by Anne-Solene Toullec

When we think of Cannabis, we automatically associate it with a drug exalted by the Rastafari movement, the 1960’s counterculture, or even contemporary artists. However, the plant we call  Cannabis (THC-Cannabis) is not the only variety in its species. Indeed, its twin sibling, known as Hemp (Fibre-Cannabis and CBD-Cannabis) can be equally as fascinating to study. It does not grow in Mecklenburgh Square Garden, but may occur elsewhere as a birdseed alien.

What is Cannabis Sativa? How does it look like? Where is it from?

Name : Cannabis sativa L.

Family: According to the modern system of classification, Cannabis belongs to the family of Cannabaceae, along with Humulus lupulus L., Hops.

Origin: Cannabis sativa is widely regarded as indigenous to temperate, western or central Asia. However, no precise area has been identified where the species occurred before humans started to use them. Scientists first speculated that its ancestral area was the southern Caspian region, and then believed that the plant was native to Siberia, China, or the Himalayas. It was finally stated that Cannabis originated in Central Asia and perhaps the Himalayan foothills (Piomelli and Russo, 2016).

This annual flowering plant, generally dioecious, which means that male and female flowers are on separate plants has digitate leaves with five to seven folioles at the base of the stalk, and alternate and uni- or trifoliate leaves near the apex.

The folioles are lanceolate and dentate (Fig. 1) (Bruneton, 2016; Expert Committee on Drug Dependence, 2018b).   

This plant adapts to many climatic conditions and grows quickly in many environments potentially reaching a height of 6 m / 20 feet (Earleywine, 2002). The male plants grow taller, topped by flowers covered with pollen, while the shorter female plant, with its larger, pollen-catching flowers (Fig.2), produces seeds and protects them with a sticky resin, which is secreted by glandular protuberances called trichomes (Fig.3), occurring in most aerial parts of the plant (Andre, 2016).

The stalk is made of several layers and contains two main types of fiber: bast or long fibers found in the bark, and hurd or short fibres located in the core or the stem. Bast fibres typically account for 20-30% of the stalk, and have been the most valuable part of the stalk for ages and are still in very high demand (Fig.4)(Canadian Hemp Trade Alliance, 2019).

From popular history to contemporary use

The species Cannabis sativa has been used by humans for over 5000 years and is one of the oldest plant sources of food and textile fibre (Kriese et al., 2004). The fibre-hemp, is so strong and durable that ship’s sails and ropes were made of it from the fifth century B.C. until the mid-nineteenth century. Humans have also fashioned cloth from hemp fibres for at least 2,400 years. Herodotus’s Histories from 450 B.C. mentioned hemp clothing in Scythian and ancient Greek civilizations, as well as the use of the seeds to produce a euphoric effect when thrown upon hot stones during funeral ceremonies, suggesting a primitive attempt to exploit the toxic properties of Cannabis. The ancient Chinese even used the plant to make shoes and clothes (Abel, 1980).    

Until 1883 fibre-hemp even was the major source for paper, used to print Bibles from Gutenbergs to the King James version. Also the first and second drafts of the Declaration of Independence of the United States of America were written on hemp paper imported from Holland (Balick and Cox, 1996). Furthermore, Cannabis has been an edible plant for centuries and its seeds have been used in cooking; for example it has been reported that wealthy Romans used hemp seeds to top off their banquets with hemp seed desserts (Abel, 1980).

The medicinal use of the Cannabis species began around in the 27^th century B.C.E., long after its first use as a fibre. Writings of that time did not differentiate THC-Cannabis and Hemp. Indeed, it was reported that the Chinese emperor Shen Nung (Fig.5) known for  introducing the pharmaceutical use of many medicinal plants,  prescribed a Cannabis tea for several different ailments such as gout, malaria, beriberi, rheumatism and poor memory. Cannabis continued to be used in traditional Chinese Medicine, and was one of the principal compounds of the first anesthetic made by a famous Chinese surgeon, Hua T’o (Abel, 1980; Earleywine, 2002).

By 1400 B.C.E. Cannabis eventually spread from China to India and got integrated into Ayurvedic medicine which used this plant to relieve stress, congestion, inflammation and asthma (Earleywine, 2002). Further west, records of the medicinal use of Cannabis appear in the Egyptian Ebers papyrus dating back around 1700 B.C.E. (Fig.6) Much later, the plant is mentioned in Assyrian texts as a medicinal agent, and in Greek and Roman sources. In ancient Rome, Dioscorides, Pliny the Elder, and Theodorus mentioned marijuana’s use as a painkilling analgesic, and Apeleius mentioned cannabis mixtures based to reduce swelling of the chest and cold-sores (Brunner, 1973).

Its subsequent spread followed the expansion of Islam, to finally reach Europe, due to both responsibilities of British physicians of the army of India and Bonaparte’s expeditions in Egypt in the 19^th century (Bruneton, 2016). In Victorian times, hemp (CBD-Cannabis) was widely used for a variety of ailments, including muscle spasms, menstrual cramps, rheumatism, and the convulsions of tetanus. Although there is no actual proof of this at all, it is said that Queen Victoria (Fig.7) used Cannabis, as her personal physician Sir J. Russel Reynolds wrote extensively on Hemp, recommending it for use in menstrual cramps (Reynolds, 1890; Brunner, 1973).

Before the advent of modern medicine and the development of synthetic medications, preparations of cannabis were widely used throughout the world as analgesics and hypnotics, particularly in the treatment of headaches, cold symptoms,  rheumatism and menstrual pain. Cannabis sativa was listed in the U.S . Pharmacopoeia until 1937, when possession, sale, and use of all parts of the cannabis plant, including  stalk fibers, and processed or sterilized seeds were declared illegal.

But at the same time, research into the pharmacology of individual cannabinoids started. In 1963 to the structure elucidation of the famous Δ⁹-THC, known as tetrahydrocannabinol was achieved followed in 1964 by CBD known as cannabidiol (Pertwee et al., 2010).

Today, researchers are increasingly interested in CBD. Many countries are even rehabilitating the cultivation of Hemp for medicinal, food, and cosmetic purposes.

Some medicines are even now in development, as well as cosmetics and beauty products.(Expert Committee on Drug Dependence, 2018a).

Phytochemistry: what compounds does it contain?

Until 2016, 545 different compounds have been isolated from hemp such as essential oils with terpenoid compounds which gives its characteristic scent, flavonoids, alkaloids, fatty acids, and sugars (Bruneton, 2016).

A total of 104 compounds, unique to the plant and which received the name of “phytocannabinoids” have been isolated and classified into 11 types, such as the (-)-delta-9-tetrahydrocannabinol (Ä⁹-THC)-broadly known as THC, (-)-delta-8 tetrahydrocannabinol  (Ä⁸-THC), canabigerol (CBG), cannabichromene (CBC), cannabiodiol (CBND), cannabielsoin (CBE), cannabicyclol (CBL), cannabinol (CBN), cannabitriol (CBT) and the increasingly famous one, cannabidiol also known as CBD (Pertwee, 2014).

Two of the most important phytocannabinoids, which both can be extracted from the female cannabis flower, may look similar but these molecules are very different.

Indeed, Δ⁹ -THC is the principal intoxicant – psychotropic – constituent, causing the high and responsible for the addiction process, whereas CBD is the principal non-intoxicant phytocannabinoid occurring in all the varieties of Cannabis sativa (Expert Committee on Drug Dependence, 2018b; Deidda et al., 2019).

Classification: What is the difference between the so called “Cannabis” and “Hemp”?

Sometimes the classification of the Cannabis species can seem a little confusing, especially if you are not a professional botanist. The first official publication which recorded the use of Latin binomials is Linnaeus’s Species Plantarum, in 1753.

A couple of years later, in 1785, Lamarck proposed two species of Cannabis: Cannabis sativa, the species largely cultivated in Western Continents, and Cannabis indica, a wild species growing in India and neighbouring countries. Even if the debate is still ongoing, the World Health Organization currently recognizes a monospecific genus (Cannabis sativa L.) with two subspecies – or varieties – (Cannabis sativa L. subspecies sativa, and Cannabis sativa L. subspecies indica (Pollio, 2016; Preedy, 2017; Expert Committee on Drug Dependence, 2018b).

In terms of their economic importance and use, broadly three types of hemp are distinguished, based on the concentrations in THC and CBD.

• THC-Cannabis : The “drug” (resin) type with high THC concentration (>1%) and low CBD concentration. Referred as Cannabis sativa sub-species indica.
• The “intermediate” type, hybrid strains with high concentration of both THC and CBD.
• CBD-Cannabis and Fiber-Hemp: The “hemp” – textile – type with low THC concentration (< 0.3% ) and high CDB concentration. In contrast to psychoactive cannabis plants, this sub-species referred as Cannabis sativa subsp. Sativa, also called ‘industrial hemp” can’t lead to intoxication and is grown to provide fiber and oilseed (Fig.8) (Bruneton, 2016; Pollio, 2016; Expert Committee on Drug Dependence, 2018b).

Pharmacology – Scientific and Clinical evidence : Does it work on health?

The pharmacologic effect of Cannabis sativa is partly due to its interactions with the endocannabinoid system whose receptors are found throughout the human body, including nervous system, internal organs, and immune cells. This system has a homeostatic role, involved in the regulation of the whole body’s functions and that can be summarized to “eat, sleep, relax, forget, and protect.” (McPartland et al., 2015)

Indeed, Δ9 -THC is responsible for producing the widely well-documented effects on the endocannabinoid system, affecting perception, mood, emotion and cognition that together constitute the psychotropic effects of cannabis (Pertwee, 2014). Consequently, this specific mechanism is responsible for the limitation of its use due to dangerous adverse effects (Bridgeman and Abazia, 2017).

Fortunately, unlike Δ9 -THC, CBD lacks psychotropic activity and in addition does have therapeutic potential, presented as an anti-inflammatory, anxiolytic, antiemetic, anti-nausea, and as a neuroprotective agent and antioxidant particularly when symptoms are refractory to other  therapies (Pertwee, 2014; Bridgeman and Abazia, 2017).

Apart from Δ9-THC, even if its pharmacological mode of action remains complex and partly unsolved, CBD is the sole cannabinoid that has been thoroughly tested in humans in numerous controlled experimental studies as well as clinical trials for several diseases affecting the nervous system like multiple sclerosis, neuropathic pain, schizophrenia, bipolarity, social anxiety disorder, insomnia, and epilepsy, for which a medicine is currently in development (Epidiolex ®. Each of these studies brought out a significant improvement of patients’ conditions after the administration of CBD via the oral route (Zhornitsky and Potvin, 2012; Devinsky et al., 2014; Pertwee, 2014; Expert Committee on Drug Dependence, 2018a).

In addition, a very promising study led in rats has shown that injected CBD enhanced the healing process of bone fracture. In view of such results, CBD could be used in the future in treatment for bone diseases such as osteoporosis, affecting one third of women over the age of 50 in the UK (Kogan et al., 2015).

Toxicity – Side effects

            Much of what is known about the adverse effects of medicinal cannabis comes from studies of recreational users of marijuana (Volkow et al., 2014). Little research has focused on the safety and side effects of CBD in humans. Thus, little is known about the toxicity of CBD consumed alone, especially during pregnancy, and breastfeeding women and children, which are critical periods of brain development.

However, during clinical studies, mild side effects have been reported along with therapeutic applications on adults. Indeed, few undesirable effects have been reported such as tiredness, diarrhoea, and changes of appetite/weight (Iffland and Grotenhermen, 2017).

Indeed, in comparison with other drugs, used for the treatment of the medical conditions listed above, CBD has a better side effect profile. Last but not least, unlike THC, tolerance for CBD does not seem to occur, greatly contributing to its low toxicity (Bergamaschi et al., 2011; Zhornitsky and Potvin, 2012; Niesink and van Laar, 2013).

However, several studies have brought out that CBD has an effect on the liver’s metabolism, although further studies are needed to confirm if interactions can occur, people taking medicines and especially narrow therapeutic index medicines must use CBD very carefully (Expert Committee on Drug Dependence, 2018a).

CBD and the wellness business: The new gold-rush?

In the cosmetic field, anti-acne effect on human skin, and  anti-inflammatory effects of CBD have been deomonstrated.

More and more hemp and/or CBD tinctures, oils, creams, or even balms are now available in health shops (Fig.10) (Oláh et al., 2014). Even dried buds are available legally in certain European countries such as Switzerland and France, without any health indication or consumption advices. Surprisingly, such products are presented as a collector’s plant. (Fig.11)

Moreover, CBD infused drinks, dehydrated proteins, and other food products are recently available on the market. Cannabis culture is now most definitely turning into more of a health and wellness stereotype, attracting more clients every day.

Indeed, according to the research firm Brightfield Group, the legal market for CBD could be worth more than $20 billion by 2022 in the United-Sates, with an increase of 55% per annum over the next five years alone in Europe (Gomez, 2018).

However, people have to be aware that as CBD oil-based products are not regulated by official health agencies, companies are not obliged to follow any standards in terms of manufacturing and quality. Consequently, there is no guarantee that the CBD oil that you can buy on fancy websites or health shops are high quality products. In fact very often quality problems of such unregulated products have been reported.

Conclusion

Hemp (CBD-Cannabis), a subspecies of Cannabis  sativa L.  is intrinsically linked to the human history and its use stretches back to thousands of years as a  plant important in everyday life thanks to its various properties both physically and chemically. After being widely spread and used all over the world, it has been banned from many countries relegated to drug of abuse status. It is a great example showing the chemical complexity of plants with a single species producing a range of distinct chemical varieties. But the return of Hemp has been going on for few years and promises to amaze the scientific community through its new medicinal properties and the large public through its new wellness and beauty applications.

Disclaimer:

In this essay we do not advise or recommend herbs for medicinal or herbal use. This information is intended for educational purposes only and should not be considered as a recommendation or an endorsement of any particular medicinal or health treatment. THC Cannabis remains, of course, a controlled drug. The use of any such product should be based on the appropriate advice of a health care professional or based on the information available in the patient information leaflet (i.e; for THR products)

© Anne-Solene Toullec 2019. All rights reserved.

About the author:

Anne-Solene Toullec Pharm.D., MSc. Student in Medicinal Natural Product and Phytochemistry at the UCL School of Pharmacy.

To contact Anne-Solene, you can write her at toullecannesolene [at] gmail.com

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