APPENDIX J – HOW SAFE IS YOUR VAPE PEN?

APPENDIX K – GLOSSARY

Broad spectrum*: Cannabis products that contains most of the original compounds found in cannabis flower often with the notable exception of THC. This term is also sometimes used for isolated cannabinoids that have been combined with terpenes in an approximation of the original chemical composition of the source flower. “full spectrum.”

Cannabidiol (CBD): CBD is the second most commonly produced compound in cannabis varieties bred for their medicinal use, and the most common in varieties bred for agriculture (commonly known as hemp). Unlike THC, CBD is a nonintoxicating compound. It is of medicinal interest for its anti-epileptic, anti- anxiety, and anti-inflammatory effects.

Cannabinoid receptor type 1 (CB1): Found primarily in the central nervous system, CB1 are responsible for the feeling of intoxication, or ‘high’, when consuming THC.

Cannabinoid receptor type 2 (CB2): Concentrated throughout the immune system, the peripheral nervous system, and the gastrointestinal system, CB2R are of interest for their immunomodulatory action.

Cannabinoids**: Cannabinoids are compounds uniquely found in cannabis plants, as well as compounds similar to those found in cannabis plants. There are three categories of cannabinoids: phytocannabinoids produced in plants like cannabis, endocannabinoids produced naturally by our bodies, and synthetic cannabinoids that are made in a lab.

o Primary cannabinoids: Generally considered to be the two most commonly expressed phytocannabinoids in mature cannabis flower - THC and CBD.

o Secondary cannabinoids: All of the phytocannabinoids excluding THC and CBD.

Cannabis oil: A term used to describe a wide variety of cannabinoid-rich products: the cannabinoid-rich resin from the flower, the various concentrated forms of cannabis extracts, and the resin when it’s infused in an edible oil for use as a tincture.

Cannabis: A common plant that has been utilized for food, fuel, fiber, and medicine for the last 12,000 years. The scientific name, cannabis sativa L., refers to the botanist Carl Linnaeus, who first identified cannabis in 1753.

Cartridge**: Cartridges are an increasingly common way to consume cannabis oil via vaporization. They work by attaching a small, extract-filled container (the cartridge) to a battery with a heating element. The cartridges themselves are often made of glass, metal, or plastic and use cotton or fiberglass as wicking material. The wick allows the extract to come into close proximity to the heating element. The resulting atomized oil is inhaled. Cartridges are popular because they are fast acting, portable, and avoid combustion - although they are not regulated, and some have been reported to get as hot at 1000℉.

Distillate*: Cannabis product created by refining the plant. Distilling to a certain chemical profile, generally on focused CBD and THC could contain some traces of other compounds. Frequently used interchangeably with “isolate.”

Endogenous cannabinoid system (endocannabinoid system, ECS): A system composed of two receptors (CB1 and CB2), the compound our bodies produce to activate them (endocannabinoids), and the enzymes that break those compounds down. The ECS regulates many systems within the body and is concentrated

in the central and peripheral nervous systems. It’s responsible for producing the effects felt by consuming some cannabinoids (like THC).

Extract**: Concentrated cannabis extracts made by using CO2, butane, propane, or a combination of these solvents to separate the active oils and waxes in flower from the plant matter. This ideally happens in a closed loop system where the solvents are completely reclaimed after extraction. The remaining plant waxes and oils are then hardened and agitated in a variety of ways resulting in many different textures. There are many terms used to describe the different textures of dabs, and they are often used as the main descriptor of the product (e.g. shatter, wax, resin). Dabs are typically consumed by placing a small amount of the concentrate on a very hot ‘nail’ in a ‘dab rig’ that looks very much like a bong. This process is referred to as “dabbing,” and due to the highly concentrated nature of the product consumed this method is not recommended for novice cannabis users.

Full spectrum*: Cannabis products that contains all of the original compounds found in cannabis flower: primary and secondary cannabinoids, terpenes, and flavonoids. Frequently used interchangeably with “broad spectrum.”

Hash, bubble hash, dry sift, kief**: These are forms of cannabis concentrate made by separating trichomes from the plant material using water, friction and/or pressurized heat. Trichomes contain the majority of the cannabinoid content in cannabis plants. They are very delicate, and relatively easy to remove. There are many techniques used to separate and collect the trichomes from the flower, and each of these methods has a different name. Hash is a catch-all phrase for most of these types of extracts. Bubble hash utilizes ice and a series of progressively finer filters to separate the trichomes from the flower. Dry sift is made by agitating the cannabis flower to separate and then collect the trichomes from the plant material. Kief generally refers to the trichomes and plant particles that accumulate as the excess leaves are trimmed away from the cannabis flower in a process known as trimming. Rosin is made by heating and pressing hash or kief into a more solid form, or by pressing and gently heating dried or fresh cannabis flower to express the oil directly.

Hemp oil: Used both to describe CBD-rich oil extracted from hemp, as well as CBD-devoid oil derived from the seeds.*

Hemp seed oil: Oil derived from the seeds of hemp plants. This oil does not contain any cannabinoids, though poor handling can result in cross-contamination with the resin-rich oil from the bract (seed covering).

Hemp: A legal term that refers to cannabis varieties that produce less than .03% THC. Often used to refer to varieties of cannabis that have been bred for industrial purposes.

Indica/sativa: Colloquial terms used to indicate effect of particular varieties of cannabis. Indica varieties are considered relaxing while sativa varieties are considered energizing. The terms' colloquial usage are subjective and have no basis in science. Biologically, the terms are unrelated to effect and instead refer to cannabis’ two subspecies that evolved in different areas (cannabis sativa sativa and cannabis sativa indica).

Isolate*: Cannabis products produced by removing everything except for a single cannabinoid, generally THC or CBD. These can be synthetic compounds. Frequently used interchangeably with “distillate.”

Terpenes: Aromatic compounds found in most plants and some insects. Terpenes are responsible for the way cannabis smells and have been associated with the range of distinct effects it produces in consumers.

Tetrahydrocannabinol (THC): The most common compound produced in cannabis varieties that have been bred for recreational and medicinal use. The activated form of THC, Δ9-THC, causes the intoxicating feelings generally associated with consuming cannabis and being ‘high’.

Vaporization**: The different forms of vaporization are frequently shortened to ‘vaping’ in conversation. Clarification is necessary to determine which form the user is referring to.

o Dry-herb vaporization – A method of consumption wherein dried cannabis flower is placed into a device. The heat sublimates the active compounds in the flower and the resulting vapor is inhaled. There are a number of different types of heating mechanisms, inhalation methods, and form factors for vaporizers.

o Oil “vaporization” – A method of consuming concentrated cannabis extract. The extract is placed into a cartridge containing a wick and atomizer. The cartridge is then attached to a battery, often pen shaped, that powers the atomizer and heats the oil, atomizing the cannabis extract as it is inhaled. This method of consumption is often referred to as ‘vaping’. A vape pen utilizes the same technology as an e-cigarette.

* Standards need to be set for these terms. They are used interchangeably with other terms and foster confusion in the marketplace.

** These definitions were taken from “Basic Cannabis Terminology,” presented in its entirety in Appendix M.

APPENDIX L – BASIC CANNABIS TERMINOLOGY

Written by Zoe Sigman. Commissioned by the Oregon Health and Sciences University (OHSU) for their Clinical Cannabis Continuing Medical Education course and sponsored by Farma.

BASIC CANNABIS TERMINOLOGY

© Farma on Hawthorne, Inc. BASIC CANNABIS TERMINOLOGY

This guide serves as a primer on the terminology most commonly used in retail cannabis establishments. The language of cannabis is often imprecise and confusing, because it derives from the black market. This guide addresses that confusion, and aims to provide medical professionals with a foundational understanding of cannabis and its myriad forms.

Dispensary - Dispensaries are the only legally permitted places to purchase cannabis products in most US jurisdictions. By law, all cannabis sold in Oregon dispensaries must be tested for potency, consistency and contaminants. Recreational cannabis sales (also known as “adult use” or “retail” sales) are limited to individuals who are 21 or older, and medical sales to individuals 18 or older with a current Oregon medical marijuana card. Customers must produce a valid government-issued ID in order to make a purchase in an Oregon dispensary. Consumption of cannabis products is not permitted at dispensaries, and all cannabis products must be packaged in approved child-resistant containers.

Most states designate one or more agencies to oversee cannabis licensing and compliance. In Oregon, the Oregon Liquor Control Commission (OLCC) has jurisdiction over all recreational cannabis businesses, and the Oregon Health Authority (OHA) has jurisdiction over the state’s medical marijuana program.

Budtender - This commonly used term describes the salespeople at cannabis retailers. In Oregon, all budtenders must pass a simple test in order to be licensed to handle and sell cannabis, much like a bartender must be licensed to serve alcohol. Dispensaries in most legal states (including OR, WA & CA) are not required to retain staff with formal medical training, which leaves staff training largely up to individual operators. Different dispensaries take vastly different approaches to employee training and retention.

THE CANNABIS PLANT

Cannabis (aka “marijuana,” “weed,” “bud”) is a flowering plant common to many parts of the world. Cannabis has been cultivated for fiber, oil, food, and medicine for millennia.1 The scientific name of the plant isCannabis sativa L. In the United States cannabis remains a Schedule I controlled substance, despite increasing public acceptance of cannabis legalization. A Note on Cannabis Classification

At present there is no standard, universally accepted means of classifying the endless varieties of cannabis plants. This makes consistency an issue for consumers. Evidence-based classification systems are being developed, but in the meantime a basic understanding of biological classification serves as a valuable tool for discussing the plant. The following terms can be heard in scientific discussions of cannabis classification: • Genotype: The genetic information that Illustration Courtesy of Walther Otto Müller. An illustration of informs the expression of a single organism. a hemp plant depicted in various developmental stages from • Phenotype: An observably distinct expression From Franz Eugen Köhler's Medizinal-Pflantzen. of a genotype. Often influenced by environmental and epigenetic factors. • Cultivar / Strain / Varietal: A distinct expression of a cannabis plant that has been produced via selective breeding and cultivation. “Strain” remains the common term used to describe different varieties of cannabis (eg, “OG Kush”). • Chemovar / Chemotype: A distinct expression of a cannabis plant that has been bred to express a specific chemical composition as defined by the chemical components found in the flowering part of the cannabis plant.2

Indica/Sativa - “Indica” and “sativa” are colloquial terms used to describe intoxicating varietals of cannabis with different effects. The terms derive from early attempts to describe the morphology of the cannabis plant.³ The morphology of the cannabis plant, however, does not dictate its chemical composition or its effects. Thus, there is currently an effort to move away from using the binary indica/sativa classification, and instead focus on specific chemical compositions (or “chemotypes”) in describing the potential effects of cannabis.

Photographs © Kenton Waltz and Curtis Taylor • “Indica” is colloquially used to describe varietals that feel more body-focused and relaxing. • “Sativa” is colloquially used to describe varietals with effects that are felt more strongly in the mind and are energizing.

Trichome: These are very small, hair-like outgrowths found on individual cannabis flowers and fan leaves. Vigorous trichome production can give cannabis the appearance of being covered in sugar or frost, and is generally sought after in the marketplace. The most common type of trichome in cannabis is composed of a stalk and a gland head, often milky-white in color. The gland head is where most of the notable compounds (cannabinoids and terpenes) are produced. Trichomes are quite fragile, and the gland head readily falls off during handling.

CANNABINOIDS

Cannabinoids are compounds that are found in the cannabis plant and compounds similar to those found in cannabis. Some cannabinoids interact with the body’s endogenous cannabinoid system (ECS) (see definition below). There are three main categories of cannabinoids, distinguished by where they are created: • Phytocannabinoids: chemical compounds found in cannabis plants. Some, but not all, cannabinoids interact with the endogenous cannabinoid system. There have been at least 127 identified to date. • Cannabigerol (CBG): Most phytocannabinoids develop from CBG, sometimes referred to as the ‘parent cannabinoid’. Different genetic signalling determines what cannabinoids CBG develops into. CBG is a non-intoxicating compound of medical interest as an antinociceptive and anxiolytic.4 • Tetrahydrocannabinolic Acid (THCA): THCA is the most common cannabinoid found in cannabis that has been bred for medicinal and recreational use. It is the raw, non-intoxicating, form of Δ9-THC. • Δ9-Tetrahydrocannabinol (Δ9-THC): When THCA is heated it is decarboxylated to become Δ9-THC, commonly referred to as simply “THC.” Δ9-THC is intoxicating and is therefore of particular interest to recreational consumers. It is also of interest to medical researchers for treatment of nausea, pain, and sleep disorders.5 • Cannabidiol (CBD): CBD is the second most common cannabinoid found in cannabis, and the most common cannabinoid in cannabis cultivated for fiber and oil production (ie, hemp). CBD is of medical interest as an antispasmodic and anxiolytic compound.6 Epidiolex, CBD purified from cannabis plants by a pharmaceutical company, has recently gained FDA approval as a treatment for Dravet Syndrome and Lennox-Gataut syndrome, rare forms of pediatric epilepsy.7 • Cannabinol (CBN): When Δ9-THC oxidizes, as happens over time, it degrades into CBN. CBN has about 25% the intoxicating effect as compared to Δ9-THC. Some have attributed sedative properties to CBN. These claims are not substantiated in scientific literature. • Tetrahydrocannabivarin (THCV): THCV is likely non intoxicating, and may antagonize the primary receptor responsible for the intoxicating effects of Δ9-THC. THCV has been investigated in rodent models and a human case study as a compound of interest for obesity and diabetes.8,9,10 • Endogenous Cannabinoids (endocannabinoids): Compounds found in the body that interact with the body’s endogenous cannabinoid system. The most frequently discussed endocannabinoids are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Both were identified after THC and CBD. • Synthetic cannabinoids: These compounds tend to have different binding affinities to receptors in the endogenous cannabinoid system, and are frequently unable to replicate effects of phytocannabinoids. Dronabinol, a synthetic Δ9-THC drug, has been approved in the US for the treatment of nausea and vomiting in cancer patients, and for appetite stimulation in HIV/AIDS patients.

Cannabinoid Bold Box = Family CBGA

CBGVA

RAW THCA CBT CBDA CBCA

THCVA CBDVA CBCVA MISCELLANEOUS

∆9-THC CBD CBC CBG

THCV CBDV CBCV CBGV HEATED

CBNA ∆8-THC CBND CBE CBLA

CBN CBL OXIDIZED

Reprinted with permission of Zoe Sigman Dr. Dedi Meiri

Terpenes/Terpenoids: Aromatic compounds common to many plants, terpenes are the primary constituents of essential oils. Cannabis has expressed over two hundred terpenes in varying quantities, with roughly a dozen showing up most frequently. It has been suggested that these different combinations of terpenes contribute to the different effects felt when consuming cannabis.11 This idea is supported by some preliminary evidence using cultivars with known effects (energizing vs. relaxing).12 ,13

The Entourage Effect: The combined effect of all active compounds found in cannabis flower, generally thought of as the effects mediated by the unique combination of the cannabinoids and terpenes in a particular flower sample.14,15 Cannabis can be considered a poly-pharmaceutical, and the large number of active compounds in the plant can make it difficult to predict the effects of human consumption.

Hemp: Hemp is legally, not genetically, distinct from cannabis. Many governments define hemp as cannabis that produces flower that has very low THC content, either none at all or ≤0.03%. The US government considers hemp to be cannabis, and is therefore included in the Class I scheduling of the plant. Traditionally grown for fiber, this form of cannabis has recently received a great deal interest as a producer of the non-intoxicating cannabinoid cannabidiol (CBD).

THE ENDOGENOUS CANNABINOID SYSTEM

The endogenous cannabinoid system16 (aka endocannabinoid system, ECS) comprises two cannabinoid receptors, endogenous cannabinoids, and the enzymes that synthesize and break down endocannabinoids. It is present in all mammals. The system was first identified identified in 1990, nearly three decades after the identification of THC.17 The ECS is found primarily throughout the central and peripheral nervous systems. It is also expressed in the skin, intestine, reproductive organs, and bones. The two ECS receptors are thought to mediate the effects of Endogenous cannabinoid system depiction by Kannaway endocannabinoids, synthetic cannabinoids, and some phytocannabinoids. There are many other receptors with which cannabinoids interact (PPARs, GPRs, TRPs, 5HTs), but none are currently considered part of the ECS. • Cannabinoid receptor type 1 (CB1R): Found primarily in the central nervous system, CB1R are responsible for the feeling of intoxication, or ‘high’, when consuming THC. • Cannabinoid receptor type 2 (CB2R): Found throughout the immune system, the peripheral nervous system, and the gastrointestinal system, CB2R are of interest for immunomodulatory action. • Phytocannabinoid promiscuity: Cannabis interacts with many other receptors and pathways in addition to the receptors that comprise the endocannabinoid system. CBD alone interacts with at least fourteen channels.18 The ability of cannabinoids to bind to so many sites makes it difficult to determine the pharmacological basis of promising medical therapies.

TYPES OF CANNABIS PRODUCTS

Flower (aka “bud”) - The flowering part of the female cannabis plant. Cannabis flowers grow on the ends of the branches of cannabis plants in tight groupings of many tiny, teardrop shaped flowers. These tight groupings are often referred to as “buds” and look more like small colorful rocks than the traditional concept of a flower. When fully mature, the flower is harvested, dried, cured (much like tobacco), and the excess leaf material is removed. This is the cannabis product most familiar to Americans.

After drying, cannabis flower is most frequently ground and consumed via inhalation through combustion or vaporization. Cannabis cigarettes (aka joints), pipes, and water pipes (aka bongs) are the most common methods used for inhaling combusted flower. It is the cannabis flower, not the iconic cannabis fan leaf, where the highest concentration of the active compounds like THC and CBD are found. These compounds are found primarily in the trichomes, hair-like protrusions that cover the flower.

Edibles - Edibles are cannabis products consumed orally. Edibles typically combine a familiar food (usually candy) with cannabis extract. Many people find the flavor of cannabis extract unappetizing. In order to mask the cannabis flavor edibles are typically made with flavorful ingredients, often those common in chocolate or candy. Oregon has implemented exacting testing guidelines to control potency and consistency in edibles.

Topicals - Topicals are cannabis-infused products intended for use on the skin. They can take the form of balms, lotions, massage oils or transdermal patches. Topicals are not intended to be taken internally, nor is the assumption that the cannabinoids present will enter the bloodstream. The vast majority of users do not report feeling intoxicated or “high” upon using a topical.

Cannabis Extracts (aka Concentrates) - Cannabis extracts comprise a range of products that share two basic traits: they are made by applying a solvent to cannabis flower to isolate and remove the active compounds, and they are almost always more potent than cannabis flower alone. Various solvents are used in the extraction process, with the most common being CO2 , alcohol, and butane. Cannabis extracts can be broken down into the following product categories, all of which are available at most dispensaries:

• Tincture - These are made by infusing cannabis flower into food-grade oil or alcohol. The resulting liquid can be ingested orally, oromucosally, or sublingually. Tinctures are typically reserved for medicinal or wellness purposes because they are potent and relatively simple to dose. Tinctures are rarely marketed as recreational products.

• Rick Simpson Oil (RSO) (aka Phoenix Tears, Organic Cannabis Oil (OCO), Full Extract Cannabis Oil (FECO)) - RSO is a concentrated form of cannabis extract made using grain alcohol as the solvent. Cannabis flower is infused in the alcohol at a low temperature, the flower is then removed, and the alcohol is evaporated. The residual plant waxes and oils are rich in cannabinoids. RSO is incredibly viscous, similar in texture to cold molasses. This extract is generally ingested orally and, like tinctures, is typically reserved for medicinal or wellness purposes.

• Cartridge - Cartridges are an increasingly common way to consume cannabis oil via vaporization. They work by attaching a small, extract-filled container (the cartridge) to a battery with a heating element. The cartridges themselves are often made of glass, metal, or plastic and use cotton or fiberglass as wicking material. The wick allows the extract to come into close proximity to the heating element. The resulting atomized oil is inhaled. Cartridges are popular because they are fast acting, portable, and avoid combustion.

• Dabs (aka shatter, wax, resin) - Concentrated cannabis extracts made by using CO2 , butane, propane, or a combination of these solvents to separate the active oils and waxes in flower from the plant matter. This ideally happens in a closed loop system where the solvents are completely reclaimed after extraction. The remaining plant waxes and oils are then hardened and agitated in a variety of ways resulting in many different textures. There are many terms used to describe the different textures of dabs, and they are often used as the main descriptor of the product (e.g. shatter, wax, resin). Dabs are typically consumed by placing a small amount of the concentrate on a very hot ‘nail’ in a ‘dab rig’ that looks very much like a bong. This process is referred to as “dabbing,” and due to the highly concentrated nature of the product consumed this method is not recommended for novice cannabis users. • Hash, bubble hash, dry sift, kief - These are forms of cannabis concentrate made by separating trichomes from the plant material using water, friction and/ or pressurized heat. Trichomes contain the majority of the cannabinoid content in cannabis plants. They are very delicate, and relatively easy to remove. There are many techniques used to separate and collect the trichomes from the flower, and each of these methods has a different name. Hash is a catch-all phrase for most of these types of extracts. Bubble hash utilizes ice and a series of progressively finer filters to separate the trichomes from the flower.Dry sift is made by agitating the cannabis flower to separate and then collect the trichomes from the plant material. Kief generally refers to the trichomes and plant particles that accumulate as the excess leaves are trimmed away from the cannabis flower in a process known as trimming. Rosin is made by heating and pressing hash or kief into a more solid form, or by pressing and gently heating dried or fresh cannabis flower to express the oil directly.

MEDICAL vs. RECREATIONAL CANNABIS:

There are two differences between ‘medical’ and ‘recreational’ cannabis: the legal distinction, and the type of consumer involved. Many states differentiate between consumers using cannabis medicinally and those using recreationally by creating a seperate medical program. Admission to medical programs allows for the use of cannabis by people with a qualifying condition, as defined by individual states. In states where medical and recreational programs coexist, medical programs are often distinguished by the lack of sales tax incorporated into the final cost of the cannabis product.

Cannabis that one consumer uses recreationally may be used medically by another consumer, there is no difference in the product itself. Nor is dosage a determining factor in types of usage. Quantities ingested by both types of consumer can vary greatly.

METHODS OF ADMINISTRATION19

Inhalation – Effects from inhaled cannabis are generally felt within a few minutes of inhalation and last around two hours. • Combustion – flower from the cannabis plant is most frequently consumed via smoking. There are several methods used to smoke cannabis, including cannabis cigarettes (aka joints, pre-rolls); glass, wooden, or ceramic pipes (aka bowls, chillums, one hitters, spoon pipes); and glass water pipes (aka bongs). Each of these methods requires breaking up or grinding cannabis flower into smaller pieces to maximize the surface area. Ceramic water pipe / bong • Vaporization – the different forms of vaporization are frequently shortened to ‘vaping’ in conversation. Clarification is necessary to determine which form the user is referring to. • Dry-herb vaporization – A method of consumption wherein dried cannabis flower is placed into a device. The heat sublimates the active compounds in the flower and the resulting vapor is inhaled. There are a number of different types of heating mechanisms, inhalation methods, and form factors for vaporizers. • Oil “vaporization” – A method of consuming concentrated cannabis extract. The extract is placed into a cartridge containing a wick and atomizer (see “cartridge” above). The cartridge is then attached to a battery, often pen shaped, that powers the atomizer and heats the oil, atomizing the cannabis extract as it is inhaled. This method of consumption is often referred to as ‘vaping,’ though it is more accurately termed oil atomization. A vape pen utilizes the same technology as an e-cigarette.

Oral Ingestion – A method of consumption where an activated form of cannabis is consumed orally, often after incorporation into a food product. Oral ingestion takes 1-4 hours to take effect, and the effects are generally felt for 6-8 hours. Chocolate, baked goods, candy, and beverages are all made into edible cannabis products (see “edibles” above). Edibles are generally made by incorporating a form of cannabis concentrate

(CO2 , BHO, or oil/butter infusion) into the food product while being prepared. There are strict laws governing the potency and consistency of cannabis products sold in legal cannabis markets.

Sublingual /Oromucosal – Tinctures and oral sprays are the most common products in this category. Generally, cannabis is infused into an oil or alcohol base to create a tincture (see “tincture” above), and that tincture can be administered sublingually as a liquid, or sprayed into the mouth for oromucosal administration.

Transdermal – The highly lipophilic nature of cannabinoids, as well as their relatively small molecular size, allows for transdermal administration. Although cannabinoids are typically unable to pass through the skin into the bloodstream, the addition of carrier compounds, such as long-chain polymers or fatty acids, may allow their passage.20

Topical – Topical cannabis products (see “topicals” above) are non-intoxicating and similar in concept to herbal muscle rubs. THC and CBD have both been shown to have anti-inflammatory effects at the skin level.21

Rectal / Vaginal – Cannabis suppositories are currently on the market in several states. There is very little research to date on their efficacy or bioavailability. REFERENCES

1 Russo, E. (2007), History of Cannabis and Its Preparations in Saga, Science, and Sobriquet. Chemistry & Biodiversity, 4: 1614-1648. doi:10.1002/ cbdv.200790144 2 Hazekamp, A. and Fischedick, J. T. (2012), Cannabis ‐ from cultivar to chemovar. Drug Test. Analysis, 4: 660-667. doi:10.1002/dta.407 3 “History of Cannabis Taxonomy.” Cannabis: Evolution and Ethnobotany, by Robert Connell Clarke and Mark David Merlin, University of California Press, 2016, pp. 314–320. 4 Cascio, M. G., & Pertwee, R. G. (2014). Known pharmacological actions of nine non- psychotropic phytocannabinoids. In R. G. Pertwee (Ed.), Handbook of cannabis (pp. 137–156). Oxford, UK: Oxford University Press. http://doi.org/10.1093/acprof:oso/9780199662685.003.0007 5 Ethan B. Russo, Jahan Marcu, Chapter Three - Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads, Advances in Pharmacology, Academic Press,Volume 80,2017,Pages 67-134, doi.org/10.1016/bs.apha.2017.03.004. 6 Alexandre R. de Mello Schier, Natalia P. de Oliveira Ribeiro, Danielle S. Coutinho, Sergio Machado, Oscar Arias-Carrion, Jose A. Crippa, Antonio W. Zuardi, Antonio E. Nardi and Adriana C. Silva. CNS & Neurological Disorders - Drug Targets (2014) 13: 953. https://doi.org/10.2174/187152 7313666140612114838 7 Devinsky O, Cross JH, Laux L, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med 2017;376:2011-2020 8 Riedel G, Fadda P, McKillop-Smith S, Pertwee RG, Platt B, Robinson L. Synthetic and plant-derived cannabinoid receptor antagonists show hypophagic properties in fasted and non-fasted mice. British Journal of Pharmacology. 2009;156(7):1154-1166. doi:10.1111/j.1476- 5381.2008.00107.x. 9 Tudge L, Williams C, Cowen PJ, McCabe C. Neural Effects of Cannabinoid CB1 Neutral Antagonist Tetrahydrocannabivarin on Food Reward and Aversion in Healthy Volunteers. International Journal of Neuropsychopharmacology. 2015;18(6):pyu094. doi:10.1093/ijnp/pyu094. 10 Jadoon, Khalid & Ratcliffe, Stuart & A. Barrett, David & Thomas, Elizabeth & Stott, Colin & Bell, Jimmy & O'Sullivan, Saoirse & D. Tan, Garry. (2016). Efficacy and Safety of Cannabidiol and Tetrahydrocannabivarin on Glycemic and Lipid Parameters in Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Pilot Study. Diabetes Care. 39. dc160650. 10.2337/dc16-0650 11 Russo, E. B. (2011), Taming THC: potential cannabis synergy and phytocannabinoid‐terpenoid entourage effects. British Journal of Pharmacology, 163: 1344-1364. doi:10.1111/j.1476-5381.2011.01238.x 12 Hazekamp, A. and Fischedick, J. T. (2012), Cannabis ‐ from cultivar to chemovar. Drug Test. Analysis, 4: 660-667. doi:10.1002/dta.407 13 Hazekamp A, Tejkalova K, Papadimitriou S (2016), Cannabis: from cultivar to chemovar II—a metabolomics approach to cannabis classification. Cannabis and Cannabinoid Research 1: 202–215. DOI: 10.1089/can.2016.0017. 14 Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British Journal of Pharmacology. 2011;163(7):1344-1364. doi:10.1111/j.1476-5381.2011.01238.x. 15 Meiri, D. (2018, August 28). The Science Behind the Entourage Effect. Keynote. Presented at the Cannabis Science Conference, Portland, OR. 16 Pertwee R.G. (2015). Endocannabinoids. Handbook of Experimental Pharmacology, vol 231. Springer, Cham 17 Lee, Martin. “The Discovery of the Endocannabinoid System.” O'Shaughnessy's, 2012, www.beyondthc.com. 18 Angelo A. Izzo, Francesca Borrelli, Raffaele Capasso, Vincenzo Di Marzo, Raphael Mechoulam, Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb, Trends in Pharmacological Sciences, Volume 30, Issue 10, 2009, Pages 515-527,ISSN 0165-6147, https://doi.org/10.1016/j.tips.2009.07.006. 19 Grotenhermen, F. Clin Pharmacokinet (2003) 42: 327. https://doi.org 10.2165/00003088-200342040-00003 20 Stinchcomb, A. L., Valiveti, S. , Hammell, D. C. and Ramsey, D. R. (2004), Human skin permeation of Δ8‐tetrahydrocannabinol, cannabidiol and cannabinol. Journal of Pharmacy and Pharmacology, 56: 291-297. doi:10.1211/0022357022791 21 Tubaro, Aurelia & Giangaspero, Anna & Sosa, Silvio & Roberto, Negri & Grassi, Gianpaolo & Casano, Salvatore & Della Loggia, Roberto & Appendino, Giovanni. (2010). Comparative topical anti-inflammatory activity of cannabinoids and cannabivarins. Fitoterapia. 81. 816-9. 10.1016/j. fitote.2010.04.009. © Farma on Hawthorne, Inc., 2018 Do not operate a vehicle or machinery under the influence of this drug. For use only by adults twenty one years of age and older. Keep out of the reach of children.