Recent Advances in the Science of Cannabis

Robert M. Strongin, Jiries Meehan-Atrash, Monica Vialpando, Robert M. Strongin, Jiries Meehan-Atrash, Monica Vialpando

• Publisher: CRC Press
• Year: 2021
• Print ISBN: 9780367224424
• eBook ISBN: 9781000467758
• Edition: 1
• Topic: Medicina
• Subtopic: Botánica

Recent Advances in the Science of Cannabis describes progress in a variety of significant areas of cannabis science. This unique book covers topics in cultivation and secondary metabolites, aroma and chemotypes, cannabinoid structures, physiology and pharmacology, as well as the development of unique topical products. State-of-the-art analytical methods and instrumentation are covered, including current developments in mass spectrometry and chromatography, as well as microbial testing. Given the popularity of smoking and vaporizing cannabis, the chemistry of vaping cannabinoid and terpene concentrates is also presented, along with emerging regulatory issues.

Key Features:

• A guide to emerging modern cannabis technology in a dynamic regulatory climate and appealing to both novices and specialists.
  
  

• Building upon pioneering studies of terpene and cannabinoid chemistry, this distinctive volume describes current best practices, technological breakthroughs and historical context.
• Written by researchers in industry and academia, a greater understanding of the risks of exposure to emissions from vaping or dabbing cannabis concentrates is provided here.
• A selection of the book content reviewing Thermal Degradation of Cannabinoids and Cannabis Terpenes has been included in "Hot 2021" RSC Advances.

1 Cultivation Stress Techniques and the Production of Secondary Metabolites in Cannabis sativa

Callie Seaman

DOI: 10.1201/9780429274893-1

Contents

1.1 Introduction

1.2 What are Secondary Metabolites?

1.2.1 Types of Secondary Metabolites

1.2.1.1 Phytocannabinoids

1.2.1.2 Terpenes/Terpenoids

1.2.1.3 Flavonoids

1.2.2 Why Secondary Metabolites Are Produced

1.2.3 Metabolic Pathways for Production

1.3 Cultivation

1.3.1 Genetic Potential

1.3.2 Indoors vs Outdoors

1.3.3 Reproduction and Propagation Techniques

1.4 Types of Stresses

1.4.1 Biotic

1.4.1.1 Microbes, Arthropods, and Herbivores

1.4.1.2 Space and Competing Plants

1.4.1.3 Physical Damage

1.4.2 Abiotic

1.4.2.1 Light Stress

1.4.2.2 Carbon Dioxide

1.4.2.3 Drought

1.4.2.4 Thermal Stress

1.4.2.5 Nutrition, Salts, and Heavy Metal Stress

1.5 Other Factors

1.5.1 Time of Harvest

1.5.2 Drying and Curing Process

1.6 Summary

Bibliography

1.1 Introduction

Cannabis sativa could be described as one of the most chemically complex plants used in Western medicine today. It has been propagated and utilized by humankind for numerous purposes through thousands of years of our history as a source of nutrition for both animals and humans, as well as for fibers, building materials, fuel, and medicine (Romero et al. 2020). Differing levels of prohibition from the 14th century to today have undoubtedly slowed progress in our understanding of the full potential of the plant.

Cannabis sativa is dioecious, meaning male and female blossoms generally appear on separate plants. It is the resinous oil produced by the unpollinated mature female flowers that holds the greatest scientific and monetary value today. Although they can be found throughout the plant, this oil contains the highest concentration of hundreds of different secondary metabolites each with a potential array of medicinal properties (Andre, Hausman, and Guerriero 2016) (Flores-Sanchez and Verpoorte 2008b). While other secondary metabolites, including flavonoids, stilbenoids, lignans, and alkaloids all have important qualities, terpenoids, comprised of terpenes and cannabinoids, are the most widely acknowledged for their medical potential.

Before the 2012 legalization of its recreational use in Colorado and Washington, there was a particular and narrow focus on the major cannabinoids, cannabidiol (CBD) and tetrahydrocannabinol (THC), driven by the interests of the therapeutic sector. Since legalization, there has been a dramatic surge in academic publications on cannabis, with end-user demand fueling a wider understanding of properties and factors beyond the plants’ psychoactive components such as flavor (de la Fuente et al. 2020). A more sophisticated understanding of cannabis has flourished as a result (Romero et al. 2020).

It has been well documented that the ratio of phytocannabinoids is important for the successful treatment of specific diseases (Lowe et al. 2018) (McPartland and Russo 2001) (Gordon 2020) (Nelson 2018) (Goldstein 2016) (Rosenburg et al. 2015). With increased research and understanding of the entourage effect, there is a greater demand from physicians for full plant extract alongside the isolate form of the compound (Romano and Hazekamp 2018) (Russo 2019) (Ben-Shabat et al. 1998) (Blasco-Benito, Seijo-Vila, et al. 2018). The ratios of phytocannabinoids and terpenes are now being further investigated to better understand their effects when used in conjunction with one another (de la Fuente et al. 2020) (Heblinski et al. 2020). In turn, this drives demand for strains to be bred to produce ratios of secondary metabolites that are disease-specific and will therefore require less processing, potentially reducing the cost of the end product (Thomas and Pollard 2016). Safeguarding patients is the top priority, but many factors must be considered when cultivating medicinal crops, with the consistency of production of both biomass and active ingredients of particular importance. In response to biotic and abiotic stress, plants produce phytoalexins, a large group of diverse secondary metabolites, which can cause a reduction in biomass. In this review, we will take a brief look at how stress to the plants affects the production of secondary metabolites such as phytocannabinoids, terpenes, and flavonoids.

1.2 What are Secondary Metabolites?

Secondary metabolites are compounds produced by the plant that are not essential for plant growth and are produced to enhance the chances of survival either through defense or increased attraction for reproduction.

1.2.1 Types of Secondary Metabolites

Approximately 565 secondary metabolites have been identified in cannabis (Romero et al. 2020), which can be split into six classes: cannabinoids, terpenes, flavonoids, stilbenoids, lignans, and alkaloids (Flores-Sanchez and Verpoorte 2008b). Here we will focus on the three most reported groups of active compounds of therapeutic interest. To date, these include over 140 cannabinoids (Gülck and Møller 2020), 110 terpenes (Hanuš and Hod 2020), and 20 flavonoids (Andre, Hausman, and Guerriero 2016). Table 1.1 summarizes the most documented secondary metabolites found in Cannabis sativa (Andre, Hausman, and Guerriero 2016).

TABLE 1.1
The Three Major Groups of Secondary Metabolites Found in Cannabis sativa

	Phytocannabinoids	Terpenes		Flavonoids
		Monoterpenes	Sesquiterpenes
Main production site	Bulbous trichomes on flowers and leaves	Bulbous trichomes on flowers and leaves	Sessile trichomes on flowers and leaves	Roots, leaves, seedlings, and stems
Precursors	Hexanoyl-CoA Olivetolic acid	Pyruvate G3P	Acetyl-CoA	Phenylalanine
Biosynthesis pathways	Polyketide pathway DOXP/MEP pathway	MEP pathway	MVA pathway	Phenylpropanoid pathway
Groups (number recorded) and examples	Δ^9-THC type (23) Δ^8-THC type (5) CBG type (16) CBD type (7) CBE type (5) CBN type (11) CBC type (9) CBT type (9) CBL type (3) CBND type (2) CBDV – cannabidivarin THCV – tetrahydrocannabivarin CBCV – cannabichromevarin CBGV – cannabigerovarin CBV – cannabivarin CBGM – cannabigerol monomethyl ether CBDHQ – cannabidiol hydroxyquinone THCP – tetrahydrocannabiphorol	β-pinene Myrcene Limonene Linalool α-pinene Terpinolene β-thujone Terpineol Cineole α-terpinene β-ocimene Borneol Geraniol Eucalyptol Isopulegol Pulegone Delta 3 Carene	α-humulene β-farnesene β-caryophyllene α-cubebene α-elemol β-farnesol Guaiol Bisabolol α-bergamotene δ-cadinene Valencene Eremophilene Nerolidol Diterpenes Camphorene	Aglycones Kaempferol Apigenin Luteolin Quercetin Vitexin Isovitexin Orientin Apigenin-7-O-Glu Cannaflavin A Cannaflavin B Cannaflavin C Anthocyanin Peonidin
Notes: The cannabinoids are split into the ten types of cannabinoids and the number identified in brackets. THC = tetrahydrocannabinol; CBG = cannabigerol; CBD = cannabidiol; CBE = cannabielsoin; CBN = cannabinol; CBC = cannabichromene; CBT = cannabicitran; CBL = cannabicyclol; CBND = cannabinodiol; MVA = mevalonate; MEP = methylerythritol phosphate (ElSohly 2017) (Flores-Sanchez and Verpoorte 2008a) (Booth and Bohlmann 2019).

1.2.1.1 Phytocannabinoids

Phytocannabinoids are primarily produced in nature by Cannabis sativa; however, research has shown that small quantities of cannabinoids have been found in hops and flaxseed (ElSohly 2017) (Andre, Hausman and Guerriero 2016). These compounds mimic our own endocannabinoids and interact with the endocannabinoid system (see also Chapter 10), enabling them to be used as a treatment for a variety of conditions, from epilepsy to pain (Gordon 2020) (Rosenburg et al. 2015). These are found in their highest concentration within the oils produced in the hair-like structures known as trichomes on the female flower and “sugar leaves” close to the flowers, though they have been detected in seeds, seedlings, roots, stems, leaves, and pollen (Aizpurua-Olaizola et al. 2016) (Frassinetti et al. 2018).

These compounds are the most studied group of secondary metabolites in cannabis research. To date, there are over 140 cannabinoids recorded that can be divided into ten main structural types (Table 1.1).

The major cannabinoids found in fresh plant material are tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA), which decarboxylate to the more psychoactive neutral forms, THC and CBD (Hanuš, Meyer et al. 2016).

Cannabinoids are composed of 22 carbon atoms in their acid form, and after decarboxylation, 21 carbons in their neutral form. They are derived from diterpene structures and are terpenophenolic and are therefore much larger than the predominant terpenes found in cannabis (Hanuš and Hod 2020).

1.2.1.2 Terpenes/Terpenoids

Terpenes are found within many plants and are volatile compounds that produce the distinctive aromas of cannabis. Their aromatic properties serve many purposes, including antimicrobial and antiherbivory defense, plant-to-plant interaction, and insect attraction for pollination (Hanuš and H...

Table of contents

• Cover
• Half-Title
• Title
• Copyright
• Contents
• Preface
• Editors
• Contributors
• Chapter 1 Cultivation Stress Techniques and the Production of Secondary Metabolites in Cannabis sativa
• Chapter 2 Aroma in Cannabis: A Foundation for Chemotype Classification
• Chapter 3 Cannabinoid Chemistry of Cannabis
• Chapter 4 Use of Mass Spectrometry for the Analysis of Cannabis sativa spp.
• Chapter 5 New Trends in the Analysis of Cannabis-Based Products
• Chapter 6 Cannabis Microbial Testing: Methodologies and Considerations
• Chapter 7 Cannabis Extract Formulations and Devices
• Chapter 8 Transdermal Delivery
• Chapter 9 Thermal Degradation of Cannabinoids and Cannabis Terpenes: A Review
• Chapter 10 Cannabis Pharmacokinetics and Pharmacodynamics
• Index