WO2019173242A1 - Enhanced smokable cannabis-based therapeutic product for treatment of sleep disorders and chronic pain and method for making same - Google Patents

Abstract

A cannabis-based therapeutic product for treatment of sleep disorders produced (a) harvesting flowers and leaves from a plurality of cannabis plants from a plurality of cannabis strains each expressing a different active cannabis compound profile; (b) individually extracting cannabis oil from the harvested flowers and leaves of each of the cannabis strains; (c) concentrating the extracted cannabis oils by at least evaporating extraneous material; and (d) combining specific amounts of the concentrated oils from one or more cannabis strains to produce a mixture possessing a specific active cannabis compound profile.

Description

ENHANCED SMOKABLE CANNABIS-BASED THERAPEUTIC PRODUCT

FOR TREATMENT OF SLEEP DISORDERS AND CHRONIC PAIN AND

METHOD FOR MAKING SAME

CROSS-REFERENCE TO RELATED APPLICATIONS

[001] This application is a PCI' filing of, and claims priority to, United States patent application number 15/954,536, tided,“CANNABIS-BASED THERAPEUTIC PRODUCT FOR

TREATMENT OF SLEEP DISORDERS”, and filed on April 16, 2018, which claims the benefit of and priority to United States provisional patent application serial number 62/638,204, tided “CANNABIS BASED THERAPEUTIC PRODUCT FOR TREATMENT OF SLEEP

DISORDERS”, and filed on March 4, 2018, the entire specification of each of which is incorporated herein by reference in its entirety.

[002] This application is also a PCT filing of, and claims priority to, United States patent application number 15/952,875, tided,“CANNABIS-BASED THERAPEUTIC PRODUCT FOR TREATMENT OF CHRONIC PAIN”, and filed on April 13, 2018, now issued as United States patent number 10,206,888 on E'ebruaiy 19, 2019, which claims the benefit of and priority to United States provisional patent application serial number 62/638,238, tided“CANNABIS- BASED THERAPEUTIC PRODUCT FOR TREATMENT OF CHRONIC PAIN”, and filed on

March 4, 2018, the entire specification of each of which is incorporated herein by reference in its entirety.

[003] This application is also a PCT filing of, and claims priority to, United States patent application number 15/951,154, tided,“ENHANCED SMOKABLE THERAPEUTIC

CANNABIS PRODUCT AND METHOD FOR MAKING SAME”, and filed on April 11, 2018, now issued as United States patent number 10,172,897 on January 8, 2019, which claims the benefit of and priority to United States provisional patent application serial number 62/638,232, tided“ENHANCED SMOKABLE THERAPEUTIC CANNABIS PRODUCT AND METHOD

FOR MAKING SAME”, and filed on March 4, 2018, the entire specification of each of which is incorporated herein by reference in its entirety.

BACKGROUND OF THE INVENTION Field of the Invention

[004] The present invention is in the field of cannabis active compound formulation for medicinal application. Specifically, the use of formulations containing cannabis-Amved compounds as medical treatments for sleep disorders and chronic pain.

[005] The present invention is in the field of therapeutic uses of the cannabis plant, and more specifically the field of therapeutic smokable products derived from cannabis .

Discussion of the State of the Art

[006] Recently, multiple states have passed legislation legalizing cannabis for medical usage. TTiis change promises to gready increase not only the market for cannabis, but also the research into further medicinally important effects of cannabis compounds, and die discovery of ways to optimize die effects of known and newly discovered cannabis compounds for medical use. Many forms of therapeutic products based on the cannabis plant are known in the art, but smokable products remain a major category. Unfortunately, smokable cannabis products are difficult to use for dierapeutic. purposes, as their chemical content varies widely based on the plant strains and plant parts used. Additionally, smokable cannabis products often present a harsh affect and poor taste.

[007] A number of medical studies have been performed providing significant evidence of the medical benefits of cannabis compounds as treatments for sleep disorders. However, no cannabis compound is currently formulated and processed for therapies for sleep disorders caused by a wide range of fiictors. What is needed is a product that provides these cannabis compounds in a form suitable for use as medications and therapies for sleep disorders caused by a wide range of factors, such as pain, sleep apnea, restless leg syndrome, nightmares, parasomnia, and post- traumatic stress disorder (PTSD).

[008] There is a large body of anecdotal evidence that cannabis, particularly smoked cannabis plant matter, provides substantial relief from chronic pain caused by numerous chronic health conditions such as cancer, multiple sclerosis, arthritis, nerve damage, back pain, fibromyalgia, and similar conditions. These conditions are often resistant to standard treatments, even treatment with opioid medications such as morphine. A substantial body of medical literature supports die anecdotal evidence tiiat cannabis compounds can provide relief from chronic, pain. However, of the several cannabis based products on the market (ajulemic acid, Cannador^®, Marinol^®, Cesamet^®) that have been studied for their use in treatment of pain, most were developed to treat other symptoms of chronic illness, and most have exhibited modest pain relief, at best One product, Sativex®, is a cannabis- derived oromucosal spray containing equal portions of THC and CBD which has been shown in dinical studies to provide relief from chronic pain. Tt was approved in Canada in 2005 for treatment of central neuropathic pain in multiple sclerosis, and in 2007 for intractable cancer pain. However, there are many other medical conditions for which cannabis- based products may be useful in treating chronic pain.

[009] What is needed is a product that provides these cannabis compounds in a form suitable for use as medications and therapies for pain, especially pain caused by chronic conditions such as cancer, multiple sclerosis, arthritis, nerve damage, back pain, fibromyalgia, and similar conditions, and especially where such pain is resultant to standard forms of treatment.

[010] What is needed is an enhanced smokable therapeutic, cannabis product that alleviates these shortcomings.

[011] SUMMARY OF THE INVENTION

[012] Accordingly, the inventor has conceived and reduced to practice, in a preferred embodiment, a plurality of formulations for cannabinoid medical and therapeutic benefits. The cannabinoid, terpene, and !lavonoid formulations used according to aspects of the invention are intended to mitigate at least one medical issue. For example, the cannabinoid Δ-9- tetrahydrocannabinol (THC) is known to have sedative effects, winch may enhance sleep and alleviate some forms of sleep disorder. As another example, the cannabinoid (CBN) has also demonstrated very potent sedative characteristics.

[013] Accordingly, the inventor has conceived and reduced to practice, in a preferred embodiment a plurality of formulations for cannabinoid medical and dierapeutic benefits. The cannabinoid, terpene, and llavonoid formulations used according to aspects of the invention are intended to mitigate at least one medical issue. For example, the tw¾ main cannabinoids in the cannabis plant Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are known to have analgesic effects by themselves, and may also serve to complement the pain-reliving effects of opioid medications commonly used as a treatment for chronic pain. As another example, the terpene myrcene has analgesic effects, and also increases the permeability of the blood-brain- barrier to other terpenes, cannabinoids, and flavonoids which raises the saturation level of at least one caimabmoid receptor, such as CB1, within tlie human body. Various formulations of cannabinoids, terpenoids, and flavonoids could be tailored to produce the desired pain-relieving effects for various classes of chronic pain, and may also provide additional benefits such as control of inflammation, which further reduces chronic pain and discomfort

[014] According to a preferred embodiment, the formulation is compounded into a pill or tablet form, or in a sublingual spray, and is administered orally.

[015] In one aspect of the invention, a method of preparing a cannabis-based therapeutic product for the treatment of sleep disorders is provided, the method comprising the steps of: (a) harvesting flowers and leaves from a plurality of cannabis plants from a plurality of cannabis strains each expressing a different active cannabis compound profile using shears; (b) individually extracting cannabis oil from the harvested flowers and leaves of each of the cannabis strains; (c) concentrating the extracted cannabis oils by at least evaporating extraneous material; and (d) combining specific amounts of the concentrated oils from one or more cannabis strains to produce a mixture possessing a specific active cannabis compound profile comprising at least 5% by weight purified cannahinol using a mixing device, wherein the one or more cannabis strains expresses known concentrations of a plurality of active cannabis compounds, the known concentrations being determined using an extract from eadi cultivar and expressed as a ratio of weight-of-compound per weight-of-extract

[016] In another embodiment, the method further comprises the step of enriching the product with a formulation comprising at least 1% by weight purified β-myrcene, prior to processing into a final product hi another embodiment, the method further comprises the step of combining medium-chain triglycerides oils infused with cannabisba&ed compounds to the concentrated extracted oils, prior to processing into a final product In another embodiment, the method further comprises adding cannabis compounds chosen from a set comprising myrcene, a pinene, ocimene, terpineol, betacatyophyllene, linalooL limonene, terpinolene, valencene, geraniol, phellandrene, carene, terpinene, fenchol, bomeol, bisabolol, phytol, camphene, sabinene, camphor, isobomeol, menthol, cedrene, nerolidol, guaiol, isopulegol, geranyl, cymene, and eucalyptol.

[017] Accordingly, the inventor has conceived and reduced to practice, in a preferred aspect, an enhanced smokable therapeutic cannabis product and method for making same. Tire cannabinoid, terpene, and flavonoid formulations used in enhanced smokable cannabis products according to aspects of the invention are intended to mitigate at least one medical issue. For example, the terpene myrcene increases the permeability of the blood-brain-banier to other terpenes, cannabinoids, and flavonoids which raises the saturation level of at least one cannabinoid receptor, such as CB1, within the human body. In another example, medium chain triglyceride (MCT) oil is mixed with oils using a formulation of the invention,

and the combined oil sprayed on cannabis plant matter. Advantageously, such oil-sprayed plant matter, when smoked, has improved taste and gives a more even bum, while also providing more of a desired therapeutic effect In an aspect, dried cannabis plant matter prepared in this way may be wrapped into a conical smokable product.

[018] 'Ilie inventors have discovered, in particular, that using the methods described herein rather than, as is commonly done in the art, infusing smokable plant material directly with hash resin, provides a superior product that tastes better, smokes more smoothly, and has predictable therapeutic effects (which may in fact be varied, according to aspects of the invention, by varying the cannabinoid profile of the oil used to spray plant matter as described herein).

[019] According to a preferred aspect, an enhanced smokable cannabis-based product is produced by separating hash resin from plant material of the cannabis plant, pressing the hash resin to expel oil, leaving spent hash resin, extracting further cannabinoids from the spent hash resin using MCT oil, enriching the extracted oil with a formulation comprising at least purified β- myrcene, and spraying the enriched oil onto dried smokable cannabis plant matter.

BRIEF DESCRIPTION OF FIGURES

[020] The accompanying drawings illustrate several embodiments and, together with the description, serve to explain the principles of the invention according to the embodiments. It will be appreciated by one skilled in the art that the particular embodiments illustrated in the drawings are merely exemplary, and are not to be considered as limiting of the scope of the invention or the claims herein in any way.

[021] Fig. 1 is a method diagram illustrating a process for preparing cannabis medicinal products, according to an embodiment [022] Fig 2 is a metiiod diagram illustrating a process for preparing an enhanced smokable therapeutic cannabis product using hash resin, according to a preferred embodiment

[023] Fig. 3 is a metiiod diagram illustrating a process for preparing an enhanced smokable therapeutic cannabis product using hash resin, according to a preferred aspect

[024] Fig. 4 is a metiiod diagram illustrating a process for preparing an enhanced smokable therapeutic cannabis product using whole plant matter, according to an aspect

DETAILED DESCRIPTION

[025] The inventor lias conceived, and reduced to practice, according to a preferred aspect, an enhanced smokable therapeutic cannabis product and method for making same.

[026] Headings of sections provided in this patent application and the title of this patent application are for convenience only, and are not to be taken as limiting the disclosure in any^¬ way.

[027] Cannabis has been extensively cultivated throughout the world for centuries. Worldwide effects-targeted cultivation has progressed to the point where there are hundreds, if not thousands, of cultivars or strains which contain differing levels of the many active compounds that give cannabis its wide range of sought-after medical effects. One family of active compounds that are specific to cannabis is the cannabinoid family, of which more than 80 have been identified that may have overlapping but different medical effect profiles. These have been further separated into subclasses comprising tetrahydrocannabinols (THC); cannabidiols (CBD); cannabichromenes (CBC); cannabinol (CBN); cannabigerols (CBG); cannabinodiol (CBDL); and other cannabinoids (cannabicyclol (CBL), cannabielsoin (CBE), cannabitriol (CBT^ and other miscellaneous types.

[028] In raw cannabis, the cannabinoids within the flowers’ trichomes are carboxylated, meaning they have a COOH carboxylic, acid group in their structure. These are mildly, if at all, psychoactive. In order for there to be psychoactivity the cannabinoids must be decarboxylated, or“decafbed” in layman’s terms. Non-psychoactive THCA, for example, is decarboxylated to THC, a psychoactive cannabinoid. Both drying (or aging) and heat accomplish this chemical reaction, but the application of heat also results in the loss of certain other cannabis components such as the terpenes, which are highly volatile. Both the decarboxylated cannabinoids and the carboxylated cannabinoids exhibit important tiierapeutic effects for health, and although one can be chemically converted into the other, carboxylated cannabinoids becoming decarboxylated cannabinoids, As used herein both will be referred to as simply cannabinoids.

[029] T¾e biological effects of the cannabinoids may be mediated through two receptors specific for a class of endogenous cell signaling molecules, such as but not limited to N- arachidonoylethanolamine also known as AEA or anandamide, a neurolransmitter that predominantly binds to the cannabinoid receptor CB1 and a second compound, 2- arachidonoylglycerol also known as 2-AG which predominantly binds to the CB2 receptor. Expression of the CB1 receptor is foimd at highest levels in the central nervous system of humans and animals, particularly in the hippocampus, basal ganglia, neocortex, and spine (although expression in peripheral organs such as but not limited to the peripheral nervous system, liver, intestines, and kidneys is also present). Activation of the CB1 receptor has been linked to feelings of euphoria and an increase in appetite, among other effects. Expression of the CB2 receptor is found in the central and peripheral nervous system, die immune system and immune response- related cells, and peripheral organs, among other areas of expression. Activation of the CB2 receptor may have an analgesic effect, reduce inflammation, and increase of immune response towards certain pathogenic bacteria and fiingi. The CB2 receptor may also mediate anti-cancer effects attributed to cannabinoids. Most recently, in relation to the CB2 receptor, it has been determined that different ligand agonists may specifically or predominantly activate specific receptor responses indicating a level of ligand functional selectivity for effects linked to the receptor.

[030] Other cannabinoid receptors are found in almost every organ of the body including the skin, die digestive tract, and even in the reproductive organs. Cannabinoid receptors interact with cells in a lock (the cell receptor) and key (the cannabinoid) type of mechanism. The combination of the cell receptors and the cannabinoids comprise the endocannabinoid system, or ECS, w'hich is an intricate network of cell receptor proteins that perform various functions in the body, and is considered to be the greatest neurotransmitter system in the body. Bearing this in mind, it becomes important to realize and understand how cannabis can have an impact on numerous health issues including, but not limited to, Alzheimer’s disease, memory loss, multiple sclerosis (MS) and other neurodegenerative diseases, and pain control and relief. [031] 'lire major differences between the various cannabinoids are determined by the extent to which they are psychologically active (psychoactive). Three substantial classes of cannabinoids, including the cannabigerols (CBGs), cannabichromenes (CBCs), and cannabidiols (CBDs), are not known to have psychoactive effects. Δ-9-tetrahydrocannabinol (THC), cannabinol (CBN), and some other cannabinoids are known to be psychoactive to varying degrees. Non-psychoactive CBD is likely the most abundant cannabinoid, contributing up to 40% of cannabis resin in some strains (particularly those referred to as hemp strains); CBD has also been implicated in lessening the psychoactive effects of THC.

[032] Of the over 80 known cannabinoid species, those most prevalent and most studied in cannabis cultivars are:

TTIC— Δ-9-tetrahydrocannabinol

CBD— cannabidiol

CBG---cannabichromene

CBN -cannabinol

CBG cannabigerol

THCv— tetrahydro cannabivarin

CBDv— cannabidivarin

Δ-8-THC Aetetrahydrocannabinol

THCA - A Otet rally drocaiinabinolic acid

CBDA— cannabidiolic acid

[033] A number of these 80-plus cannabinoids display a plurality of important medical effects. The subset of the aforementioned cannabinoids for which these medically beneficial effects are characterized and confirmed are presented here with their chemical formulae and structures.

[034] THC: As used herein, THC refers to Δ-9-tetrahydrocannabinol, the chemical formula for which is C¾iHao0₂ and the structure of which is:

[035] THC is recognized as the primary psychoactive compound in cannabis and is the most common cannabinoid. Along with its psychoactive properties, THC may be medically used to alleviate several types of pain including the nerve-related pain of diabetic neuropathy and multiple sclerosis. Additionally, THC may be effective in alleviation of the symptoms of FTSD and reduction of nausea and vomiting, particularly that caused by chemotherapy. It has been shown to aid those with anorexia, as well as cancer and HIV associated wasting syndrome as it is an appetite stimulant It improves breathing for asthmatics, acting as a potent bronchodilator, it relieves eye pressure in patients with glaucoma, improves insomnia, sleep apnea, and reduces nightmares. THC aids those with inflammatory bowel diseases such as Crohn’s disease, ulcerative colitis and leaky gut, as well as other intestinal diseases by decreasing intestinal permeability and strengthening intestinal tight junctions. THC slows and prevents Alzheimer’s disease and helps control seizures. 'IHC reduces pain and tremoi-s and improves sleep for those with Parkinson’s disease. THC, CBD, CBG, and CBC togedier work synergistically as a powerful cancer tumor- fighting combination. This combination is more powerful than any single one of these working alone.

[036] CBD: As used herein, CBD stands for cannabidiol, the chemical formula for which is C21H30O2 and the structure of which is:

[037] CBD, or cannabidiol, is a non-psychoactive member of die cannabinoids and is one of die most prevalent chemical compounds in the cannabis plant. Found predominandy in the resin glands of the female plant, this compound can stop muscle spasms and epileptic seizures, and can reduce idiopathic anxiety, a prevalent and significantiy debilitating aspect of mental illness. It is used to treat nicotine addiction, osteoporosis, diabetes, cancer, obsessive-compulsive disorder, Lupus, Parkinson’s disease, and motor disorders, and soothes neuropathic and chronic pain. It has anti-inflammatory, antioxidant, neuroprotectant, anxiolytic, antidepressant, analgesic, antitumor, and anti-psychotic effects. CBD is powerftd all by itself, but it is even more powerful when combined with other cannabinoids such as THC. [038] CBC: As used herein, CBC stands for cannabichromene, the chemical formula for which is C21H30O2 and the structure of which is:

[039] Cannabichromene, or CBC, is the third most prevalent cannabinoid in the marijuana plant in general. In some strains CBC is more prevalent than CBD, and like CBD it is non psychoactive.

[040] even more so when combined with TOC. It has anti-tumor effects and shows promise in fighting breast cancer. When combined with CBD, THC, and CBG, the cancer fighting effects are intensified. It may be useful as an antidepressant and may be more powerful than the other cannabinoids in this capacity. CBC shows antiviral and mild antifungal activity. While CBC addresses several other health issues, including inflammation, cancer, depression, and fungal infections, it also increases the number of brain cells and therefore is useful in the treatment of several brain related disorders. CBC promotes neurogenesis in individuals at any age. This not only affects memoty and learning, but can off-set certain dementias which occur when the brain stops growing new' cells. It is likely that CBC can alleviate to some extent certain forms of depression and neuro-degenerative diseases via this particular mechanism of neurogenesis.

[041] CBN: As used herein, CBN stands for cannabinol, the chemical formula for which is CaiHaeOa and the structure of which is:

[042] Cannabinol, or CBN, emerges when the dried cannabis flower becomes stale; over time, TOC and CBD, which are generated by enzymatically-driven synthesis from CBG, break down through oxidative degeneration into CBN. CBN has antibiotic properties, including against methicillin -resistant Staphylococcus aureus (MRSA), and also has pain-relieving properties through die release of endoiphins. It may delay the onset of, and reheve symptoms of, degenerative motor neural diseases such as amyotrophic lateral sclerosis (ALS) and MS. It works as an appetite stimulant and is more powerful than CBD and CBG in this regard. It has been found to have potent sedative characteristics, making it possibly the most potent single sedative of all the cannabinoids. When combined with THC, CBN has also been found to be effective at lowering the ocular pressure which produces blindness in glaucoma patients. CBN also promises to be useful in future for lowering blood pressure overall

[043] CBG: As used herein, CBG stands for cannabigerol the chemical formula for which is C₂₁H₃₂O₂ and the structure of which is:

[044] CBG, or cannabigerol, is found in cannabis early in the growth cycle, making it somewhat difficult to find in large quantities (CBG is synthesized from smaller constituents, and serves as the feedstock for enzymatic synthesis of THC, CBD, and other cannabinoids, and so CBG is regarded as the source of all cannabinoids. It is non-psychoactive and can also be cultivated in hemp, in which it occurs in greater quantities. CBG has antibiotic properties stronger than CBN and comparable to CBD and is effective against various types of bacteria and fungi. It has therapeutic potential for skin conditions like psoriasis and eczema. CBG is reportedly a more potent pain reliever than THC, and functions as an antidepressant and mood-stabilizer by preventing the uptake of GABA and by increasing serotonin levels in the brain.

[045] THCV : As used herein, THCV stands for tetrahydrocannabivarin, the chemical formula for which is and the structure of which is:

[046] THCV, or tetrahydrocannabivarin, is one of the several cannabinoids that works in synergy with THC, and mitigates some of the negative psychoactive impacts of THC. THCV’s medical uses are antiepileptic, anticonvulsant, and anti-seizure; it is neuroprotective and mitigates some of die short-term memory and speech impairment that comes from THC; it promotes weight loss by suppressing the appetite and possibH' decreasing body fat and boosting energy metabolism.

[047] CBDV: As used herein, CBDV stands for cannabidivarin, the chemical formula for which is CiyHhbOa and the structure of which is:

[048] Cannabidivarin, or CBDV, is a slightly-degraded close relative of CBD. It hi used as an anticonvulsant, an antiepileptic, and has antiemetic properties (as well as aiding those with gastrointestinal issues).

[049] Δ-β-THC: As used herein, Δ-8-THC stands for Δ-8-tetrahydrocannabinol, the chemical formula for which is C21II30O2 and the structure of which is:

[050] Δ-8-tetrahydrocannabinol is different from Δ-9-tetrahydrocannabinol in that it is less psychoactive. It has both neuroprotective and anti-anxiety properties, as well as being anti-emetic, and may be a stronger appetite stimulant tiian Δ-9-THC, making it an important consideration for people undergoing chemotherapy. [051] THCA: As used herein, THCA stands for Δ-9-tetrahydrocannabinolic acid, the chemical formula for which is C22H30O4 and the structure of which is:

[052] Δ-9-tetralrydrocannabinolic add, or THCA, is a non-psychoactive compound found in cannabis prior to decarboxylation to the psychoactive version, THC, by application of heat or drying or both. THCA levels are particularly high in the live or freshly harvested plant, but as the plant dries, THCA slowly converts to THC, a process expedited by smoking or vaping. Because THCA readily converts to the psychoactive THC upon heat application such as smoking or vaping, it cannot be inhaled or absorbed into the body by these particular means. THCA shows anti-inflammatory properties and may thus be used in treatment of arthritis and lupus. Its neuroprotective properties may make THCA a candidate for treatment of neurodegenerative diseases; its anti-emetic properties making it a possible treatment for nausea and appetite loss, and its antiproliferative properties making it a candidate in treatment in certain cancers such as but not limited to prostate cancer. [053] CBDA As used herein, CBDA stands for cannabidiolic acid, the chemical fonnula for which is Cz>H$iOi and ihe structure of which is:

-

[054] Cannabidiolic acid, or CBDA cannot administered by smoking or vaporizing because doing so decarboxylates it to CBD, similar to THCA conversion to THC. Ihe therapeutic uses for CBDA include antibacterial, anti -emetic, anti-inflammatory', and cancer cell anti -proliferative.

[055] Another family of active compounds present in, but not exclusive to, cannabis are the terpenes and decarboxylated terpenes, which are known as terpenoids. Decarboxylation occurs with the removal of the COOH functional group, and can be seen in drawings of the structures. These two terms are commonly used interchangeably, and although they are not chemically identical in structure or chemical formula as terpenoids are decarboxylated versions of some terpenes and exist in plants in this decarboxylated form, for the purposes of this invention both will be referred to as simply terpenes. Though cannabis contains up to 200 different terpenes and terpenoids, there are approximately 10 primary terpenes and 20 secondary terpenes that occur naturally in significant concentrations in tire cannabis plant

[056] Terpenes are vital components of cannabis, and are important medicinally active compounds that are found in up to 1.5% of the total extraction. They are a large and diverse dass of organic compounds, produced by a wide variety of plants giving them their flavor, aroma, and color. Terpenes are die building blocks of a plant’s essential oils, and essential oils contain mixtures of the various terpenes found in the plants from which they were extracted.

[057] The isoprene skeleton (CsHa) may lie found in naturally occurring terpenes (also known as isoprenoids), but these terpene compounds do not arise from isoprene itself Terpenes may be thought of as multiples of isoprene subunits, which is the cornerstone of the“isoprene rule” for terpenes.

[058] The ten primary terpenes and twenty secondary terpenes that occur in significant concentrations are as follows:

[05Θ] The primary terpenes are: myrcene, α-pinene, ocimene, terpineol, β -caryophyllene, linalool, limonene, terpinolene, valencene, and geraniol.

[060] The secondary terpenes are: phellandrene, carene, terpinene, fenchol, bomeol, bisabolol, phytol, camphene, sabinene, camphor, isobomeol, menthol, cedrene, nerolidoL guaiol, isopulegol, geranyl acetate, cymene, eucalyptol, and pulegone.

[061] These terpenes have non-psychoactive therapeutic effects and may be safely used to treat a variety of health conditions. They may also be combined with each other and with

cannabinoids, yielding a whole new range of health effects. Some combinations of terpenes act in synergy with boosting effects, while others act as antagonists with effects that inhibit. Some terpenes increase the assimilation of THC, while others may affect the flow of dopamine and serotonin, two of the main regulators of mood and behavior. [062] Cannabinoid -terpenoid interactions have the potential to produce synergy with respect to the treatment of pain, inflammation, depression, anxiety, addiction, mood and behavior, epilepsy, cancer, fungal infections and bacterial infections, including MRSA.

[063] The primary and secondary terpenes with some of their medical actions are as follows:

[064] Myrcene— Myrcene, specifically β-myrcene, is a monoterpene and the most common terpene produced by cannabis (some varieties contain up to 60% (l-myrcene as a fraction of the total teipene content). A -myrcene is not found in nature, and was first synthesized in 1965. The chemical formula for β -myrcene is CioHie and the structure is:

[065] Myrcene is found in most varieties of cannabis as well as menthol, lemon grass, and hemp, and is widely used in the perfume industry'. Its aroma has been described as musky, earthy, and herbal.

[066] Myrcene has some very special medicinal properties, including lowering the resistance across the blood-brain barrier allowing itself and many other chemicals to cross the barrier more easily and quickly. Myrcene also increases cell membrane permeability, and in the case of cannabinoids like THC, β-myrcene allows the cannabinoid to take effect more quickly. More uniquely still, β-myrcene has been shown to increase the maximum saturation level of the CB1 receptor, allowing for a greater maximum psychoactive effect Myrcene has anti microbial and anti-septic, properties, and acts as a natural anti-depressant, anti-carcinogen and anti-inflammatory agent It is a potent analgesic, and is anti-mutagenic It blocks the action of cytochrome, aflatoxin B and other pro-mutagenic carcinogens. It acts as an inhibitor of gastric and duodenal ulcers. Its sedative and relaxing effects make it ideal for the treatment of insomnia and pain.

[067] α-Ptaene— Alpha-pinene is a monoterpene alkene isolated from pine needle oil as well as from cannabis . There are two strucdiral isomers of pinene found in nature: α-pinene and β- pinene, with α-pinene being the most widely encountered terpenoid in nature. With an aroma and flavor of pine, this is partially where pine trees get their scent. The chemical formula is CioHiti and tire structure is:

[068] Pinene is one of the principal monoterpenes that is important physiologically in both plants and animals. It tends to react with other chemicals, forming a variety of other teipenes (like limonene), as well as other compounds.

[069] Medicinally, tt-pinene has an anti-tumor effect and has shown anti-cancer activity. Alpha pinene is used as an anti-inflammatory, expectorant, bronchodilator, memory enhancer, as a local antiseptic, and it may decrease oil production in oily skin. It acts as a broad spectrum antibiotic and is highly effective against MRSA when combined with the cannabinoids CBD and CBN, all three working in synergy' with each other. Alpha-pinene increases alertness and counteracts some of die negative effects of the cannabinoids THC, such as anxiety. It is also believed that the negative memory effects of THC may be lessened if mixed with cc-pinene.

[070] Odmene- Odmene is a group of isomeric monoterpenes found in a wide variety of fruits, spices, and plants. Alpha-ocimene and the two β-odmenes, cis ^-ocimene and iians fi ocimene, differ in the position of the isolated double bond: in the alpha isomer it is terminal, β-ocimene exists in two stereoisomeric forms, cis and trans, with respect to the central double bond.

Ocimene is often found naturally as a mixture of its various forms. Hie chemical formula is CioHifi and the three structures are:

[071] oc-ocimene

[072] cis-P-odmene

[073] trans-P-ocimene

[074] Ocimene is recognized by its sweet, fragrant, herbaceous, and woodsy aromas, which feature prominently in several perfumes as well as flavorings, and which help plants defend themselves in their natural environment. Ocimene occurs naturally in botanicals as diverse as cannabis, mint, parsley, pepper, basil, mangoes, orchids, kumquats, and allspice.

[075] Ocimene’s potential medical benefits include: antiviral, antifungal, antiseptic, decongestant, and antibacterial.

[076] T erpineol— F o und in cannabis as well as in over 150 other plants, terpineol exists as four isomers: a-terpineol, β-terpineol, γ-terpineol and terpinen-4-ol, are four dosely related monoterpene alcohols. These are found mixed in plants and their essential oils, witli a-terpineol comprising the majority of the mixture. The chemical formula is CioHieO and die four structures are:

[077] Terpineol has a floral aroma, resembling lilacs, clove, citrus, or apple blossoms, and other than cannabis it also occurs naturally in lilacs, pine trees, lime blossoms, and eucalyptus, as well as contributing to the distinctive, pine smoke-based aroma of lapsang souchong tea. From a flavor perspective, terpineol tastes like mint and anise. Terpineol is most frequently found in cannabis strains which also contain high levels of α-pinene. Due to a-pinene’s strong aroma, terpineol may be difficult to detect by odor when the tw-o occur simultaneously as the scent of oc- pinene masks the more delicate floral scent of terpineol.

[078] Terpineol, specifically α-terpineol, is known to have calming, relaxing effects and is a mild sedative. Terpineol inhibits skin acne, acts as an antibiotic, anti-inflammatory, antioxidant and has anti-malaria properties. TeipineoPs most important property is its anti cancer property ' it is able to kill tumors directly.

[079] p-Caryophyllene ^ cary ophyllene is a bicyclic sesquiterpene with the formula CisH u and the structure:

[080] B-caryophyllene is found in many plants such as various cannabis strains, Thai basil, cloves, cinnamon leaves and black pepper, oregano, and other edible herbs; in minor quantities, it may be found in lavender as well as in many green, leafy vegetables. Its aroma has been described as peppery', woody spicy, and hoppy, as in hops used for brewing beer, to wtich cannabis is closely related.

[081] B-caryophyllene is the only terpene known to interact with the endocannabinoid system, and does so at the CB2 receptor, which does not produce a high (that is, the CB-2 receptor is not implicated in cannabis psychoactivity), β-caryophyilene selectively binds to the CB2 receptor where it is a functional CB2 agonist, giving it an anxiolytic and anti depressant effect and showing that β-caryophyllene may be useful in treating anxiety and depression. B-caryophyllene also has anti-oxidant, anti-inflammatory, anti-cancerous, and local anesthetic effects. Further, β- catyophyllene is unique for being both a terpene and a dietary caimabinoid, a food component which acts as a caimabinoid and binds to CB2 receptors.

[082] Other phytocannabinoids in combination, especially cannabidiol (CBD) and β- caryophyllene, when delivered orally, appear to be promising candidates for the treatment of chronic pain due to their high safety and low advene effects profiles.

[083] β-caryophyllene, through its CB2 receptor-dependent pathway, may be an excellent therapeutic agent to prevent nephrotoxicity (poisonous effect on the kidneys) caused by anticancer chemotherapy drugs such as cisplatm.

[084] β -caryophyllene has antioxidant and antinociceptive (blocks the sensor)' neuron detection of pain stimuli) properties. This suggests that high-caryophyllene strains may be useful in treating a number of medical issues such as arthritis and neuropathy pain. It is anti-inflammatory because of its ability to bind directly to the endocannabinoid receptor known as CB2. It is also protective of the cells lining the digestive tract which offers promise for treating some ulcers, and is antifungal. β-caryophyllene holds promise for cancer treatment

[085] Iinalool— Linalo ol is a terpene alcohol that occurs as two enantiomers d-linalool and 1- linalool, with the chemical formula CioHisO and the structures:

[086] Iinalool has a floral lavender aroma with a hint of spice. In addition to cannabis,

Iinalool may be found in an array of flowers and spice plants such as lavender, bay laurel, sweet basil, mint, cinnamon, citrus and even some fungi. Iinalool is a critical precursor in the formation of vitamin E.

[087] Iinalool may be used as an anti-inflammatory or as an immune booster, and may significantly reduce lung inflammation caused by cigarette smoke as well as reducing lung irritation potentially caused by inhaling cannabis smoke. Iinalool helps to restore cognitive and emotional function partially via its anti-inflammatory effect, and may therefore be used to treat various forms of dementia, and particularly Alzheimer’s disease. It helps with insomnia, and because it also lessens the anxiety brought on by pure TTIC, it helps in the treatment of anxiety and psychosis. Linalool has anesthetic effects and is calming, relaxing and mood lifting, and helps reduce headaches and migraines, Linalool may be useful to help treat liver cancer, and also helps to modulate motor movements, giving it anti-epileptic properties. It is an effective insecticide against fruit flies, fleas, and cockroaches, making it useful as an insect repellant and for use in and around the home and garden.

[088] Iimonene— Limonene is a monocyclic monoterpene and one of two major compounds formed from pinene. It exists as two enantiomers, d-limonene and 1-limonene, and has the chemical fonnula CioHie. The sinictiires are:

[089] Iimonene has a citnisy aroma and the more common d-isomer smells like oranges. While it is found in cannabis, it is also present in citrus fruit and especially lemons, juniper, and peppermint It assists in the absorption of other terpenes through the skin and other body tissues. Limonene has anti fungal, antibacterial, and anti-depressant effects; it promotes a general uplift in mood and attitude, and it helps promote weight-loss. It is a strong antioxidant and exerts anti- carcinogen properties as it may reduce tire formation of some tumor growths and alleviate fat buildup in tire liver induced by diet Limonene is known to increase blood pressure which is useful for those with low blood pressure. It has very tow toxicity and adverse effects are rarely associated with iL

[090] Terpinolene— Terpinolene, also called δ-terpinene (δ-terpinene), is one of a class of isomeric monoterpenes, all of which have the chemical fonnula CioHie, and which differ from each other only in the position of die carbon -carbon double bonds. Hie α-terpinene, y-tei-pinene, δ-terpinene (terpinolene) are all found in plant essential oils, whereas β-terpinene is synthetically prepared from sabinene. The chemical structures are:

[091] Terpinolene is characterized by a fresh, piney, floral, herbal, sometimes smoky or woody, and occasionally citrusy aroma and flavor. It is found in a variety of fragrant plants including cannabis, nutmeg, tea tree, conifers, citrus, apples, cumin, marjoram, sage, rosemary, Monterey cypress, and lilacs. It is used in soaps, perfumes, cosmetics, flavorings, and in the semiconductor industries.

[092] Terpinolene is a central nervous system depressant used to induce drowsiness or sleep or to reduce psychological excitement Tt has a sedative effect when inhaled, making it useful for insomnia and anxiety.

[093] Terpinolene markedly reduces the expression of the AKT1 gene, which produces the protein AKT1 kinase, an enzyme that plays a vital role in various important signaling pathways and cellular processes. AKT1 kinase helps regulate cell growth and division (proliferation), differentiation, cell survival, and apoptosis (cell death) when cells become damaged or are no longer needed. The AKT1 gene belongs to the class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous. The activation of AKT is connected with many types of cancers as it increases cell proliferation and suppresses apoptosis. By suppressing the AKT1 gene expression, both rampant cell proliferation and lack of apoptosis are suppressed, making terpinolene a valuable anti-cancer agent

[094] Terpinolene, together with vitamins A and E, prevents the oxidation of“bad cholesterol”

(low-density lipoprotein, or LDL) and is therefore helpful in the treatment of heart disease. [095] Terpinolene’s potential medical benefits include: antioxidant, sedative, antibacterial, antifungal, insect repellent, anti-proliferative (anti-cancer) and non-genotoxic, making it very safe and very healing.

[096] Valencene— Valencene is a bicyclic sesquiterpene with chemical formula C₁₅H₂₄ and is foimd in Valencia oranges as well as cannabis. The chemical structure is:

[097] It has a sweet, fresh, citrusy, woody, aroma and flavor and is used in both the flavor and perfume industries.

[098] Valencene is toxic to ticks and mosquitoes at lesser concentrations than DEBT and doesn’t have the toxicity of DEET. Valencene is an effective insect repellent for ticks, mosquitos, and other insects. It is also anti-inflammatory, and may lower the levels of inflammatory markers in macrophages.

[099] Geraniol— Geraniol is an acyclic monoterpene alcohol whose fonnula is CioHisO and which boils at about 447 'F and frequendy occurs in strains that also produce linalool. Not only from cannabis, geraniol is also found in rose, geranium, lime, lemon, lemongrass, nutmeg, bergamot, carrot, coriander, lavender, blueberry, blackberry, and tobacco. Geraniol emits a roselike scent that makes it a popular perfume additive. TTie chemical formula is:

[100] Geraniol is an effective mosquito repellent, an antioxidant, and shows a potential protective effect against neuropatiiy. It is anti cancer and inhibits the growth and biosynthesis of colon cancer cells, and when combined with famesol and perill alcohol, suppress pancreatic tumor growth making it especially useful for cancer of the pancreas which currendy is extremely difficult to cure. Secondary teipenes:

[101] Phdlaadrene - Phellandrene refers to a pair of cyclic monoterpenes that have a similar molecular structure and similar chemical properties, α-phellandrene and β-phellandrene, which are double-bond isomers of each other. In α-phellandrene, both double bonds are endocyclic (within the ring structure) and in β-phellandrene, one of them is exocyclic (external to the ring structure). Phellandrene has the chemical formula CioHi_b and is described as pleasant, fresh, citrus)', minty and peppery-woody. The chemical structures are:

α-phellandrene β -phellandrene

[102] Phellandrenes are used in the perfume and the flavoring industries because of their pleasing aromas and because they are absorbed through the skin, α-phellandrene may form dangerous, explosive peroxides on contact with air at elevated temperatures, β-phellandrene is non-hazardous, and both phellandrenes may be found in cannabis as well as in spices such as allspice, cinnamon, garlic, dill, pepper, parsley, and in the essential oils of angelica, eucalyptus, lavandula, mentha, fennel, ginger, and fiinus spedes.

[103] Insoluble in water but miscible with etiier, phellandrene is one of the easiest teipenes to identify in the lab. When a solution of phellandrene in a solvent (or an oil containing phellandrene) is treated with a concentrated solution of sodium nitrate and then with a few drops of glacial acetic acid, very large ciystals of phellandrene nitrate speedily form

[104] Phellandrene has special medicinal values and has been used in traditional Chinese medicine to treat digestive disorders. It is one of the main compounds in turmeric leaf oil, which is used to prevent and treat systemic fimgal infections. Phellandrene possesses antidepressant properties and is also used as an insecticide. [105J Carene -A3-Carene is a bicyclic monoterpene with a sweet, pungent odor. It is found naturally in cannabis and in many healthy, beneficial essential oils, including cypress oil, juniper berry oil and fir needle essential oils, and is a main constituent of pine and cedar resin. It is also present in bell pepper, basil oil, grapefruit and orangejuic.es, citrus peel oils from Emits like lemons, limes, mandarins, tangerines, oranges, kmnquats, and it is a major component of turpentine, comprising as high as 42% depending on die source. The chemical formula is CioHie and the chemical structure is:

[106] Δ-3-Carene is used as a flavoring in many products.

[107] It is nontoxic but may cause imitation when inhaled. It is possible that high

concentrations of δ-3-carene in some strains may be partly responsible for symptoms of coughing, itchy throat, and eye afflictions when smoking cannabis.

[106] Δ-3-carene is an effective anti-inflammatory. In higher than natural concentrations, 5-3- carene may be a central nervous system depressant and a skin irritant. It is often used to dry out excess body fluids, such as tears, runny noses, sweat, and menstrual flows.

[109] Terpinene— Terpinenes are a group of isomeric terpenes with die chemical formula CioHit, and diis group is composed of three natural isomeric terpenes and one synthetic one that differ from each other in the positions of die carbon to carbon double bond. A-terpinene, δ terpinene (terpinolene), and γ-terpinene are naturally occurring, whereas β-terpinene is not found in nature but may be synthetically produced from sabinene. Δ-terpinene is also called

terpinolene. The chemical structures are:

[110] Terpinene is a major component of essential oils made from citrus ftuils, and has a lemon odor. A-terpinene is widely used in the flavor, perfume, cosmetics, soap, pharmaceutical industries, as well as in food and confectionaiy.

[111] Terpinene is considered to be a well-tolerated additive in the pharmaceutical industry, and it has very strong antioxidant properties.

[112] Fenchol - Fenchoi, also called l,3,3 trimethyl-2-norbomanol, is a terpene and an isomer of bomeol with the chemical formula CioHieO and the chemical formula is:

[113] This particular terpene is an enantiomer, d-fenchol or (1 /Z)-endo-(+)-fenchol, but it has no mirror image foimd in nature, thus it is enantiopure.

[114] Found in cannabis, it also occurs naturally in basil, fennel, nutmeg, pine, rosemary oil, lime oil, beer and more. It lias a bitter, lime flavor and is used extensively in perfumes, flavorings, soaps, detergents, and personal care products. It is known to exhibit antibacterial properties. [115] Bomeol - Bomeol, a terpene alcohol, has tire chemical formula CioHiaO and exists naturally as two enantiomers, 1-bomeol and d-bomeol, both of which are found in nature. It is easily oxidized to camphor, has an aroma of camphor, mint, and earth, and is a component of many natural essential oils. It is found in cannabis resin and herbs like thyme, rosemary, and cinnamon. The chemical structure is:

[116] Bomeol is used in the perfume industry, as well as in dietary and herbal supplements in the USA.

[117] Bomeol is used as a calming sedative, it is used to fight fatigue, stress, to relax, and to recover from illness. Bomeol is used as an anti-inflammatory, an anti-nociceptive^/analgesic, a skin tonic, a local anesthetic, as an anti insomnia, anti-septic, a digestive aid, a sedative and an antispasmodic. It is used to improve circulation, to reduce pain and swelling, as a bronchodilator, a cough suppressant, and an insect repellanL

[118] Bisabolol - Also called levomenol, a-bisabolol is a natural monocyclic unsaturated sesquiterpene alcohol with the chemical formula CisHasO and a chemical structure of:

[119] A bisabolol is found in cannabis , the Brazilian shrub candeia, and German chamomile. It has a floral aroma.

[120] Abisabolol, which is nontoxic and nonirritating to the skin, possesses anti-inflammatory and wound healing properties, as well as antimycotic and antibacterial effects, and may be used as a deodorizer. It is a potent inhibitor of fungi, Candida albicans, and gram-positive bacteria. It shows promise in the treatment of certain cancers as it induces apoptosis in leukemia.

[121] Phytol— Phytol is a natural linear diterpene alcohol with the chemical formula C20H40O that may be used as a precursor to prepare synthetic forms of vitamin E and vitamin Kl. Foimd in cannabis and green tea, phytol results from the degradation of chlorophyll and is an oily liquid that is nearly insoluble in water, but soluble in most organic solvents. The chemical structure is:

[122] Phytol inhibits the enzyme that degrades the neurotransmitter GABA (y-aminobutyric acid), which may partially account for its relaxing effect In the body, phytol is essential in activating enzymes that have a positive effect on the production of insulin. It is beneficial in regulating blood glucose, for reducing blood pressure and for reducing cholesterol levels in blood.

[123] Camphene Cainph ene is a bicyclic monoterpene with the chemical formula CioHie and the chemical structure:

[124] Camphene readily volatilizes at room temperature and has a pungent odor similar to camphor. Tt is a minor component of many essential oils such as turpentine, cypress, neroli, valerian camphor, citronella and ginger. It is used as a flavoring for food, and in die perfume industry. It is produced industrially by cataly tic isomerization of die more common ot-pinene.

[125] Camphene is found in essential oils extracted from cannabis and certain trees, and it may play a critical role in cardiovascular health. Camphene possesses antioxidant, anti-inflammatory, and antibiotic characteristics, and shows promise for pain relief.

[126] Camphene may reduce plasma cholesterol and triglycerides. Given the importance this plays in heart disease, camphene might be used as an alternative to pharmaceutical drugs which cause intestinal problems, liver damage, and muscle inflammation. [127] Sabinene— Sabinene is a bicyclic monoterpene with the chemical formula CioHie, and exists as d and 1 enantiomers. The chemical structures are:

[128] It has an aroma of spice, pine, and orange, and is found in many plants including cannabis, Norway spruce, black pepper, basil, and Myristica fragrans—tiie. world’s main source of nutmeg. It is used in the perfume industry and in the food industry as a flavoring.

[129] Sabinene has antioxidant and anti-inflammatory properties, and benefits liver function, digestion, relieves arthritis, and may soothe skin conditions.

[130] Camphor---' Camphor is a w-axy, flammable, white crystalline solid with the chemical formula CioHieO. Camphor occurs naturally as d-camphor, the 1-enantiomer being synthetically produced.

[131] It is commonly found in cannabis, rosemary leaves, camphor basil, and in Cinnamomum campbora , which goes by several common names including camphor tree, camphorwood, and camphor laurel. Camphor is also found in kapur trees, and a few other related trees in the laurel family, notably Ocotea nsambarensis.

[132] The ancient Egyptians used camphor as one of the ingredients used for mummification. It has been used as an ingredient in sweet and savory foods in medieval Europe and Arabia.

Camphor is readily absorbed through the skin, and when applied topically produces a cooling sensation similar to that of menthol. It acts as a slight local anesthetic, relieves pain, itching and swelling, and has antimicrobial properties. It is used as a cough suppressant, a decongestant, an insect repellant notably for cockroaches and fleas, and is used to make mothballs. Camphor has been used to treat sprains, swellings, inflammation, and fevers. In very small quantities taken internally, it is used to treat minor heart symptoms and fatigue. Camphor increases heart rate, is a skin vasodilator, and reduces appetite.

[133] Isobomeol— Isobomeol is a bicyclic terpene alcohol with the chemical formula CIOHIHO and the chemical structure:

[134] Isobomeol is a waxy solid with an odor similar to that of camphor, and is found in cannabis and mugworL Isobomeol exhibits antiviral properties and is a potent inhibitor of herpes simplex vims type 1. Besides being antiviral, it also has antioxidant, anti-inflammatoiy, and antimicrobial properties.

[135] Menthol -Menthol is a terpene alcohol with the chemical formula CioHaoO and the chemical structure:

[136] Menthol is found in cannabis and in members of the mint family such as com mint and peppermint Menthol is a white or colorless crystalline solid at room temperature. It is used in candies, cigarettes, cosmetics, personal care products, and medicines.

[137] Menthol produces a cooling sensation on the skin and soft tissues of the mouth by activating the TRPM8 receptor protein that senses the change in temperature in cold-sensing nerves. However, menthol gives a cool sensation without any actual fall in temperature in that area. This lowers inflammation in the area, causing the nearby blood vessels to dilate, and increases blood flow to the area which delivers fresh nutrients to repair the area and removes any toxic wastes generated. This process speeds healing. Menthol may also bind to another receptor called kappa opioid receptor that may also produce a numbing effect.

[138] Menthol exhibits analgesic properties and is used topically to treat inflammatory pain caused by conditions such as arthritis, bursitis, tendonitis, muscle strains or sprains, backache, bone pain, braising, and cramping.

[139] Menthol cigarettes have a lower cancer risk and cause far less cigarette related cancers than their non-mentholated counterparts, making menthol an important and possibly mitigating component of inhaled cannabis.

[140] Cedrene-- -Cedrene is a sesquiterpene with the chemical formula CisHa_t and exists in two isomeric forms, α-cedrene andr|3-cedrene, which differ in the position of one double bond.

[141] Cedrene is a light yellowish transparent oil with the aroma of cedar wood and is found in cannabis, fenugreek, and in the essential oil of cedar.

[142] Cedrene possesses antiseptic, antimicrobial, antifungal, and anticancer properties, particularly against T-cell lymphoma, which may occur in the blood as leukemia or in lymph nodes (lymphoma), skin, or other areas of the body.

[143] Nerohdal· -Also known as peraviol, nerolidol is a naturally occurring sesquiterpene alcohol present in various plants with a floral odor, and has the chemical formula CisIIa_feO. It exists in two isomeric forms, ds and trans, winch differ in their geometry about the central double bond. The chemical structures are:

[144] Nerolidol has a floral, citrus, woody, fresh bark aroma, and may be found in Cannabis saliva, neroli, niaouli, ginger, jasmine, lavender, tea tree, citronella, lemon grass, and Brassavola nodosa, a Mexican orchid.

[145] Nerolidol is widely used in perfumes as both a base note fragrance component and as a fixative; it is also used in cosmetics, personal care products, detergents and cleaning products, and as a food flavoring agent

[146] It has anti fungal, anti-leishmaniasis (an infection caused by protozoan Leishmania parasites, which are spread by the bite of phlebotomine sand flies) and anti -malarial properties. It also produces a sedative effect. It may enhance skin penetration for the transdermal delivery of therapeutic drugs.

[147] Guaiol— Guaiol, also called champacol, is a sesquiterpenoid alcohol found in several plants, including Cannabis inciica, guaiacum and cypress pine. Tt is a crystalline solid at room temperature with the chemical formula CisHaeO and the structure:

[148] Guaiol has a woody, rosy, floral aroma Cannabis strains known to contain guaiol include

Liberty Haze, Blue Kush, Chocolope, and Medical Mass.

[149] Guaiol has been used for centuries as a treatment for diverse ailments ranging from coughs to constipation to arthritis and syphilis. It is also an effective insect repellent and insecticide. Guaiol’s potential medical properties include: Antimicrobial, Anti-inflammatory, laxative, diuretic, and insect repellant

[150] Isopulegol— Isopulegol is a monoterpene alcohol found in cannabis, com mint, European pennyroyal, lemongrass and geranium, and possesses a minty aroma It has the chemical fonnula CioHieO and tire structure:

[151] Isopulegol is used as a flavoring agent in food, in cosmetics, and in perfumes, personal care products, and cleaners. It is a chemical precursor to menthol, and shows many promising routes for therapeutic use. Isopulegol possesses gastroprotective, anti-convulsive, antiinflammatory, antioxidant, and stress-reducing effects, and it reduces the severity of seizures and anxiety in animal models.

[152] Geranyl Acetaie Geranyl acetate has several other names including geraniol acetate, and is a monoterpene ester with a sweet, strong, floral rose and fruity aroma. It is a colorless liquid at room temperature and has the chemical formula C12H20O2 with the structure:

[153] It is used in the fragrance and flavor industries, and is found in products such as soaps, detergents, personal care products, fabric softeners, and as a middle note in perfumes.

[154] Geranyl acetate is found in a variety⁷ of natural essential oils, such as cannabis, dtronella, palmarosa, geranium, coriander, neroli, lemongrass, petitgrain, carrot, sassafras, rose, and many others. It exhibits strong· antimicrobial, antifungal, and anti-inflammatory⁷ effects.

[155] Cymene- -Also called p-cymene, para-cymene, methyl-isopropyl benzene, and 1-isopropyl·· 4-methylbenzene among others, this aromatic, para substituted benzene ring is an alkylbenzene monoterpene with the formula CIOHM and the structure:

[156) The other two isomers of methyl-isopropyl-benzene are o-cymene (ortho cymene) and m- cymene (meta cymene), however only p-cymene is a naturally occurring compound. It has a citrusy-woody-spicy odor with herbal hints, and is found in cumin, thyme, anise, coriander, mace, oregano, eucalyptus and in angelica root and angelica seed oil, bay leaf oil, basil oil, carrot seed oil, clove bud oil, clary sage oil, and grape fruit oil. It is used in flavoring beverages, cakes and confectionery, as well as in the fragrance, paint, and furniture industries.

[157] P-cymene has documented anti-inflammaioiy effects, it shows potential protective effects against acute lung injury, and is effective against pathogenic bacteria, especially Escherichia coli. When combined with carvacrol it is also antibacterial and possibly even more so. P-carvacrol, thymol and p-cymene work synergistically together and have anti-fungal properties; p-cymene by itself showed strong antifungal activity against numerous Candida species. P-cymene also shows anti-inflammatory, antinociceptive and analgesic properties.

[158] Eucalyptol— Eucalyp tol has many other names, including l.frcineol, cajeputol; 1,8-epoxy- p-menthane, and eucalyptole, Eucalyptol is a cyclic monoterpenoid ether and it is the main component of eucalyptus essential oil having the chemical fonnula CioHisO and the chemical structure:

[159] Eucalyptol has a minty, earthy, spicy aroma and is found in several plants including

Cannabis satiia, camphor laurel, bay leaves, tea tree, mugwort, sweet basil, wormwood, rosemary, common sage, and other aromatic plants. Eucalyptol is used in flavorings in baked goods, confectionery, meat products, beverages, and mouth wash; in fragrances, cigarettes and cosmetics.

[160] Eucalyptol has many medicinal uses, it relieves pain, suppresses coughs, and improves concentration and inner balance. Plants containing eucalyptol enhance meditation and concentration. Eucalyptol has potent antifungal effects and is used as an insecticide and insect repellent Eucalyptol inhibits cytokine production in lymphocytes and monocytes, giving it an anti-inflammatory effect, and it reduces inflammation and pain when applied topically. It is able to kill in vitro leukemia cells of two culttired leukemia cell lines. Eucalyptol is effective for controlling asthma and reduces airway mucus hypersecretion by its anti-inflammatory cytokine inhibition, and it is an effective treatment for nonpurulent rhinosinusitis.

[161] Pulegone- -Pulegone, a monocyclic monoterpenoid, is a secondary terpene component of cannabis. It exists naturally in two enantiomeric forms, d-pulegone and Ipulegone, with d- pulegone being the most abundant The chemical formula is CioHieO and the structure is:

[162] It lias an aroma of peppermint and camphor, and it is found in several plants besides cannabis, such as catnip, peppermint, spearmint, pennyroyal, and rosemary. It is used for flavoring foods, drinks, and dental products, as a spice, it is used as fragrance components in detergents and cosmetics, it is used in herbal medicines, perfumery, and aromatherapy.

[163] Pulegone is an emmenagogue, a mucolytic, and is good for congestion of the respiratory system. Pulegone may have significant sedative and fever -reducing properties. It may also alleviate the side effects of short-term memory loss sometimes associated with higher levels of THC. Pulegone is a powerful insecticide.

[164] Traditionally, plants containing pulegone, such as pennyroyal, have been used as herbal teas for non-ulcer dyspepsia, primary⁷ dysmenorrhoea, secondary amenorrhoea and oligomenorrhoea, as an abortifacient, and as a diaphoretic. Pennyroyal essential oil has been used for the same conditions. Pulegone is a hepatotoxic (liver poison) and nephrotoxic (kidney poison) constiment of the folklore abortifacient pennyroyal oil.

[165] Today, Mentha piperita (peppermint) and Mentha pulegium (pennyroyal) are used for colds, headache, migraine, as a diuretic, antispasmodic, anticonvulsive, anti-emetic, heart stimulant, sedative, and to treat the symptoms of inflammatory bowel syndrome. Rosemary inhibits acetylcholinesterase in the brain yielding· more acetylcholine and allowing nerve cells to communicate more effectively with one another, giving promise for treatment of memory issues and dementias.

[166] One other terpene foimd in cannabis that bears mentioning is humulene.

[167] Humulene— Humulene is a monocyclic sesquiterpene containing an 11-membered ring and is also known as (X-humulene and a-caryophyllene (an isomer of β- caryophylletie).

Humulene is often found in combination with it’s isomer, β -caryophyllene, it has the chemical formula C₁₅H₂₄ and the structure is:

[168] Humulene is found in Cannabis sativa strains, hops and Vietnamese coriander, pine trees, orange trees, marsh elders, tobacco, sage, ginseng, ginger, and sunflowers, among other plants. Humulene is what gives beer its distinct“hoppy” aroma, and also contributes to the same hoppy aroma in cannabis.

[16Θ] Humulene is anti-tumor, anti-bacterial, is a strong anti-inflammatory', and is anorectic (suppresses appetite). It is often blended with β-caryophyllene and used as a potent remedy for inflammation. Humulene aids in weight loss by acting as an appetite suppressant.

[170] In die body, terpenes act on receptors and neurotransmitters. They readily combine with, or dissolve in, lipids or fats. Terpenes may act as serotonin uptake inhibitors, tiiey may enhance norepinephrine activity, they may increase dopamine activity, and they may augment synaptic γ- aminobulyric acid (GABA) levels by inhibiting re-uptake. These actions are similar to many of the commonly prescribed anti-depressant drugs used today

[171] 'Ilie differences in the amounts and types of both cannabinoids and terpenes, along with the other lesser compounds within the cannabis varieties, imbue the various cannabis extracts with medicinal significance. Adding or increasing one or more of these compounds can alter the effects of cannabis extract, as certain compounds work in synergy to augment desirable effects while other compounds act as antagonists to inhibit undesirable effects.

[172] Cannabis has numerous beneficial impacts on sleep. It can improve the quality and duration of sleep, reduce waking episodes, reduce nightmares, increase stage 3 sleep, and help treat various sleep disorders. Cannabinoids may reduce disturbances of sleep due to sleep apnea, pain from chronic illness or injury, restless leg syndrome, narcolepsy, and parasomnia

(sleepwalking, talking during sleep, grinding teeth, night terrors, etc.). Cannabinoids may also increase restfulness and reduce nightmares in people who have suffered severe stress, such as sufferers of post-traumatic stress disorder (FTSD).

[173] The cannabinoid Δ-9-tetrahydrocannabinol (THC) has been shown to have a sedative effect, and can reduce the amount of time it takes for a person suffering from insomnia to fall asleep. THC also improves the quality of sleep, and increases the duration of stage 3 sleep. Stage 3 (also known as deep sleep, slow wave sleep, or delta sleep) is the most restful and restorative stage of sleep. This is the stage of sleep where the need for sleep is reduced, human growth hormone is released which relieves stress, and the immune system restores itselfj and the brain is reset for learning the next day.

[174] Cannabidiol (CBD), the second major cannabinoid in cannabis, may be usefiil on its own to increase total sleep time. On the other hand, CBD tends to act as a stimulant, so certain amounts of cannabidiol (CBD) may be added to the formulation to offset drowsiness which may occur from taking THC alone. CBD may also be useful on its own in treating narcolepsy (overwhelming, and sometimes very sudden, daytime drowsiness).

[175] Cannabinol (CBN) is another major cannabinoid in cannabis. CBN is a powerful sedative with little or no psychoactive effect. CBN may be used alone as a sedative, or in combination with CBD, THC, and other cannabinoids to produce the desired drowsiness. [176] In one exemplary aspect of the embodiment, different combinations of THC, CBD, and CBN may be used to obtain the desired amount of restfulness while minimizing the effects of morning drowsiness.

[177] Cannabis has been used to treat pain since at least the third millennium BC. In recent decades, and especially since changes in state laws allowing medical use of cannabis, there has developed a substantial body of anecdotal evidence that cannabis, particularly smoked cannabis plant matter, provides substantial relief from chronic pain caused by numerous chronic health conditions such as cancer, multiple sclerosis, arthritis, nerve damage, back pain, fibromyalgia, and similar conditions. In fact, smoked cannabis plant matter appears to be a preferred method of pain treatment by tiiose with chronic medical conditions, even though other forms of administration of cannabis are available for medical use. This preference is likely due to a variety of factors. First, smoking cannabis allows the user to easily control the dosage, as the effects are felt quickly, and additional amounts can be smoked if the initial effects are insufficient Second, the concentrations of active cannabis compounds in the bloodstream are high compared to oral administration, and more powerful, as the active cannabis compounds go directly into the bloodstream instead of being processed into other compounds by the liver. Third, the combined effect of the dozens of cannabis compounds in cannabis plant matter may provide a more pleasant subjective effect, or other benefits such as reduced inflammation, beyond that of a purified cannabinoid medical product In an aspect of the embodiment cannabis compounds can be selected in formulations designed to specifically to address each of these issues, while avoiding the detriments of smoked cannabis plant matter, such as respiratory irritation and the increased potential for lung disease. Further arguing in favor of specifically-formulated cannabis based products is the fact that certain modern North American and European strains of cannabis display relatively high concentrations of THC (a potent psychoactive compound), but relatively litde CBD or other phytocannabinoid content

[178] A substantial body of medical literature supports the anecdotal evidence that cannabis can be used to treat chronic pain. The endocannahinoid system is active in the control of pain. Compounds fomid in cannabis act on the endocannahinoid system, and certain of these compounds have a powerful analgesic effect F'or example, THC is believed to be ten times more powerful than morphine in mediating pain in wide dynamic range neurons in the

ventroposterolateral nucleus of the thalamus. Cannabidiol (CBD) is also believed to have strong analgesic effects, due to its function as an endocannabinoid modulator, likely through its ability to promote signaling of the adenosine receptor A2A by inhibiting the adenosine transporter. Cannabigerol (CBG), a“minor cannabinoid” found in small quantities in cannabis, is believed to have even greater analgesic activity than THC.

[179] Chronic pain conditions are often resistant to standard treatments, including treatment with opioid medications such as morphine. There is some medical evidence that suggests that cannabinoids are complementary to treatment with opioids, offering additional pain reduction on top of that provided by the opioids. Combining cannabis treatments for chronic pain with opioid treatments for chronic pain may have the benefit of reducing patient pain levels, reducing reliance on (and addiction to) opioids, or both.

[180] The inventor has conceived, and reduced to practice, a variety of cannabis formulations for the treatment of sleep disorders. Such formulations may be of particular value in the treatment of sleep disorders due to a variety of factors, including insomnia caused by pain or discomfort due to chronic conditions such as cancer or multiple sclerosis, insomnia caused by post traumatic stress disorder (PTSD), sleep apnea, restless leg syndrome, narcolepsy, and parasomnia (sleepwalking, talking during sleep, grinding teeth, night terrors, etc.), as well as others. Cannabis treatments for sleep disorders may be especially useful where the underling condition causing the insomnia is also being treated by cannabis formulations.

[181] The inventor has conceived, and reduced to practice, a variety of cannabis formulations for the treatment of chronic pain. In one exemplary aspect of die embodiment, different combinations of THC, CBD, and CBG may be used to obtain the desired amount of pain relief due to chrome illnesses. In another exemplary' aspect of the embodiment, different combinations of THC, CBD, and CBG may be used to complement and enhance opioid pain treatments, and to manage pain while reducing dependence on opioids.

[182] The inventor has also conceived, and reduced to practice, a variety of cannabis formulations for the delivery of an enhanced cannabinoid effect employing the terpene myrcene. This not only raises the saturation level of a predominant cannabinoid receptor such as CB1 for cannabinoids such as THC, but also increases permeability of the cell membrane and decreases the resistance across the blood-brain barrier for medicinal compounds known to be present in cannabis extracts, thus potentiating the effects of these medically effective compounds at several major sites of action.

[183] In one exemplary aspect of the embodiment, the formulation to treat sleep disorders may be: 5mg Δ-9-tetrahydrocannabinol (THC), 5mg cannabidiol (CBD), and 5mg cannabinol (CBN). The combined mixture may be compounded into a pill or tablet form, or into a sublingual spray, to lie administered orally.

[184] In one exemplar_)' aspect of die embodiment, the formulation to treat sleep disorders may be: 5mg Δ-9-tetrahydrocannabinol (THC), 5mg cannabidiol (CBD), and 5mg caimabigerol (CBG). The combined mixture may be compounded into a liquid form for inhalation using a vaporizer.

[185] In another aspect of the embodiment, the terpene myrcene will be added to the formulation to raise die saturation level of a predominant cannahinoid receptor such as CB1 for cannabinoids such as THC, increase permeability of the cell membrane, and decrease the resistance across the blood-brain barrier for medicinal compounds known to be present in cannabis extracts, thus potentiating the effects of these medically effective compounds at several major sites of action.

[186] One or more different formulations may be described in the present application. Further, for one or more of the formulations described herein, numerous alternative embodiments may be described. It should be understood tiiat these are presented for illustrative purposes only, the described embodiments are not intended to be limiting in any sense. In general, embodiments are described in sufficient detail to enable those skilled in the art to practice one or more of the formulations, and it is to be understood that other embodiments may be utilized and that structural, compound constituent, constituent compound ratio, constituent compound isomer, constituent compound concentration and other changes may be made without departing from the scope of the particular formulations. When an active compound with multiple naturally occurring isomers is cited, it is to be understood that a mixture containing concentrations of those isomers as are found in nature in cannabis is in use unless otherwise specified. Accordingly, those skilled in the art will recognize that one or more of the formulations may be practiced with various modifications and alterations. Particular features of one or more of the formulations may be described with reference to one or more particular embodiments or figures that form a part of the present disclosure, and in which are shown, by way of illustration, specific embodiments of one or more of the formulations. It should be understood, however, that such features are not limited to usage in the one or more particular embodiments or figures with reference to which they are described. The present disclosure is neither a literal description of all embodiments of one or more of die formulations nor a listing of features of one or more of the formulations that must be present in all embodiments.

[187] Cannabinoids, terpenes and flavonoids employed in aspects are to be assumed isolated and purified by previously published means best suited lor that active compound which may include but are not limited to ITPLC, also known as high pressure liquid chromatography, distillation, fractional distillation, steam distillation, supercritical fluid extraction, either with or without additional, modifying solvents as well as other methods known to those skilled in the art.

[188] When single cannabinoids, multiple cannabinoid mixtures, caimabinoid-terpene mixtures, cannabinoid-terpene-flavonoid, terpene, multiple terpene and terp ene-flavonoid mixtures are listed in embodiments, they are to be assumed administered by methods previously cited to both retain the stability of all active compounds cited in a formulation and to effect delivery of all active compounds within the formulation. These delivery methods may comprise, but are not limited to, administering the orally, anally, or via injection compounds containing a known amount of the formulation, inhalation of vapor comprising the formulation, administration of sublingual tinctures of the formulation, extracts of the formulation, oils of the formulation, capsules of the formulation and tablets of the formulation as well as other administrative methods known to be applicable to those with ordinary skill in the art

[189] It will be readily apparent that more than one method of administration may be used for delivery of a single formulation cited in an embodiment, and that any method of administration that maintains both constituent active compound stability and high bioavailability of each active compound may be employed for a single cited formulation.

[190] Techniques and mechanisms described or referenced herein will sometimes be described in singular form for clarity. However, it should be noted that particular embodiments include multiple iterations of a technique or multiple manifestations of a mechanism unless noted otherwise. Detailed Description of Examples

[191] Rg. 1 is a method diagram illustrating a process 100 for preparing cannabis medicinal products, according to a preferred aspect The overall process of creating medicinal products from the cannabis plant may comprise six stages: cultivation 101, extraction 102, concentration 103, separation 104, secondary concentration 106, and processing 106. At the cultivation stage

101, the cannabis plants are grown and harvested. The harvested plant matter, or selected portions of it, is sent for extraction 102, at which point essential oils of the plant are extracted using one of many select techniques common in the art, which contain some plant matter in the form of chlorophyll, plant waxes, plant lipids, plus substantial amounts of cannabinoids, terpenes, and fiavonoids. Extraction processes may include, for example, super critical COS extraction, hydrocarbon solvent extraction, hydrofluorocarbon extraction, or other gas-based and solvent- based extraction methods commonly used in the ait These oils are concentrated 103 via evaporation. In the separation stage 104, the cannabis compounds are separated from the concentrated oils via a variety of processing methods, usually involving high pressure liquid chromatography, flash chromatography, or the like, but which may include other separation methods according to a preferred aspect At this stage, the purified cannabis compounds (cannabinoids, terpenes, and fiavonoids) are sent for further concentration 105 via evaporation. Said concentrated, purified cannabis compounds may then be processed 106 with other ingredients, for example, products produced in the processes described below in Figs. 2, to create a final product which may be in the form of, for example, smokable, pills, tablets, salves, injectables, tinctures, and die like.

[192] According to a preferred aspect, additional amounts of the terpene myrcene is added to die product in step 106 to take advantage of die unique advantages presented by β myrcene, which is shown to increase the permeability of the cell membrane, decrease the resistance across the blood-brain barrier, and increase saturation at the CB1 receptor site for a plurality of compounds including itself, other terpenes, and cannabinoids including but not limited to THC. for example, infusing myrcene as well as THC into the product in step 106 may ensure that THC’s (or, for other therapeutic effects, cannabinoids such as CBD, CBN, or CBG) maximal activation level may be increased by a biologically significant amount, and that increase may be achieved at a faster rate. Formulations including selected THC, other cannabinoids and terpenes in the presence of myrcene may significantly augment the efficacy of such formulations for the desired biological and medicinal effects.

[193] In an aspect, additional amounts of the terpene myrcene is added to the product in step 106 to take advantage of the unique advantages presented by β-myrcene, which is shown to increase the permeability of the cell membrane, decrease the resistance across the blood-brain barrier, and increase saturation at the CB1 receptor site for a plurality of compounds including itself, other terpenes, and cannabinoids including but not limited to THC. For example, infusing myrcene as well as THC into the product in step 106 may ensure that TOC’s (or, for other therapeutic effects, cannabinoids such as CBD, CBN, or CBG) maximal activation level may be increased by a biologically significant amount, and that increase may be achieved at a fester rate. Formulations including selected 'TOC, other cannabinoids and terpenes in the presence of myrcene may significantly augment the efficacy of such formulations for the desired biological and medicinal effects. One analgesic and anti-inflammatory formulation may be: 0.30%w/W to 50% β-myrcene, 20%w/w to 35%w/w caimabidiol (CBD), 10%w/vv to 25%w/w a-pinene, 5%w/w tol5%w_'/w terpineol, and lO%¼₇V to 30% bomeol. Another myrcene-enhanced analgesic and antiinflammatory formulation may be 0.25%w/W to 40%w/W β-myrcene, 10%w₇\v to 2⁽Mwfw caimabidiol (CBD), 5%w,¼ to 15%w,¼ p-cymene and 15%w/w to 30% bomeol.

[194] Fig: 2 is a method diagram illustrating a process 200 for preparing an enhanced smokable therapeutic cannabis product using hash resin, according to a preferred embodiment The inventors have discovered, in particular, that using the methods described herein rather than, as is commonly done in the art, infusing smokable plant material directly with hash resin, provides a superior product that tastes better, smokes more smoothly, and has predictable therapeutic effects (which may in fact be varied, according to aspects of die invention, by varying the cannabinoid profile of the oil used to spray plant matter in step 206, as described below). According to a preferred aspect, dried cannabis plant matter is treated to separate hash resin 201, as is known in the art, and the remaining plant matter is further dried until it is substantially moisture-free 202.

Tn another step, die hash resin is pressed to expel oils 203 (which are used for other purposes); it will be appreciated by those having ordinary skill in the art that the resulting oil will be very rich in cannabinoids and terpenes (as well as flavonoids), as described above. Further, the pressed hash resin is treated with an oil rich in medium-chain triglycerides (MCT oil) 204, which extracts a substantial amount of TOC and other cannabinoids; this MCT-based, THC-infused oil represents a recovered fraction of the THC present in the hash resin. The THCinfused MCT' oil may be further enriched 205 by addition of pure β-myrcene and other desired cannabinoids, terpenes, and llavonoids as desired (for different aspects, different cannabinoid profiles may be used to enrich the THC-infused MCT oil, depending on the desired therapeutic effect).

[195] According to a preferred aspect, the terpene myrcene is added to MCT oil 205 to take advantage of the unique advantages presented by β-myrcene, which is shown to increase the permeability of the cell membrane, decrease the resistance across the blood- brain barrier, and increase saturation at the CB1 receptor site for a plurality of compounds including itself other terpenes, and cannabinoids including but not limited to THC. For example, infusing myrcene as well as THC into the MCT oil prior to spraying dried, smokable cannabis plant matter 205 may ensure that THC’s (or, for other therapeutic effects, cannabinoids such as CBD, CBN, or CBG) maximal activation level may be increased by a biologically significant amount, and that increase may be achieved at a faster rate. Formulations including selected THC, other cannabinoids and teipenes in die presence of myrcene may significantly augment die efficacy of such formulations for die desired biological and medicinal effects.

[196] In an aspect, in order to achieve a cannabisbased product that may act as a sleep aide, cannabisbazed compounds which have demonstrated sedative properties, for example CBN, may be used. When combined with other compounds, such as THC and CBD, the final product may help induce sleep. For example, the product may comprise 10% w/w to 35% w/w Δ-9- tetrahydrocannabinol (THC), 1.5% w/w to 45% w/w CBN, 5% wAv to 35% w/w CBD, and 5% w/w to 35% w/w CBC. One or more terpenoids may also be added, for example, via infused MCT oil as discussed in Fig. 2, for more therapeutic effects in addition to treating sleep disorders.

[197] In another aspect, a myrcene-enhanced product may be formulated so that the final product may have a fast-acting effect For example, the product may comprise 10% w/w to 35% w/w Δ-9-tetrahydrocannabinol (THC), 1.5% wyw to 45% w/w CBN, 5% w/w to 35% w/w CBD, 5% w/w to 35% wAv CBC, and .15% w/w to 10% wAv β-myrcene. One or more terpenoids may also be added, for example, via infused MCT oil as discussed in Fig. 2, for more therapeutic effects in addition to treating sleep disorders.

[198] fig. 3 is a method diagram illustrating a process 300 for preparing an enhanced smokable dierapeutic. cannabis product using hash resin, according to a preferred aspect According to the embodiment, in a first step 301, dried cannabis plant matter is treated to separate hash resin, as is known in the art, and the remaining plant matter is, in step 302, further dried until it is substantially moisture-free. In step 303, the hash resin is pressed to expel oils (which are used for other purposes); it will be appreciated by those having ordinary skill in the art that the resulting oil will be very rich in cannabinoids and terpenes (as well as flavonoids), as described above. In step 304, the pressed hash resin is treated with an oil rich in medium-chain triglycerides (MCT oil), which extracts a substantial amount of TIIC and other cannabinoids; this MCT-based, TTIC- infused oil represents a recovered fraction of the THC present in the hash resin. The THC- infused MCI’ oil may, in step 305, be further enriched by addition of pure β-myTcene and other desired cannabinoids, terpenes, and flavonoids as desired (for different aspects, different cannabinoid profiles may be used to enrich the THC-infused MCT oil, depending on the desired therapeutic effect). Then, in step 306, the THC-infused MCT oil is sprayed in a fine, atomized mist onto dried cannabis plant material, thus adding selected additional cannabinoids and other compounds to die smokable material, beyond what is naturally present in the plant material. Advantageously, such oil-sprayed plant matter, when smoked, has improved taste and gives a more even bum, while also providing more of a desired therapeutic effect (depending on which cannabinoids, terpenes, and/or flavonoids are added in step 105). In an aspect, dried cannabis plant matter prepared in this way may be wrapped into a conical smokable product in step 307.

[199] According to a preferred aspect, the terpene myrcene is added to MCT oil in step 305 to take advantage of the unique advantages presented by β-myrcene, which is shown to increase the permeability of the cell membrane, decrease the resistance across the blood-brain barrier, and increase saturation at the CB1 receptor site for a plurality of compounds including itself other terpenes, and cannabinoids including but not limited to TFiC. For example, infusing myrcene as well as THC into the MCT oil prior to spraying dried, smokable cannabis plant matter in step 305 may ensure that THC’s (or, for other therapeutic effects, cannabinoids such as CBD, CBN, or CBG) maxima] activation level may be increased by a biologically significant amount, and that increase may be achieved at a faster rate. Formulations including selected THC, other cannabinoids and terpenes in the presence of myrcene may significantly augment the efficacy of such formulations for the desired biological and medicinal effects.

[200] fig. 4 is a method diagram illustrating a process 400 for preparing an enhanced smokable therapeutic cannabis product using whole plant matter, according to an aspect Similar to the process described with reference to Fig. 3 above, process 400 starts with dried cannabis plant matter from which trichomes have been removed. In step 401, the dried plant matter is treated with an oil rich in medium-chain triglycerides (MCT oil), which extracts a substantial amount of THC and other cannabinoids; this MCT-based, THC-infused oil represents a recovered fraction of die THC present in the mature plant (while trichomes are where most THC is present, cannabis plants have THC distributed throughout, but in quantities that generally have made it uneconomically to exploit). The THC-infused MCT oil may, in step 402, be further enriched by addition of pure β-myrcene and other desired cannabinoids, terpenes, and flavonoids as desired (for different aspects, different caimabinoid profiles may be used to enrich the THCinfused MCT oil, depending on the desired therapeutic effect). Then, in step 403, the THCinfused MCT oil is sprayed in a fine, atomized mist onto dried cannabis plant material, thus adding selected additional cannabinoids and other compounds to the smokable material, beyond what is naturally present in the plant material Advantageously, such oil-sprayed plant matter, when smoked, has improved taste and gives a more even bum, while also providing more of a desired therapeutic effect (depending on which cannabinoids, terpenes, and/or flavonoids are added in step 402). In an aspect, dried cannabis plant matter prepared in this way may be wrapped into a conical smokable product in step 404.

[201] In an aspect, the terpene myrcene is added to MCT oil in step 402 to take advantage of the unique advantages presented by β-myrcene, which is shown to increase the permeability of the cell membrane, decrease the resistance across the blood-brain barrier, and increase saturation at the CB1 receptor site for a plurality of compounds including itself, other terpenes, and cannabinoids including but not limited to THC. For example, infusing myrcene as well as THC into the MCT oil prior to spraying dried, smokable cannabis plant matter in step 402 may ensure that THC^*s (or, for other therapeutic effects, cannabinoids* such as CBD, CBN, or CBG) maximal activation level may be increased by a biologically significant amount, and that increase may be achieved at a faster rate. Formulations including selected THC, other cannabinoids and terpenes in the presence of myrcene may significantly augment the efficacy' of such formulations for the desired biological and medicinal effects.

[202] It will be appreciated by those having ordinary' skill in the art that the THC-infused MCT oil produced from dried plant material using process *100 will generally have lower cannabinoid concentrations (before enrichment) than those produced from hash resin using process 300, but this disadvantage is offset by the lower cost of the raw materials used in process 400 and by the fact that the THCinfused MCI' oil resulting from step 401 will generally have a much richer cannabinoid profile relative to that produced in step 303.

[203] According to a preferred aspect, THC-infused MCT oils produced by either method may be enhanced by enriching with formulations comprising specific cannabinoid profiles to target specific desired therapeutic, effects. For example, a myrcene- enhanced formulation may be used to increase appetite in response to medical conditions such as advanced cancer, chemotherapy for cancer, and anorexia nervosa. One appetite-enhancing formulation may be: 0.15% wAv to 30% w/w β-myrcene, 10% w/w to 40% w/w Δ-9-tetrahydrocannabinol (THC), 5% w/w to 20% w/w cannabinol (CBN), and 5% w/w to 10% w/w Δ-8-tetrahydrocamiabinol and 10%w/w to 25% w/w cannabidiol (CBD).

[204] Another appetite-enhancing formulation may be 0.20% w/w to 35% w/w β-myrcene, 5% w/w to 20% w/w Δ-9-tetrahydrocarmabinol (THC), 30% w/w to 40% w/w Δ-8-tetrahydrocannabinol, 5% w/w to 2.5% Δ-9-tetrahydrocannabinolic acid (THCV) and 5% w/w to 15% pinene.

[205] Still another myrcene-enhanced appetite-enhancing formulation may be 0.25% w/w to 40% w/w β-myrcene, 10% w/w to 20% w/w Δ-9-tetrahydrocannabinol (THC), 20% w/w to 45% Δ-8- tetrahydrocannabinol, 15%w/w to 25%w/w cannabinol (CBN) and 5% w/w to 15% w/w linalool.

[206] According to another aspect, a myrcene-enhanced formulation may be used to treat nausea in response to medical conditions such as radiation therapy, chemotherapy, bacterial and persistent viral infections. One anti-emetic formulation may be: 0.10% w/w to 25% w/w β-myrcene, 5%w/w to 20%wAv Δ-9-tetrahydrocannabinol (THC), 20%w/w to 35%w/w Δ-8-tetrahydrocannabinol, 15%w/w to 25% w/w cannabidiol (CBD) and 15%w/w to 25% pulegone. Another antiemetic formulation for the treatment of nausea may be: 15%wAv to 30%w/w β-myrcene, 10%w,¼ to 30% w/w Δ-9-tetrahydrocarmabinol (THC), 5%w/w to 20%wy\v Δ-8-tetrahydrocannabinol, 20%w/W to 40%w/w cannabidiohc acid (CBDA) and 10% w/w to 25% pinene.

[207] In another exemplary' aspect, a myrcene-enhanced formulation is provided to treat chronic pain in response to medical conditions such as osteoarthritis, rheumatoid arthritis, and lasting pain caused by injury and surgery. One analgesic and anti-inflammatory formulation may be: 0.30%w/w to 50% β-myrcene, 20%w/w to 35%w/w cannabidiol (CBD), 10%w/w to 25%w/w oc · pinene, 5¾w/w tol5%wAv terpineol, and 10%w/w to 30% bomeol. Another myrcene-enhanced analgesic and anti-inflammatory formulation may be 0.25%w/W to 40%w₇\v β-myrcene, 10%w₇\v to 20%wvw cannabidiol (CBD), 5% w/w to 15%w,\v p-cymene and 15%w/W to 30% bomeol.

[208] It will be appreciated by one having· ordinary skill in the art that various formulations targeting specific therapeutic effects may be enabled by enriching THC-infused MCT oil with specific cannabinoid and myrcene formulations, which specific formulation-enriched THC- infused MCT oils may then be sprayed onto smokable plant material as described above.

[209] A person with ordinary skill in the ait will be aware of a range of possible modifications of the various embodiments described above. Accordingly, the present invention is defined by the claims and their equivalents.

Claims

What is claimed is:

1. A method of preparing a cannahisbased therapeutic product for die treatment of sleep disorders, the metiiod comprising die steps of:

(a) harvesting flowers and leaves from a plurality of cannabis plants from a plurality of cannabis strains each expressing a different active cannabis compound profile using shears;

(b) individually extracting cannabis oil from the harvested flowers and leaves of each of the cannabis strains;

(c) concentrating the extracted cannabis oik b)' at least evaporating extraneous material; and

(d) combining specific amounts of the concentrated oils from one or more cannabis strains to produce a mixture possessing a specific active cannabis compound profile comprising at least 5% by weight purified cannabinol using a mixing device, wherein the one or more cannabis strains expresses known concentrations of a plurality of active cannabis compounds, the known concentrations being determined using an extract from each cultivar and expressed as a ratio of weight-of-compound per weight-ofex tract.

2. The method of claim 1, further comprising the step of enriching the product with a formulation comprising at least 1% by weight purified β-myrcene, prior to processing into a final product.

3. The method of claim 1, further comprising die step of combining medium-chain triglycerides oils infused with cannabisbased compounds to the concentrated extracted oils, prior to processing into a final product.

4. The method of claim 1, wherein the combined formulation is made into pill form.

5. The method of claim 1, wherein the combined formulation is made into spray form.

6. The method of claim 1, wherein the combined formulation is used to treat plant matter to use in a smokable form.

7. The method of claim 1, further comprising cannabis compounds chosen from a set comprising myrcene, a pinene, ocimene, terpineol, beta-caryophyllene, linalool, limonene, terpinolene, valencene, geraniol, phellandrene, carene, terpinene, fenchol, bomeol, bisabolol, phytol, camphene, sabinene, camphor, isobomeol, menthol, cedrene, nerolidol, guaiol, isopidegol, geranyl, cymene, and eucalyptol.

8. A cannahishased treatment product for sleep disorders produced according to the method of claim 1.

9. A cannabisbased treatment product for sleep disorders produced according to the method of claim 2.

10. A cannabis based treatment product for sleep disorders produced according to die method of claim 3.

11. A camtabishased treatment product for sleep disorders produced according to the method of claim 4.

12. A cannabisha&ad treatment product for sleep disorders produced according to the method of claim 5.

13. A cannabisha&ed treatment product for sleep disorders produced according to the method of claim 6.

14. A cannabisha&ed treatment product for sleep disoitiers pnxluced according to the method of claim 7.

15. A method of preparing a cannabisba&ed therapeutic product for the treatment of chronic pain, the method comprising die steps of:

(a) separating hash resin from plant material of a cannabis plant of a specific strain;

(b) pressing the hash resin to expel oil, leaving spent hash resin; (c) extracting further caimabinoids from the spent hash resin using MCT oil;

(d) separating the cannabis compounds from the oils using high pressure liquid

chromatography or flash chromatography;

(e) mixing cannabis compounds obtained via steps (a)-(d) from one or more strains of cannabis in obtain a formulation therapeutically-effective for use in treating chronic pain; and

(f) processing the formulation from step (e) into a pill, tablet, or liquid suitable for therapeutic administration to a human patient

16. The method of claim 15, wherein the formulation comprises 0.30% w/w to 50% w/w β myrcene, 20% w/w to 35% w/w cannabidiol (CBD), 10% w/w to 25% w/W a-pinene, 5% w/w tol5% w/w terpineol, and 10% w/w to 30% w/w bomeol.

17. The method of claim 15, wherein the formulation comprises 0.25% w/w to 40% w/w β- myrcene, 10% w,W to 20% w/w cannabidiol (CBD), 5% w/w to 15% w/w p-cymene and 15% wfw to 30% w/w bomeol.

18. A tianaa/vsbased treatment product for chronic, pain produced according to the metiiod of claim 16.

19. A cannabis-based treatment product for chronic pain produced according to the method of claim 17.

20. A method of preparing an enhanced smokable therapeutic cannabis product, the method comprising the steps of:

(a) separating hash resin from plant material of a cannabis plant;

(b) pressing the hash resin to expel oil, leaving spent hash resin;

(c) extracting further cannabinoids from the spent hash resin using medium chain triglyceride oil;

(d) enriching the extracted oil with a formulation comprising at least purified β-myrcene; and

(e) spraying the enriched oil onto dried smokable cannabis plant matter.

21. The method of daim 20, further comprising the step of wrapping the dried smokable plant matter into a conical smokable product after spraying.

22. The method of daim 20, wherein the formulation comprises at least 25% by weight of purified THC.

23. TTie method of daim 20, wherein the formulation comprises at least 25% by weight of purified CBD.

24. The method of daim 20, wherein the formulation comprises at least 25% by weight of purified

THC and 25% by weight of purified CBD.

25. A smokable therapeutic cannabishased product produced according to the method of claim

20.

26. A smokable therapeutic cannabis-based product produced according to the method of claim

21.

27. A smokable therapeutic cannabishased product produced according to the method of claim 22.

28. A smokable therapeutic cannabis- based produd produced according to the mediod of claim

23.

29. A smokable therapeutic cannabis- based product produced according to the mediod of daim

24.