PSYCHOACTIVE EFFECTS

CROSS-REFERENCE TO RELATED APPLICATIONS

[001] This application is a PCT filing of, and claims priority to, United States patent application number 15/968,053, titled, "SMOKABLE CANNABIS-BASED PRODUCT WITH REDUCED PSYCHO ACTIVE EFFECTS”, and Bled on May 1, 2018, which claims benefit of, and priority to. United States provisional application number 62/641,681 tided,“SMOKABLE CANNABIS- BASED PRODUCT WITH REDUCED PS Y CHO ACTIVE EFFECTS, filed on March 12, 2018, tire entire specification of each of which is incorporated herein by reference.

BACKGROUND OF THE INVENTION

Field of the Invention

[002] The disclosure relates to the field of cannabis- based formulations, particularly to a formulation for reduced psychoactive effects commonly associated with the use of cannabis-based products.

Discussion of the State of the Art

[003] In the field of consumable cannabis, many states have passed legislation legalizing use of such cannabis for both medical and recreational usage. Pending legislation in additional states may greatly affect the current landscape of cannabis usage, as; more people may he introduced to the use of cannabis either as a recreational endeavor or as a treatment for a plurality of medical issues and diseases. While the uses of medical cannabis and recreational cannabis appear to differ, there is a similarity in delivery of both medical and recreational cannabis to the consumer. Consumable cannabis; be it smoked, vaporized, or consumed in some other form, may not come from the same hatch of catmahis or even the same manufacturing method, resulting in possible distinguishable differences between batches of consumable cannabis,

[004] There may also be instances in which it may be desired for a product which is less potent, for instance, to provide a means of recreational usage without hindering motor-skill or using the product as a delivery mechanism to achieve benefits and curative effects provided by various cannabinoids. Some of the adverse effects commonly associated with consumption of cannabis- based compounds may include a“cannabis high , waxped perception of time, impaired short term memory, and the like. Although less potency may be achieved through consumption of lesser quantities, this may lead to the user not feeling satiated, which may lead to using more product, and consequently experiencing the effects of the additional cannabis,

[005] What is needed is a product that provides these cannabis compounds in a form which may allow a user of said product to experience a less potent effect, but without comprising the quantity of consumption.

SUMMARY OF THE INVENTION

[006] Accordingly, the inventor has conceived, and reduced to practice, a smokable cannabis- based product with reduced psychoactive effects and method for producing the same. In a typical embodiment, a formulation may include higher concentrations of cannabinoids that exhibits little to no psychoactive effects, as wdl as cannabinoids that have been shown to reduce the psychoactive effects commonly associated with the use of cannabis-based products.

[007] In a typical embodiment, a smokable cannabi -based product is provided that may be made front plant matter with lower concentrations of the psychoactive compounds found in cannabis-based products. Th e plant mailer used may be parts of tire cannabis plant that naturally has lower concentration of compounds, strains that naturall has lower tetrahydrocannabinol (THC) content, post-extraction plant matter that may still have residual amounts of cannabis- compounds, and the like.

[008] According to one aspect, a method of preparing a smokable cannabis-based product with reduced psychoactive effects and method for producing the same, comprising the steps of: (a) separating portions with known low tetrahydrocannabinol content from harvested plant material of the cannabis plant at least a portion of which comprising cannabis plant fan leaves; (b) separating plant matter which has previously been used in a cannabis oil extraction process; (c) combining specific amounts of materials separated in steps (a) and (b) to produce a cannabis plant material mixture possessing a specific active cannabis compound profile 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 cuitivar and expressed as a ratio of weight-of-compound per weight-ofextraet and (d) loading the mixture of cannabis plant material into a cylindrical smokable tube using a loading device.

[009] According to another aspect, the cannabis compound profile formulation comprises at least 10% by weight of purified D-9-tetrahydrocannabinol. According to another aspect the cannabis compound profile formulation at least 45% by weight of purified cannabidiol. According to another aspect, the cannabis plant material mixture further comprises hemp plant matter. According to another aspect, the cannabis compound profile formulation comprises at least 5% by weight of p urified b-myrcene. According to another aspect, the method further comprises cannabis compounds chosen from a set comprising myreene, a pinene, oeimene, terpineol, beta.- caryophyllene, linalool, limonene, terpinolene, valencene, gerauiol, phellandrene, carene, terpinene, fenchol, borneol, bisabolol, phytol, camphene, sabinene, camphor, isoborneol, menthol, cedrene, nerolidol, guaiol, isopulegol, geranyl, cymene, and eucalyptol.

BRIEF DESCRIPTION OF ΊΉE DRAWING FIGURES

[010] The accompanying drawings illustrate several aspects and, together with the description, serve to explain the principles of the invention according to the aspects, it will be appreciated by one skilled in die art that the particular arrangements 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.

[011] Fig, 1 is a diagram illustrating an exemplary' method for manufacturing smokable cannabis with defined active compound composition, according to a preferred aspect of the invention,

[012] Fig. 2 is an exemplary method diagram illustrating a. generalized method for

manufacturing smokable cannabis with defined active compound composition, according to a preferred aspect of the invention,

[013] Fig. 3 is an exemplary table diagram illustrating an analysis of active compound make-up of multiple hypothetical cannabis strains, according to a preferred aspect of the invention

[014] Fig, 4 is an exemplary diagram illustrating a method to confirm that labeled smokable cannabis delivery devices comprise the cannabis active compound profile of their intended type.

[015] Fig, 5 is a method diagram Illustrating a process for preparing cannabis medicinal products, according to an embodiment. DETAILED DESCRIPTION

[016] The inventor has conceived, and reduced to practice, a smokable cannabis-based product with reduced psychoactive effects and method for producing the same.

[017] Cannabis has been extensively cultivated throughout the world for centuries. Worldwide effects-targeted cultivation has progressed to tire 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 i s the cannahinoid 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: tetrahydrocannahinols (THC); cannabidiols (CBD); cannabichromenes (CBC); cannahinoi (CBN); cannabigerois (CBG); cannabinodiol (CBDL); and other cannabinoids (cannabicydol (CBL), eannabieisoln (CBE), cannabitriol (CBT) and other miscellaneous types

[018] In raw cannabis., the cannabinoids within tire flowers’ trichomes are carboxyiated, 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“deearbed ^" in layman’s terms. Non-psychoadive TIICA, 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 Joss of certain other cannabis components such as the terpenes, which are highl volatile. Both the decarboxylated cannabinoids and the carboxyiated cannabinoids exhibit important therapeutic effects for health, and although one can be chemically converted into the other, carboxyiated cannabinoids becoming decarboxylated cannabinoids, As used herein both will be referred to as simply cannabinoids,

[019] The biological effects of tire 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 neurotransmitier that predominantly binds to the cannabinoid receptor CB1 and a second compound, 2- arachidonoylglyeerol also known as 2-AG which predominantly binds to the CB2 receptor. Expression of the CB1 receptor is found at highest levels in ihe 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 tire central and peripheral nervous system, the immune system and immune response- related cells, and peripheral organs, among other areas of expressi n. Activation of the CB2 receptor may have an analgesic effect, reduce inflammation, and increase of immune response towards certain pathogenic bacteria and fungi. The CB2 receptor may also mediate anti-cancer effects attributed to caxmabinoids. 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,

[020] Other cannabinoid receptors are found in almost every organ of the body including the skin, the digestive tract and even in tire reproductive organs. Cannabinoid receptors interact with cells in a Jock (the cell receptor) and ke (the cannabinoid) type of mechanism. The combination of (lie cell receptors and the caxmabinoids comprise the endocannabinoid system, or ECS, which is an intricate network of cell receptor proteins that perform various functions in the body, and is considered to be tire greatest neuro transmitter 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 neuro degenerative diseases, and pain control and relief.

[021] The major differences between the various cannabinoids are determined by the extent to which they are psychologically active (psychoactive). Three substantial classes of caxmabinoids, including the ca mabigero!s (CBGs), cannabichromenes (CBCs), and cannabkliols (CBDs), are not known to have psychoactve effects. D-9-tetrahydrocannabmol (THC), cannabinol (CBN), and some other caxmabinoids 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.

[022] Of the over 80 known carmabmoid species, those most prevalent: and most studied in cannabis cultivars are: THC- D-lMeirahydrocannahinoi

CBD— cannabidiol

CBC— cartnabichromene

CBH- cannabinoI

CBG—cannahigerol

ΊHCv—ieirahy droeannabiv rin

CBDv— can n abid ivarin

D-feTHCreATtetrahy dro cairn abinol

THCA - D-9-tefrahydrocann binolic acid

CBDA— cannahidiolic acid

[023] 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

[024] THC: As used herein, THC refers to D-9-tetrahydrocannabinol, the chemical formula for which is C ₂₁ H ₃₀ O ₂ and the structure of which is:

[025] THC is recognized as the primary' psychoactive compound in cannabis and is the most common caxmabinoid. 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 he effective in alleviation of the symptoms of PTSD and reduction of nausea and vomiting, particularly that caused by chemoth erapy. 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 will inflammatory bowel diseases such as Crohn’s disea.se, 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. THC reduces pain and tremors and improves sleep for those nidi Parkinson’s disease. THC. CBD, CBC, and CBC together work synergistic-ally as a powerful cancer tumor fighting combination. This combination is more powerful than any single one of these working alone.

[026] CBD: As used herein, CBD stands for cannabidiol, tire chemical formula for which is GsiHsoCB and the structure of which is:

[027] CBD, or cannabidiol, is a non-psychoactive member of die cannabinoids and is one of the most prevalent chemical compounds in the cannabis plant. Found predominantly 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 significantly debilitating aspect of menial 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, anti tumor, and anti-psychotic: effects. CBD is powerful ail by itself, but it is even more powerful when combined with other cannabinoids such as THC.

[028] CBC: As used herein, CBC stands for cannabichromene, tlie chemical formula for which is C ₂₁ H ₃₀ O ₂ and the structure of which is:

[029] 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.

[030] CBC is anti-inflammatory and even more so when combined with THC It has anti-tumor effects and shows promise in fighting breast cancer. When combined with CBD, THC, and CBC, 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 memory 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.

[031] CBN: As used herein, CBN siands for cannabinol, ihe chemical formula for which is

C21H2 ₀ O2 and the structure of which is:

[032] Cannabinol, or CBN, emerges when the dried cmaabJsQowet becomes stale; over time, THC and GBD, which are generated by enzymatically-driven synthesis from CBG, break down through oxidative degeneration into CBN, CBN has antibiotic properties, including against methici!iin-resistant Staphylococcus aureus (MRSA), and also has pain-relieving properties through the release of endorphins. It may delay the onset of, and relieve symptoms of, degenerative motor neural diseases such as amyotrophic lateral sclerosis (ALS) an 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. [033] CBGi As used herein, CBG stands for cannabigerol, the chemical formula for which is GuHaaQa and the structure of which is:

[034] CBG, or cannabigerol, is found in caimahis 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 enzy matic synthesis of THC, CBD, and other cannabinoids, and so CBG is regarded as the source of all cannabinoids. It is non-psychoac.tive 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.

[035] THCV: As used herein, THCV stands for tetrahydrocannahivarin, tire chemical formula for which is CiaHzsOz and the structure of which is:

[036] THCV, or ieirahydrocamiabivarim is one of the several cannabinoids that works in synerg 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 the short-term memoty and speech impairment that comes from THC; it promotes weight loss by suppressing the appetite and possibly decreasing body fat and boosting energy metabolism. [037] QBDV: As used herein, CBDV stands for caimahidivarm, the chemical formula for which is CusHaoCA and the structure of which is:

[038] Catmabidivarin, or CBDV, is a slightly-de graded dose relative of CBD. It is used as an anticonvulsant, an antiepileptic, and has antiemetic properties (as well as aiding those with gastrointestinal issues).

[039] D-8-THC: As used herein. D-8-TFIC stands for D-8-tetrahydrocannahinol the chemical formula lor which is C _¾I H3 _O 0 ₂ and the structure of which is:

[040] D-8- tetrahydrocannabinol is different from Addtetrahydrocannabinol in that it is less psychoadive. It has both neuroprotective and anti-anxiety' properties, as well as being anti-emetic, and may be a stronger appetite stimulant than D-9-THC, snaking it art important consideration for people undergoing chemotherapy.

[041] THCA: As used herein, THGA stands for D-9-tetrahydrocaimabinoiic acid the chernieai formula for which is C22H30O4 sard the structure of which is:

[042] D-9-tetrahydroeannabinolic add, or THCA, is a non-psychoactive compound found in cannabis prior in decarboxylation to the psychoadive version, THC, by application of beat 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 arihriiis 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 anti-proliferative properties making it a candidate in treatment in certain cancers such as but not limited to prostate cancer,

[043] CBDA: As used herein, CBDA stands for cannabidiolic acid, the chemical formula for which is Q _& H ₃₀ O ₄ and the sirudure of which is:

[044] Camiabidiohc acid, or CBD A, cannot administered by smoking or vaporizing because doing so decarboxylaies it to CBD, similar to THCA conversion to THC. The therapeutic uses for CBDA include antibacterial, anti-emetic, anti-inflammatory, and cancer ceil anti-proliferative,

[045] Another family of active compounds present in, but not exclusive to, cannabis are the terpenes and decarboxylated terpenes, which sue known as terpenoids. Decarboxylation occurs w th 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 thev are not chemically identical in sirudure or chemical formula as terpenoids ar e 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 the cannabis plant.

[046] 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 class 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

[047] The isoprene skeleton (CsH ) may be 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.

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

[049] The primary'· terpenes are: myrcene, a-pinene, ocimene, terpineol, b-earyophyilene, linalool, limonene, terpinolene, valencene, and geraniol.

[050] The secondary _' terpenes are: phel!andrene, earene, terpinene, fenchol, borneol, bisabolol, phytol, camphene, sabinerte, camphor, isohomeol, menthol, eedrene, nerolidol, guaioi,

isopulegol, geranyl acetate, cymene, eucalyploL and pu!egone.

[051] 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 camiabinoids, 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.

[052] Caimabinoid-terpenoid interactions have die 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 MKSA,

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

[054] Myrcene— Myrcene, specifically b-myrcene, is a monoterpene and the most common terpene produced by cannabis (some varieties contain up to 60% b-myrcene as a fraction of the total terpene content). Amyrcene is not found in nature, and was first synthesized in 1065. The chemical formula for b -myrcene is ChoHjs and the structure is:

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

[056] Myrcene has some very special medicinal properties, including lowering the resistance across die blood-brain harrier allowing itself and many other chemicals to cross the harrier more easily and quickly. Myrcene also increases cell membrane permeability, and in the case of cannabinoids like THC, b -myrcene allows tire cannabinoid to take effect more quickly. More li) uniquely still, b -myrcene has been shown to increase the maximum saturation level of die 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, ai!atoxin B and other pro-mutagenic carcinogens. It acts as an inhibitor of gastric and duodenal ulcers. Its

15 sedative and relaxing effects make it ideal for the treatment of insomnia and pain.

[057] tt-Rsienn-Alpha-pinene is a monoterpene alkene isolated from pine needle oil as well as from cannabis. There are two structural isomers of piuerte found iu nature: a-pinerte and b- pirtene, with cf-pinene being the most widely encountered terpenoid in nature. With art aroma and flavor of pine, this is partially where pine trees get their scent. The chemical formula is

20 CioHi _o and the structure is:

[058] Pinene is one of the principal monoteipenes that is imporiant physiologiadly in both plants and animals. It tends to react with other chemicals, forming a variety of other terpenes (like limonene), as well as other compounds.

[059] Medicinally, a-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 cannahinoids CBD and CBN, all three working in synergy with each other, Alpha-pinene increases alertness and counteracts some of the negative effects of the eannabinoids THC, such as anxiety. It is also believed that the negative memory effects of THC may be lessened if mixed with «--pinene.

[060] Odmene-Ocimene is a group of isomeric monoteipenes found in a wide variety of fruits, spices, and plants. Alpha- ocirnene and the two b-ocirnenes. cis-[hocimene and tnms-p-oc nene, differ in the position of the isolated double bond: in tire alpha isomer it is terminal b-ocimene exists in two stereoisomer! c forms, ets and trans, with respect to the central double bond.

Ocirnene is often found naturally as a mixture of its various forms. The chemical formula is Cic-Hio and die three structures are;

06 j cis-p-oeimene

[063] bans- b-ocimene

[064] 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 cannabi , mint, parsley, pepper, basil, mangoes, orchids, kumquats, and allspice.

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

[066] Terpineol— Found in cannabis as well as in over 150 other plants, terpineol exists as four isomers: cc-terpineoL b-terpineol, g-terpineoi and terpinen-4-ol, are four closely related

monoterpene alcohols. These are found mixed in plants and tlieir essential oils, with a-terpineol comprising the majority of the mixture. The chemical formula is CxoHxeO and the four structures are:

[067] 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 a-pinene. Due to a-pinene’s strong aroma, terpineol may he difficult to delect by odor when the two occur simultaneously as the scent of a- pirtene masks the snore delicate floral scent of terpineol. [068] Terpineol, specifically a-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, TerpineoFs most important property is its anti-cancer property ^' it is able to kill tumors directly.

[069] b-CaryophylIene— b-caryophyllene is a bieyclic sesquiterpene with the formula C15H24 and the structure:

[070] B-caryophyJlene 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 which cannabis is closely related.

[071] B-caryophyJlene 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 psychoactivify). b-caryophyllene selectively binds to the CB2 receptor where it is a functional CB2 agonist, giving it an anxiolytic and anti-depressant effect and showing that b-caryophyllene may be useful in treating anxiety and depression. B-caryophyllene also has anti-oxidant, anti-inflammatory, anti-cancerous, and local anesthetic effects. Further, B caryophy!iene is unique for being both a terpene and a dietary cannabinoid, a food component which acts as a cannabinoid and binds to CB2 receptors.

[072] Other phytocannabinoids in combination, especially cannabidiol (CBD) and b- caryophyllene, when delivered orally, appear to be promising candidates for the treatment of chronic pain due to their high safety and low adverse effects profiles. [073] b-caryophyilene, through its CB2 receptor-dependent athway, may be an excellent therapeutic agent to prevent nephrotoxicity (poisonous effect on the kidneys) caused by anti- cancer chemotherapy drugs such as cisplatin.

[074] b-earyophyilene has antioxidant and antinociceptive (blocks the sensory neuron detection of pain stimuli) properties. This suggests that high-caryophyl!ene strains may be useful in treating a number of medical issues such as arthritis and neuropathy pain. It is anti-inllainrnatoiy because of its ability to bind directly to the endoeannabinoid receptor known as CB2. It is also protective of the cells lining the digestive tract which offers promise for treating some ulcers, and is anti fungal, b-caryophyllene holds promise for cancer treatment

[075] linalool— Linalool is a terpene alcohol that occurs as two enantiomers d-liualool and 1- linalooi, with the chemical formula CioHisO and the structures:

[076] Linalool has a floral lavender aroma with a hint of spice. In addition to cannabis, linalool 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. Linalool is a critical precursor in the formation of vitamin E

[077] Linalool 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 potentiall caused by inhaling cannabis smoke. Linalooi helps to restore cognitive and emotional function partially via its and -inti amrnaiory 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 tire anxiety brought on by pure THC, 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 repel!ant and for use in and around the home and garden.

[078] Limonene— Limonene is a monocyclic monoterpene and one of two major compounds formed from pinene. It exists as two enantiomers, ddimonene and I-limonene, and has the chemical formula CxoHi _t» . The structures are:

[079] Limonene has a citrusy 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 and-fungal, anti-bacterial, 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 the formation of some tumor growths and alleviate fat buildup in the liver induced by diet, Limonene is known to increase blood pressure which is useful for those with low blood pressure. It has very low toxicity and adverse effects are rarely associated with it.

[080] Terplnolen -Terpinolene, also called 6-terpinene (d-terpinene), is one of a class of isomeric monoterpenes, all of which have the chemical formula CioHie _, and which differ from each other only in the position of the carbon-carbon double bonds. The a-terpinene, y-terpinene, 6-ierpinene (terpinoiene) are all found in plant essential oils, whereas b-terpinene is synthetically prepared from sabinene. The chemical structures are:

[081] 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, Montere cypress, and lilacs. It is used in soaps, perfumes, cosmetics, flavorings, and in the semiconductor industries.

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

[083] Terpinolene markedly reduces the expression of die AKT1 geue, 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 ceil 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 AKT I gene expression, both rampant cell proliferation and lack of apoptosis are suppressed, making terpinolene a valuable anti-cancer agent,

[084] Terpinolene, together with vitamins A and E, prevents fee oxidation of“bad cholesterol” (low-density lipoprotein, or EDI.) and is therefore helpful in the treatment of heart disease. [085] Terpinolene’s potential medical benefits include: antioxidant, sedative, antibacterial, antifungal, insect repellent, anti-proliferative (anti-cancer) and non-genotoxic, making it vary safe and very healing

[086] Valencene— Valencene is a hicyclic sesquiterpene with chemical formula CtsHn and is found in Valencia oranges as well as cannabis. The chemical structure is:

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

[088] Valencene is toxic to ticks and mosquitoes at lesser concentrations than DEET 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.

[088] Geranioi— Geranioi is an acy clic monoterpene alcohol whose formula is CioHisO and which boils at about 447 "F and frequently occurs in strains that also produce linalooL Not only from cannabis , geranioi is also found in rose, geranium, lime, lemon, lemongrass, nutmeg, bergamot, carrot coriander, lavender, blueberry, blackberry, and tobacco. Geranioi emits a rose- like scent that makes it a popular perfume additive. The chemical formula is:

[090] Geranioi is an effective mosquito repellent, an aniioxidani, and shows a potential protective effect against neuropathy. It is anti-cancer and inhibits the growth and biosynthesis of colon cancer cells, and when combined with famesol and peril! alcohol, suppress pancreatic tumor growth making it especially useful for cancer of the pancreas which currently is extremely difficult to cure. [091] Secondary terpenes:

[092] Pheliandrene-Phellandrene refers to a pair of cyclic monoterpenes ili ! have a similar molecular structure and similar chemical properties, a-phellandrene and b-phellandrene, which are double-bond isomers of each other. In a-phellandrene, both double bonds are endocyclic (within tire ring structure) and in b-phe!landrene, one of them is exocydic (external to the ring structure). Phellandrene has the chemical formula CioHn, and is described as pleasant, fresh, ciirasy, inty and peppery-woody. The chemical structures are:

ec-phellandrene b-phellandrene

[093] Phellandrenes are used in the perfume and die flavoring industries because of their pleasing aromas and because they are absorbed through the skin ci-phellandrene may form dangerous, explosive peroxides on contact with air at elevated temperatures, b-phellandrene is noil-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, entha, fennel, ginger, and Fi ns species

[094] Insoluble in water but miscible with ether, phellandrene is one of the easiest terpenes 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 crystals of phellandrene nitrate speedily form.

[095] 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 fungal infections. Phellandrene possesses antidepressant properties and is also used as an insecticide. [096] Carene-A-3-Carene is a bicyelie monoterpene with a sweet, pungent odor. It is found naturally in cannabis id 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 orange juic.es, citrus peel oils from fruits like lemons, limes, mandarins, tangerines, oranges, kumquats, and it is a major component of turpentine, comprising as high a 42% depending on the source. The chemical formula is CioHxe and the chemical structure is:

[097] D 3-Carene is used as a flavoring in many products.

[098] It is nontoxic, but may cause irritation when inhaled. It is possible that high concentrations of d-3-caxene in some strains may be partly responsible for symptoms of coughing, itchy throat, and eye afflictions when smoking cannabis .

[099] D-3 carene is an effective anti-inflammatory. In higher than natural concentrations, 6 -3- carene may be a central nervous system depressant and a skin irritant. It is often used to dry out excess bod fluids, such as tears, runny noses, sweat, and menstrual flows,

[100] Terpinene— -Terpinenes are a group of isomeric terpen es with die chemical formula

CioHie and this group is composed of three natural isomeric terpenes and one synthetic one that differ fro each other in the positions of die carbon to carbon double bond, A-terpinene, d - terpinene (terpinolene), and y-terpinene are naturally occurring, whereas b-terpinene is not found in nature but may be synthetically produced from sabinene, D-terpinene is also called

terpinolene. The chemical structures are

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

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

[103] Fenehoi-Fenchol, also called l,3,3 irimethyl-2-norbornanoi, is a terpene and n isomer of bomeol with the chemical formula CinHiaO and the chemical formula is:

[104] This particular terpene is an enantiomer, d-fenchol or (1 j?}-endo-(+-}-fenchol, but it has no mirror image found in nature, thus it is enantiopure.

[105] Found in cannabis , it also occurs naturally in basil, fennel, nutmeg, pine, rosemary oil, lime oil, beer and more. It has a bitter, lime flavor and is used extensively in perfumes, flavorings, soaps, detergents, mid persomtl care products. It is known to exhibit antibacterial properties. [106] Bomeol-Borneol, a terpene alcohol, ha tlie chemical formula CioHisO and exists naturally as two enantiomers, 1-borneol 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 man natural essential oils, It is found in cannabis resin and herbs like thyme, rosemary, and cinnamon. The chemical structure is:

[107] Borneol is used in the perfume industry, as well as in dietary and herbal supplements in tire USA

[108] Borneol is used as a calming sedative, it is used to fight fatigue, stress, to relax, and to recover from illness Borneo! is used as: an anti-inflammatory, an anti-nodeeptive/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 broncho dilator, a cough suppressant, and an insect repellanti

[109] Bisabolol - Also called levornenol oc-bisabolol is a natural monocyclic unsaturated sesquiterpene alcohol with the chemical formula Ci.sH _¾¾ t) and a chemical structure of:

a-bisabolol

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

[111] A-bisabolol, which is nontoxic and nonirritating to the skin, possesses anti-inflammatory aud 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 grain -positive bacteria. It shows promise in the treatment of certain cancers as it induces apoptosis in leukemia.

[112] Phytol— Phytol is a natural linear diterpene alcohol with die chemical formula CZGHIOO that may be used as a precursor to prepare synthetic forms of vitamin E and vitamin Kl. Found 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:

[113] Phytol inhibits the enzyme that degrades the neurotra.nsmitier GABA {y-aminobntyiic 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.

[114] Camphene- Camphene is a bicydic monoterpene with the chemical formula CjoHxe and the chemical sirndure:

Camphene readily volatilizes at room temperature and has a pungent odor similar to camphor. It is a minor component of many essential oils such as turpentine, cypress, rteroli, valerian camphor, citronelia and ginger. It is used as a flavoring for food and in the perfume industry. It is produced industrially by catalytic isomerization of the more common ct-pinene.

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.

[116] 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, [117] Sabfoene-Sabinene is a bicydic monoterpene with the chemical formula C oH-.e and exists as d and 1 enantiomers. The chemical structures are:

d Sabinene 1 Sabinene

[118] It has an aroma of spice, pine, and orange, and is found in many plants including cannabis , Norway spruce, black pepper, basil, and Myiistica h ^~ agrans—xhe world’s main source of nutmeg. If is used in the perfume industry and in the food industry as flavoring.

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

[120] Camphor- Camphor is a waxy, flammable, white crystalline solid with the chemical formula CieHieO. Camphor occurs naturally as d-camphor, the 1-enantiomer being synthetically produced.

1- and d-carnphor

[121] It is commonly found in cannabis , rosemary leaves camphor basil, and in Cinnamomum camphors 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 tire laurel family notably Ocotea usambarensis.

[122] The ancient Egyptians used camphor as one of tire 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 eongh suppressant, a decongestant, an insect: re ellant 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,

[123] Xsobomeol— Isoborneol is a hicyche terpene alcohol with tire chemical formula CioH _t sO and tire chemical structure

[124·] Isoborneol is a -waxy solid with an odor similar to that of camphor, and is found in cannabis and mugwort. Isoborneol exhibits antiviral properties and Is a potent inhibitor of herpes simplex virus iype 1 . Besides being antiviral, it also has antioxidant, anti-inflammatory, and antimicro bial prop ertie .

[125] Menthol-Menthol is a terpene alcohol with the chemical formula CioHatO and the chemical structure:

[126] 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.

[127] Menthol produces a cooling sensation on the skin and soft tissues of the mout 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,

[128] 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, bruising, and cramping.

[129] Menthol cigarettes have a lower cancer risk and cause far less cigarette related cancers than their nonmentholated counterparts, making menthol an important and possibly mitigating component of inlutled cannabis,

[130] Cedren -Cedrene is a sesquiterpene vddi the chemical formula CxsHai and exists in two isomeric forms, a-cedrene and-p-cedrene, which differ in the position of one double bond.

«-cedrene b-cedrene

[131] 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.

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

[133] Nerolidol—A!so known as peruviol, nerolidol is a naturally occurrin sesquiterpene alcohol present in various plants with a floral odor, and has the chemical formula CisHaaO. It exists in two isomeric forms, cis and trans, which differ in their geometry about the central double bond. The chemical strucUrres are:

of [134] Nerolidol has a floral, citrus, woody, fresh bark aroma and may be found in Cannabis saliva neroli, niaouli, ginger, jasmine, lavender, tea tree, citroneila, lemon grass, and Bmssavoh. nodosa, a Mexican orchid.

[135] 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.

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

[137] Guaiol— Guaiol, also called champacol, is a sesquiterpenoid alcohol found in several plants, including Cannabis indica, guaiacum and cypress pine it is a crystalline solid a.t room temperature with die chemical formula CrsHasO and the structure:

[138] Guaiol has a woody, rosy, floral aroma. Cannabis sixains known to contain guaiol include Liberty Haze, Blue Kush, Choeolope, and Medical Mass.

[139] 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. GuaioPs potential medical properties include: Antimicrobial, Anti-inflammatory, laxative, diuretic, and insect repellant.

[140] Isopulegoi— Isopulegol Is a monoterpene alcohol found in cannabis , corn mint, European pennyroyal, iemongrass and geranium, and possesses a. minty aroma. It has the chemical formula CxoHxsO and the structure:

[141] 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, anii- inilammatory, antioxidant, and stress-reducing effects, and it reduces the severity of seizures and anxiety in animal models.

[142] Geranyl Acetate- Geratiyi acetate has several other names including geraniol acetate, and is a monoterpene ester witli 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:

[1 3] 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.

[144] Geranyl acetate is found in a variety of natural essential oils, such as cannabis , citron elia, pahnarosa, geranium, coriander, neroli, lemongrass, peiitgrain, carrot, sassafras, rose, and many others. It exhibits strong antimicrobial, antifungal, said anti-inflammatory effects.

[145] Cymene-~Also called p-eyrnene, para-cymene, methyl-isopropyl-benzene, and [-isopropyl- 4-methylbenzene among others, this aromatic, para substituted benzene ring is an aiky!benzene monoterpene with the formula CioHu and the structure:

[146] The other two isomers of methyl-isopropyl-benzene are o-cyrnene (ortho cymene) and m-· cymene (meta cymene), however only p-cymene is a naturally occurring compound. It has a citmsy-woody- picy 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.

[1 7] P-cymene has documented anti-inflammatory effects, it shoves 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 synergistieally together and have anti-fungal properties; p-cymene by itself showed strong antifungal activity against numerous Candida species, P-cymene also shows anti-inflammator> , antinociceptive and analgesic properties.

[148] Eucaiyptol— Eucalyp tol has many other names, including 1,8-cineol, eajeputol; 1,8-epoxy- p-menfhane, and eucalyp toie. Eucaiyptol is a cyclic monoterpenoid eiher and it is the main component of eucalyptus essential oil having the chemical formula CuiHjaO and the chemical structure:

[14:9] Eucaiyptol has a minty, earthy, spicy aroma and is found in several plants including Cannabis sativa, camphor laurel, bay leaves, tea tree, mugwort, sweet basil, wormwood, rosemary, common sage, and other aromatic plants. Eucaiyptol is used in flavorings in baked goods, confectionery, meat products, beverages, and mouth wash; in fragrances, cigarettes and cosmetics.

[150] 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 cultured 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 rhinosixmsifis

[151] Pulegone—Pulegone, a monocyclic monoterpenoid, is a secondary terpen e component of cannabis. It exists naturally in two enantiomeric forms, d-pulegone surd 1-pulegone, with d- pulegone being the most abundant. The chemical formula is C _t oHieO and the structure is:

d-pulegone

[152] It has an aroma of peppermint and camphor, and it is found in several plants besides cannabis , such as catnip, peppermint, spearmint, pennyroyal, turd 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.

[153] Puiegone is an em enagogue, a mucolytic, and is good for congestion of the respiratory system. Puiegone 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, Puiegone is a powerful insecticide

[154] Traditionally, plants containing puiegone, such as pennyroyal, have been used as herbal teas for non-ulcer dyspepsia, primary dysmenorrhoea, secondary amenorrhoea and oligomenorrhoe , as an abortiiaeieni, and as diaphoretic. Pennyroyal essential oil has been used for the same conditions. Pnlegone is a hepatotoxic (liver poison) and nephrotoxic (kidney poison) constituent of the folklore abortifacient pennyroyal oil.

[155] Today, Mentha piperita (peppermint) and Mentha pu!egium (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.

[156] One other terpene found in cannabis that bears mentioning is hnmulene.

[1.57] Humulene— Humulene is a monocyclic sesquiterpene containing an 11-membered ring and is also known as «-hnmulene and a-caryophy!lene (an isomer of b-caryophyllene).

Humulene is often found in combination with it’s isomer, b-caryophyilene, it has the chemical formula CVJHs and the structure is:

d in Cannabis sativa strains, hops and Vietnamese coriander, pine trees, s, tobaccc age, ginseng, ginger, and sunflowers, among other plants.

Humulene is what gives beer its distinct“hoppy” aroma, and also contributes to the same hoppy aronra in cannabis.

[159] Humulene is anti-tumor, anti-bacterial, is a strong anti-inflammatory, and is anorectic (suppresses appetite). It is often blended with b-caryophy!lene and used as a potent remedy for inflammation. Humulene aids in weight loss lay acting as an appetite suppressant.

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

[161] The differences in the amounts and types of both cannabinoids and terpenes, along with the oilier 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.

[162] Cannabis as 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 those with chronic medical conditions, even though other forms of administration of cannabis are available for medical use. This preference is likely due to a variet of factors. First, smoking cannabis Gloves the user to easily control the dosage, as (lie effects tire 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 catmabmoid 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 feet that certain modern North American and European strains of cannabis display relatively high concentrations of THC (a potent psychoactive compound), but relatively' little CBD or other phytocannabinoid content. [163] A substantial body of medical literature supports the anecdotal evidence that cannabis can be used to treat chronic pain. The endocannabinoid system is active in the control of pain. Compounds found in cannabis act on the endocannabinoid system, and certain of these compounds have a powerful analgesic effect. For example, THC is believed to be ten times more powerful than morphine in mediating pain in wide dynamic range neurons in the

ventroposteroiateral 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 tire adenosine receptor A2A by inhibiting the adenosine transporter. Cannabigerol (CBG), a“tumor cannabinoid” found in small quart titles in cannabis^ is believed to have even greater analgesic activity than THC.

[164] 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 provide by the opioids. Combining cannabis treatments for chronic pain with opioid treatments for chronic pain may have the benefit of reducin patient pain levels, reducing reliance on (and addiction to) opioids, or both.

[165] The inventor has conceived, and reduced to practice, a variety of cannabis formulations for the treatment of chronic pain. In one exemplary aspect of the embodiment, different combinations of THC, CBD, and CBG may be used to obtain the desired amount of pain relief due to chronic illnesses. In another exemplary aspect of tire 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.

[166] The inventor has also conceived, and reduced to practice, a variety of cannabis

formulations for the delivery of an enhanced cannabinoid effect employing tire terpene myrcene. This not only raises the sattirat.ion level of a predominant cannabinoid receptor such as CB! 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. [167] In one exemplary aspect of the embodiment the formulation to treat sleep disorders may be: 5mg D-9-ietrahydrocannahinoi (THC) 5mg earmabidiol (CBD), and 5rng eannabigerol (CBG). The combined mixture may be compounded into a liquid form for inhalation using a vaporizer.

[168] In another aspect of tire embodiment, the terpen e myrcene will he added to the

formulation to raise the 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 he present in cannabis extracts, thus potentiating the effects of these medically effective compounds at several major sites of action.

[169] One or snore 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 that 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 he made without departing from tire 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 l e 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 the formulations nor a listing of features of one or more of the formulations that must be present in all embodiments. [170] Cannabinoids, terpenes and flavonoids employed in aspects are to be assumed isolated and purified by previously published means best suited for that active compound which may include but are not limited to HPLC, 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

[171] When single cannabinoids, multiple cannabinoid mixtures, cannabinoidderpene mixtures, ciinnabinoid terpene-flavonoid terpene, multiple terpene and terpene-fiavonoid 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 nest 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 formulati n, capsules of the formulation and tablets of the formulation as w _' ell as other administrative methods knowni to be applicable to those with ordinary skill in the art,

[172] 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.

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

174] Fig. 1 is a diagram illustrating an exemplary method for manufacturing smokable cannabis with defined active compound composition 100, according to a preferred aspect of the invention. Multiple cnliivars or strains of cannabis 105, 125 may be used, and parts or components may be harvested from any such cultivar or strain, Each cultivar is expected to produce a significant level of one or more active cannabis compounds such as but not limited to: d-9-teLrahydrocannahmol (THC) cannabidiol (CBD), cannabichromene (CBC), b-myrcene, and menthol, as well as potentially a number of other active compounds found in cannabis. From cultivars 105, 125, flowers 107, 127 and leaves 110, 130 may be harvested although other pails (such as stems or roots) of cultivars 105, 125 may also be harvested if desired for alternative manufacturing uses, and need not be discarded. Harvested material is shredded 160a, 160b by manual shredding methods and/or mechanical shredding methods, to a mesh size ranging from 2 millimeters (mm) to 5mm for width and a mesh size ranging from 5mm to 15mm for length, of shredded plant material 115, 135. Any plant material 115 135 that is undesirable, such as stems or stem fragments, or plant remnants t at are too small for inclusion, may be removed after shredding process 160a, 160b, or may l:>e preserved for other purposes, and need not necessarily be discarded immediately. Plant material 115, 135 may now be sterilized by radiation 185a, 185b (it should be appreciated that sterilization methods such as, but not limited to, ultraviolet radiation or heat over an extended time period may be used, according to a desired use case of the invention) or in a solution of water and 1-10% hydrogen peroxide for 15 to 90 minu tes. Sterilization 185a, 185b of plant material 115, 135 should not reduce potency of target active cannabis compounds but should eliminate undesirable microbial contaminants. It should be appreciated that, depending on tire sterilization method used, some active cannabis compounds may be activated during the sterilization process if these compounds are found in material and are desired in the final product.

[175] Plant material 115, 135 from cultivars 105, 125 may then be combined into calculated ratio-based batches 150 of material to achieve target concentrations of specific active cannabis compounds based upon component make-up of cultivars 105, 125. In the instance where desired active cannabis compounds and/or desired concentration of active cannabis compounds are not found, a pre-existing solution 170 of desired and purified active compound composed of a known concentration may be added to material batches 150 prior to analysis 195. Detailed composition of active compounds within material batches 150 may be identified using analysis 195 methods of isolation and assay. Material batches 150 may also be analyzed for microbial contamination within acceptable standards 190. Once passing all analyses 190, 195, material batches 150 may be manually or mechanically loaded into a hollowed-out cylindrical-type shape delivery device 180a, 180b composed of hemp paper or oilier substance (it should be appreciated that other devices may be used such as but not limited to; devices composed of plastic or metal, devices comprising filters or tipping paper, or other devices known to those skilled in the art according to a desired use basis of the invention). Once material batches 150 tire loaded into delivery device 180a, 180b, devices 180a. 18Gb are then toasted at a temperature ranging from 18(FF to 220 ^? F for a duration between 3 to 15 minutes. Finished products may then be labeled, packaged, and distributed.

[176] Fig. 2 is an exemplary method diagram illustrating a generalized method for

manufacturing smokable cannabis with defined active compound composition 200, according to a preferred aspect of the invention. One or more cannabis cultivars may be selected for harvesting material based upon known active cannabis compounds found in cultivar strains 201a, 201b, 201n. This material is processed 202 by harvesting from cultivars, diving plant materials, and shredding to a size range of 5mm to 15mm length and 2mm to 5mm width, Undesirable components including stems and stem fragments may be discarded 203 but need not necessarily be immediately discarded. Material is then sterilized 204 by heat, ultraviolet radiation, or other sterilization methods, and samples tested 205 for efficacy of sterilization. Plant materials from multiple cultivar strains 201a, 201b, 2GIn may be mixed together 206 to create material hatches with desired active cannabis compound profiles. In cases where desired compound profiles are not achieved, pre- existing solutions of purified active cannabis compound concentrations 220 may be added to batches. Active compound levels within each batch may be assayed (analyzed) 207 prim: to being loaded into delivery devices 208. Batch samples ma be analyzed again for compound potency and for microbial contamination 209, Finished products may then be toasted, labeled, packaged, and sent for distribution 210 to consumers.

[177] Fig. 3 is an exemplary table diagram illustrating an analysis of active compound make-up of multiple hypothetical cannabis strains 300, according to a preferred aspect of the invention. Different cannabis strains may express differing levels of desired compounds and compound potency. Table 300 denotes a small number of possible active compounds and amounts of each listed compound, expressed as a percent weight compound/total weight extracted material (Itwhcoinp un AytioiaiE _Atf aci [%wta/Wtt] ) . Active compound liberation as in the case of smoked, dried, or vaporized buds 301a, or kief, hash, or tincture 301b, may change active compound levels and ratios due to processing mechanics, Given these possible changes, liberation methods should be independently tested 302 for analysis accuracy 303. Table is set up into columns of cannabis strains 310, and active compounds found within strains; deita-fhtetrahydrocannahinol (THC) 311, cannabinoids (CBD) 312, terpenoids 313, and 314 represents any additional compounds that can be tested for. Column 310 lists a plurality of hypothetical cannabis strains; strain A 315, strain B 316, strain C 317, strain D 318, and strain n 319. Columns 311, 312, 313, and 314, list active cannabis compounds that may be found in each strain of column 310. All active compound levels are listed in wTon^mind/whoiaiEman some as mean ± variance 331, 336, 341 while other compounds 332, 333, 334, 337, 338, 333, 341, 342, 343, 344 are listed as ranges. Levels may vary widely between strains; THC 311 levels may vary from 26% 332 for strain B 316 while strain D 318 may have levels at 0.42% 334 CBD 312 levels could vary from 30% 339 in strain D 318 to an unmeasurable level 337 in strain B 316. The terpenoids 313, which are a large family of related compounds, follow similar variability between strains. Please note that this figure is presented solely to effectively illustrate that large differences may exist between strains in the levels of active cannabis compounds. As the total level of a single active compound and the combination of the levels of two or more active compounds may affect the cannabis experience, illustration of a small number of compounds was necessary to make seival salient points. The small number of strains and compounds as well as the combination of all terpenoids into one column was to produce a clear basis for disclosure and does not in any way reflect the function of the embodiments.

[178] Fig. 4 is an exemplary diagram illustrating a method to confirm that labeled smokahie cannabis delivery devices comprise the cannabis active compound profile of their intended type 400. One or more cannabis eultivars 410, 420, 430 may express differing profiles of active cannabis compounds such as bnt not limited to; d-fftetrahydrocannabinol (THC), eannabidiol (CBD), eannabichromene (CBC), beta-myrcene, and menthol among a plurality of other active cannabis compounds. Flowers 412, 422, 432 and leaves 414, 424, 434 may be harvested from eultivars 410, 420, 430 and harvested material Is then shredded manually 460a, mechanically 460b, or by a combination of both methods 460c, Sizes may range from 2mm to 5mm in width and 5mm to 15mm in length as a means for finished product to fit inside smokable delivery device 448. Each batch of material 413, 423, 433 may be assayed 415, 425, 435 for active cannabis compound profiles to confir potency. Calculated ratios 413a, 423a, 433a of plant material 413, 423, 433 are then mixed into a single material batch 440 for desired active cannabis compound profile. If batch 440 fails to produce desired active compound profile, pre-existing exogenous solutions composed of desired active compound concentrations 450 may be added to material batch 440, Material batch 440 may then be sterilized 470 by methods such as radiation, ultraviolet irradiation or heat over extended periods of time, or by other sterilization methods known to those skilled in the ark Material batch 440 is then tested for residual microbial contamination 441 and analyzed to confirm formulated batches 440 active cannabis compound potency 445. In cases of Insufficient potency, batch material 413, 423, 433 may be reformulated 413a, 423a, 433a, into a new batch 440 and retested 450, 470, 441, 445 until desired potency standard is met. Standard compliant batches 440 are then loaded into a cylindrical-type delivery device 448 toasted between 180 ^fi F to 220 ^® F for 3 to 15 minutes, labeled, packaged, and sent for distribution to consumers.

[179] In various embodiments, functionality for implementing systems or methods of the present invention may be distributed among any number of manufacture stations or devices. For example, various harvesting devices, processing devices, such as shredders, tube loaders and packagers may be employed for performing various functions in connection with the present invention, and such modules may be variously implemented within a configuration which combines multiple functions or performs each function within distinct components.

[180] Fig. 5 is a method diagr am illustrating a process 500 for preparing cannabis medicinal products according to an embodiment. The overall process of creatin medicinal products from tlie cannabis plant consists of six stages: cultivation, extraction, concentration, separation, secondary concentration, and processing. At the cultivation stage 501, the cannabis plants are grown and harvested. The harvested plant matter, or selected portions of it, Is sent for extraction 502, at which point essential oils of die plant are extracted which contain some plant matter in the form of chlorophyll, plant waxes, plant lipids, plus substantial amounts of cannabinoids, terpenes, and ilavonoids. Extraction processes may include, for example, super critical C()2 extraction, hydrocarbon solvent extraction, hydroi!uorocarhon extraction, or other gas-based and solvent-based extraction methods commonly used in the art. These oils are concentrated 503 via evaporation. In the separation stage 504, the cannabis compounds are separated from the concentrated oils via a variety of processing methods, usually involving high pressure liquid chromatography or flash chromatography. At this stage, the purified cannabis compounds

(cannabinoids, terpenes, and ilavonoids) are sent for further concentration 505 via evaporation. Said concentrated purified cannabis compounds are then processed 506 with other ingredients to create medicinal products, for example pills, tablets, salves, injectables, etc. [181] In an aspect, additional amounts of the terpene rnyrcene is added to the product in step 506 to tale advantage of the unique advantages presented by b-nryreene 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 terpen es, and cannabinoids including but not limited to THC, .For example, infusing myrcene as well as THC info the product in step 506 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 rnyrcene may significantly augment the efficacy of such formulations for die desired biological and medicinal effects.

[182] In another aspect, there may be excess plant matter that may not be generally used. For example, during cultivation step 501, there may be portions of tire cannabis plant that are known in tire art have lower concentrations of THC, for example, fan leaves. These portions may Ire harvested r step 507, and used in production of a smokable cannabis product with less psychoactive effects, Another possible source of plant matter which contains lower concentration of cannabis-based compounds that may be cultivated is the post-extracted plant matter of extraction step 502. These post-extraction plant matter may contain a known concentration of cannabis-based compounds found in (lie pre-extraction plant matter, albeit at a lower concentration, and may be collected in step 508, For example, using theoretic strain A from the table from Fig. 4, after undergoing the extraction process, wherein a majority of the cannabis- based oils are extracted, there may be, for instance, 10% w/w to 15% w/w of cannabis- based compounds left behind. This would give an approximate concentration of 3% w/w THC, .03% w/w CBD, and .11% w/w terpenoids for post-extraction of theoretic strain A, The plant matter collected in step 507, and step 508, may then be combined to create a final product noth a lower concentration of psychoactive compounds in siep 509, for example, using tire techniques described in Fig. 1, 2, and 4,

[183] In an aspect, in order to achieve a less potent smokable cannabis-based product, a combination of non-psychoactive cannabinoids and other cannabinoids that may mitigate the psychoactive effects of THC may be used in total composition of end product, Non-psydroactive cannabinoids may include, but is not limited to, cannabidio! (CBD), eannabfrhromene (CBC), and cannabinol (CBN), Also, it may be possible to user plant matter from a cannabis plant strain that contains only trace amounts of THC, for example, hemp plants, which may contain less than 1% wfw of THC but may contain abundant amounts of CBD. Compounds that enhances the effects of THC, such as b-myrcene may be excluded. For example, the product may comprise 5% wy'w to 25% w/w AT-tetrahydrocannabinol (THC), 25% w/w to 65% w, v CBD, 5 %w/w to 35% w/w

CBC, and 5% w/w to 20% wy'w CBN. The formulation discussed above may also be augmented with terpenoids to give the final product therapeutic effects, for example, for pain relief, for sleep aid, for relaxation, and the like.

[184] In another aspect the formulation mentioned above may include b-myrcene so that users may experience the mild effects quickly. For example, the product may comprise 0,15% w/w to 30% w/w b myrcene, 5% w/w to 25% wy'w D-9-tetrahydrocannabinol (THC), 25% w/w to 65% w/w

CBD, 5 %w/w to 35% w/w CBC, and 5% wyw to 20% wy'w CBN The formulation discussed above may also be augmented with terpenoids to give the final product therapeutic effects, for example, for pain relief, for sleep aid, for relaxation, and the like.

[185] it will be appreciated by one skilled in the art that the formulations above are combinations that typically do not occur naturally. The compounds may be required to undergo extraction processes, testing processing, further refining processes, and the like before combining into a final product. The formulations also do not signify any limitation of the present invention, and may include oilier cannabis-derived compounds, for instance, one or more terpenes may be included to provide relief for various physiological aliments.

[186] The skilled person will be aware of a range of possible modifications of the various aspects described above. Accordingly, the present invention is defined by the claims and their equivalents.