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To this date, cosmetic regulatory compliance of CBD as an ingredient itself relies on the part of the plant from which it is extracted. For instance, seeds when not accompanied by tops are acceptable, although these do not contain CBD, whereas CBD prepared from Cannabis extracts or tinctures from flower/fruiting tops where the resin has not been separated, as well as the separated resin, are not allowed for use. Indeed, the UN 1961 Single Convention on Narcotic Drugs defines controlled cannabis as “the flowering or fruiting tops of the cannabis plant”, but does not consider Cannabis sativa seeds or leaves as controlled substances (as long as they are not accompanied by the tops).

Specific European and national legislation as well as international conventions apply to establish which type of extracts and derivates of the Cannabis sativa L. plant may be used in products, including food and cosmetics. Keep reading to find out more about hemp, an incresingly popular ingredient in cosmetics, and the differences in the extracts and derivates of the Cannabis sativa L. plant.

Can cannabidiol (CBD) be used in cosmetics?
Cannabidiol (CBD) is a type of cannabinoid that can be synthetically produced or isolated from Cannabis plants and used as a single ingredient. In cosmetics, CBD can function as an antioxidant and facilitate anti-aging properties.

In this context, Regulation (EC) No. 1223/2009 for cosmetics bans the use of CBD derived from resin, tinctures and extracts of Cannabis, as well as cannabinoids, resin and various extracts (e.g. Cannabis Sativa flower extract, Cannabis Sativa flower/leaf/stem extract) from cosmetic use (Annex II). Synthetically produced CBD is acceptable for end use.

What is hemp?
Hemp is a variety of Cannabis sativa L. Hemp is a dioecious plant, which means that it can be separated into male and female plants. In hemp fields, there is usually a concentration of female hemp and sporadic placed males to pollinate the females and produce nutrient-rich seeds. Hemp has been used for over 10,000 years to make paper and fibres for clothing and fabric, but also in cosmetic products, particularly as an oil but also as other extracts and derivatives.

Marijuana and CBD are not the same even if they both come from the same plant. CBD is a single, isolated compound in the cannabis plant, while marijuana contains many naturally occurring compounds, including THC and CBD. Hemp seed oil, extracted from the seeds of Cannabis sativa L., Cannabaceae, has next to no THC or CBD.

What is the difference between hemp, CBD and marijuana?
The Cannabis plant contains over 80 biologically active chemical compounds (cannabinoids). However, the most known ones are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Different taxonomic classifications of the genus Cannabis vary in their THC and CBD content. For example, Cannabis indica originally from India contains a high THC content associated with marijuana hashish production, whereas Cannabis sativa L. from Europe and western Eurasia has a high CBD content, traditionally associated with the textile industry, and more recently to applications within the cosmetic, food and pharmaceutical sectors. Unlike THC, CBD has no psychoactive effects.

Historically, industrial hemp or simply, hemp, that is, C. sativa L. plants grown for fibre and/or seeds, was frequently cultivated over the world, mainly for the production of technical textiles, until the first half of the 21st century. In the US, hemp was widely grown from the colonial period into the mid-1800s. In the early 1900s and prior to the late 1950s, hemp continued to be grown, being considered as an agricultural commodity: the US Department of Agriculture (USDA) supported its production, and USDA researchers continued to publish information related to hemp production and also reported on hemp’s potential for use in textiles and in paper manufacturing [31] . In Europe, at the end of the 1950s, Italy was the second country in the world after Russia for the areas under hemp cultivation (over 100,000 hectares) and was the world’s best for the quality of the obtained products [32] . However, following the discovery of the psychotropic activity of THC, and the increasing awareness of its deleterious effects on human health, many countries began to take measures in an effort to stem the use of C. sativa L. plants’ flowers and leaves for their psychotropic effects. The first provision was taken in the US and Canada. In the US, between 1914 and 1933, 33 states passed laws restricting legal production to medicinal and industrial purposes only. In 1937, the Marihuana Tax Act defined hemp as a narcotic drug, without any distinguishing between low THC plants (hemp) and high THC (drug hemp or simply, marijuana) ones: both were considered schedule I controlled substances, and it was required that farmers growing hemp hold a federal registration and special tax stamp. This effectively limited further production expansion; in fact, after 1943, production of hemp started to decline until the late 1950s when no production was recorded. Finally, in 1970, The Controlled Substances Act (CSA) was issued, and it placed the control of selected plants, drugs, and chemical substances under federal jurisdiction. Among the selected plants, there were also C. sativa L. ones to which were given the statutory definition of marijuana and were put in the Drug Enforcement Administration (DEA) schedule of controlled substances [31] . In Canada, the cultivation of hemp has been prohibited due to the presence of THC, in 1938 with the Canadian Opium and Narcotics Act [33] [34] . In 1961, the United Nation (UN) endorsed and adopted the single convention on narcotic drugs, which established a universal system for limiting the cultivation, production, distribution, trade, possession, and use of narcotic substances to medical and scientific purposes, with a special focus on plant-derived substances, among which is cannabis. In the article 28, paragraph 2 of this convention, cannabis was defined as “the flowering or fruiting tops of the C. sativa L. plant (excluding the seeds and leaves when not accompanied by the tops) from which the resin has not been extracted, by whatever name they may be designated”. The same article described a system of control required if a country decides to permit the cultivation of C. sativa L. that is not for industrial or horticultural purposes [4] [35] . Ten years later, in 1971, the UN endorsed the convention on psychotropic substances which established an international control system for psychotropic substances, among which is THC [36] . In line with these directives, in 1975 the Italian Republic issued the law n. 685/1975, introducing cannabis (intended as a drug product obtained from C. sativa L. plants) in the schedule of controlled substances.

The high intrinsic genetic variability rate of C. sativa L. has been further accentuated by the long history of its domestication. Indeed, the different intended uses of the C. sativa L. cultivation’s products have led over the years, to an artificial phenotypic selection of specific features of the domesticated plants, useful for increasing the yield and/or the quality of the commercial interest’s cultivation products [26] . The direct consequence of this selection was the unaware artificial creation of the C. sativa L. varieties, each with specific genotypic and phenotypic features, which at first, induced the taxonomists and botanists to erroneously recognize two or three different species of C. sativa L., embracing a polytypic concept of the Cannabis genus [27] . To further complicate the taxonomic classification of the Cannabis genus, there has been also the fact that C. sativa L. is a crop which tends to exist in “crop-weed complexes”, that is complexes of domesticated forms in cultivation and related ruderal (weedy) forms growing outside of cultivation, developing morphological characteristics also very different from those of the domestic progenitor, as a consequence of adaptation to the wild environment [28] . However, it must be considered that, despite the high genetic variability of C. sativa L., the varieties that genotypically and phenotypically differ, are interfertile. Therefore, taking into account the Darwinian definition of biological species, “a group of organisms that can reproduce with one another in nature and produce fertile offspring”, C. sativa L. varieties cannot be consider as different species of the Cannabis genus. For this reason, to date, the polytypic concept has been definitely given up and replaced by the monotypic one. According to this, a single species of Cannabis genus exists, namely C. sativa L., which includes several varieties or cultivars ( cvs ) that genotypically and phenotypically differ, but they all are interfertile and therefore, they belong to the same species [29] [30] .

Cannabis sativa L., commonly known as hemp, is an herbaceous, anemophilous plant belonging to the Cannabaceae family.

4. Chemical Phenotype and Taxonomy of C. sativa L.

Several works clarified well the cannabinoids’ biosynthetic pathway [14] [15] [16] [17] [18] [19] . According to these studies, a common precursor of all the main cannabinoids exists, and it is the cannabigerolic acid (CBGA). In the cytosol, CBGA is converted into the acidic form of the three main cannabinoids, from which other related cannabinoid compounds will originate, namely tetrahydrocannabinol acid (THCA), that in the acidic form has no psychoactive activity; cannabidiolic acid (CBDA); and cannabichromenic acid (CBCA). This conversion is catalysed by an oxidocyclase specific for each cannabinoid (THCA-synthase, CBDA-synthase, and CBCA-synthase, respectively) (Figure 2). Finally, the acidic form of each cannabinoid undergoes non-enzymatic decarboxylation to their neutral and active form, i.e., THC with psychoactive activity, CBD, and CBC that is found at high levels in juvenile plants [20] [21] , respectively.

Essentially, C. sativa L. can be grown for three main purposes: industrial, narcotic/recreational, and medicinal [4] [4]. Traditionally, C. sativa L. plants were cultivated primarily as a fibre crop for the production of textiles and ropes, especially in the western world. Despite their high nutritional value, the seeds of this plant were initially considered as a by-product of the fibre production, and hence, they were mainly used as animal feed. From the first half of the 21st century, the cultivation of this crop declined because of the progressive diffusion of synthetic fibres and the use of some narcotic strains of the C. sativa L. plant for the production of intoxicant drugs. Only since the last two decades, there has been a reintroduction of the the C. sativa L. cultivation exclusively for industrial purposes, and in this context, Canada has been the first western country to restore this crop, followed by Europe and the US. Nowadays, a growing interest for the seeds of the C. sativa L. plant, commonly named hempseeds, has been developed due to the increased knowledge about their high nutritional value and potential functionality.

It is considered one of the most ancient cultivated plants and due to its long history of cultivation, it is difficult to identify its exact centre of origin. According to phylogenetic studies based on molecular analysis and studies on sequence homology of ancient and modern DNA extracted from archaeobotanical and modern samples, respectively, most researchers agreed that this plant species originated in central Asia and was introduced in Europe as a cultivated and domesticated agricultural plant during the Bronze age (approximately, from the 22th until 16th century BC) [1] [2] . Nevertheless, a recent work by McPartland and colleagues [2] provided evidence that C. sativa was indigenous also to Europe. Currently, there are no more traces of wild-type hemp and only domesticated (i.e., individuals of a species chosen and selected by humans for characteristics making them useful to people) and ruderal (i.e., forms growing outside of cultivation) hemp plants exist. Independently to its origin, the nowadays-domesticated form of C. sativa L. is widespread and cultivated not only in the Asian countries, but also in Canada, the United States (US), Europe, and Africa. It is a multipurpose, sustainable, and low environmental impact crop which can be useful for several application fields, from the agricultural and phytoremediation to food and feed, cosmetic, building, and pharmaceutical industries. Indeed, from this highly versatile plant, it is possible to obtain various products of industrial interest such as fibre and shives; bio-building and thermal insulated materials; seeds, flour and oil with important nutritional and functional features; and bioactive compounds of pharmacological interest [3] (Figure 1).

Elucidation of the cannabinoids’ biosynthetic pathway has been essential to demonstrate that the concentration of each cannabinoids in the plant is genetically determined, so that various genotypes related to different chemical phenotypes, diverging in types and concentration of cannabinoids (i.e., cannabinoids profile), exist. These phenotypes are known as “chemotypes” or “biotypes”, and three different principal chemotypes were commonly identified [8] [20] [22] on the basis of the two main cannabinoids (i.e., THC and CBD) content and ratio:

Hobbs JM, Vazquez AR, Remijan ND, et al. Evaluation of pharmacokinetics and acute anti-inflammatory potential of two oral cannabidiol preparations in healthy adults. Phytother Res. 2020;34(7):1696-1703. View abstract.

Srivastava, M. D., Srivastava, B. I., and Brouhard, B. Delta9 tetrahydrocannabinol and cannabidiol alter cytokine production by human immune cells. Immunopharmacology 1998;40(3):179-185. View abstract.

Agriculture Improvement Act, S. 10113, 115th Cong. (2018) or S. 12619, 115th Cong. (2018).

Side Effects

Wade, D. T., Collin, C., Stott, C., and Duncombe, P. Meta-analysis of the efficacy and safety of Sativex (nabiximols), on spasticity in people with multiple sclerosis. Mult.Scler. 2010;16(6):707-714. View abstract.

Pavlovic R, Nenna G, Calvi L, et al. Quality Traits of "Cannabidiol Oils": Cannabinoids Content, Terpene Fingerprint and Oxidation Stability of European Commercially Available Preparations. Molecules. 2018 May 20;23(5). pii: E1230. View abstract.

Wiemer-Kruel A, Stiller B, Bast T. Cannabidiol Interacts Significantly with Everolimus-Report of a Patient with Tuberous Sclerosis Complex. Neuropediatrics. 2019. View abstract.

Zuardi AW, Crippa JA, Hallak JE, et al. Cannabidiol for the treatment of psychosis in Parkinson’s disease. J Psychopharmacol 2009;23(8):979-83. View abstract.