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cannabis sativa l cbd oil

Transparency and traceability
Following baseline regulatory compliance, for the formulation and subsequent claims made about natural and organic cosmetics, transparency and traceability are key to ensure that any substance extracted or derived from hemp used in a product ensures certain verifiable qualities. When using raw materials from Cannabis in cosmetics, brands should choose reliable supply chains that give proof of the traceability of these plant extracts from crop-to-shop. This is a key aspect for regulatory compliance but also for end consumers because it reassures them about the origin and qualities of these substances when used in a cosmetic product.

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.

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.

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.

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.

How about detectable THC levels in cosmetics?
Under Regulation (EU) No. 1308/2013, Cannabis sativa L. is considered as an agricultural product and as an “industrial plant” that may be grown legally as long as their THC content does not exceed 0.2%. However, for cosmetics, national legislations from EU Member States on controlled substances may apply. For instance, in France no THC is allowed, while in Luxembourg a THC concentration up to 0.3% is permitted.

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] .

Figure 2. The cannabinoid synthetic pathway: cannabigerolic acid (CBGA) is the common precursor of all main cannabinoids. It is synthesized through an alkylation of the phenolic moiety of olivetolic acid with the terpenoid component of geranyl pyrophosphate (GPP). The reaction is catalysed by a geranylpyrophosphate:olivetolate geranyltransferase (GOT). Olivetolic acid is originated in the cytosolic polyketide pathway through an aldol condensation of hexanoyl-Coenzyme A (CoA) with three molecules of malonyl-CoA, that is catalysed by the polyketide synthase (PKS) enzyme in the presence of olivetolic acid cyclase (OAC). The GPP is synthesized by the plastidial methylerythritol phosphate (MEP) pathway. In the cytosol, CBGA is converted into the acidic form of the three main cannabinoids, tetrahydrocannabinol acid (THCA) that in the acidic form has no psychoactive activity, cannabidiolic acid (CBDA) and cannabichromenic acid (CBCA). GPS: geranyl pyrophosphate synthase; IPP: isopentenyl diphosphate; OAC: olivetolic acid cyclase.

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.

3. The Cannabinoids Synthesis in C. sativa L.

From a practical point of view, the main discrimination factor among the C. sativa L. cvs is the THC content, which, essentially for legal reasons, as described in the next paragraph, is an useful tool to discriminate between the drug-type plants with high THC content, used for medical or recreational purposes, and the fibre-type plants with low THC content, commonly named industrial hemp.

C. sativa L. plants grown for an industrial purpose, are cultivated to obtain fibre, seeds, and their derivatives. These plants are popularly called “industrial hemp” or “fibre-type” hemp, and they contain low-THC level (i.e., <0.3 or 0.2%), whereas, C. sativa L. plants cultivated for narcotic/recreational purposes are characterized by high-THC level and those cultivated for medicinal purposes are characterized by high-THC and high-CBD levels.

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).

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.