Cannabis

“Cannabis” is the generic term for products of the plant, Cannabis sativa L

• Cannabis is a widely distributed plant¹ that is one of the oldest sources of fiber, food, oil, and medicine²
• Cannabis, and all of its cannabinoid components, is a controlled substance classified as a Schedule I agent in the US; this classification denotes a drug with a high potential for abuse and no currently accepted medical use³

Cannabis sativa L.

The scientific name of the cannabis plant⁴

The two varieties of cannabis – sativa and indica – are considered subspecies; Cannabis sativa subsp. sativa contains <0.3% (dry weight) of THC and Cannabis sativa subsp. indica contains >0.3% of THC.^4,5 Current botanical thinking, however, now refers only to a single species – Cannabis sativa L.

Hemp and Related Terms

Hemp

Strains of Cannabis sativa L. historically grown for fibrous materials found in stalks and seeds; contain minimal amounts of THC⁵ and low levels of CBD.⁴ Used industrially to develop items, such as clothing fiber.⁴ The flowering portions of the hemp variety may be used to extract CBD.⁴ Cannabinoids extracted from hemp plants are considered marijuana and are classified as a Schedule I substance.^11‡

^‡ The Controlled Substances Act does not define hemp, per se. Its definition of marijuana includes all parts of the Cannabis sativa L. plant, and the seeds and resin extracted from any part of such plant; it exempts all marijuana stalk, fiber, and sterilized seeds (and preparations made from them).¹²

Hemp Oil / Hempseed Oil

An oil extracted from cannabis seeds by cold pressing. It contains only trace amounts of cannabinoids and terpenes, and is high in unsaturated fatty acids; used in paints and varnishes and in manufacturing soap and a wide variety of food products.⁴

CBD Oil

An extract obtained from the flowering portions of the hemp plant, then dissolved in another oil (coconut, sesame, etc). It typically contains no THC and has no psychoactive properties.¹³

Cannabis Oil*

Concentrated cannabis extracts, often containing very high concentrations of THC^14,15

Why is this term considered ambiguous? The constituents are often unclear; the relative amounts of cannabinoids are not always specified.

*For this term there is no scientifically accepted definition.

Cannabinoids

Cannabinoids

Term used to refer to molecules that are found in the cannabis plant and/or that interact with cannabinoid receptors, as well as the derivatives, and transformation products of those molecules.^16-19 They can be classified as phytocannabinoids, endocannabinoids, or synthetic cannabinoids.

Endocannabinoids

Chemicals produced by the body²⁰ that target cannabinoid receptors²¹

Synthetic Cannabinoids

Cannabinoids produced in the laboratory to structurally or functionally mimic the endocannabinoids or phytocannabinoids²⁰

Phytocannabinoids

Over 100 naturally occurring chemicals found in the cannabis plant with a chemical structure related to endocannabinoids.²⁰ The most well-characterized, so far, are described below⁶:

• CBD: Cannabidiol, one of the major cannabinoids derived from cannabis or synthesized. CBD is under evaluation for its anticonvulsant properties, among other therapeutic uses. CBD has very low affinity at the cannabinoid receptors, type 1 (CB₁) and type 2 (CB₂), and is not believed to be psychoactive.⁷
• THC: Δ⁹-Tetrahydrocannabinol, a major phytocannabinoid derived from cannabis, is thought to be the pharmacologically most active cannabinoid of the cannabis plant, largely responsible for its psychoactive properties due to its agonist activity at CB₁ receptors (behavioral, cognitive, and psychotropic effects)⁷
• CBDV: Cannabidivarin, a variant of CBD with some animal evidence supporting anticonvulsant and other effects under investigation²²
• THCV: Tetrahydrocannabidivarin – structurally similar to THC, it is an antagonist at CB₁²³
• THCA: Δ¹-Tetrahydrocannabinolic acid, the most abundant cannabinoid in cannabis bred for recreational use; as a nonpsychoactive precursor of THC, THCA converts to THC when heated (to temperatures greater than those found in the human body) or smoked²¹

Terpenes/Terpenoids

The primary aromatic principles found in cannabis, providing the scent and flavor of the cannabis plant^24,25

CBD-Rich (sometimes referred to as “Enriched”) Extracts*

Preparations from cannabis plants that are higher in CBD than plants bred historically for recreation.²⁶

The term “enriched” is often used inappropriately.

*For this term there is no scientifically accepted definition.

FDA-Approved Formulation of CBD*

Controlled CBD preparation that meets Food and Drug Administration standards of purity, consistency, stability, safety, and efficacy; it can be plant-derived or synthetic.²⁷

*For this term there is no scientifically accepted definition.

Endocannabinoid System and Related Terms

Endocannabinoid Receptors

Binding sites for cannabinoids within the brain and body²⁸

Endocannabinoid System

Communication system within the brain comprising identified cannabinoid receptors, the endocannabinoids that target the receptors, and the downstream effects^29,30

Entourage Effect*

This term originates in endocannabinoid science, but is commonly used to suggest that combining multiple constituents of the whole cannabis plant may result in enhanced therapeutic effects. More data in patients are needed to support or refute this theory in specific disease states.^7,31

Why is this term considered ambiguous? Although the observation of synergy may suggest that adequate efficacy requires a cumulative effect of multiple cannabis constituents, additional testing needs to be done. Preclinical and clinical evidence suggests that some purified cannabinoids are efficacious when administered alone.⁷

*For this term there is no scientifically accepted definition.

References

1.ElSohly M, Gul W. Constituents of Cannabis sativa. In: Pertwee RG, ed. Handbook of Cannabis. Oxford, UK: Oxford University Press; 2014:3-22. https://global.oup.com/academic/product/handbook-of-cannabis-9780199662685?cc=us&lang=en&

2.Hillig KW, Mahlberg PG. A chemotaxonomic analysis of cannabinoid variation in cannabis (Cannabaceae). Am J Bot. 2004;91:966-975. http://www.ncbi.nlm.nih.gov/pubmed/?term=Hillig+Am+J+Bot.+2004%3B91%3A966-975

3.Cannabis and cannabinoids–Health professional version. National Cancer Institute website https://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq#section/all. Accessed June 20, 2016.

4.Small E, Marcus D. Hemp: a new crop with new uses for North America. In: Janick J, Whipkey A, eds. Trends in New Crops and New Uses. Alexandria, VA: ASHS Press; 2002:284-326. https://www.hort.purdue.edu/newcrop/ncnu02/v5-284.html

5.Legitimacy of Industrial Hemp Research. Section 7606 of 2013 Farm Bill. http://www.votehemp.com/PDF/Pages_from_farm0127.pdf. Accessed September 15, 2016.

6.What Is marijuana? National Institute on Drug Abuse website. https://www.drugabuse.gov/publications/research-reports/marijuana/what-marijuana. Accessed June 20, 2016.

7.Rosenberg EC, Tsien RW, Whalley BJ, Devinsky O. Cannabinoids and epilepsy. Neurotherapeutics. 2015;12:747-768. http://www.ncbi.nlm.nih.gov/pubmed/?term=7.%09Rosenberg+EC%2C+Tsien+RW%2C+Whalley+BJ%2C+Devinsky+O.+Cannabinoids+and+epilepsy.+Neurotherapeutics.+2015%3B12%3A747-768

8.Hall W. Recreational cannabis: sought-after effects, adverse effects, designer drugs, and harm minimization. In: Pertwee RG, ed. Handbook of Cannabis. Oxford, UK: Oxford University Press; 2014:645-646. https://global.oup.com/academic/product/handbook-of-cannabis-9780199662685?cc=us&lang=en&

9.Dept of Justice. Drug Enforcement Administration. 21 CFR Chapter II. Federal Register; Vol. 81, No. 156. 2016; 53688-53766. http://www.deadiversion.usdoj.gov/fed_regs/rules/2016/fr0812.pdf

10.Sevigny EL, Pacula RL, Heaton P. The effects of medical marijuana laws on potency. Int J Drug Policy. 2014;25:308-319. http://www.ncbi.nlm.nih.gov/pubmed/?term=11.%09Sevigny+EL%2C+Pacula+RL%2C+Heaton+P.+The+effects+of+medical+marijuana+laws+on+potency.+Int+J+Drug+Policy.+2014%3B25%3A308-319

11.Coppen JJW. Gums, Resins and Latexes of Plant Origin. Rome, Italy: Food and Agriculture Organization of the United Nations;1995;142. http://www.fao.org/3/a-v9236e.pdf

12.Controlled Substances Act. Title 21 United States Code (USC) Controlled Substances Act (21 USC 802(d) (16). http://www.deadiversion.usdoj.gov/21cfr/21usc/. Accessed June 20, 2016.

13.Seed Guides Info. Hemp oil: benefits, nutrition, side effects and facts. http://www.seedguides.info/hemp-oil/. Accessed August 22, 2016.

14.Romano LL, Hazekamp A. Cannabis oil: chemical evaluation of an upcoming cannabis-based medicine. Cannabinoids. 2013;1:1-11. http://www.bedrocan.nl/userfiles/file/cannabs%20oil%20hazekamp%20Romano.pdf

15.United Nations Office on Drugs and Crime. Recommended methods for the identification and analysis of cannabis and cannabis products. New York: United Nations, 2009. https://www.unodc.org/documents/scientific/ST-NAR-40-Ebook.pdf. Accessed June 20, 2016.

16.Agurell S, Dewey WL Willett RE, eds. The Cannabinoids: Chemical, Pharmacologic, and Therapeutic Aspects. New York: Academic Press, 1984. https://books.google.com/books?id=x7y7ruiagigC&pg=PR3&lpg=PR3&dq=The+Cannabinoids:+Chemical,+Pharmacologic,+and+Therapeutic+Aspects.+New+York:+Academic+Press,+1984&source=bl&ots=zM7FV_28Cb&sig=oqa5W6rA3jY81d0pDUdkXayaBvo&hl=en&sa=X&ved=0ahUKEwj6pIWWmZ7PAhWD4SYKHShkBsUQ6AEIJzAB#v=onepage&q=The%20Cannabinoids%3A%20Chemical%2C%20Pharmacologic%2C%20and%20Therapeutic%20Aspects.%20New%20York%3A%20Academic%20Press%2C%201984&f=false

17.Agurell S, Halldin M, Lindgren JE, et al. Pharmacokinetics and metabolism of delta 1-tetrahydrocannabinol and other cannabinoids with emphasis on man. Pharmacol Rev. 1986;38:21-43. http://www.ncbi.nlm.nih.gov/pubmed/?term=Agurell+S%2C+Halldin+M%2C+Lindgren+JE%2C+et+al.+Pharmacokinetics+and+metabolism+of+delta+1-tetrahydrocannabinol+and+other+cannabinoids+with+emphasis+on+man.+Pharmacol+Rev.+1986%3B38%3A21-43

18.Mechoulam R ed. Marijuana: Chemistry, Pharmacology, Metabolism and Clinical Effects. New York: Academic Press, 1973. http://www.abebooks.com/servlet/BookDetailsPL?bi=11751137525&searchurl=tn%3Dmarijuana%2Bchemistry%2Bpharmacology%2Bmetabolism%2Bclinical%2Beffects%26sortby%3D17

19.Appendino G, Chianese G, Taglialatela-Scafati O. Cannabinoids: occurrence and medicinal chemistry. Curr Med Chem. 2011;18:1085-1099. http://www.ncbi.nlm.nih.gov/pubmed/?term=Appendino+G%2C+Chianese+G%2C+Taglialatela-Scafati+O.+Cannabinoids%3A+occurrence+and+medicinal+chemistry.+Curr+Med+Chem.+2011%3B18%3A1085-1099

20.Grotenhermen F. Cannabinoids and the endocannabinoid system. Cannabinoids. 2006;1:10-14. https://www.cannabis-med.org/data/pdf/en_2006_01_2.pdf

21.Wohlfarth A, Mahler H, Auwärter V. Rapid isolation procedure for Δ9-tetrahydrocannabinolic acid A (THCA) from cannabis sativa using two flash chromatography systems. J Chromatogr. 2011;3059-3064. http://www.ncbi.nlm.nih.gov/pubmed/21944900

22.Hill AJ, Mercier MS, Hill TD, et al. Cannabidivarin is anticonvulsant in mouse and rat. Br J Pharmacol. 2012;167:1629-1642. http://www.ncbi.nlm.nih.gov/pubmed/?term=31.%09Hill+AJ%2C+Mercier+MS%2C+Hill+TD%2C+et+al.+Cannabidivarin+is+anticonvulsant+in+mouse+and+rat.+Br+J+Pharmacol.+2012%3B167%3A1629-1642

23.Williams CM, Jones NA, Whalley BJ. Cannabis and Epilepsy. In: Pertwee RG, ed. Handbook of Cannabis. Oxford, UK: Oxford University Press; 2014:547-563. https://global.oup.com/academic/product/handbook-of-cannabis-9780199662685?cc=us&lang=en&

24.Brenneisen R. Chemistry and analysis of phytocannabinoids and other cannabis constituents. In: ElSohly MA, ed. Marijuana and the Cannabinoids. Totowa, New Jersey: Humana Press; 2007:17-50. http://www.hampapartiet.se/09.pdf

25.Clarke RC, Watson DP. Cannabis and natural cannabis medicines. In: ElSohly MA, ed. Marijuana and the Cannabinoids. Totowa, New Jersey: Humana Press; 2007:17-50. http://www.hampapartiet.se/09.pdf

26.Hussain SA, Zhou R, Jacobson C, et al. Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: a potential role for infantile spasms and Lennox–Gastaut syndrome. Epilepsy Behav. 2015;47:138-141. http://www.ncbi.nlm.nih.gov/pubmed/?term=Hussain+Epilepsy+Behav.+2015%3B47%3A138-141

27.Guidelines for the use of non-pharmaceutical grade compounds in laboratory animals. National Institutes of Health website https://oacu.oir.nih.gov/sites/default/files/uploads/arac-guidelines/pharmaceutical_compounds.pdf. Accessed June 20, 2016.

28.Pertwee RG. Cannabinoid pharmacology: The first 66 years. Br J Pharmacol. 2006;147:S163-S171. http://www.ncbi.nlm.nih.gov/pubmed/16402100

29.Cristino L, Di Marzo V. Established and emerging concepts of cannabinoid action on food intake and their potential application to the treatment of anorexia and cachexia. In: Pertwee RG, ed. Handbook of Cannabis. Oxford, UK: Oxford University Press; 2014:455-472. https://global.oup.com/academic/product/handbook-of-cannabis-9780199662685?cc=us&lang=en&

30.Di Marzo V. Targeting the endocannabinoid system: to enhance or reduce? Nat Rev Drug Discov. 2008;7:438-455. http://www.ncbi.nlm.nih.gov/pubmed/18446159

31.Ben-Shabat S, Fride E, Sheskin T, et al. An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. Eur J Pharmacol. 1998;353:23-31. http://www.ncbi.nlm.nih.gov/pubmed/9721036

32.Kalra EK. Nutraceutical – Definition and introduction. AAPS PharmSci. 2003;5:Article 25. http://www.ncbi.nlm.nih.gov/pubmed/14621960

33.Koch A, Brandenburger S, Türpe S, Birringer B. The need for a legal distinction of nutraceuticals. Food Nutr Sci. 2014;5:905-913. http://file.scirp.org/pdf/FNS_2014050214150316.pdf

34.Dietary Supplement Health and Education Act of 1994. National Institutes of Health website. https://ods.od.nih.gov/About/DSHEA_Wording.aspx. Accessed June 20, 2016.

35.Dietary supplements. Food and Drug Administration website. http://www.fda.gov/Food/DietarySupplements/default.htm. Accessed June 20, 2016.

36.FEDERAL FOOD, DRUG, AND COSMETIC ACT. [21 U.S.C. § 321(ff)(3)(B)(ii)]. https://legcounsel.house.gov/Comps/Federal%20Food,%20Drug,%20And%20Cosmetic%20Act.pdf. Accessed December 16, 2016.