Cannabis as Medicine

Betty Wedman-St.Louis

• Publisher: CRC Press
• Year: 2019
• ISBN:
  9780429620041
• Edition: 1
• Topic: Medicine
• Subtopic: Alternative & Complementary Medicine

For hundreds of years cannabis has been used as a therapeutic medicine around the world. Cannabis was an accepted medicine during the second half of the 19th century, but its use declined because single agent pain medications were advocated by physicians who demanded standardization of medicines. It was not until 1964 when the chemical structure of THC (delta 9-tetrahydrocannabinol) was elucidated and its pharmacological effects began to be understood.

Numerous therapeutic effects of cannabis have been reviewed, but cannabis-based medicines are still an enigma because of legal issues. Many patients could benefit from cannabinoids, terpenoids and flavonoids found in Cannabis sativa L. These patients suffer from medical conditions including chronic pain, chronic inflammatory diseases, neurological disorders, and other debilitating illnesses.

As more states are legalizing medical cannabis, prescribers need a reliable source which provides clinical information in a succinct format. This book focuses on the science of cannabis as an antioxidant and anti-inflammatory supplement. It discusses cannabis uses in the human body for bone health/osteoporosis; brain injury and trauma; cancer; diabetes; gastrointestinal conditions; mental health disorders; insomnia; pain; anxiety disorders; depression; migraines; eye disorders; and arthritis and inflammation. There is emphasis on using the whole plant — from root to raw leaves and flowers discussing strains, extraction and analysis, and use of cannabis-infused edibles.

Features:

Provides an understanding of the botanical and biochemistry behind cannabis as well as its use as a dietary supplement.

Discusses endocannabinoid system and cannabinoid receptors.

Includes information on antioxidant benefits, pain receptors using cannabinoids, and dosage guidelines.

Presents research on cannabis treatment plans, drug-cannabis interactions and dosing issues, cannabis vapes, edibles, creams, and suppositories.

Multiple appendices including a glossary of cannabis vocabulary, how to use cannabis products, a patient guide and recipes as well as information on cannabis for pets.

1	What is Hemp?

Miles Sarill

CV Sciences

CONTENTS

References

The passage of the Agricultural Improvement Act of 2018 establishes a marked shift in United States federal policy toward the cultivation and utilization of hemp, while distinguishing it from the drug varieties of cannabis [1]. As farmers begin to cultivate hemp, as herbalists begin extracting its constituents, and as patients and consumers begin ingesting these extracts, we must ask: “What is hemp?” The distinctions between true agricultural hemp and drug-type cannabis plants (i.e., marijuana) extend beyond legal importance. In this chapter, the botanical, genetic, agricultural, and phytopharmacological characteristics of this plant will be discussed.

Hemp is a cultivar of the plant Cannabis sativaL. and is defined by the US federal government as containing less than 0.3% Δ-9-tetrahydrocannabinol (THC) or its carboxylic acid form THCA by dry weight. THC is converted from THCA upon heat exposure in a process known as decarboxylation and is a principal constituent mediating the psychoactive, euphoric and sometimes psychotoxic effects of consumption of drug-type cannabis plants [2]. It is important to note that THC is but one of many phytocannabinoids found in cannabis, with as many as 120 being reported [3]. The dominant phytocannabinoid in agricultural hemp is cannabidiol (CBD), which is presently being researched for its antioxidant, immunomodulatory, anticonvulsant, and cytoprotective properties without any abuse potential or psychotoxicity [4,5]. Hence, although THC-rich cannabis strains are most popular for adult recreational use and show clinical efficacy in various medicinal applications, hemp-derived CBD preparations are becoming increasingly popular for both legal and practical reasons (Figure 1.1).

FIGURE 1.1 The two molecules may appear similar, but the ring closure in Δ-9-tetrahydrocannabinol distinguishes a completely different pharmacodynamic quality in comparison to cannabidiol.

Hemp has been incorporated into various civilizations’ agricultural practices globally for at least 10,000 years [6]. Hemp is a major crop in the production of fiber, food, and fuels and has been used in antiquity across many cultures to produce textiles, rope, and paper [7]. Evidence for the use of fiber hemp to produce food and medicinal extracts can be found in ancient Chinese texts extending back to at least 2,000 years [8]. Modern industrial uses of hemp fiber include the production of plastic-like composite materials and concrete alternatives [9,10]. Hemp seeds are edible and rich in amino acids, minerals, and essential fatty acids including the ω-3 polyunsaturated fatty acid alpha-linolenic acid [11]. Hemp is a bio-accumulator and has been examined as an important crop in soil restoration and regenerative agriculture [12,13]. Given that hemp may be useful for restoring soil from toxins including heavy metals, dioxins, etc., medicinal-grade hemp cultivated for phytocannabinoid extraction must be grown in low-pollution environments.

It has been suggested that cannabis genus plants can be further characterized into sativa, indica, and ruderalis species [14]. Other botanists prefer to categorize indica varieties as a subspecies of cannabis sativa [15]. The botanical differences between these species include their morphology, with C. sativa plants generally being taller and having narrower leaves than the smaller, bushier C. indica cultivars [16]. A common notion that is propagated among dispensaries and patient communities are that C. indica species have more relaxing and sleep-inducing properties compared to the uplifting and energizing properties of C. sativa drug-type strains [17]. Terpenoids, the scent molecules present in the cannabis plant, exert their own biological activity and may account for some of the pharmacological differences between C. sativa and C. indica strains [17, 18 and 19].

Dividing the cannabis genus into sativa, indica, and ruderalis varieties may not be the most appropriate designation. Agricultural hemp is a cultivar of C. sativa but recent genetic research, however, illustrates that hemp shares some characteristics more in common with C. indica drug-type cultivars [20]. Researchers genotyped 81 marijuana and 43 hemp samples, analyzing single-nucleotide polymorphisms (SNPs) to establish and associate differences between C.sativa and C. indica ancestry, at a genome-wide level. In addition to the fact that many drug-type cannabis strain names did not reflect their associated genetic identity, true agricultural food and fiber hemp was found to have significant genomic differences from drug varieties of cannabis sativa, and more closely resemble some C. indica strains.

An important genetic distinction between agricultural food and fiber hemp in comparison to drug-type cannabis plants may be SNPs in the gene THCA synthase [21]. This gene codes for the enzyme that is responsible for the final step in the production of THCA in plants. THCA and other cannabinoids are produced by the plant in response to light exposure, to prevent damage to the leaves. Often medicinal and recreational cannabis growers will incorporate bright indoor lighting to encourage the highest expression of THCA, which may be a strain on the energy grid. True agricultural hemp can be grown outdoors, supporting the putative environmental benefits of cultivation, without leading to heightened THCA expression due to the aforementioned SNP.

Perhaps rather than trying to fit hemp into any specific cannabis subspecies, defining the chemical composition of the plant in terms of its cannabinoid expression is a more useful distinction. Cannabis varieties can be divided into five different chemical phenotypes (chemotypes). Type I chemotype plants are most often considered drug-type plants with a lowCBD/THC content ratio, due to the high expression of THCA or THC. An intermediate chemotype II displays roughly 1:1 CBD/THC ratios. Type III chemotype plants are the category that most agricultural hemp fit into, with a dominant expression of CBD with concentrations exceeding 0.5% dry weight and THC less than 0.3% dry weight. An additional type IV chemotype exists with cannabigerol (CBG) as the dominant cannabinoid, and type V with no significant detectable cannabinoids present in the plant [22,23].

Ratios of cannabinoids are not the only factor to consider when examining a hemp or cannabis plant. It is imperative to remember that cannabis is a plant of at least 400 different molecules including as many as 120 cannabinoids, terpenoids, alkaloids, polyphenols including flavonoids and stilbenoids, lignamides, tocopherols, and tocotrienols [3,19,24, 25, 26, 27, 28 and 28]. Different parts of the plant contain different constituents, with the highest percentage of cannabinoids present in trichromes located primarily in the flowering tops, but also present in other aerial parts [28]. Extraction of the seeds provides highly unsaturated fatty acids along with the novel anti-neuroinflammatory phenylpropanamide family of compounds including cannabisin B and N-trans-caffeoyltyramine [25]. Roots of the cannabis plant have an herbal history of being recommended for inflammation associated with arthritis and gout. Interestingly, however, cannabis and hemp roots contain virtually no CBD, THC, or other cannabinoids. Instead, extracting the root provides bitter alkaloids cannabisativine and triterpenoids friedelin and epifriedelanol exerting an anti-inflammatory effect [26, 27, 28 and 29].

A dominant terpenoid present in agricultural hemp is β-caryophyllene (BCP), a sesquiterpene present in many pungent herbs including Nigella sativa seed oil and oregano [30,31]. BCP is being studied as a powerful anti-inflammatory and antinociceptive. The effects of BCP in inflammation and immunomodulation extend to its role as an agonist of the cannabinoid receptor type 2 (for an in-depth discussion on the endocannabinoid system and cannabinoid receptors, please read further chapters) [32]. In contrast, strains dominant in the monoterpene β-myrcene are known to promote a sedative effect. β-myrcene is a GABA_A receptor agonist at the benzodiazepine site and is known to cause “couch-lock,” which may account for the sedative properties of β-myrcene dominant C.indica strains [17,33].

Beyond botanical morphology or classifying cannabis plant chemotypes based on cannabinoid levels, assessing content of terpenoids represents a novel chemotaxonomic approach. Researchers assessed 2,237 individual cannabis flower samples for cannabinoid and terpenoid content. It was found that CBD-dominant hemp-like type III cannabis plants display a unique profile of terpenes statistically different from drug-type cannabis varieties. Type III samples contained higher content of BCP relative to other terpenes such as β-myrcene, whereas the content of BCP was lower in most other varieties tested [19].

Because of the wide biological diversity of phytonutrients present in the hemp plant, extraction of a broad-spectrum of constituents is necessary to achieve the greatest bioactivity. Allopathic medicinal and pharmacological paradigm focuses on utilizing one compound to regulate one re...