1: Introduction

UPDATED date

Cannabis research papers are now coming out at the rate of about four thousand articles a year[PubMed_2021]. The number is still larger if one includes articles on individual cannabis compounds. Most of these articles are medically relevant — many present convincing results in animal models of serious illnesses. There is a pressing need to get this vital research into the hands of patients, families, and physicians.

This book to presents research about the medical benefits of cannabis compounds for physical and mental afflictions such as arthritis, intractable pain, Alzheimer's disease, schizophrenia, alcoholism, heart disease, and cancer. The word "research" is essential here. There have been many anecdotal stories of miraculous cannabis cures and treatments.

In this online web supplement, the book's medical claims are backed up by copious references to online medical research. Mousing over a citation () brings up its corresponding reference, which is linked to the referenced work.

The resulting book presents information on the relevance of 29 cannabis compounds to 72 medical conditions, including 14 types of cancer. The provided information suggests treatment strategies for patients and physicians.

Topics covered in this introductory chapter include

  1.  A sketch of the book's main topics.
  2. Types of cannabis compounds.
  3. Types of medical evidence.
  4. Procurement and use of cannabis compounds.
  5. Comparison with previous work.

1.1 Topics Covered  

Chapter 2 explains the relationship between common forms of arthritis and inflammation. It then identifies cannabis compounds that can slow the progress of arthritis by reducing inflammation.

Chapter 3 covers pain and nausea: ordinary physical pain, arthritis pain, neurological pain, and cancer pain.

Chapter 4 shows how cannabis compounds help with Alzheimer's disease, epilepsy, traumatic brain injury, and other neurological conditions.

Chapter 5 discusses psychiatric conditions such as schizophrenia, depression, and post-traumatic stress disorder.

Chapter 6 is about compounds that can lead to addiction, including tobacco, alcohol, opioids, cocaine, and marijuana.

Chapter 7 presents what is known about how cannabis compounds affect strokes and cardiovascular conditions.

Chapter 8 discusses 17 types of cancer and presents the main cancer-fighting tasks performed by cannabis compounds.

Chapter 9 brings together all that is accomplished in Chapters 2 through 8. It gives a concise picture showing the relationship between cannabis compounds and the medical conditions studied. This information provides what strain developers need to develop new medically beneficial cannabis strains.

Appendix A lists cannabis compounds involved in treating medical conditions.

Appendix B discusses the ability of cannabis compounds to lower levels of inflammatory cytokines. Several chapters rely on Appendix B.

Appendix C is a short essay on the history of cannabis. It is included partly to show how cannabis terminology has evolved.

 Appendix D is a list of toxic compounds. This appendix is included as background for the discussion of neurological conditions.

Appendix E is a glossary of medical terms.

1.2 Types of Cannabis Compounds  

Cannabis compounds fall into three main groups: cannabinoids, terpenes, and flavonoids. The quintessential cannabinoid, THC, achieves its effects primarily by interacting with the two cannabinoid receptors, CB1 and CB2. Cannabinoids are compounds that interact with the cannabinoid receptors or are structurally similar to compounds that do. The naturally occurring cannabinoids are found in the buds of female cannabis plants. The nine cannabinoids studied in this book are CBD, CBDA, THC, THCA, CBC, CBG, CBGA, THCV, and Δ8-THC.

Terpenes are light-weight oily compounds found not only in cannabis but in most other plants. Terpenes are construed to include oxidized terpenes called terpenoids[Ruzicka_1953]. The following 21 terpenes are studied in this book:

borneol
camphene
d-limonene
eucalyptol
geraniol
guaiol
linalool
menthol
nerolidol
terpineol
terpinolene 
valencene
α-bisabolol
α-humulene
α-pinene
α-terpinene
β-caryophyllene
β-caryophyllene oxide
β-eudesmol
β-pinene
γ-terpinene

Except for β-Caryophyllene, terpenes do not interact with the cannabinoid receptors.

In addition to cannabinoids and terpenes, cannabis plants also contain other compounds used in traditional folk medicine[Ryz_2017][Frassinetti_2018]. They are found in cannabis roots, seeds, and sprouts. The flavonoid apigenin is an example. Cannabis testing laboratories do not yet test for flavonoids. They are beyond the scope of this book.

1.3 Types of Evidence  

The following list presents seven types of evidence used in this book. Understanding evidence types is essential in studying cannabis compounds because there is precious little evidence resulting from large-scale double-blind, placebo-controlled studies of the sort used in the FDA's drug-approval process. This book aims to present available evidence accurately.

In the absence of large-scale studies, the research results reported in this book are technically just hypotheses. What is true of one person's personal story may be true for another person. What is true of nude mice may be true for humans. And so forth. 

In addition, there is the issue of replication. In medical science, the exact replication of an experiment is usually not attempted. Instead, related studies may get compatible results. Or not. In this book, when two studies conflict, both are reported.

Finally, there is the question of the reliability of individual results. Virtually all of the scientific results are from refereed research papers. A few of the published papers are from many years ago. They document the fact that some of the more significant results have been known to the scientific community for some time.

1.4 Procurement and Use  

The following chapters reveal, for selected medical conditions, cannabis compounds that may help. Having determined what cannabis compounds are relevant to a given medical condition, there are two ways to proceed: to obtain cannabis strains that feature the desired compounds or to buy the individual compounds directly.

Part 3 of Backes's Cannabis Pharmacy[Backes_2014] lists 50 strains of cannabis and gives an indication of what cannabis compounds are emphasized in each strain. Commercially available strains have been through many generations of strain development. None are the native indica or sativa strains found in the wild.  However, choosing strains whose ancestry is mostly sativa or mostly indicia does afford some control over terpene content, as is shown in the following chart[Casano_2011].

Sativa verus Indicia terpene content

Legend. Mostly Indica=black bars, mostly Sativa=white bars. Break on Y-axis is 0.7. Numbers on X-axis refer to individual compounds: 1=α-pinene, 2=unk1, 3=unk2, 4=camphene, 5=β-pinene, 6=sabinene, 7=Δ-3-carene, 8=α-phellandrene, 9=β-myrcene, 10=α-terpinene, 11=limonene, 12=1.8 cineole, 13=γ-terpinene, 14=cis-β-ocimene, 15=trans-β-ocimene, 16=α-terpinolene, 17=unk3, 18=unk4, 19=β-caryophyllene, 20=unk5, 21=unk6, 22=unk7, 23=unk8, 24=unk9, 25=unk10, 26=unk11, 27=unk12, 28=unk13.

The above chart suggests that myrcene is the most abundant cannabis terpene. It has sedative properties and is responsible for the sedative effect of indica cannabis strains. However, it is omitted from this book because the FDA has banned its use as a food additive on the grounds that it is carcinogenic[myrcene-fda].

Reputable online merchants provide independent third-party lab reports identifying the cannabis compounds contained in their products. States with medical cannabis programs commonly post third-party analyses of approved cannabis products. The state of Connecticut, for example, posts these in an extensive online cannabis registry[Department_of_Consumer_Protection][Rahn_B_2019].

It is currently impossible to obtain a cannabis strain whose compounds are designed to handle a specific medical condition. However, work towards this goal has begun[Lewis_2017].

Aside from choosing a cannabis strain, the second option is selecting and consuming individual cannabis compounds. In addition to CBD, THC, CBDA, and THCA, several other cannabinoids are available over the internet. Pure cannabinoids are solids that are usually sold as tinctures dissolved in oil or alcohol. But water-soluble powders have been developed. A cannabinoid solution is more bioavailable and digests faster than a tincture. Several techniques for creating powders are in use, but the most common method is to create a powder whose particles are so fine that they stay in suspension when dissolved in water[Schmidt_2020].

Individual terpenes are also available. They, too, are fat-soluble, but they are volatile oils rather than solids. They are also much more potent than cannabinoids. Some are used as seasonings, but most are not suited to ingestion. From Lawless’s The Encyclopedia of Essential Oils, it is apparent that terpenes can be applied in any of the following ways[Lawless_2013]:

dissolved in oils and lotions and applied to the skin
dissolved in massage oils and creams
infused into hot and cold compresses
released in vapor via evaporation
released in steam
added to bathwater

1.5 Comparison with Previous Work  

This book covers 57 medical conditions organized into seven areas, the largest area being cancer which includes 16 types. A total of 31 cannabis compounds are investigated. This web supplement to this book includes approximately 900 references. Three other books contain similar material.

Backes's Cannabis Pharmacy[Backes_2014] is a comprehensive treatment of medical cannabis. Part 3 lists 50 cannabis strains, giving detailed information on each. Of particular note is the mention of each strain's key cannabis compounds. This type of information is essential for choosing varieties for specific medical conditions. Part 4 lists 50 medical conditions and provides a detailed readout on how THC and CBD help each condition. Part 4 cites 637 references.

Part 2 of Holland's The Pot Book[Holland_2010] discusses the potential harms and risks associated with cannabis, information that is also covered in Chapter 6 of this book. Holland’s Chapters 24-28 and 37 overlap the main content of this book. They discuss clinical applications of cannabinoids, emphasizing physical pain. CBD, THC, and synthetic cannabinoids are investigated. Other phytocannabinoids and terpenes are not covered. These chapters cite 280 references.

Frye's The Medical Marijuana Guide[Frye_2018] covers a wide range of topics, but its main overlap with this book comes in Chapter 5, which covers the use of CBD and THC in treating 40 severe medical conditions. Chapter 5 cites 101 references.

References  
Rendered according to the Citations Online architecture

Ryz_2017. Cannabis Roots: A Traditional Therapy with Future Potential for Treating Inflammation and Pain [exposition]. Full text. Ryz N, Remillard D, Russo E. Cannabis and Cannabinoid Research. Online 2017 August 1.

Frassinetti_2018. Nutraceutical potential of hemp (Cannabis sativa L.) seeds and sprouts [in vitro study]. Abstract. Frassinetti S, Moccia E, Caltavuturo L, et al. Food Chemistry. 2018 April 22.

Ruzicka_1953. The Isoprene Rule and the Biogenesis of Terpenic Compounds. German abstract, English translation. Ruzicka L. Experientia. Published 1953.

PubMed_2021. (Marijuana research published during 2021). PubMed query. The United States National Library of Medicine (NLM). U.S\. Department of Health & Human Services. Performed 2022 January 26.

cam_2013. Compiling a NCI best case submission [requirements document]. Full text. Office of Complementary and Alternative Medicine. National Cancer Institute. Updated January 23, 2013.

Faggion_2012. Guidelines for reporting pre-clinical in vitro studies on dental materials [requirements document]. Abstract. Faggion C M. Elsevier Journal of Evidence Based Dental Practice. published November 22, 2012.

Lieu_2010. A middle Ground [in The Ethics of Animal Experimentation]. Full text. Lieu S. Huntington's Outreach Project for Education at Stanford. Published 2010 July 6.

PDQ_2019. PDQ Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies [exposition]. Full text. Integrative, Alternative, and Complementary Therapies Editorial Board. National Cancer Institute. Updated 2019 January 15.

Casano_2011. Variations in terpene profiles of different strains of Cannabis sativa L [plant study]. Abstract, full text. Casano S, Grassi G, Martini V, Michelozzi M. Acta Horticulturae. Online 2011 December 31.

 myrcene-fda. FDA Removes 7 Synthetic Flavoring Substances from Food Additives List. Article. Center for Food Safety and Applied Nutrition. FDA. 2018 October 5.

Department_of_Consumer_Protection. Medical Marijuana Brand Registry [independent lab analyses]. Database. Department of Consumer Protection. The State of Connecticut. Online 2015 March 24 and later.

Rahn_B_2019. Connecticut Medical Marijuana Strain Name Guide [lexicon]. Full text. Rahn B. Leafy. Updated 2019 March 5.

Lewis_2017. Pharmacological Foundations of Cannabis Chemovars [Project Description]. Abstract. Lewis M, Russo E, Smith K. Planta Medica. Online November 21, 2017.

Schmidt_2020. Water-Soluble Cannabinoids: A Challenge and Solution for the Cannabis Beverage Market. Full text. Schmidt E. ACS Laboratory. 2020 February 6.

Lawless_2013. Part I.4\. How to Use Essential Oils at Home [in The Encyclopedia of Essential Oils: The Complete Guide to the Use of Aromatic Oils In Aromatherapy, Herbalism, Health, and Well Being]. Amazon, page 35. Lawless J. Red Wheel. 2013 June 1.

Frye_2018. The Medical Marijuana Guide: Cannabis and Your Health. Kindle. Frye P. Rowman & Littlefield. Published 2018 November 8.

Backes_2014. Cannabis Pharmacy: The Practical Guide to Medical Marijuana. Kindle. Backes M. Black Dog & Leventhal. Published 2014 September 9.

Holland_2010. The Pot Book: A Complete Guide to Cannabis. Kindle. Holland J (editor). Park Street Press. Published 2010 September 23.