondary product, the traditional methods did not consider the functionality or quality of the protein and often the processing steps used were detrimental to protein quality.

Sequential extraction of protein from hemp seed

Aqueous extraction is the most common method used for extraction of protein and has been applied to whole seed, cake and meal, usually after oil is expelled by pressing or solvent extracted (Shen et al. 2021 ; Pihlanto et al. 2020 ). Tang et al. (Tang et al. 2006 ) prepared hemp seed protein isolate (86.9% protein, wet basis) by alkaline extraction and isoelectric precipitation, starting from de-fatted hemp seed meal (50.2% protein) obtained after dehulling and defatting using supercritical CO 2 at < 40 °C. Compared to soy protein isolate prepared using a similar process, the hemp seed isolate had superior amino acid composition although its techno-functional properties (solubility, emulsifying activity and water holding capacity) were inferior (Tang et al. 2006 ). Using a similar process to Tang et al. (Tang et al. 2006 ), hemp seed protein isolate (84.15% protein) was extracted from a commercial defatted hemp seed meal (44.32% protein) (Malomo et al. 2014 ). Some high molecular weight proteins were not extracted from the hemp seed meal when using alkaline extraction and the authors reported that the pH of minimum protein solubility was pH 3.0 for defatted hemp seed meal and pH 4.0 for the hemp seed protein isolate (Malomo et al. 2014 ). The authors also found that the emulsifying properties of these fractions were different and dependent on pH (Malomo et al. 2014 ). Alkaline extraction/isoelectric precipitation of defatted hemp seed meal (47.9% protein) produced a protein isolate (91.44% protein) with a lower protein content than that produced using micellisation (salt extraction followed by dialysis and ultrafiltration) (98.87% protein) (Hadnađev et al. 2018 ). The pH of minimum solubility was pH 5.0 for the alkali-extracted protein isolate while that for protein extracted using micellarisation was higher at pH 6.0. In addition, the alkali-extracted protein had a higher degree of denaturation and water holding capacity but the fat holding capacity was not significantly different (Hadnađev et al. 2018 ). These variations in functionality provide opportunities to match differently prepared isolates to a range of applications.

The presence of fat in the starting material for isolation of protein is generally regarded as undesirable and often solvent extracted material is used. A recent review suggests that total de-fatting using solvent may not be necessary for some applications of protein-enriched fractions (Carre 2021 ). A study on the extractability of hemp seed protein from un-defatted hemp seed press cake under different hydration conditions, pH, ionic strength and press-cake liquid ratio suggested that pH was the most influential factor determining protein recovery (Potin et al. 2019 ). These authors found that pH > 9.0 significantly enhanced protein yields but increasing pH increased pigmentation and suggested that further steps are required to purify the protein (Potin et al. 2019 ).

Recently, newer approaches are being explored to obtain both high quality oil and protein fractions from plant sources. Using a non-solvent process, a highly digestible rapeseed protein isolate (90% protein) which is soluble between pH 2.0 and pH 12.0 with desirable emulsifying and foaming properties for applications in a range of manufactured food was reported, although the details of the process were not disclosed (Dereuder 2019 ).

Simultaneous aqueous extraction of an oleosome-protein extract

Simultaneous extraction of oleosomes (oil bodies) and protein from oil seed meals have the advantage of being a relatively mild process not requiring organic solvents, high temperature or extreme pH. These methods also do not affect the solubility of protein (Ntone et al. 2020 ). There is a report on the properties of a spray-dried commercial hemp seed protein concentrate derived from filtration of the heavy aqueous stream of a liquid–liquid phase separation process for hemp oil body extract. It was suggested that a functional hemp protein concentrate (71% protein, 32.5% fat, 2.8% ash) with an isoelectric point of pH 5.2–5.3 was obtained. The hemp protein concentrate isolated from full-fat hemp was a good foam stabiliser (Galves et al. 2019 ). A recent research study examined the recovery of hemp oleosomes from hemp milk. The hemp milk was produced by separation of a previously colloid-milled dehulled hempseed/water mixture using a clarifier separator and hemp oil bodies were separated from the hemp milk by centrifugation (Garcia et al. 2021 ).

Extraction of phytochemicals

Other bioactive components may be extracted from de-fatted hemp seed cake and serve as extracts for preparation of functional foods with health promoting properties (Rupasinghe et al. 2020 ). A comparison of conventional extraction of hemp seed cake with a mixed solvent with ultrasound-assisted extraction showed that higher amounts of polyphenols and flavonoids are extracted with the application of ultrasound and further that the antioxidant capacity of the extracts were also increased (Teh and Birch 2014 ).

Applications in food

There is significant potential of hemp-based ingredients to be used in a range of food applications (Leonard et al. 2020 ; Rupasinghe et al. 2020 ; Xu et al. 2021 ). However, there is also emerging interest in the use of other parts of the plant (e.g. sprouts; leaves; sap extract from leaves). The use of hemp ingredients in food is subject to the ingredients having low levels of THC and CBD. There are different limits for these components in hemp food products in various countries and jurisdictions. As an example, the permissible levels allowed in Australia, the EU and the USA for various hemp products (Government of South Australia 2020 ) are given in Table 1 .

Table 2 provides examples of selected applications of hemp seed products in formulated foods. Overall, hemp seed flour has superior nutritional quality compared to wheat flour and may be used for fortifying food products, as it is higher in protein, fat, minerals, fibre, essential amino acids and essential fatty acids compared to wheat flour (Rusu et al. 2021 ). The high level of polyunsaturated fatty acids in hemp seed oil means that it may be used as a nutritious oil for salad dressings but is it is not suitable for deep frying due to the high level of unsaturation in the oil. Proteins from oilseeds like hemp are seen as alternative protein sources to animal protein, contributing to the production of acceptable meat analogues (Zahari et al. 2020 ), and a acting as a valuable source of nutritional and bioactive components (Arrutia et al. 2020 ; Kotecka-Majchrzak et al. 2020 ).

Hemp seed products are emerging ingredients in the food industry. With this comes the challenges of development of ingredients with consistent composition and techno-functionality. Starting with the application in mind and understanding functionality in the end application will help in the design of fit-for-purpose ingredients through appropriate breeding technologies, post-harvest handling practices and processing operations to develop sought-after value-added ingredients for the food industry.

Recommendations

A successful and profitable industrial hemp supply has to be built to addresses a market-led opportunity. Solutions to overcome current barriers and enable the supply chain to flourish requires identification of a whole-of-supply chain approach with multiple stakeholders. For the food industry, consumer acceptance of hemp food ingredients and products will be of vital importance. Some of the issues that need further attention, to add to the growing body of knowledge in the industrial hemp industry, include the following:

Reliable seed supply of stable and genetically defined cultivars

Breeding strategies to enable production of hemp crops with low THC under stressed conditions (e.g. understanding gene expression for cannabinoids under hot conditions and in drought)

Breeding (new cultivars)/farm management practices (digital agriculture) to reduce water requirements whilst maintaining desired farm productivity

Robust processes (e.g. safe and reliable feminisation protocols) for consistent seed supply

Mechanical harvesting processes for improved efficiency

Post-harvest:

Safe storage and transport conditions for maintaining hemp seed quality

Food safety protocols and pest-control measures

Processing of hemp seed:

Pre-conditioning of seeds for improved processability

More sustainable methods for separation and processing of hemp seed

Improved processing protocols for obtaining protein fractions of consistent quality

Novel methods to protect hemp seed oil against oxidation (e.g. encapsulation)

Developing processes for separation of protein and intact oleosomes

Systematic characterisation of inherent nutritional and functional properties of hemp seed flour, protein fractions and hemp seed oil obtained using various processes

Food applications:

Developing ingredients with fit-for-purpose functionality in end applications

Testing applications of hemp seed protein in traditional food applications (e.g. bakery, snacks) and in new emerging markets (e.g. meat analogues, alternative dairy)

Communication to improve consumer understanding (e.g. difference between Cannabis for recreational drug use and industrial hemp with low THC for food use)

Education about the nutritional properties of hemp seed ingredients and products

Development of recipes containing hemp ingredients

Market/Trade:

Harmonised specifications for trade of hemp seed ingredients (i.e. hemp seed, hemp protein, hemp seed oil)

Standardised methodology for testing and analysis of THC in food products

Understanding of heterogenous regulations for cannabinoids in hemp food products in various jurisdictions

Conclusions

The growing of industrial hemp, containing low levels of THC, to provide food ingredients and incorporation into finished products is a significant opportunity. The market-led opportunities hold promise for hemp seed, which was traditionally regarded as a by-product of the hemp fibre industry. Hemp seed is a valuable product in its own right for the food industry, which can be further developed into value-added ingredients. The excellent attributes of hemp seed are their high nutritional value (high in nutritious protein and oils) and the techno-functionality of the hemp protein for a world that is short of protein. The ability to increase the productivity of the hemp crop with consistently low THC content will be a pre-requisite for investment in the industrial hemp industry as farmers need assurance that their crops can be harvested for the use they were grown for. Overall, the opportunity to build a whole supply chain is particularly attractive for the farm sector wishing to diversify and plant sustainable crops with potential for economic returns.

Availability of data and materials

No new data or materials were generated in this manuscript.

Abbreviations

(-)-cannabidiol

Molecular weight

(–)- trans -Δ 9 -tetrahydrocannabinol

United States Dollar

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Acknowledgements

Mary Ann Augustin would like to thank Meryn Scott, CSIRO, for conducting the literature search on hemp ingredients for food.

The authors acknowledge the University of Adelaide’s School of Agriculture, Food and Wine and CSIRO for financial support.

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Burton, R.A., Andres, M., Cole, M. et al. Industrial hemp seed: from the field to value-added food ingredients. J Cannabis Res 4 , 45 (2022). https://doi.org/10.1186/s42238-022-00156-7

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The hemp plant Cannabis sativa Linn, referring to industrial hemp, is a high-yielding annual industrial crop grown providing fibers from hemp stalk and oil from hemp seeds. Although hemp is a niche crop, hemp production is currently undergoing a renaissance. More than 30 countries grow hemp, with China being the largest hemp producing and exporting country. Europe and Canada are also important actors in the global hemp market. Traditionally, hemp as a fiber plant has been used for the production of apparels, fabrics, papers, cordages and building materials. The hurds, as waste by-product of fiber production, were used for bedding of animals, the seeds for human nutrition, e.g., as flour, and the oil for a wide range of purposes, from cooking to cosmetics. Hemp has also been an important crop throughout human history for medicine. Other more recent applications include materials for insulation and furniture, automotive composites for interior applications and motor vehicle parts, bioplastics, jewelry and fashion sectors, animal feed, animal bedding, and energy and fuel production. Foods containing hemp seed and oil are currently marketed worldwide for both animal and human nutrition. They also find applications in beverages and in neutraceutical products. Hemp oil is also used for cosmetics and personal care items, paints, printing inks, detergents and solvents. It is estimated that the global market for hemp consists of more than 25,000 products. Currently, the construction and insulation sector, paper and textile industries, and food and nutrition domains are the main markets while the cosmetics and automotive sector are growing markets. Innovative applications, e.g., in the medical and therapeutic domains, cosmeceuticals, phytoremediation, acoustic domain, wastewater treatment, biofuels, biopesticides and biotechnology, open new challenges. Hemp is also the object of numerous fundamental studies. This review presents and discusses the traditional and new uses of industrial hemp.

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Source : G. Crini, Chrono-environnement, Besançon, France

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Adapted from Rehman et al. ( 2013 )

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Rachel A. Burton, Mike Andres, … Mary Ann Augustin

Hemp Usage in Textile Industry

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Yu Y, Zhan JB, Wan H, Zhang Y, Li LW, Yu J, Yu TT, Xie J, Yue BS (2017) Manufacturing technology and application of hemp cigarette paper with dense ash integration. In: 3rd international conference energy material environmental engineering. Book series: IOP conference series earth and environmental science 61. UNSP 012078. https://doi.org/10.1088/1755-1315/61/1/012078

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Crini, G., Lichtfouse, E., Chanet, G. et al. Applications of hemp in textiles, paper industry, insulation and building materials, horticulture, animal nutrition, food and beverages, nutraceuticals, cosmetics and hygiene, medicine, agrochemistry, energy production and environment: a review. Environ Chem Lett 18 , 1451–1476 (2020). https://doi.org/10.1007/s10311-020-01029-2

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A Review of Hemp as Food and Nutritional Supplement

Affiliations.

• 1 National Reference Center for Environmental Health, Zoo-Prophylactic Institute of Southern Italy, Portici, Italy.
• 2 Multidisciplinary Center on Cannabinoid Research-REICA, Zoo-Prophylactic Institute of Southern Italy, Portici, Italy.
• 3 Department of Public Health, "Federico II" University, Naples, Italy.
• 4 Epidemiology Unit, Istituto Nazionale Tumori "Fondazione G. Pascale", IRCCS, Napoli, Italy.
• 5 Department of Oncology and Hematology, Regional Reference Center for Rare Tumors, AOU Federico II of Naples, Naples, Italy.
• 6 Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
• 7 CNR NANOTEC, Campus Ecotekne of the University of Salento, Lecce, Italy.
• 8 Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana," University of Salerno, Baronissi, SA, Italy.
• PMID: 33614949
• PMCID: PMC7891210
• DOI: 10.1089/can.2020.0001

The term "hemp" refers to Cannabis sativa cultivars grown for industrial purposes that are characterized by lower levels of tetrahydrocannabinol (THC), the active principle responsible for Cannabis psychotropic effects. Hemp is an extraordinary crop, with enormous social and economic value, since it can be used to produce food, textiles, clothing, biodegradable plastics, paper, paint, biofuel, and animal feed, as well as lighting oil. Various parts of the hemp plant represent a valuable source of food and ingredients for nutritional supplements. While hemp inflorescence is rich in nonpsychoactive, yet biologically active cannabinoids, such as cannabidiol (CBD), which exerts potent anxiolytic, spasmolytic, as well as anticonvulsant effects, hempseed has a pleasant nutty taste and represents a valuable source of essential amino acids and fatty acids, minerals, vitamins, and fibers. In addition, hempseed oil is a source of healthy polyunsaturated fatty acids, and hemp sprouts are rich in antioxidants. This review article aims to provide a comprehensive outlook from a multidisciplinary perspective on the scientific evidence supporting hemp beneficial properties when consumed as food or supplement. Marketing of hemp-derived products is subjected to diversified and complex regulations worldwide for several reasons, including the fact that CBD is also the active principal of pharmaceutical agents and that regulatory bodies in some cases ban Cannabis inflorescence regardless of its THC content. Some key regulatory aspects of such a complex scenario are also analyzed and discussed in this review article.

Keywords: Cannabis; cannabidiol; cannabinoids; hemp; hemp food.

Copyright 2021, Mary Ann Liebert, Inc., publishers.

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A Review of Hemp as Food and Nutritional Supplement

Pellegrino cerino.

1 National Reference Center for Environmental Health, Zoo-Prophylactic Institute of Southern Italy, Portici, Italy.

2 Multidisciplinary Center on Cannabinoid Research—REICA, Zoo-Prophylactic Institute of Southern Italy, Portici, Italy.

3 Department of Public Health, “Federico II” University, Naples, Italy.

4 Epidemiology Unit, Istituto Nazionale Tumori “Fondazione G. Pascale”, IRCCS, Napoli, Italy.

Carlo Buonerba

5 Department of Oncology and Hematology, Regional Reference Center for Rare Tumors, AOU Federico II of Naples, Naples, Italy.

Giuseppe Cannazza

6 Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.

7 CNR NANOTEC, Campus Ecotekne of the University of Salento, Lecce, Italy.

Jacopo D'Auria

Ermete ottoni, andrea fulgione, antonio di stasio, biancamaria pierri.

8 Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana,” University of Salerno, Baronissi, SA, Italy.

Alfonso Gallo

The term “hemp” refers to Cannabis sativa cultivars grown for industrial purposes that are characterized by lower levels of tetrahydrocannabinol (THC), the active principle responsible for Cannabis psychotropic effects. Hemp is an extraordinary crop, with enormous social and economic value, since it can be used to produce food, textiles, clothing, biodegradable plastics, paper, paint, biofuel, and animal feed, as well as lighting oil. Various parts of the hemp plant represent a valuable source of food and ingredients for nutritional supplements. While hemp inflorescence is rich in nonpsychoactive, yet biologically active cannabinoids, such as cannabidiol (CBD), which exerts potent anxiolytic, spasmolytic, as well as anticonvulsant effects, hempseed has a pleasant nutty taste and represents a valuable source of essential amino acids and fatty acids, minerals, vitamins, and fibers. In addition, hempseed oil is a source of healthy polyunsaturated fatty acids, and hemp sprouts are rich in antioxidants. This review article aims to provide a comprehensive outlook from a multidisciplinary perspective on the scientific evidence supporting hemp beneficial properties when consumed as food or supplement. Marketing of hemp-derived products is subjected to diversified and complex regulations worldwide for several reasons, including the fact that CBD is also the active principal of pharmaceutical agents and that regulatory bodies in some cases ban Cannabis inflorescence regardless of its THC content. Some key regulatory aspects of such a complex scenario are also analyzed and discussed in this review article.

Introduction

Cannabis is a genus of flowering plants belonging to the family of Cannabaceae. According to some authors, the Cannabis genus includes three different species, such as Cannabis sativa , C. indica , and C. ruderalis. 1 Alternatively, it is considered as monospecific ( Cannabis sativa L.) with two subspecies [ Cannabis sativa L. subsp. sativa and Cannabis sativa L. subsp. indica (Lam.) E. Small & Cronq.] and four varieties [ Cannabis sativa L. subsp. sativa var. sativa ; Cannabis sativa L. subsp. sativa var. spontanea Vavilov; Cannabis sativa L. subsp. indica (Lam.) E. Small & Cronq. var. indica ; and Cannabis sativa L. subsp. indica (Lam.) E. Small & Cronq., var. kafiristanica (Vavilov)]. 2 Such a taxonomy was proposed by Small and Cronquist combining fruit morphology and (−)-trans-Δ9-tetrahydrocannabinol (THC) content. 2 Cannabis plants have been used for thousands of years for recreational, medicinal, or religious purposes. 3

Currently, there are ∼147 million people worldwide who consume Cannabis , primarily because of its intoxicating properties mediated by THC. 4 Most people, who simply have knowledge of Cannabis as a recreational drug, ignore the enormous social, industrial, and economic value of “hemp.” Hemp is the term used as opposed to “marijuana” to refer to Cannabis varieties characterized by lower THC levels and grown for industrial purposes. 5 Hemp is a versatile crop, which can be grown at high latitudes 6 and can be used to produce food, textiles, clothing, biodegradable plastics, paper, paint, biofuel, and animal feed, as well as lighting oil. 7 In 1938, the Popular Mechanics magazine defined hemp as “the new billion-dollar crop,” with about 30,000 different products derived from the fiber and the stalk of plant.

Over the past decades, to counteract its widespread use as a recreational drug, the authorities had banned cultivation of any variety of Cannabis without making a distinction based on the THC content, which severely and unfairly harmed the hemp industry. During the past few years most Western countries have recognized the incontrovertible economic, potential, and social value of industrial hemp and even promoted its cultivation through ad hoc legislative interventions, which have established a legal threshold for THC concentration in the dry plant material (e.g., 0.2% in the European Union). 8 In the United States, hemp is not considered as a controlled substance subject to Drug Enforcement Administration (DEA) regulation and can be produced according to the 2014 farm bill provision, although some aspects are still overseen by DEA, including the importation of viable seeds. 9

Hempseeds and inflorescence are extensively used worldwide as source of food and supplement ingredients. Hemp inflorescence is rich in nonpsychoactive, yet biologically active cannabinoids, such as cannabidiol (CBD), which exerts potent anxiolytic, spasmolytic, as well as anticonvulsant effects, among others. 10 CBD nutritional supplements account for approximately one-third of the global 1.34 billion dollar market for CBD. 11 Hempseed has a pleasant nutty taste and represents a valuable source of essential fatty acids, minerals, vitamins, and fibers, as well as of essential amino acids contained in the highly digestible proteins edestin and albumin. 12 Hempseed oil is composed for its greater part (>90%) of polyunsaturated fatty acids 13 known for their beneficial effects against cardiovascular diseases, cancer, and inflammatory conditions. 14 , 15

Hemp sprouts can also be consumed as food. Compared to hempseeds, hemp sprouts are characterized by higher content in total polyphenols, flavonoids, and flavonols, known for their positive cardiovascular and metabolic effects. 16 Besides the multiple potential advantages—most of which are yet to be proved in large prospective trials—associated with the hundreds of different compounds found in hemp, dietary consumption of hemp products may also carry potential risks for public health, mostly related to the excessive exposure to psychoactive and nonpsychoactive cannabinoids, that may be present as undesired contaminants 17 or may be purposely consumed in excessive and potentially harmful amounts. Presently, marketing of CBD-based dietary supplements, which is under intense debate in the scientific community, 18 is differently regulated in the United States, Europe, and the rest of the world.

The aim of this narrative review is to provide a comprehensive analysis of the available scientific evidence on the composition, nutritional properties, as well as safety of hemp consumed as food and nutritional supplements, with a focus on the related complex socioeconomic and regulatory aspects.

Hemp Bioactive Compounds

The extensive research that has probably made Cannabis the most studied plant in human history has allowed to identify hundreds of different compounds with potential biological activity, including more than 120 terpenoids, 100 cannabinoids, 50 hydrocarbons, 34 glycosidic compounds, 27 nitrogenous compounds, 25 noncannabinoid phenols, 22 fatty acids, 21 simple acids, 18 amino acids, 13 simple ketones, 13 simple esters and lactones, 12 simple aldehydes, 11 proteins, glycoproteins, and enzymes, 11 steroids, 9 trace elements, 7 simple alcohols, 2 pigments, as well as vitamin K. 19

Two recently published studies using an optimized method for chemical characterization of hemp identified 189 lipids, including 52 phospholipids and 80 sulfolipids, 20 and 147 compounds belonging to the classes of flavonoids, proanthocyanidins, and phenolic acids. 21 Nonpsychoactive cannabinoids reported in hemp include the abovementioned CBD, as well as cannabichromene (CBC), cannabigerol (CBG), cannabinol, cannabicyclol, cannabielsoin, cannabitriol, and others. 22 Part of their biological activity can be explained by the interaction with the endocannabinoid system, which includes two G protein-coupled cannabinoid receptors (CB1 and CB2) and two endogenous ligands (anandamide and 2-arachidonoylglycerol). 23 , 24

The endocannabinoid system is physiologically involved in regulation of appetite, pain, mood, memory, inflammation, insulin sensitivity, as well as fat and energy metabolism, with a wide variety of potential therapeutic implications for treatment of pain, neuropsychiatric disorders, neurological diseases, and inflammatory bowel, which may benefit from CB1 activation, as well as for treatment of obesity, type 2 diabetes, and hepatic or kidney disorders, which may benefit from CB1 antagonism. 25

CBD is biosynthesized as a carboxylic acid through the same metabolic pathway as THC, with the exception of the last chemical reaction that is catalyzed by CBD acid synthase instead of THC acid synthase. 26 CBD exerts a wide range of biological effects, including anticonvulsant, anxiolytic, anti-inflammatory, immune-modulating, and antineoplastic activity, as shown in multiple pre-clinical models. CBD dose-dependent anticonvulsant activity was also shown in a 4-aminopyridine model prepared using mouse hippocampal brain slices at concentrations ranging from 0.01 to 100 μM, as well as in vivo in a pentylenetetrazole model of generalized seizures, at doses of 1, 10, and 100 mg/kg. 27 , 28

A potent anxiolytic effect of CBD has also been shown in pre-clinical models. In mice undergoing 2 weeks of chronic unpredictable stress, CBD repeated administration at the dose of 30 mg/kg exerted a potent anxiolytic effect through the CB1 cannabinoid receptor, as suggested by evidence of higher hippocampal anandamide levels associated with CBD administration and reversal of CBD effects through administration of a CB1-selective antagonist. 29

Interestingly, CBD spectrum of biological activities includes immune-modulating and anti-inflammatory properties. In a mouse paw model of acute carrageenan-mediated inflammation, oral daily administration of CBD at doses ranging from 5 to 40 mg/kg for 3 days was able to reduce edema, prostaglandin E2 plasma levels, tissue cyclooxygenase activity, production of oxygen-derived free radicals, and nitric oxide after three doses of CBD. 30 Anti-inflammatory effects may be explained by inverse agonism activity toward the CB2 receptor, 31 which inhibits immune cell migration both in macrophages 32 and human neutrophils. 33 CBD may also exert potent and specific activity against neuroinflammation processes, which are involved in a number of neurodegenerative disorders. 34

In an experimental murine multiple sclerosis model obtained through inducing autoimmune encephalomyelitis through immunization with myelin oligodendrocyte glycoprotein, CBD (5 mg/kg) administered for 3 days–3 weeks after myelin antigen administration at the time of disease onset was able to slow progression and reduce severity of the autoimmune encephalomyelitis. Clinical activity was accompanied by histologic evidence of diminished axonal damage and microglial activation and by in vitro evidence of decreased T cell proliferation in response to the myelin antigen. 35

CBD also presents antineoplastic activity shown in several pre-clinical models. Among five different cannabinoids, including CBD, CBG, CBC, cannabidiol acid, and THC acid, CBD exhibited the strongest in-vitro antineoplastic activity in a panel of different cancer cell types, with an IC(50) between 6.0 and 10.6 μM. 36 The underlying mechanism of action may be mediated by CBD-induced production of reactive oxygen species and desensitization of transient receptor potential cation channel, subfamily A, member 1 (TRPA1), 36 which plays a critical role in maintaining cellular homeostasis in response to oxidative stress. 37

TRPA1 is also desensitized by the strong agonistic activity exerted by another cannabinoid lacking psychotropic effects, CBC, which results in a potent anti-inflammatory effect, as shown in a mouse model of colitis induced by dinitrobenzene sulfonic acid. 38 CBG has also proven to reduce inflammation in an experimental murine model of colitis. 39 CBG may also reduce intraocular pressure, as shown after chronic topic administration to the eyes of cats. 40

Terpenes found in hemp, which confer the typical aroma and flavor, may also exert multiple biologically relevant effects. β-Myrcene and limonene are among the most abundant terpenes in hemp. In a mouse model of osteoarthritis, myrcene showed meaningful anti-inflammatory activity in human chondrocytes. 41 In vitro studies also suggest that β-myrcene may be useful to treat pain through interaction with transient receptor potential cation channel subfamily V member 1 (TRPV1) channels. 42 Limonene may exert antiallergic activity.

In an in vitro study conducted in human eosinophilic leukemia HL-60 clone 15 cells, limonene was capable of inhibiting reactive oxygen species production even at low concentrations (7.34 mmol/L), while at 14.68 mmol/L concentration limonene was able to decrease monocyte chemotactic protein-1 (MCP-1) synthesis, which suggests a potential clinical action against bronchial asthma, 43 as also confirmed by reduced allergic airway inflammation obtained with limonene inhalation in an experimental mouse model. 44 Another terpene found in hemp, β-Caryophyllene, has shown potent anxiolytic effects in mice. 45 Finally, cannaflavin A and B are two flavones with potent antioxidant activity found in hemp inflorescence that have shown to reduce prostaglandin E2 synthesis in cultures of human rheumatoid synovial cells 46 and may therefore provide anti-inflammatory effects in humans. 47

Hemp Supplements

As a plant-derived, easily extractable, biologically active compound with large therapeutic index and overall excellent safety profile, CBD is currently marketed both as a mainly hemp-derived dietary supplement, subjected to evolving legislation and regulatory actions, and as a drug, such as Epidiolex (CBD only) and Sativex (THC and CBD in 1:1 ratio), with specific approval indications worldwide.

Epidiolex is currently both European Medical Agency- and Food and Drug Administration approved against seizures associated with Lennox–Gastaut or Dravet syndrome in patients 2 years of age or older on the grounds of high quality scientific evidence from randomized controlled trials. 48 , 49 Concordantly with its biological activity discussed above and demonstrated in pre-clinical models, accumulating evidence from clinical trials suggests that CBD as a pharmaceutical agent has the potential to gain a number of additional indications for the treatment of sleep disorders, social phobia, post-traumatic stress syndrome, substance abuse and dependence, schizophrenia, bipolar disorder, depression, and Parkinson's disease. 50

While CBD has been administered up to 6000 mg/day in phase I studies, 51 Epidiolex recommended that starting dose for the approved indications is 5 mg/kg, which can be increased up to 20 mg/kg/day. 52 Compared to placebo, Epidiolex has shown dose-dependent increased incidence of alanine aminotransferase elevations above thrice the upper limit of normal (13% vs. 1%, mainly in patients treated at the 20 mg/kg daily dose). 52 Dose-dependent CBD potential for inducing liver toxicity when administered at pharmacological doses is confirmed by pre-clinical experiences in the mouse model. 53

In Epidiolex registrative trials, somnolence and sedation were reported in 34% and 27% of patients consuming 20 versus 10 mg/kg/day, while the risk of suicidal behavior associated with Epidiolex versus placebo was ∼3.5 fold. 48 Decreased appetite, fatigue, diarrhea, transaminase elevation, rash, sleep disorders, as well as infections, were also reported in >10% of subjects treated with Epidiolex. 48 In view of the variety of potentially life-threatening adverse events, as well as of the recommended precautions and warnings, besides potential drug–drug interactions reported with CBD at pharmacological doses, the FDA has prohibited marketing of CBD as an ingredient for nutritional supplements, 18 which appears in contradiction with United States federal court ruling establishing that hemp-derived products, including those containing CBD, could be freely marketed under the 2014 Farm Bill. 54

The scenario is also confusing in Europe, where CBD-containing products (e.g., CBD-enriched hemp oil) have been classified as novel foods because their use was not widespread in Europe before 1997, 55 which makes it mandatory to apply for authorization to place dietary CBD products on the market. One application requesting CBD to be authorized as a novel food with a daily intake of up to 130 mg or 1.86 mg/kg body weight has been filed by Cannabis Pharma, s.r.o. (Czech Republic) and remains currently pending. 56

Despite such a regulatory and legislative confusion, the importance of the CBD issue from a public health perspective lies in its widespread self-administration without any medical supervision and wide availability as a supplement, with a market worth for retail sales of hemp-derived CBD products of $170 million in 2016 in the United States alone and a projected market worth of hemp-derived CBD of $22 billion in 2022. 57 Furthermore, in view of the lack of stringent controls of marketed products by the competent authorities, mislabeling of CBD supplements is frequent, which may represent a fraud for consumers, as well as pose a risk for their health.

In a study involving 88 CBD liquid products, including oil and vaporization liquid, marketed by 31 different companies, CBD median levels were 9.45 mg/mL (range 0.10–655.27 mg/mL), which was lower compared to the median labeled concentration of 15.00 mg/mL (range 1.33–800.00). CBD-containing oil to be consumed orally was inaccurately labeled in 55% of cases. 58 The FDA has sent warning letters to several companies requesting them to stop claiming that their CBD products may treat or even cure serious diseases, including cancer. 59

The widespread use of CBD products has been poorly investigated. One study recruited 2409 individuals who participated in an online survey designed to assess the reasons, risks, and modalities behind CBD consumption. 60 Approximately a third of participants reported some nonserious adverse event, with the most frequently occurring adverse events being dry mouth (11.12%), euphoria (6.43%), hunger (6.35%), red eyes (2.74%), and sedation/fatigue (1.78%). Among the 1483 users who reported using CBD to treat a medical condition, which most frequently included pain, anxiety, depression, and sleep disorders, approximately one-third of participants stated that CBD alone could manage their medical condition by itself.

Importantly, ∼40% of participants were motivated to consume CBD as part of a healthy lifestyle. Despite its numerous limitations, including the lack of data regarding the dose consumed and timing of consumption, as well as the absence of a control group, this study has the merit to capture consumers' motivations behind CBD use, which is essential to direct further research and investigations, as well as regulatory interventions.

Despite the large consumption of CBD as a nutritional supplement, evidence from pre-clinical and clinical studies exploring the effects of CBD as a dietary ingredient is scarce to nonexisting. In one pre-clinical study conducted in eight dogs and eight cats, 61 CBD administered at the daily dose of 4 mg/kg for 12 weeks did not cause any alteration in complete blood count or serum chemistry, with the exception of one cat showing persistent abnormalities in alanine aminotransferase levels. Dogs presented few adverse events, including loose stool and vomiting occurring for <5% of the observation time, while cats showed multiple adverse events, including licking and head shaking, observed for 35.4% and 25.2% of the observation time, respectively.

In a small interventional prospective trial, including 12 individuals receiving up to 90 mg of single oral doses of CBD and assessed for cardiovascular and cognitive functions after CBD consumption, increased cerebral perfusion and reduced blood pressure compared with baseline were reported in a subgroup of participants receiving 90 mg CBD, without any clinically evident adverse events or laboratory alteration in blood count, inflammation, or metabolic markers. 62

Although adequate trials assessing CBD effects when administered as nutritional supplement in large populations and for a prolonged period of time are lacking, the clinical evidence summarized here allows to hypothesize that the acceptable dose for supplementation in adults may be comprised between the total dose of 5–10 mg/day, obtained by roughly estimating CBD exposure through historic use patterns based on the available data on smoked Cannabis 63 and the pharmacological total daily doses >350 mg a day, that is, in the range of 50–100 mg a day. This may represent the dose range for testing CBD hemp supplements as part of a healthy diet.

The need for further research is becoming more compelling as multinational companies such as Coca-Cola are planning to supplement some of their products with CBD, 64 which will expand the variety of CBD-supplemented food and beverages—as an example, a Californian company is marketing CBD-supplemented wine, 65 while New York-based company Sovereign Vines has produced a wine with special tastes and flavors of hemp.

Hemp has been a valuable source of food for mankind for millennia, as shown by the hempseeds found in tombs dating back to the third millennium before Christ in China, where roasted hempseed can still be bought on the street as snacks. 66 Although hemp leaves, sprouts, and flowers can be consumed as a raw food by preparing juices and salads, 67 hempseeds represent the most common part of the hemp plant to be consumed as food. The true seed is an achene, enveloped by a subtle and hard pericarp, and matures 3–6 weeks after the fertilization of female flower. 68 Hempseeds provide ∼500–600 Kcal/100 g of product and are composed of approximately one-fourth of proteins, one-fourth of carbohydrates, and one-third of fat, 69 with some significant variations among different genotypes. 70

Hempseeds are rich in polyunsaturated fatty acids, which also vary among different genotypes. One study of seven different hempseed cultivars (“Bialobrzeskie,” “Felina 32,” “Tygra 75,” “Futura 27,” “Santhica,” “Fedora 17,” and “Finola”) showed that “Finola” had the highest content of γ linolenic and α-linolenic acids and the lowest content in oleic acid and saturated fatty acids, such as palmitic and stearic acids. 70

Hempseed proteins represent a valuable source of sulfur-containing amino acid methionine and cystine and provide high quantities of arginine, an essential amino acid with beneficial cardiovascular properties. Accumulating evidence supporting the antihypertensive effect of hydrolyzed hempseed proteins, possibly mediated by inhibition of angiotensin-converting enzyme and renin, 71 provided the rationale for an ongoing human trial testing hemp protein powder as an antihypertensive nutritional intervention. 72

This trial is going to enroll 35 individuals showing systolic blood pressure >130 mmHg or elevated diastolic blood pressure ≤110 mmHg, who will be randomized to a dietary intervention consisting of either 25 g of casein or 25 g of hempseed protein or 22.5 g of hempseed protein added with 2.5 g of hempseed protein hydrolysate derived enriched with bioactive peptides. 72 Finally, as little as 50 mg of hempseeds can cover 50–100% of the recommended daily intake of several minerals, including copper, magnesium, and zinc, and provide >100% of the daily recommended dose of vitamins A, D, and E. 73

Hempseeds can also be used to make flour and oil with valuable nutritional properties. In one study, flour of hemp “Fedora” contains moisture, protein, lipids, carbohydrates, and ash in the proportion of 7.9±0.9, 30.7±1.2, 13.6±1.9, 41.6±2.5, and 6.2±0.5%, respectively, with a high content of total polyphenols quantified with the Folin–Ciocalteu method (744±29 gallic acid equivalents). 74 Up to 10% of flour obtained from hempseed added to wheat flour did not affect dough stability and dough strength, but improved the nutritional value of the final product by increasing the levels of proteins and minerals. 75 In another study, the addition of hemp flour to starch to make gluten-free bread was associated with improvement in palatability in terms of flavor and color, as well as in the nutritional value, with increased levels of fibers and proteins. 76 Crackers made from hemp flour have also improved nutritional value. 77

Hempseed oil is the most commonly used edible hemp derivative, with potential uses also in the cosmetic industry as a sun cream due to its capacity to absorb UV rays and its high content in vitamin E (100 mg/100 mL). 78 Hempseed oil consists of >800% unsaturated fats with an established cardioprotective effect such as linoleic acid (18:2 omega-6) and α-linolenic acid (18:3 omega-3), which are found in hemp oil at an optimal ratio of 2/3:1. 74 , 79 Of note, despite the nutritional value of a balanced content in omega-6:omega-3 fatty acids, most commercially available cooking oils are selected to have a low content in omega-3 fatty acids to improve their stability, as omega-3 fatty acids rapidly turn rancid because of the presence of three double bonds. 80

In one study evaluating the composition of hempseed oil derived from seven cultivars, including “Novosadska,” “Secuieni,” “Beniko,” “Felina 34,” “Futura 75,” “Tiborszállási,” and “Carmagnola Seleccionata,” the total amount of unsaturated fatty acids was 82–86%, with 51.9–55.7% of linoleic acid and 12.3–15.3% of α-linolenic acid, while γ-linolenic acid, which is involved in inflammatory processes, 81 ranged from 0.8% in domestic “Novosadska” cultivar to 2.46% in “Beniko”. 82 Hempseed oil also has a high antioxidant capacity due to its content in phenols and flavonoids, with 267.5±8.84 mg of gallic acid equivalents and 2780.4 mg ±133.06 of quercetin equivalents in 100 g of fresh cold-pressed hempseed oil from “Finola” cultivar, 83 while β-caryophyllene and myrcene have been found at concentrations of 740 and 160 mg/L, respectively. 84

With its pleasant, nutty-favored taste, with somewhat of a bitter aftertaste, 85 hempseed oil may be used in cooking as a replacement for olive oil, which has established benefits for cardiovascular health. 86 Small quantities of hempseed oil (2 g/day) did not produce any effect in plasma levels of total cholesterol, high and low density cholesterol, triglycerides, nor did it induce any effect in terms of platelet aggregation and levels of circulating inflammatory markers in a trial 87 in a 12-week trial, including 86 healthy participants. These results were confirmed in another trial enrolling 36 children with primary hyperlipidemia, who did not show any improvement in their lipid profile after consuming 3 g of hempseed oil. 88

Interestingly, daily consumption of 30 mL hempseed versus flaxseed oil was associated with an improvement in the total cholesterol to high density lipoprotein cholesterol ratio 89 in another small trial enrolling 14 individuals. In another controlled, randomized single-blind crossover study, 20 participants with atopic dermatitis were instructed to consume 30 mL of olive versus hempseed oil during a 20 week period. Importantly, consumption of hempseed oil resulted in subjective decreases in both skin dryness and itchiness along with reduced use of topical medications, while this effect was not reported for olive oil. Although limited, these results suggest that hempseed oil can be part of a diet with potential health advantages. Finally, hemp sprouts may also represent an attractive functional food due to their content in flavonoids and flavanols, 90 although clinical trials exploring palatability and potential benefits associated with their consumption are lacking.

Future Directions

Hemp potential as an extraordinary source of supplement ingredients and a healthy food remains largely to be investigated in adequately powered clinical trials. FDA position to consider hemp-derived CBD as a drug only with prohibition to market it as a supplement appears as a legitimate safeguard against uncontrolled use of an active principal approved as a drug, which carries the risk of serious adverse events, drug–drug interaction, and cannot and should not be used without medical supervision.

Nevertheless, we believe that CBD is likely to be safely consumed as a nutritional supplement up to a dose of 1–2 mg/kg, as also reported in the position paper by European Industrial Hemp Association. 91 Unfortunately, while data regarding the effects associated with very high doses of CBD (up to 6000 mg/day) for short periods, 51 data obtained in population studies with a double-blind design and with sufficient power to capture even infrequent adverse effects are currently lacking unfortunately.

Regulatory agencies are allowed to err on the side of prudence provided that sufficient impulse is given to the design and conduction of such clinical studies. Prohibition of CBD marketing as a supplement ingredient within certain dose limits may limit consumers' right to have access to a naturally occurring substance obtained from THC-free hemp, which can be freely marketed. In contrast, interventions aimed at guaranteeing hemp-derived food safety are compulsory. After analyzing the cannabinoid profile by a liquid chromatography method coupled to high-resolution mass spectrometry in 10 commercially available organic hempseed oils, Citti et al. 92 reported noninsignificant concentrations of THC and CBD besides other 30 cannabinoids, which is probably due to contamination of seeds with inflorescence, as cannabinoids are not found in hempseeds.

The Zoo-Prophylactic Institute of Southern Italy (IZSM) is the first public Italian Institution operating under the supervision of the Italian Ministry of Health and with jurisdiction over food safety to provide assessment of THC content in food and hemp products in Accredia-certified internal laboratories, with enormous implications for public health and hemp law enforcement ( www.reica.org ). A large, IZSM-sponsored observational study, the HEMPEDOCLE study, is going to recruit ∼900 Cannabis users, including 600 individuals who consume hemp-derived Cannabis products as food or supplement. This trial is going to prove or disprove safety of dietary hemp products and measure subsequent cannabinoid exposure in participating subjects.

Conclusions

Hemp use in the food and supplement industry is predicted to expand in the coming years as demand grows, with enormous social, economic, and sanitary implications. Legislative and regulatory interventions should aim at encouraging adequate clinical research to prove or disprove safety of hemp-derived products, which has not been done so far independently by the industry or by the scientific community.

Abbreviations Used

Authors' contributions.

P.C., C.B., G.C., and A.G. drafted the article. All authors equally contributed to literature search and critical revision for important intellectual content and finally approved the article.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

Cite this article as: Cerino P, Buonerba C, Cannazza G, D'Auria J, Ottoni E, Fulgione A, Di Stasio A, Pierri B, Gallo A (2021) A review of hemp as food and nutritional supplement, Cannabis and Cannabinoid Research 6:1, 19–27, DOI: 10.1089/can.2020.0001.