Terpenes are usually classified by the number of isoprene units in the molecule

With the increase in production,advanced and standardized processing technologies,including drying,extraction and purification,are required to ensure the quality and safety of these products for food applications,as well as the processing efficiency and sustainability of hemp.Some terpenes,on the other hand,are considered generally regarded-as-safe substances,which are permitted to be added and have been used in foods.However,the incorporation of hemp terpenes in foods and preservation of terpenes during processing is still challenging,requiring further research.In recent years,many studies have been conducted to identify the functionalities and pharmaceutical values of hemp CBD and terpenes,as well as extraction technologies of CBD.However,there is currently not a comprehensive review that discusses the potential of hemp CBD and terpenes as future functional food ingredients and evaluates the available and potential processing technologies for hemp.Therefore,this article reviews the legal regulations,challenges in incorporating hemp CBD and terpenes in foods and potential solutions,as well as current research status and future prospects in processing technologies of hemp biomass.Through this review,we expect to draw a clearer image for food manufacturers and researchers on the potential of applying hemp CBD and terpenes as future functional food ingredients and provide information for standardizing and improving the processing technologies of hemp for efficient production of high quality and food-safe products.Future research needs are also identified in this article.In the hemp plant,cannabinoids mainly reside in the flowers and leaves.More specifically,they are primarily stored in the glandular and non-glandular epidermal appendages called trichomes,which are transparent glandular ‘hairs’ on the surface of inflorescence and leaves.

The cannabinoids are chemically bounded with the cell walls,secretory vesicles and fibrillar material in the secretory cavity of the disc cell.In this section,the physical properties and chemistry of CBD,cannabis growing system health benefits,potentials and associated challenges as future functional food ingredients are discussed.Chemically,cannabinoids are a type of molecules that contain terpenoids and alicyclic units.Currently,more than 120 types of cannabinoids have been found in hemp plants.Fig.3 shows the biosynthetic pathway of cannabinoids in hemp plant.The basic reaction in the cannabinoids synthesis involves the alkylation of the phenolic moiety of olivetolic acid with the terpenoid component of geranyl pyrophosphate ,which produces cannabigerolic acid ,the common precursor of all major cannabinoids in the hemp.CBGA can then convert into other cannabinoids such as tetrahydrocannabinolic acid ,cannabichromenic acid and cannabidiolic acid ,etc.,through the enzymatic catalytic reactions by THCA-synthase,CBCA-synthase and CBDA-synthase.It is worthy of mentioning that only the acidic cannabinoids exist naturally in hemp plants.According to their molecular structures,cannabinoids are non-polar,and thus have low solubility in aqueous solution.The boiling points of cannabinoids ranged from 157 °C to 220 °C,which is not volatile.However,CBD is thermally unstable and very sensitive to photolytic reaction and oxidation.The acidic form cannabinoids are not considered to be pharmacologically active since they do not affect the endocannabinoid system of human body in the same way as the neutral forms.Therefore,a decarboxylation process is usually needed to convert the CBDA to CBD,which involves the removal of a carboxyl group from the acidic molecule and the release of a CO2 under high temperature.The reaction mechanisms of the decarboxylation process are illustrated in Fig.3B.Recently,research has proven the functionalities of CBD,which include pain relief,reduction of anxiety/distress,nausea and promotion of relaxation.

In addition,since CBD is not psychoactive,it does not result in addictive effect as caused by THC.At present,there is an increasing prevalence of lifestyle induced chronic diseases,and consumers are pursuing healthier diets,seeking more functional foods reinforced with functional ingredients.Currently,the global health and wellness market is at $1.5 trillion,and is projected to increase annually at 5%–10%.In 2019,the global functional food market was $250 million,and was projected to $440 billion by 2022.Therefore,there is a high potential in this rising trend to add hemp CBD in foods or beverages as future functional food ingredients.However,there are several challenges that are limiting the development of CBD-containing foods,which involves legal regulations,consumer awareness,and technological deficiencies.Legal regulations and policies are one of the most important factors in directing the developments of markets and products.Currently,regulations on the hemp CBD varies country by country,and CBD is in the ‘grey zone’,of which the legality is not clearly defined.In the United States,the 2018 Farm Bill removed industrial hemp from the definition of marijuana,which allowed more research to be done on hemp.However,it is still prohibited in federal level to add CBD to any foods,beverages or nutrient supplements.FDA has not waived it from the illegal ingredients list due to safety concerns of the non-approved CBD products and the fact that CBD was first studied as a drug.In fact,in 2018,FDA approved the first and by far the only medicine containing CBD for the treatment of seizures associated with two rare and severe forms of epilepsy,Lennox-Gastaut syndrome and Dravet syndrome.Even though it is still not approved in federal level in the US,some food products are already in the markets in some states as they deregulated the CBD,such as tea,coffee and chocolate,etc..In Canada,cannabis is nationally legalized,but phyto-cannabinoids such as CBD is in the Prescription Drug List and cannot be legally sold in self-care natural health products or cosmetics.

Canadian Health Food Association has recently released a report,which emphasized the potential positive economic impacts of permitting CBD in NHPs,foods and beverages for the economic recovery.In Europe Union ,CBD was catalogued into ‘novel foods’ in January 2019,and the EU has required extensive testing and authorization of CBD products from food safety authorities.In addition,different countries have different standards in legalizing the THC level in the products.China was projected to be largest producer and consumer of hemp CBD,given the long cultivating traditional and production area,however,recently a national level regulation forbids any use of CBD in foods or cosmetics.The strict regulations have a significant impact on the development of the hemp industry,and the major food manufacturers are conservative in entering the CBD market.In fact,due to these strict regulations and the influence of pandemic on the global logistics,the hemp market and product development process have been significantly impacted.The hemp biomass and CBD are oversupplied in the market,and the price of CBD has hit the rock bottom in the first half of year 2021.The enthusiasm of farmers in cultivating hemp is cooling down.However,we envision that this ‘downturn’ could be temporary.With more research works done and more scientific evidence published proving the health benefits and safety of CBD,the regulations shall be more relaxed and standardized,which will be a strong booster for both the CBD-food market and in return benefit more related research to be conducted.In most cultures,the words ‘hemp’ and ‘cannabis’ are associated with ‘drugs’ and ‘illegal’,and thus are repelled.The word ‘CBD’ is still unfamiliar to most people in the world,not to mention its health benefits.Therefore,to promote the use of CBD as functional food ingredients,educating the consumers about the health benefits,safety,and its distinction from ‘drug’ is as important as the relaxing of legal regulations.At the same time,it is critical to find the right market position and target consumer groups.Currently,regular CBD consumers are buying CBD to obtain a functionality or health benefit,and usually taking it as a dietary supplement/medicine,which only represent a niche market.It is important to identify the types of foods that are compatible with CBD.Incorporating CBD into staple foods and beverages may potentially expand the consumer base,which is currently challenging and require more extensive research.The consumer needs for the CBD reinforced foods are another important factor to be considered in the product developments.For example,an afternoon pick-me-up ‘CBD-containing coffee’ or a sports drink need to be fast-responding,meanwhile it should not cause any adverse side effect to the human health.

Additionally,the food products need to be shelf-stable and maintain the activity of CBD under normal storage conditions,particularly given the fact that CBD is not a very stable substance.Besides the regulation and consumers aspects,there are currently some technological challenges that need to be resolved to add hemp CBD in foods and beverages.The types of products that can be reinforced with CBD are dependent on the physical and chemical properties of CBD.As discussed above,CBD is a highly non-polar molecule,meaning it has low aqueous solubility.Therefore,it is difficult to incorporate it into most aqueous-based food and beverage systems.Besides,recent studies have shown that the bio-accessibility of CBD is relatively poor in animal and human bodies,which may be due to the low cell penetration rate.In addition,CBD has relatively poor stability,which is affected by various factors such as temperature,humidity,pH,oxygen,light,and the solvent types,etc..Its instability suggests that CBD is vulnerable to deteriorate when it is inappropriately added to food systems or exposed under stress conditions.The oral ingestion of cannabinoids usually results in long lasting and slow effects,hydroponic rack system which is not desirable for the fast-responding needs,and is identified as an area of improvement.Currently,studies on the solubility and stability in various food and beverage systems are not well reported.The studies on the bioaccessbility of CBD in human body are also scarce.More extensive research in these aspects is urgently needed to address these challenges.The outcomes will provide scientific evidence to support the feasibility of adding CBD into foods and further prove their health benefits.Although the most of CBD-containing foods are considered illegal at present,the future can still be bright and optimistic.The 2018 Farm Bill of the U.S.opened the gate of industrial hemp to industries and researchers.Following that,more and more capital investments are putting into the hemp industry and scientific research.According to statistics,the global market size of hemp was $5.73 billion,and was expected to grow to $27.72 billion by 2028.This allows more universities and research institutions to conduct necessary research,which in return will be beneficial for the development of CBD-containing foods.Although current regulations prohibit the use of CBD as food ingredients,we envision that some regulations will ease up in the near future.This will depend on more scientific studies to be conducted and evidence that proves the health benefits and determines any side effects of CBD to human beings.In fact,United Nations has recently removed cannabis from its most rigid drug control list,the ‘Schedule IV of the 1961 Single Convention on Narcotic Drugs’,which was a huge win for the hemp industry.More organized and standardized regulations all over the world will also be helpful for the development of CBD-containing food products.In technological aspects,some studies have been conducted to improve the solubility,stability and bio-accessbility of CBD in medicine or food systems.Encapsulation,emulsification and microfluidization are being used to incorporate various bio-active compounds into food and beverage systems in the industry and offer potential solutions to the development of CBD-containing foods.

Micro-encapsulation is one possibility to improve the solubility and reduce the oxidative susceptibility of sensitive bio-active compounds,where the hydrophobic molecule is encapsulated and dispersed in aqueous phase.Feng et al.applied sesame oil as a delivery system for CBD in medicines and revealed that adding of medium-chain triglyceride improved the solubility of CBD and superior bio-availability.Lange and Schilderink found that micro-encapsulated CBD had higher CBD bio-accessibility compared to CBD-isolate without micro-encapsulation.Mozaffari et al.discovered that the CBD bio-accessbility was improved with the incorporation into a food system made of olive oil and baby food,which might be attributed to the improved efficiency of micelle forming from hydrolyzed lipids.Nanotechnology has already been applied in drug delivery systems and can be another promising solution.Durán-Lobato et al.developed cannabinoid-loaded lipid nanoparticles through solvent-emulsion evaporation and improved the stability of the products.With more relaxed regulations and more scientific research being conducted,it is envisioned that the technological challenges in the development of CBD edibles may be overcome in the future.Terpenes are another type of bio-active compounds and secondary metabolites found in hemp,which are gaining increasing interest in recent years.There are currently more than 120 terpenes already identified from hemp.The most distinct characteristic of terpenes is the smell,which depicts the unique aromatic characteristics of hemp plant and is used by the plant to repel and defense against herbivores,attract pollinators,and inhibit the microbial growth.Depending on the variety of hemp,the typical terpene contents in hemp range from 0.125% to 0.278% weight in leaves and 1.283% to 2.141% in the inflorescence on a dry basis.Although hemp is abundant in terpenes,it is not the only source.In fact,terpenes are found in lots of fruits,vegetables and herbs.Chemically,terpenes are hydrocarbons consisting of small isoprene units linked to one another to form chains.The biosynthetic pathway of terpenes is shown in Fig.4.Interestingly,terpenes and cannabinoids share a common precursor,which is the GPP,a 10-carbon molecule.As a result,the contents of terpenes and cannabinoids in the hemp are usually positively correlated.Monoterpenes are composed of two isoprenes such as pinene,limonene,myrcene etc..Sesquiterpenes consist of 3 isoprene units,such as humulene,farnesol and caryophyllene.More complex terpene molecules include triterpenes that are made of 6 isoprene units,and polyterpenes.As shown in Fig.4A,the monoterpenes and sesquiterpenes are the major terpene species found in the hemp.