Cannabinoid formulations

FIELD OF THE INVENTION

The disclosure is directed to cannabinoid formulations. More particularly, the cannabinoid formulations can be designed to align with an individual's genotype based on a defined list of polymorphisms.

BACKGROUND OF THE INVENTION

Medical use of cannabis and associated phytocannabinoids is becoming widely accepted in the United States and Canada as an alternative form of medicine. Many states have legalized its use for qualified medical conditions such as chronic pain, epilepsy, sleep disorders, anxiety, cancer, glaucoma, nausea, ALS, Alzheimer's disease, Crohn's disease, Post-traumatic Stress Disorder (PTSD), arthritis, fibromyalgia, and others. Every individual has an endocannabinoid system comprised of chemical receptors in the brain, immune system and central nervous system (for example, cannabinoid receptors CB1 and CB2).

Single nucleotide polymorphisms (SNPs) are stable genetic markers throughout the human genome, which can be tested for their association with various disease traits. These markers can also be associated with various traits that can determine an individual's sensitivity to certain compounds present in cannabis such as cannabinoids, terpenes, nitrogenous compounds, flavonoids, non-cannabinoid phenols and other miscellaneous chemical constituents. These endogenous endocannabinoid SNP markers can be tested in a patient and used as biomarkers that may predict how a patient will react or respond to the metabolism of compounds such as delta-9-THC, cannabidiol, other cannabinoids, and terpinoids found in cannabis. Furthermore, these biomarkers may suggest the best modality of treatment based on an individual's genetic profile and presence of specific enzymes or lack thereof that may result in negative side-effects from these compounds.

The invention provides cannabinoid formulations that are designed to align with an individual's genotype based on a defined list of polymorphisms.

SUMMARY OF THE INVENTION

It is against the above background that the present invention provides certain advantages and advancements over the prior art. This disclosure relates to cannabinoid formulations that are designed to align with an individual's genotype based on a defined list of polymorphisms, and provide more reliable methods for achieving consistent and predictable results. The inventors have found that specific phytocannabinoid ratios, secreted plant based oils, and terpene profiles align with a subject's genotype.

These and other features and advantages of the present invention will be more fully understood from the following detailed description taken together with the accompanying claims. It is noted that the scope of the claims is defined by the recitations therein and not by the specific discussion of features and advantages set forth in the present description.

In an aspect, the disclosure provides formulations comprising a cannabidiol (CBD) and a tetrahydrocannabinol (THC), wherein the formulation has a CBD:THC ratio from about 50:1 to about 1:50. In some embodiments, the formulations further comprise at least one terpene selected from alpha-bisabolol, alpha-phellandrene, alpha-pinene, alpha-terpinene, beta-caryophyllene, beta-ocimene, beta-pinene, bisabolol, bomeol, cadinene, camphene, camphor, cannabinoids, carene, caryophyllene oxide, cedrene, citral, citronellol, curcuminoids, cymene, delta-3-carene, eucalyptol, eugenol, fenchol, gamma-terpinene, geraniol, geranyl acetate, ginkgolides, guaiol, humulene, isobomeol, isopulegol, limonene, linalool, menthol, myrcene, nerol, nerolidol, ocimene, para-cymene, phytol, pinene, pulegone, sabinene, salvinorin, terpineol, terpinolene, theramine and valencene. In certain embodiments, the at least one terpene comprises a primary terpene and a secondary terpene. In some embodiments, the formulations comprise less than about 25%, about 20%, about 15%, about 10%, about 5%, about 4%, about 3%, about 2%, or about 1% terpenes.

In some embodiments, the formulation comprises a primary terpene that is myrcene and a secondary terpene that is linalool, and has a CBD:THC ratio of about 1:1 to about 1:5. In certain embodiments, the formulation comprises 5% myrcene and 3% linalool, and has a CBD:THC ratio of 1:1. In an embodiment, the formulation comprises 5% myrcene, 3% linalool, CBD, and is essentially free of THC.

In some embodiments, the formulation comprises a primary terpene that is pinene and a secondary terpene that is terpineol, and has a CBD:THC ratio of about 20:1 to about 1:1. In certain embodiments, the formulation comprises 5% pinene and 3% terpineol, and has a CBD:THC ratio of 4:1. In an embodiment, the formulation comprises 5% pinene, 3% terpineol, CBD, and is essentially free of THC.

In some embodiments, the formulation comprises a primary terpene that is limonene and a secondary terpene that is linalool, and has a CBD:THC ratio of about 20:1 to about 2:1. In certain embodiments, the formulation comprises 5% limonene and 3% linalool, and has a CBD:THC ratio of 1:1. In an embodiment, the formulation comprises 5% limonene, 3% linalool, CBD, and is essentially free of THC.

In some embodiments, the formulation comprises a primary terpene that is limonene and a secondary terpene that is pinene, and has a CBD:THC ratio of about 1:1 to about 1:20. In certain embodiments, the formulation comprises 5% limonene and 3% pinene, and has a CBD:THC ratio of 1:2. In an embodiment, the formulation comprises 5% limonene, 3% pinene, CBD, and is essentially free of THC.

In some embodiments, the formulation comprises a primary terpene that is linalool and a secondary terpene that is bomeol, and has a CBD:THC ratio of about 18:1 to about 4:1. In certain embodiments, the formulation comprises 5% linalool and 1% bomeol, and has a CBD:THC ratio of 4:1. In an embodiment, the formulation comprises 5% linalool, 1% bomeol, CBD, and is essentially free of THC.

In some embodiments, the formulation comprises a primary terpene that is beta-caryophyllene and a secondary terpene that is humulene, and has a CBD:THC ratio of about 1:1 to about 1:10. In certain embodiments, the formulation comprises 5% beta-caryophyllene and 3% humulene, and has a CBD:THC ratio of 1:1. In an embodiment, the formulation comprises 5% beta-caryophyllene, 3% humulene, CBD, and is essentially free of THC.

In some embodiments, the formulation comprises a primary terpene that is beta-caryophyllene and a secondary terpene that is myrcene, and has a CBD:THC ratio of about 1:1 to about 1:6. In certain embodiments, the formulation comprises 5% beta-caryophyllene and 5% myrcene, and has a CBD:THC ratio of 1:2. In an embodiment, the formulation comprises 5% beta-caryophyllene, 5% myrcene, CBD, and is essentially free of THC.

In some embodiments, the formulations comprise less than about 0.03% THC. In certain embodiments, the formulations are essentially free of THC.

In some embodiments, the formulation comprises a CBD:THC ratio of about 1:1 to about 1:3. In certain embodiments, the formulation comprises branched-chain amino acids, L-glutamine, piperine, magnesium stearate, MCC, and silicon dioxide, wherein the CBD:THC ratio is about 1:2. In an embodiment, the formulation comprises branched-chain amino acids, L-glutamine, piperine, magnesium stearate, MCC, silicon dioxide, CBD, and is essentially free of THC.

In some embodiments, the formulations as disclosed herein comprise from about 0.1 to about 100 mg/mL of the CBD. In other embodiments, the formulations as described herein comprise from about 0.1 to about 100 mg/mL of the THC.

In some embodiments, the formulations as described herein are formulated for buccal, dermal, intranasal, intravenous, nasal, ophthalmic, oral, sublingual, topical, or transdermal administration.

In some embodiments, the formulations as described herein further comprise cannabigerol (CBG), cannabinol (CBN), cannabidvarin (CBDV), cannabidiolic acid (CBDA), tetrahydrocannabinolic acid (THCA), or tetrahydrocannabivarin (THCV).

In some embodiments, the formulations as described herein further comprise black pepper, branched-chain amino acids (BCAA), cayenne, cedarwood, chamomile, coconut oil, geranium, ginger, ginger oil, glutamine, guava, juniper berry, lavender, lemon, lemon oil, lemongrass, lime, lime oil, orange, orange oil, mango, marjoram, menthol, mint, mint oil, peppermint, peppermint oil, piperine, geranium, rosemary, sandalwood, or tangerine.

In another aspect, the disclosure provides methods for treating a sleeping disorder, stress or depression, inflammation, anxiety, or for improving wellness or recovery comprising administering a pharmaceutically effective amount of any of the formulations as disclosed herein.

In yet another aspect, the disclosure provides methods for treating a subject comprising:

- (a) determining the subject's DNA genotype;
- (b) matching the subject with any of the formulations as disclosed herein based on the subject's DNA genotype; and
- (c) administering a pharmaceutically effective amount of any of the formulations as disclosed herein to the subject.

In some embodiments of the method of treating, the subject's DNA genotype is assessed to identify one or more single nucleotide polymorphisms (SNPs) and a pharmaceutically effective amount of any of the formulations as disclosed herein is administered to the subject as disclosed in Table 10.

DETAILED DESCRIPTION OF THE INVENTION

The disclosure involves compositions comprising selective formulations comprising cannabinoid molecules and terpenes that can be extracted from cannabis plants. The cannabinoid formulations as disclosed herein are designed to selectively affect a subject based on the subject's personal genetics, which results in important insights into the subject's optimal cannabis experience. Thus, the formulations can be personalized to comprise specific cannabinoid ratios and terpene profiles that help the subject achieve optimum results. The formulations disclosed herein provide numerous benefits and advantages, and allow a wide range of prevention, treatment, and management options for subjects based on their specific genotype.

All publications, patents and patent applications cited herein are hereby expressly incorporated by reference for all purposes.

Before describing the present invention in detail, a number of terms will be defined. As used herein, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. For example, reference to a “nucleic acid” means one or more nucleic acids.

It is noted that terms like “preferably,” “commonly,” and “typically” are not utilized herein to limit the scope of the claimed invention or to imply that certain features are critical, essential, or even important to the structure or function of the claimed invention. Rather, these terms are merely intended to highlight alternative or additional features that can or cannot be utilized in a particular embodiment of the present invention.

For the purposes of describing and defining the present invention it is noted that the term “substantially” is utilized herein to represent the inherent degree of uncertainty that can be attributed to any quantitative comparison, value, measurement, or other representation. The term “substantially” is also utilized herein to represent the degree by which a quantitative representation can vary from a stated reference without resulting in a change in the basic function of the subject matter at issue.

As used herein, the term “and/or” is utilized to describe multiple components in combination or exclusive of one another. For example, “x, y, and/or z” can refer to “x” alone, “y” alone, “z” alone, “x, y, and z,” “(x and y) or z,” “x and (y or z),” or “x or y or z.”

As used herein, the terms “polynucleotide,” “nucleotide,” “oligonucleotide,” and “nucleic acid” can be used interchangeably to refer to nucleic acid comprising DNA, RNA, derivatives thereof, or combinations thereof.

In one aspect, the disclosure provides formulations comprising a cannabidiol (CBD) and a tetrahydrocannabinol (THC), wherein the formulation has a CBD:THC ratio from about 50:1 to about 1:50. In some embodiments, the CBD:THC ratio of the formulations described herein will be greater than or equal to 50:1, 45:1, 40:1, 35:1, 30:1, 25:1, 20:1, 19:1, 18:1, 17:1, 16:1, 15:1, 14:1, 13:1, 12:1, 11:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3: 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12: 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, 1:25, 1:30, 1:30, 1:35, 1:40, 1:45, 1:50, or lower. In certain embodiments, the formulations as disclosed herein do not contain THC, or are essentially free of THC.

In some embodiments, the formulations further comprise at least one terpene. Examples of terpenes include, but are not limited to: alpha-bisabolol, alpha-phellandrene, alpha-pinene, alpha-terpinene, beta-caryophyllene, beta-ocimene, beta-pinene, bisabolol, bomeol, cadinene, camphene, camphor, cannabinoids, carene, caryophyllene oxide, cedrene, citral, citronellol, curcuminoids, cymene, delta-3-carene, eucalyptol, eugenol, fenchol, gamma-terpinene, geraniol, geranyl acetate, ginkgolides, guaiol, humulene, isobomeol, isopulegol, limonene, linalool, menthol, myrcene, nerol, nerolidol, ocimene, para-cymene, phytol, pinene, pulegone, sabinene, salvinorin, terpineol, terpinolene, theramine and valencene. In certain embodiments, the formulations comprise at least a primary terpene and a secondary terpene.

As used herein, the term “cannabinoid” refers to the chemical compounds found in cannabis that mimic and supplement body biochemicals—endocannabinoids—that interact and ultimately control receptors found in every cell in the human body. Cannabinoids in Cannabis, especially THC and CBD, modulate the receptors CB1 and CB2, which are involved in the function of nearly every body system, disease and condition. The cannabinoid receptor type 1 (CB1 receptor), is primarily expressed in the brain, and is encoded by the gene CNR1. Mutations of this gene alter the endocannabinoid system and response to THC. Genetic variants are associated with an increased risk of anxiety, onset of paranoia, and addiction. The cannabinoid receptor type 2 (CB2 receptor), is encoded by the gene CNR2, and is primarily expressed in the periphery, but may also be expressed in the brain following neuroinflammatory conditions. Mutations of this gene are associated with difficulty in controlling pain, including neuropathic pain and diabetic neuropathy.

Over 600 cannabinoids have been identified, but only Δ-8 tetrahydrocannabinol (Δ-8 THC), Δ-9 tetrahydrocannabinol (Δ-9 THC), and hydroxyl metabolites of those are psychoactive. Cannabinoids commonly found in cannabis include, but are not limited to, CBC, CBCV, CBD, CBDA, CBDV, CBG, CBGV, CBL, CBN, CBV, THC, THCA, THCV. The amount of each cannabinoid depends on the strain.

In some embodiments, the formulations as disclosed herein can further comprise cannabigerol (CBG), cannabinol (CBN), cannabidvarin (CBDV), cannabidiolic acid (CBDA), tetrahydrocannabinolic acid (THCA), or tetrahydrocannabivarin (THCV). In certain embodiments, the formulations as disclosed herein can comprise one or more of CBC, CBCV, CBD, CBDA, CBDV, CBG, CBGV, CBL, CBN, CBV, THC, THCA, and THCV.

Cannabichromene (CBC) is non-psychoactive and does not affect the psychoactivity of THC. CBC is typically more common in tropical cannabis varieties. Effects include anti-inflammatory and analgesic.

Cannabichromevarin (CBCV) is a propyl cannabinoid, which means it has a propyl chain in its molecular structure. Instead of having a pentyl chain like its counterpart, cannabichromene (CBC), it branches off to have a propyl chain. CBCV could relieve seizures in children and infants.

Cannabidiol (CBD) is a non-psychoactive compound in cannabis that has significant medical benefits. In the general population, high doses of CBD is expected to produce sedative and calming effects, while lower CBD doses have been shown to enhance mood.

Cannabidiolic acid (CBDA) is a cannabinoid found in raw cannabis, meaning fresh flowers and leaves that are unheated. CBDA is decarboxylated to CBD with heat and light exposure.

Cannabidivarin (CBDV) is a non-psychoactive cannabinoid known for its anticonvulsant effects. Both cannabidivarin (CBDV) and cannabidiol (CBD) activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro and thus have a potential for the treatment of neuronal hyperexcitability.

Cannabigerol (CBG) is a non-psychoactive cannabinoid found in the fresh cannabis plant. CBG is made by the decarboxylation of CBGA. CBG is a highly potent agonist for u2 adrenoceptor and a blocker of serotonin 5-HT1A receptor. This activity can decrease anxiety and muscle tension.

Cannabigerovarin (CBGV) is the propyl homologue of cannabigerol (CBG). CBGV is a potent inhibitor of LPI-induced GPR55 signaling. CBGV has been shown to be holding great potential for treating cancer. CBGV was shown to be cytostatic in leukemic cells and caused a simultaneous arrest at all phases of the cell cycle.

Cannabicyclol (CBL) is a non-psychotomimetic cannabinoid found in the Cannabis species. CBL is a degradative product like cannabinol. Light converts cannabichromene to CBL.

Cannabinol (CBN) is a non-psychoactive cannabinoid found in fresh cannabis, usually in low amounts. Unlike other cannabinoids, CBN does not stem from cannabigerol (CBG). CBN is formed by decarboxylation of CBNA. CBN has exhibited pain relief properties.

Cannabivarin (CBV), also known as cannabivarol, is a non-psychoactive cannabinoid found in minor amounts in the hemp plant Cannabis sativa. It is an analog of cannabinol (CBN) with the side chain shortened by two methylene bridges (—CH2-). CBV is an oxidation product of tetrahydrocannabivarin (THCV, THV).

Tetrahydrocannabinol (THC) is the most well-known and most abundantly available cannabinoid in cannabis plants. THC is also the component in cannabis that is responsible for the psychoactive effects, or the “high.” Also known as delta-9-tetracannabinol, it was first isolated in 1964.

Tetrahydrocannabinolic acid (THCA) is a non-psychoactive cannabinoid found in raw cannabis, meaning fresh flowers and leaves that are unheated. THCA is decarboxylated to psychoactive THC with heat and light exposure. This decarboxylation is what happens when one vaporizes or smokes flower.

Tetrahydrocannabivarin (THCV) is a non-psychoactive cannabinoid in cannabis, and a precursor of THC and CBD. THCV acts like a CB1 antagonist, and may aid in weight reduction. THCV has also shown to be useful for glycemic control in patients with type 2 diabetes.

As used herein the terms “terpene” and “terpinoid” can be used interchangeably and refer to a large and diverse class of organic compounds, produced by a variety of plants. They are often strong smelling and may have a protective function. Terpenes are known to play a role in traditional herbal remedies and are under investigation for antibacterial, antineoplastic, and other pharmaceutical functions. Terpenes can act synergistically with cannabinoids to provide a therapeutic effect. Terpene can be acyclic, monocyclic, bicyclic, or multicyclic, and can be derived biosynthetically from units of isoprene, which has the molecular formula C₅H₈. The basic molecular formulae of terpenes are multiples of that, (C₅H₈)_nwhere n is the number of linked isoprene units. The isoprene units may be linked together “head to tail” to form linear chains or they may be arranged to form rings. Non-limiting examples of terpenes include hemiterpenes, monoterpenes, sesquiterpenes, diterpenes, sesterterpenes, triterpenes, sesquarterpenes, tetraterpenes, polyterpenes, and norisoprenoids. Examples of terpenes can include: alpha-bisabolol, alpha-phellandrene, alpha-pinene, alpha-terpinene, beta-caryophyllene, beta-ocimene, beta-pinene, bisabolol, bomeol, cadinene, camphene, camphor, cannabinoids, careen, caryophyllene oxide, citral, citronellol, curcuminoids, delta-3-carene, eucalyptol, eugenol, fenchol, gamma-terpinene, geraniol, ginkgolides, humulene, limonene, linalool, menthol, myrcene, nerol, nerolidol, ocimene, para-cymene, phytol, pinene, pulegone, salvinorin, terpineol, terpinolene, or valencene.

Alpha-bisabolol, also known as levomenol, is a natural monocyclic sesquiterpene with a mild, floral, peppery odor. It has also been used for hundreds of years in cosmetics because of its perceived skin healing properties. Bisabolol has been effective at blocking the effects of mutagens on genetic integrity in liver cells. Bisabolol has also exhibited strong effects on Campylobacter which are involved in severe food poisoning. Furthermore, bisabolol has been associated with pain relief and neuroprotection, with possible uses in Parkinson's and Alzheimer's.

Alpha-phellandrene has an aroma that is described as herbaceous, citrus, peppery, minty, and slightly green/woody. Strains containing large amounts of alpha-phellandrene can often be identified by their exceptionally minty taste. Alpha-phellandrene can be naturally sourced from corn parsley (Ridolfia segetum) and the elemi tree (Canarium luzonicum). Alpha-phellandrene is absorbed easily through the skin, a quality that has made it a valued substance in the perfume industry. Alpha-phellandrene has a long history in traditional Chinese medicine as a treatment for digestive disorders. More recent research has suggested that alpha-phellandrene possesses anti-depressive effects.

Alpha-pinene is an alkene and contains a highly reactive four membered ring perpendicular to the main ring, prone to skeletal rearrangements. Both the − and + enantiomers are seen in nature − alpha pinene is mostly seen in European pines, and + alpha pinene mostly in North American pines. The racemic mixture is seen in eucalyptus and citrus oils. Pinene is used in nature with the ozone to condense aerosols that could harm the environment.

Beta-caryophyllene is an important terpene found in cannabis. Beta-caryophyllene has been shown to act as a full agonist of the CB2-receptor, although it does not act on the CB1-receptor. It has also been shown to exert anti-inflammatory and analgesic effect. Beta-caryophyllene is a sesquiterpene, with a sweet, woody, spicy, clove-like smell. It is a unique terpene due to its large size and structure. Due to these properties, beta-caryophyllene is able to activate several receptors in the body, including CB2, which is usually activated most by CBD. Beta-caryophyllene has been shown to be an effective analgesic by regulating neuroinflammation and thermal hyperalgesia. Also as an antioxidant, beta-caryophyllene is effective as demonstrated by preventing lipid oxidation and scavenging other radicals. As an anti-inflammatory, beta-caryophyllene has been proven to mediate kidney inflammation and its side effects. Furthermore, beta-caryophyllene has been eluted to be a gastric-protective.

Bisabolol (also known as α-bisabolol or levomenol) is a fragrant chemical compound produced by the chamomile flower and other plants such as the candeia tree in Brazil. It is also produced by various cannabis strains. While it has long been widely used in the cosmetics industry, bisabolol has more recently become the subject of research for the medical benefits it displays in cannabis. Bisabolol's effects and benefits can include anti-inflammatory, anti-irritant, antioxidant, anti-microbial, and analgesic.

Bomeol is a bicyclic monoterpene with a balsam, camphor, herbal, woody scent. Bomeol is commonly used in Asian traditional medicine. Bomeol has demonstrated more potent effects than the local anesthetic, lidocaine, and can also be eaten for its analgesic effects. Bomeol has acted as an anticoagulant in stroke models, and alleviates the mechanisms of proinflammatory cytokines in general. The terpene has induced fungicidal activity against several species of fungi. In addition, bomeol has elucidated to help drugs cross the blood brain barrier at a higher rate than without bomeol.

Cadinenes are bicyclic sesquiterpenes. The term cadinene has sometimes also been used in a broad sense to refer to any sesquiterpene with the so-called cadalane (4-isopropyl-1,6-dimethyldecahydronaphthalene) carbon skeleton. Cadinene can be derived from that of the Cade juniper (Juniperus oxycedrus L.).

Camphene is a particularly pungent, herbaceous terpene that possesses a camphoraceous, cooling, woody aroma with notes of citrus and mint. In the 1900s Camphene was well known for its use as a fuel source for lamps and as a component of turpentine. Research suggests that camphene may be able to decrease nociceptive pain. Recent studies show that camphene may have a future in treating lung inflammation due to its promising ability to increase cell viability and improve mitochondrial membrane potential while decreasing lipid peroxidation.

Camphor has a strong, characteristic scent that is often familiar to those who have been acquainted with mothballs or Vicks® Vaporub™. Isolated camphor can be naturally sourced from the camphor laurel (Cinnamomum camphora), rosemary (Rosmarinus oficinalis), and the East African camphorwood (Ocotea usambarensis). Camphor has a historic past—the Chinese used it to embalm bodies and produce pigments used as ink. In medieval times bags of camphor in its powder or crystalline form were worn to defend from illness. In modem medicine, camphor is an active ingredient in various nasal decongestants and chest rubs. This is likely due to its anti-spasmodic and decongestant properties. Camphor has also been promoted as a natural insecticide.

Carene or delta 3-carene is terpene found in basil, bell peppers, rosemary, and cannabis that promotes the drying up of excess liquid and has anti-inflammatory effects. Side effects often associated with this terpene are dry mouth and red eyes. Carene has a pungent and pleasant earthy aroma that is piney in resemblance. Carene is a bicyclic monoterpene with a unique propanol ring; is has a sweet citrusy odor. Carene has been implicated in helping differentiate and stimulate calcium production in bone cells. The terpene is also effective as a toxin for mosquitos.

Caryophyllene oxide is an oxygenated terpinoid, usually a metabolic by product of caryophyllene. Its use as an antifungal is highly effective with certain species. In addition, caryophyllene oxide has also been indicated as an anticoagulant with platelets.

Citral exudes an aroma reminiscent of citrus (particularly lemon/lime). Isolated citral can be naturally sourced from lemon myrtle (Backhousia citriodora), lemongrass (Cymbopogon), lemon verbena (Aloysia citrodora), lemons, limes, and oranges. Citral's attractive scent has led it to be a favored ingredient in perfumes, soaps, and other cleaning products. Citral exhibits a gastro-protective effect (potentially useful for those suffering from gastrointestinal issues). It has been suggested that the inhalation of citral's fragrance may lead to normalized hormone levels, promoting homeostasis. Through this interaction with the body's neuroendocrine system, it is possible that citral may be used to treat those suffering from major depressive disorders.

Citronellol is a sweet, floral terpene with an aroma reminiscent of roses and citrus. Isolated citronellol can be naturally sourced from rose and geranium. Citronellol is used in perfumes, aromatherapy and has been approved by the FDA as safe for food use. A natural mosquito repellent and antimicrobial agent, citronellol is generally gentle when applied to the skin. Inhalation of citronellol may lead to deep sedation.

Eucalyptol, also known as 1,8 cineole, has a fresh, strong eucalyptus, camphoraceous, minty odor. It is a cyclic ether monoterpene. Eucalyptol has been popularly used on the skin, gums, or other topical areas. The terpene is toxic to several species of bacteria including Staphylococcus aureus. Further research has proven eucalyptol to be a potential treatment for Alzheimer's, as it lowered the inflammation caused by amyloid beta plaques. Eucalyptol is also an anti-inflammatory for sinuses and the digestive system. As an antioxidant, eucalyptol was effective at preventing lipid oxidation. In addition, eucalyptol has been effective in battling leukemia and colon cancer cells. Asthma remedies have also been used with eucalyptol.

Eugenol emits a strong, clove-like aroma. Isolated Eugenol can be naturally sourced from cloves (Syzygium aromaticum), wormwood (Artemisia absinthium), cinnamon (Cinnamomum verum), nutmeg (Myristica fragrans), and Japanese star anise (Illicium anisatum). Eugenol is a common additive in clove cigarettes. As it can have calming and anti-inflammation effects, it is popularly used in various perfumes and massage oils. Eugenol has antiseptic and anesthetic properties when applied topically. A combination of eugenol and tea tree oil is known to be effective in treating fungal infections.

Fenchol, or 1,3,3-trimethyl-2-norbomanol is a terpene and an isomer of bomeol. The naturally occurring enantiopure (1R)-endo-(+)-fenchol is used extensively in perfumery. Fenchol is also, a scent from basil.

Gamma-terpinene has a sweetly herbaceous aroma augmented with notes of citrus. Isolated gamma-terpinene can be naturally sourced from tea tree (Melaleuca alternifolia) and Lippia multiflora. Gamma-terpinene is a major component of citrus essential oils. Its pleasant scent and taste has lead gamma-terpinene to be used widely as a flavor and fragrance additive in the cosmetic and food industries. Gamma-terpinene has exhibited antimicrobial properties and may be used to deflect a variety of human pathogens. Gamma-terpinene has also been noted as a promoter of antioxidant, anti-inflammatory, and antiproliferative activities.

Geraniol has a sweet, floral, fruity, rosy, waxy, citrus smell. The terpene has been known as a good mosquito repellent, but unfortunately attracts bees. Geraniol is toxic to bacteria and certain fungi. Further uses for the terpene include anti-inflammatory action. Also as a topical drug enhancer and anti-inflammatory, geraniol has proven useful.

Humulene is one of the main terpenes in hops, from which it gets its name. Humulene is also called alpha-caryophyllene. Like beta-caryophyllene, humulene is a cannabinoid and sesquiterpene, although it does not contain a cyclobutane ring. Humulene is a powerful anti-inflammatory and an anti-pain compound. It also has anti-cancer properties. Humulene is unique because, like THCV, it acts as an appetite suppressant, showing promise for weight loss treatments.

Limonene is a terpene found in certain strains of cannabis that conveys a pleasant citrus aroma. Limonene has been shown to help with inflammation, anxiety, acid reflux, allergies and depression. Limonene has been shown to be a potent antidepressant and anti-anxiety treatment comparable to some traditional medicines. Limonene has also been inferred to be an anti-inflammatory, lowering or preventing key stages in the reaction. Limonene was elucidated in being a potential treatment for breast, prostate and pancreatic cancer.

Linalool is a minor terpene found in certain strains of cannabis that is also produced in a variety of mints and herbs, including lavender. When combined with other major terpenes and cannabinoids, linalool may alleviate a number of conditions including pain, inflammation, depression, insomnia, anxiety and substance abuse. Linalool is a terpene alcohol with a citrusy, floral, sweet, bois de rose, woody, green, blueberry scent. Linalool is able to act on the opioidergic and cholinergic systems to relieve pain, a unique pathway for terpenes. Linalool also acts as an anticonvulsant, having similar effects to diazepam. Linalool has been used as a relaxant and as a treatment for anxiety for thousands of years. In scientific studies, linalool was proven to sedate mice and also mitigate anxiety.

Myrcene is the most commonly detected terpene in cannabis, and is a monoterpene that is an important precursor to many terpenes. Myrcene is also widely identified in plants, such as cloves, hops, lemon grass, and bay. It has been associated with having sedative, muscle relaxant and hypnotic properties and is commonly used for aromatic therapy of stress-relief. Myrcene is hypothesized to help compounds enter cells through enhancing membrane permeation. Myrcene has been shown to be an analgesic in mice and did not cause tolerance to the effect. Myrcene is also noted to have antioxidant effects with mutagenic compounds. Another benefit to myrcene is its ability to relax muscles and induce sleep.

Nerol is a strong, fresh terpene with a sweet rose aroma. Isolated nerol can be naturally sourced from neroli (Citrus aurantium), lemongrass (Cymbopogon citratus), and hops (Humulus lupulus). Nerol is used for its fragrance in perfumes and cosmetics and as a flavor agent in the food industry. Nerol may be used as a sedative, spasmolytic agent, and vasodilator. Nerol also possesses antiviral qualities.

Nerolidol is a sesquiterpene and that smells similar to fresh bark. There are two isomers present in nature, cis and trans. The terpene has been eluted to be a toxin against harmful protozoa like malaria and leishmaniasis. Furthermore, nerolidol is effect in delivering drugs through the skin.

Ocimene and beta-ocimene is a monoterpene with a fruity, floral, some say wet cloth smell. Ocimene has exhibited anti-inflammatory effects in white blood cell through a variety of pathways. Antifungal effects are also seen with the human specific Candida species. And very interestingly ocimene showed specificity and effectiveness against SARS virus.

Para-cymene is a constituent of a number of essential oils, most commonly the oil of cumin and thyme. Significant amounts are formed in sulfite pulping process from the wood terpenes.

Phytol is a mild floral terpene with a green, slightly balsamic aroma. Isolated phytol can be naturally sourced from barley (Hordeum vulgare L.) and green tea (Camellia sinensis). Phytol is a breakdown product in the decomposition of chlorophyll and acts as a precursor in the formation of vitamins E and K. Phytol plays an essential role in the human body by activating enzymes responsible for the production of insulin, and thereby helping to regulate blood glucose and cholesterol levels. Studies have shown that phytol may relieve insomnia, especially when used in conjunction with the terpene linalool. Phytol may also be used topically to reduce itchiness and treat wounds due to its anti-inflammatory and pain relieving qualities.

Pinene consists of two isomers, alpha and beta, depending on the position of the double bond within the molecule. Pinene is a terpene in cannabis that carries the aroma of pine. It is also present in orange peels, basil, pine needles and parsley. Pinene may help with asthma and anxiety, while reducing inflammation, enhancing relaxation and improving focus.

Pulegone emits a minty, faintly camphoraceous aroma. Isolated pulegone can be naturally sourced from pennyroyal (Mentha pulegium), catnip (Nepeta cataria), and peppermint (Mentha piperita). Pulegone is used by the candy and fragrance industries for its pleasant peppermint-like odor and flavor. Preservation and enhancement of memory is one of the effects of pulegone. This is due to pulegone's inhibition of the protein acetylcholinesterase. Thus, the memory is less affected by THC when it consumed with pulegone.

Terpineol has a citrusy, lime aroma with hints of lilac and apple blossom. Isolated terpineol can be naturally sourced from pine trees (Pinus), cajuput (Melaleuca cajuputi), and petitgrain (Citrus aurantium). Terpineol is most often used therapeutically to help manage pain and inflammation, and to reduce the frequency of seizures. Other medicinal values of terpineol include gastroprotection and promotion of antibacterial activities. Inhalation of terpineol may lead to a deep sedation.

Terpinolene is a terpene with a complex smoky, floral, herbal, or woody odor, commonly used in perfumes and soaps. It is naturally found in cannabis as well as other pleasantly fragrant plants including nutmeg, lilac, tea tree and apples. Terpinolene aids with sleep and may also be used to help fight bacterial or fungal infections. Terpinolene is a common terpene primarily isolated from trees. Terpinolene also goes by the name delta-terpinene. Terpinolene is not an analgesic or an anti-inflammatory, yet most cannabinoids and terpenoids are one of the two or both. Terpinolene was concluded to be effective against several species of bacteria. Terpinolene is able to increase total antioxidant capacity levels in white blood cells without changing the total oxidative stress level. Terpinolene is further effective in fighting glial cell cancer and leukemia.

Valencene is a bicyclic sesquiterpene with a sweet, fresh, citrusy, grapefruit, woody, orange odor. The terpene has been shown to be toxic and repel ticks and mosquitoes at lesser concentrations than DEET and without the toxicity to humans. Valencene has also been deduced to be and anti-inflammatory, lower the levels of inflammatory markers in macrophages.

As used herein, the term “primary terpene” refers to a terpene that is the most abundant terpene in a formulation either in absolute content as a % by dry weight, or in relative content as a % of the terpene in each formulation. For example, in a formulation comprising 5% limonene and 3% pinene, limonene would be the primary terpene.

As used herein, the term “secondary terpene” refers to a terpene that is the second most abundant terpene in a formulation either in absolute content as a % by dry weight, or in relative content as a % of the terpene in each formulation. For example, in a formulation comprising 5% limonene and 3% pinene, pinene would be the secondary terpene.

In an embodiment, the disclosure provides a formulation wherein the primary terpene is myrcene and the secondary terpene is linalool, and having a CBD:THC ratio of about 1:1 to about 1:5. In certain embodiments, the formulation comprises 5% myrcene, 3% linalool, and has a CBD:THC ratio of 1:1. In an embodiment, this formulation is essentially free of THC. In some embodiments, the disclosure relates to a method of treating a sleeping disorder by administering a pharmaceutically effective amount of the formulation.

Cannabis may help one fall asleep faster due its sleep-promoting effects. THC has well characterized sedative properties in rodents and humans. THC was also able to improve sleep in patients with obstructive sleep apnea and is being studied in restless legs syndrome.

THC (and CBD) may also improve sleep indirectly by relieving symptoms of other conditions that make sleeping difficult, including pain, anxiety, PTSD, and multiple sclerosis.

One study showed improved sleep quality in neuropathic pain patients after treatment with a mix of THC and CBD. CBD increased awake activity during sleep. For this reason, low CBD ratios are recommended near bedtime. However, CBD was also noted to have promise for excessive daytime sleepiness. CBN is a cannabinoid produced by degradation of THC through sunlight, heat and dry conditions. CBN is reported to have stronger sedative effects than THC itself.

Myrcene is a sedating terpene which is recognized by its musky, skunky smell. Its sedative and relaxing effects make it ideal for the treatment of insomnia and pain. Some contend that myrcene is the main cannabis terpene contributing to “couch-lock”. Studies in rodents have shown that myrcene has several properties associated with sedatives, such as slowed motor activity, increased muscle relaxation, and increased sleeping time. Myrcene also exhibited anti-convulsant effects. Myrcene appears to work by enhancing activity of the inhibitory GABAA receptor. This mechanism is shared with benzodiazepines, which are sedative drugs used for anxiety and sleep. Some have proposed that myrcene works synergistically with THC to increase its sedative properties.

Studies in rodents have shown that myrcene has several properties associated with sedatives like for example prenobarbytal, which is evidenced by induction of P-450 (P-450 2B subfamily) enzyme (see PubMed ID (PMID): 8257941), slowed motor activity, increased muscle relaxation, and increased sleeping time. Myrcene also exhibited anti-convulsant effects. Recently, it was shown in rodent models that administration of J3-myrcene protects oxidative and histological damage in the heart tissue after global ischemia-reperfusion and may be useful safe alternative treatment for cardiac tissue after ischemic stroke (see PMID: 27487280). It can also exert fungistatic and fungicidal activities and serve as potent antioxidant (see PMID: 28680993; PMID: 21245202) Myrcene appears to work by enhancing activity of the inhibitory GABAA receptor.

This mechanism is shared with benzodiazepines, which are sedative drugs used for anxiety and sleep. Myrcene has a potential to be used as an analgesic, without developing tolerance to it. It appears to be a novel pain medication, without side effects of aspirin-like drugs, but more in human studies are needed (see PMID: 1753786). Some have proposed that myrcene works synergistically with THC to increase its sedative properties. Although, caution is warranted because high doses of myrcene might be anxiogenic (see PMID: 12587690).

Linalool may lessen the anxious emotions provoked by pure THC, thus making it helpful in the treatment of anxiety and other THC side effects. Linalool possesses anxiolytic and antidressant properties (see PMID: 26151006; PMID: 25771248). Studies in rodents have demonstrated the sedative effects of linalool, including decreased anxiety and reduced motor activity without a loss of coordination. Linalool also increased sleep and had anticonvulsant properties. Linalool may work in several ways. First, it is an antagonist of the NMDA receptor. This means that it can reduce activation of this receptor by glutamate, the main excitatory neurotransmitter of the brain. Other NMDA antagonists also have strong sedative properties. Second, it enhances GABAA activity, although it does this in a different way than myrcene since it does not bind the same receptor site. Based on the data in animal models, it might also possess antihypertensive properties, prevent development of cardiac hypertrophy, increase levels of the anti-inflammatory cytokine (IL-10), increase vasodilator responsiveness and reduce sensitivity to the sympathetic agonist (see PMID: 29454617). It has a beneficial potential for weight management and weight loss (see PMID: 29321988). Linalool may work in several ways. First, it is an antagonist of the NMDA receptor. This means that it can reduce activation of this receptor by glutamate, the main excitatory neurotransmitter of the brain. Other NMDA antagonists also have strong sedative properties. Second, it enhances GABA_Aactivity, although it does this in a different way than myrcene since it does not bind the same receptor site.

In another embodiment, the disclosure provides a formulation wherein the primary terpene is pinene and the secondary terpene is terpineol, and having a CBD:THC ratio of about 20:1 to about 1:1. In certain embodiments, the formulation comprises 5% pinene, 3% terpineol, and has CBD:THC ratio of 4:1. In an embodiment, this formulation is essentially free of THC. In some embodiments, the disclosure relates to a method of improving concentration by administering a pharmaceutically effective amount of the formulation.

THC may cause temporary impairments in memory and concentration. For this reason, low THC ratios are recommended when one needs to concentrate. Interestingly, a low dose THC was able to boost brain levels of the neurotransmitter acetylcholine. Low THC doses could also stimulate neurogenesis, which was linked to cognitive improvements. CBD can reduce the impact of THC on memory. Although studies in humans are needed, CBD could reverse some hyperactivity patterns in rats. CBD can reduce the impact of THC on memory. More research on this topic is summarized in: PMID: 29432803; PMID: 29098186; PMID: 25799920; and PMID: 27811555.

Pinene is a reported to add a unique dimension to the personality of certain cannabis strains. Many strains with pinene as the dominant terpene are reported to promote alertness. Although the science behind the effects of pinene are not fully established, it is possible that pinene may improve memory through its antioxidant effects or boosting brain levels of acetylcholine. Acetylcholine is important for memory and cognition, but its release is decreased by THC. Through inhibition of acetylcholine metabolism, pinene and some other terpenes may improve cognitive impairment from THC. Pinene also had antidepressant effects in rodents, with mechanisms involving the serotonergic, adrenergic, and dopaminergic systems.

Terpineol can add a calming element that those with hyperactivity may find useful. Terpineol reduced locomotor activity in mice. Like some of the other cannabis terpenes, terpineol can enhance activity of the inhibitory GABAA receptor. Terpineol also possesses pain reducing properties, anti-nociceptive/reducing pain (see PMID: 29380385).

In yet another embodiment, the disclosure provides a formulation wherein the primary terpene is limonene and the secondary terpene is linalool, and having a CBD:THC ratio of about 20:1 to about 2:1. In certain embodiments, the formulation comprises 5% limonene and 3% linalool, and has a CBD:THC ratio of 1:1. In an embodiment, this formulation is essentially free of THC. In some embodiments, the disclosure relates to a method for treating stress or depression by administering a pharmaceutically effective amount of the formulation.

One of the important functions of the endocannabinoid system is adaptation to stress. Chronic stress is a risk factor for development and progression of depression and anxiety. THC can reduce anxiety, although it can also increase anxiety if the dose is too high. THC could be beneficial for certain disorders worsened by stress, such as migraines. In rodents, THC also showed antidepressant effects. CBD has shown anti-anxiety effects in humans, although studies are still ongoing. The mechanism appears to be both through the serotonin system and through boosting levels of endocannabinoids in the brain. CBD also showed antidepressant effects in rodents, although this has not been confirmed in humans. CBD could reduce certain side effects of THC, such as the psychotomimetic effects that occur in some people.

Limonene could contribute to an increase in attention span, mental focus and overall well-being. In rodents, limonene had anti-anxiety, anti-stress, and anti-depressant effects. Studies in rodents have demonstrated that linalool can decrease anxiety and reduce motor activity without a loss of coordination. In rat models with methamphetamine treatment, limonene reverses the increase in dopamine levels in the nucleus accumbens. These results suggest that limonene may inhibit stimulant-induced behavioral changes via regulating dopamine levels and 5-HT receptor function (see PMID: 24462212). S-limonene could also inhibit HPA reactivity under stress through the GABA(A) receptor (see PMID: 19763039), and exhibit anti-depressants properties (see PMID: 24661285).

During testing on the effects of limonene, participants experienced an increase in attention, mental focus, well-being and even libido. There are also undergoing trials for using limonene to treat depression and anxiety (see PMID:22364736; PMID:24125633; www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/limonene; PMID: 23554130; PMC4670880; PMC3165946; www.oncologyreviews.org/article/view/oncol.2011.31; PMID: 25388013; and PMID: 24160248).

Linalool may increase sleep and possess anticonvulsant properties. Linalool may lessen the anxious emotions provoked by pure THC, thus making it helpful in the treatment of anxiety and other THC side effects. Linalool also possesses antidepressant properties, possibly through effects on the serotonin system. Linalool may work in several ways. First, it is an antagonist of the NMDA receptor. This means that it can reduce activation of this receptor by glutamate, the main excitatory neurotransmitter of the brain. Other NMDA antagonists also have strong sedative properties. Second, it enhances GABAA activity, although it does this in a different way than myrcene since it does not bind the same receptor site.

In an embodiment, the disclosure provides a formulation wherein the primary terpene is limonene and the secondary terpene is pinene, and having a CBD:THC ratio of about 1:1 to about 1:20. In certain embodiments, the formulation comprises 5% limonene and 3% pinene, and has a CBD:THC ratio of 1:2. In an embodiment, this formulation is essentially free of THC. In some embodiments, the disclosure relates to a method for treating fatigue by administering a pharmaceutically effective amount of the formulation.

CBD has been proposed as a treatment for excessive daytime sleepiness. Cannabis is also being tested in fibromyalgia, which includes chronic fatigue as a symptom. Although so far there is limited evidence of the efficacy of pure THC, some studies have shown improvements with medical cannabis.

Rodent studies indicate that limonene may reduce stress, anxiety, and depression, all of which can contribute to fatigue. Stress system activation was reduced by limonene through actions on the GABA system. Limonene may also have some regulation of the dopamine and serotonin systems, which are important for energy and motivation.

Pinene is a reported to add a unique dimension to the personality of certain cannabis strains. Many strains with pinene as the dominant terpene are reported to promote alertness.

High levels of pinene were associated with an excitatory effect in the brain. Pinene may also promote alertness through antioxidant effects or boosting brain levels of acetylcholine. However, controlled studies are needed in humans to confirm these effects.

In another embodiment, the disclosure provides a formulation wherein the primary terpene is linalool and the secondary terpene is bomeol, and having a CBD:THC ratio of about 18:1 to about 4:1. In certain embodiments, the formulation comprises 5% linalool and 1% bomeol, and has a CBD:THC ratio of 4:1. In some embodiments, the disclosure relates to a method for treating anxiety by administering a pharmaceutically effective amount of the formulation.

The relationship between THC and anxiety is complicated. Most people are aware that over-consuming THC is capable of causing anxiety and even panic. However, THC can reduce stress-induced anxiety when consumed at the appropriate dose. CBD is capable of reducing anxiety, both after a single dose and when consumed over time. CBD works in several different ways to counteract anxiety. CBD can have a rapid effect through activation of a type of serotonin receptor called the 5-HT1A receptor. CBD can also boost levels of naturally occurring endocannabinoids in the brain such as anandamide. Over time, anandamide can stimulate neurogenesis in certain parts of a subject's brain. This has been linked to improvements in anxiety and stress resilience. CBD is also able to reduce anxiety generated by THC.

Linalool has been used for centuries as a sleep aid. Linalool may lessen the anxious emotions provoked by pure THC, thus making it helpful in the treatment of anxiety and other THC side effects. Studies in rodents have demonstrated the sedative effects of linalool, including decreased anxiety and reduced motor activity without a loss of coordination. Linalool also increased sleep and had anticonvulsant properties. Linalool may work in several ways. First, it is an antagonist of the NMDA receptor. This means that it can reduce activation of this receptor by glutamate, the main excitatory neurotransmitter of the brain. Other NMDA antagonists also have strong sedative properties. Second, it enhances GABAA activity, although it does this in a different way than myrcene since it does not bind the same receptor site.

Bomeol (also referred to as moxa) is a terpene in cannabis that can be used to relieve pain, reduce inflammation, lower anxiety, neuroprotectant, antioxidant, and treat heart disease. A study completed in 2013 (www.hindawi.com/j oumals/tswj/2013/808460/abs/) showed that this terpene produces a significant reduction of nociceptive pain while also displaying anti-inflammatory activity in mice. Unlike other medications used to treat pain and inflammation, bomeol did not impair motor coordination. Another study from 2003 also confirmed that bomeol can be used as a topical to numb pain and may be as effective as lidocaine (PMID: 12473382). In addition to reducing pain and inflammation, bomeol can be used to manage anxiety.

In yet another embodiment, the disclosure provides a formulation wherein the primary terpene is beta-caryophyllene and the secondary terpene is humulene, and having a CBD:THC ratio of about 1:1 to about 1:10. In certain embodiments, the formulation comprises 5% beta-caryophyllene and 3% humulene, and has a CBD:THC ratio of 1:1. In an embodiment, this formulation is essentially free of THC. In some embodiments, the disclosure relates to a method for treating inflammation by administering a pharmaceutically effective amount of the formulation.

THC can activate both cannabinoid CB1 and CB2 receptors, which are expressed in many immune cells. Although CB2 is more commonly associated with an anti-inflammatory effect, CB1 also plays a role in activation of some immune cells. There are many studies demonstrating the anti-inflammatory properties of CBD. CBD general reduces activation of immune cells and has shown activity in many animal models of inflammatory and autoimmune conditions, including irritable bowel syndrome. The effect of CBD may involve activation of a type of intracellular receptors called PPARs, boosting endocannabinoid levels, or through other mechanisms. THC and CBD, both alone and in combination, have been tested in many studies of pain. This is a complex topic due to the number of different types of pain (inflammatory, neuropathic, migraine, etc.). Although there is still much to learn, these cannabinoids may be an effective way for some people to treat pain.

β-caryophyllene is the only cannabis terpene known to interact directly with the endocannabinoid system. It is a full agonist of the cannabinoid CB2 receptor. This means that β-caryophyllene is able to fully activate the CB2 receptor, whereas THC is generally only capable of partial activation. The CB2 receptor is present in many cell types throughout the body, but there are particularly high levels in immune cells. Activation does not result in an intoxicating effect, but it is an important regulator of inflammation and pain. CB2 activation resulted in improvement in several animal models of diseases, such as stroke, multiple sclerosis, Parkinson's disease, alcoholic liver disease, asthma, irritable bowel syndrome, and both neuropathic and inflammatory pain. For example, CB2 activation has improved several animal models of diseases (see bmcneurol.biomedcentral.com/articles/10.1186/1471-2377-6-12, such as stroke, multiple sclerosis, Parkinson's disease, alcoholic liver disease, asthma, irritable bowel syndrome, Inflamation onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2005.03380.x/full and both neuropathic and inflammatory pain; onlinelibrary.wiley.com/doi/10.1038/sj.bjp.0707505/full).

Humulene has been used in Chinese medicine for generations. Humulene possesses both anti-inflammatory and pain reducing properties, as well as immune boosting properties (see PMID: 17559833; herb.co/marijuana/news/humulene; PMID: 18053325; PMID: 12802719; and PMID: 19921589). The anti-cancer properties ofhumulene were first highlighted in a 2003 study (see PMID: 12802719), which suggests it may be a result of humulene's ability to produce Reactive Oxygen Species (ROS). ROS have various roles in cancer, contributing to the death of cancer cells through apoptosis at some levels; although at other levels ROS can actually increase the growth rate of tumors. Both ROS maximizing and ROS minimizing approaches have been developed and are commonly used, though ROS maximizing strategies seem to be more common. A demonstration of the entourage effect can be seen in a 2007 study (see PMID: 18053325), which showed that β-caryophyllene potentiates the anti-cancer effects of humulene.

In an embodiment, the disclosure provides a formulation wherein the primary terpene is beta-caryophyllene and the secondary terpene is myrcene, and having a CBD:THC ratio of about 1:1 to about 1:6. In certain embodiments, the formulation comprises 5% beta-caryophyllene and 5% myrcene, and has a CBD:THC ratio of 1:2. In an embodiment, this formulation is essentially free of THC. In some embodiments, the disclosure relates to a method for improving wellness by administering a pharmaceutically effective amount of the formulation.

Myrcene is a sedating terpene which is recognized by its musky, skunky smell. Its sedative and relaxing effects make it ideal for the treatment of insomnia and pain. Some claim that myrcene is the main cannabis terpene contributing to “couch-lock”. Studies in rodents have shown that myrcene has several properties associated with sedatives, such as slowed motor activity, increased muscle relaxation, and increased sleeping time. Myrcene also exhibited anti-convulsant effects. Myrcene appears to work by enhancing activity of the inhibitory GABAA receptor. This mechanism is shared with benzodiazepines, which are sedative drugs used for anxiety and sleep. Some have proposed that myrcene works synergistically with THC to increase its sedative properties.

In an embodiment, the disclosure provides a formulation comprising less than about 0.03% THC, and having a CBD:THC ratio of about 1:0.2 to about 1:0. In an embodiment, this formulation is essentially free of THC.

Cannabidiol, (CBD) is the major non-psychoactive component of Cannabis sativa. CBD activates 5-HT1A serotonin receptor, which helps with anxiety, addiction, appetite, sleep, nausea, vomiting. It also binds to TRPV1 receptors, which moderates perception of pain, inflammation, body temperature as well as blocks G protein receptor GPR55, which may decrease bone reabsorption and the spread of cancer cells. CBD activates peroxisome proliferator activated receptors (PPARs), which has been shown to produce anti-cancer effect and help with Alzheimer's. CBD benefits include acting in some experimental models as an anti-inflammatory, anticonvulsant, antioxidant, antiemetic, anxiolytic and antipsychotic agent, and is therefore a potential medicine for the treatment of neuro-inflammation, epilepsy, oxidative injury, vomiting and nausea, anxiety and schizophrenia.

In an embodiment, the disclosure provides a powder-based formulation that is encapsulated for oral administration, and having a CBD:THC ratio of about 1:1 to about 1:3. In certain embodiments, the formulation comprises branched-chain amino acids (BCAA; L-leucine, L-isoleucine, L-valine), L-glutamine, piperine (for example, BioPerine®), Magnesium stearate, MCC, or silicon dioxide. In an embodiment, the formulation has a CBD:THC ratio of about 1:2. In an embodiment, this formulation is essentially free of THC. In some embodiments, the disclosure relates to a method for improving recovery (for example, following a workout or exercise) by administering a pharmaceutically effective amount of the formulation.

Piperine may help with nutrient absorption through its ability to increase the level of absorption of nutrients (referred to as “bioenhancement”), and improve metabolism as well as immune function. Piperine may also help improve dopamine and serotonin levels, which can improve memory and mental skills

Branched-chain amino acids (BCAA) are amino acids having an aliphatic side-chain with a branch, and include leucine, isoleucine, and valine. BCAAs are among the essential amino acids for humans, accounting for 35% of the essential amino acids in muscle proteins and 40% of the preformed amino acids required by mammals. BCAAs fill several metabolic and physiologic roles. Metabolically, BCAAs promote protein synthesis and turnover, signaling pathways, and metabolism of glucose. Oxidation of BCAAs may increase fatty acid oxidation and play a role in obesity. Physiologically, BCAAs take on roles in the immune system and in brain function. BCAAs are broken down effectively by dehydrogenase and decarboxylase enzymes expressed by immune cells, and are required for lymphocyte growth and proliferation and cytotoxic T lymphocyte activity. Lastly, BCAAs share the same transport protein into the brain with aromatic amino acids (Trp, Tyr, and Phe). Once in the brain BCAAs may have a role in protein synthesis, synthesis of neurotransmitters, and production of energy.

In some embodiments of the formulations as disclosed herein, the formulations can comprise less than about 25%, about 20%, about 15%, about 10%, about 5%, about 4%, about 3%, or about 2% or less of any one terpene. In certain embodiments, the formulations as disclosed herein can comprise 0%, 0.01%, 0.02%, 0.04%, 0.06%, 0.08%, 0.10%, 0.12%, 0.14%, 0.16%, 0.18%, 0.20%, 0.22%, 0.24%, 0.26%, 0.28%, 0.30%, 0.32%, 0.34%, 0.36%, 0.38%, 0.40%, 0.42%, 0.44%, 0.46%, 0.48%, 0.50%, 0.52%, 0.54%, 0.56%, 0.58%, 0.60%, 0.62%, 0.64%, 0.66%, 0.68%, 0.70%, 0.72%, 0.74%, 0.76%, 0.78%, 0.80%, 0.82%, 0.84%, 0.86%, 0.88%, 0.90%, 0.92%, 0.94%, 0.96%, 0.98%, 1.0%, 1.02%, 1.04%, 1.06%, 1.08%, 1.10%, 1.12%, 1.14%, 1.16%, 1.18%, 1.20%, 1.22%, 1.24%, 1.26%, 1.28%, 1.30%, 1.32%, 1.34%, 1.36%, 1.38%, 1.40%, 1.42%, 1.44%, 1.46%, 1.48%, 1.5%, 1.6%, 1.7% 1.8%, 1.9%, 2.0%, 2.2%, 2.4%, 2.6%, 2.8%, 3%, 3.2%, 3.4%, 3.6%, 3.8%, 4.0%, 4.2%, 4.3%, 4.4%, 4.6%, 4.8%, 5.0%, 5.2%, 5.4%, 5.6%, 5.8%, 6.0%, 6.2%, 6.4%, 6.6%, 6.8%, 7.0%, 7.2%, 7.4%, 7.6%, 7.8%, 8.0%, 8.2%, 8.4%, 8.6%, 8.8%, 9.0%, 9.2%, 9.4%, 9.6%, 9.8%, 10.0%, 11.0%, 12.0%, 13.0%, 14.0%, 15.0%, 16.0%, 17.0%, 18.0%, 19.0%, 20.0%, 25.0%, or greater based on dry weight. In some embodiments the absolute content of any one terpene can be between about 0.01% and about 25.0%.

In some embodiments of the formulations as disclosed herein, the formulations can comprise from about 0.1 mg/mL to about 100 mg/mL of the CBD. In certain embodiments, the formulations as described herein comprise 0.01 mg/mL, 0.02 mg/mL, 0.03 mg/mL, 0.04 mg/mL, 0.05 mg/mL, 0.06 mg/mL, 0.07 mg/mL, 0.08 mg/mL, 0.09 mg/mL, 0.1 mg/mL, 0.2 mg/mL, 0.3 mg/mL, 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL, 0.7 mg/mL, 0.8 mg/mL, 0.9 mg/mL, 1.0 mg/mL, 1.1 mg/mL, 1.2 mg/mL, 1.3 mg/mL, 1.4 mg/mL, 1.5 mg/mL, 1.6 mg/mL, 1.7 mg/mL, 1.8 mg/mL, 1.9 mg/mL, 2.0 mg/mL, 2.1 mg/mL, 2.2 mg/mL, 2.3 mg/mL, 2.4 mg/mL, 2.5 mg/mL, 2.6 mg/mL, 2.7 mg/mL, 2.8 mg/mL, 2.9 mg/mL, 3.0 mg/mL, 3.1 mg/mL, 3.2 mg/mL, 3.3 mg/mL, 3.4 mg/mL, 3.5 mg/mL, 3.6 mg/mL, 3.7 mg/mL, 3.8 mg/mL, 3.9 mg/mL, 4.0 mg/mL, 4.1 mg/mL, 4.2 mg/mL, 4.3 mg/mL, 4.4 mg/mL, 4.5 mg/mL, 4.6 mg/mL, 4.7 mg/mL, 4.8 mg/mL, 4.9 mg/mL, 5.0 mg/mL, 10 mg/mL, 15 mg/mL, 20 mg/mL, 25 mg/mL, 30 mg/mL, 35 mg/mL, 40 mg/mL, 45 mg/mL, 50 mg/mL, 55 mg/mL, 60 mg/mL, 65 mg/mL, 70 mg/mL, 75 mg/mL, 80 mg/mL, 85 mg/mL, 90 mg/mL, 95 mg/mL, 100 mg/mL or more of CBD. In some embodiments, the formulations as described herein comprise 0.01 g, 0.02 g, 0.03 g, 0.04 g, 0.05 g, 0.06 g, 0.07 g, 0.08 g, 0.09 g, 0.1 g, 0.2 g, 0.025 g, 0.3 g, 0.4 g, 0.5 g, 0.6 g, 0.7 g, 0.8 g, 0.9 g, 1.0 g, 1.1 g, 1.2 g, 1.3 g, 1.4 g, 1.5 g, 1.6 g, 1.7 g, 1.8 g, 1.9 g, 2.0 g, 2.1 g, 2.2 g, 2.3 g, 2.4 g, 2.5 g, 2.6 g, 2.7 g, 2.8 g, 2.9 g, 3.0 g, 3.1 g, 3.2 g, 3.3 g, 3.4 g, 3.5 g, 3.6 g, 3.7 g, 3.8 g, 3.9 g, 4.0 g, 4.1 g, 4.2 g, 4.3 g, 4.4 g, 4.5 g, 4.6 g, 4.7 g, 4.8 g, 4.9 g, 5.0 g, 10 g, 15 g, 20 g, 25 g, 30 g, 35 g, 40 g, 45 g, 50 g, 55 g, 60 g, 65 g, 70 g, 75 g, 80 g, 85 g, 90 g, 95 g, 100 g, or more of CBD.

In some embodiments of the formulations as disclosed herein, the formulations can comprise from about 0.1 to about 100 mg/mL of the THC; however in certain embodiments the formulation may not contain THC, or are essentially free of THC. In certain embodiments, the formulations as described herein comprise 0.00 mg/mL, 0.01 mg/mL, 0.02 mg/mL, 0.03 mg/mL, 0.04 mg/mL, 0.05 mg/mL, 0.06 mg/mL, 0.07 mg/mL, 0.08 mg/mL, 0.09 mg/mL, 0.1 mg/mL, 0.2 mg/mL, 0.3 mg/mL, 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL, 0.7 mg/mL, 0.8 mg/mL, 0.9 mg/mL, 1.0 mg/mL, 1.1 mg/mL, 1.2 mg/mL, 1.3 mg/mL, 1.4 mg/mL, 1.5 mg/mL, 1.6 mg/mL, 1.7 mg/mL, 1.8 mg/mL, 1.9 mg/mL, 2.0 mg/mL, 2.1 mg/mL, 2.2 mg/mL, 2.3 mg/mL, 2.4 mg/mL, 2.5 mg/mL, 2.6 mg/mL, 2.7 mg/mL, 2.8 mg/mL, 2.9 mg/mL, 3.0 mg/mL, 3.1 mg/mL, 3.2 mg/mL, 3.3 mg/mL, 3.4 mg/mL, 3.5 mg/mL, 3.6 mg/mL, 3.7 mg/mL, 3.8 mg/mL, 3.9 mg/mL, 4.0 mg/mL, 4.1 mg/mL, 4.2 mg/mL, 4.3 mg/mL, 4.4 mg/mL, 4.5 mg/mL, 4.6 mg/mL, 4.7 mg/mL, 4.8 mg/mL, 4.9 mg/mL, 5.0 mg/mL, 10 mg/mL, 15 mg/mL, 20 mg/mL, 25 mg/mL, 30 mg/mL, 35 mg/mL, 40 mg/mL, 45 mg/mL, 50 mg/mL, 55 mg/mL, 60 mg/mL, 65 mg/mL, 70 mg/mL, 75 mg/mL, 80 mg/mL, 85 mg/mL, 90 mg/mL, 95 mg/mL, 100 mg/mL or more of THC. In some embodiments, the formulations as described herein comprise, 0.00 g, 0.01 g, 0.02 g, 0.025 g, 0.03 g, 0.04 g, 0.05 g, 0.06 g, 0.07 g, 0.08 g, 0.09 g, 0.1 g, 0.2 g, 0.3 g, 0.4 g, 0.5 g, 0.6 g, 0.7 g, 0.8 g, 0.9 g, 1.0 g, 1.1 g, 1.2 g, 1.3 g, 1.4 g, 1.5 g, 1.6 g, 1.7 g, 1.8 g, 1.9 g, 2.0 g, 2.1 g, 2.2 g, 2.3 g, 2.4 g, 2.5 g, 2.6 g, 2.7 g, 2.8 g, 2.9 g, 3.0 g, 3.1 g, 3.2 g, 3.3 g, 3.4 g, 3.5 g, 3.6 g, 3.7 g, 3.8 g, 3.9 g, 4.0 g, 4.1 g, 4.2 g, 4.3 g, 4.4 g, 4.5 g, 4.6 g, 4.7 g, 4.8 g, 4.9 g, 5.0 g, 10 g, 15 g, 20 g, 25 g, 30 g, 35 g, 40 g, 45 g, 50 g, 55 g, 60 g, 65 g, 70 g, 75 g, 80 g, 85 g, 90 g, 95 g, 100 g, or more of THC.

A formulation is said to be “essentially free” of a particular component (i.e., THC, CBD, or a terpene), if that particular component is absent from the formulation or if the particular component is present in the formulation, but in an amount which is insufficient to promote any substantial effect in a subject, or is present at a concentration below a detectable limit. Additionally, it will be recognized that a formulation which is essentially free of a particular component may nonetheless contain trace amounts of the particular component in the formulation. For example, a formulation may contain no intentionally added THC and/or may contain no THC within conventional detection limits (thus, the term “essentially free of THC” encompasses the term “lacking THC”).

In certain embodiments of the formulations as disclosed herein, the formulations can comprise less than about 5%, about 4%, about 3%, or about 2%, or about 1% or less of any one or more of: black pepper, branched-chain amino acids (BCAA), cayenne, cedarwood, chamomile, coconut oil, geranium, ginger, ginger oil, glutamine, guava, juniper berry, lavender, lemon, lemon oil, lemongrass, lime, lime oil, orange, orange oil, mango, marjoram, menthol, mint, mint oil, peppermint, peppermint oil, piperine, geranium, rosemary, sandalwood, or tangerine. In certain embodiments, the formulations as disclosed herein can comprise about 0.01%, 0.02%, 0.04%, 0.06%, 0.08%, 0.10%, 0.12%, 0.14%, 0.16%, 0.18%, 0.20%, 0.25%, 0.30%, 0.40%, 0.50%, 0.60%, 0.70%, 0.80%, 0.90%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 2.0%, 2.2%, 2.4%, 2.6%, 2.8%, 3%, 3.2%, 3.4%, 3.6%, 3.8%, 4.0%, 4.2%, 4.3%, 4.4%, 4.6%, 4.8%, 5.0% or greater based on dry weight.

In some embodiments, the formulations are formulated for buccal, dermal, intranasal, intravenous, nasal, ophthalmic, oral, sublingual, topical, or transdermal administration. As different medical conditions can warrant different routes of administration, various forms for a particular formulation may exist. Methods for administration of the formulations described herein include, but are not limited, to inhalation (for example, dry powder inhalers, vaporizers, nebulizers, metered dose inhalers), smoking (e.g., dried buds), drinking, eating extracts or food products infused with concentrates or extracts, and taking capsules.

Exemplary forms can include, but are not limited to, adhesive topical patch, aerosol, balm, capsule, chewing gum, cream, drops, elixir, emulsion, film, gas, gel granule, hydrogel, liniment, liquid, lollipop, lotion, lozenge, ointment, paste, pill, powder, skin patch, spray, strip, syrup, tablet, or tincture (a solvent extract of plant or animal material, or of a low volatility substance). For example, a composition formulated for oral administration can comprise a liquid gel capsule, a soft gel capsule, a tablet, a chewable tablet, a chewable wafer, an extended release formulation, a “gummy” candy (chewable lozenge; e.g. pectin or gelatin base), a lozenge, a pastille (e.g. polyol base), chewing gum, an effervescing tablet, or a liquid formulation. Gummies, lozenges, tablets, and capsules may, for example, be generated with sugar or as sugar free formulations.

In some embodiments, the formulations further comprise one or more of: binders, natural flavoring agents, artificial flavoring agents, disintegrants, emulsifiers, glidants (flow aids), granulating agents, natural colorants, artificial colorants, lubricants, preservatives, or sweetening agents. The formulations may include varied and numerous inactive ingredients known within the art to improve the formulation, delivery, preservation, appearance, palatability, and administration of the active ingredients.

In some embodiments, formulations are low in sugar (<40% sugar, less than about 30% or less than about 20% sugar), or are sugar-free. Sugar substitutes can include, but are not limited to, aspartame, sucralose, saccharin, stevia, monk fruit sweetener, erythritol, sorbitol, xylitol, mannitol, maltitol, and hydrogenated glucose or maltose syrups or maltodextrins, or combinations thereof.

Non-limiting examples of binders can include: acacia, tragacanth, gelatin, starch, cellulose based materials such as methyl cellulose and sodium carboxy-methyl cellulose, alginic acids and salts thereof, magnesium, aluminum silicate, polyethylene glycol, guar gum, polysaccharide acids, bentonites, sugars, invert sugars and the like.

Non-limiting examples coloring agents can include: known FD&C dyes and natural coloring agents such as grape skin extract, beet red powder, beta-carotene, annatto, carmine, turmeric, or paprika. The amount of coloring used may range from about 0.05 to about 5% by weight of the total composition.

Non-limiting examples of optional flavoring agents can include: synthetic flavors oils and flavoring aromatics, natural oils, plant extracts. Examples include almond oil, anise oil, avocado oil, bay oil, canola (rapeseed) oil, cedar leaf oil, cinnamon oil, coconut oil, clove oil, eucalyptus, flaxseed oil, grape seed oil, macadamia oil, nutmeg oil, olive oil, oil of wintergreen, peanut oil, peppermint oil, pine kernel oil, pomegranate seed oil, pumpkin seed oil, safflower oil, sesame oil, sage oil, soya bean oil, sunflower oil, thyme oil, omega 3 fatty acids (for example, ALA (alpha-linolenic acid), EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid)), omega 9 fatty acids, and combinations thereof. Examples of flavoring agents can also include, but are not limited to, almond, apple, banana, berry, bubblegum, caramel, citrus, cherry, chocolate, coconut, grape, green tea, honey, lemon, licorice, lime, mango, maple, mint, orange, peach, pineapple, raisin, strawberry, vanilla, watermelon, and combinations thereof. Flavoring agents may be present in an amount ranging from about 0.05 to about 5% by weight of the total composition.

Non-limiting examples of emulsifiers can include: lecithin, polysorbates, or sorbitan monooleates, and combinations thereof.

In certain embodiments, the formulations may further comprise an ingredient useful for increasing the storage stability of the formulations. In some embodiments this is an antioxidant. Suitable antioxidants can include molecules that inhibit the oxidation of other molecules. Non-limiting examples of antioxidants can include, but are not limited to, vitamin A, vitamin C, vitamin E, alpha-carotene, astaxanthin, beta-carotene, canthaxanthin, lutein, lycopene, zeaxanthin, flavonoids (such as apigenin, myricetin, eriodictyol, theaflavin, genistein, resveratrol, malvidin), cinnamic acid, chicoric acid, chlorogenic acid, rosmarinic acid, curcumin, xanthones, eugenol, citric acid, oxalic acid, and lipoic acid.

In an aspect, the disclosure relates to methods for treating a subject comprising: (a) determining the subject's DNA genotype; (b) matching the subject with a formulation as disclosed herein based on the subject's DNA genotype; and (c) administering a pharmaceutically effective amount of the formulation to the subject. In some embodiments of the method of treating a subject, the subject's DNA genotype is assessed to identify one or more single nucleotide polymorphisms (SNPs), and based on the SNP, a pharmaceutically effective amount of any of the formulations as disclosed herein is administered to the subject. A number of exemplary SNPs, with formulations, are discussed in Table 10.

In some embodiments, the formulations disclosed herein can be used to treat one or more of the following: acquired hypothyroidism, acute gastritis, agoraphobia, aids related illness, alcohol abuse, alcoholism, alopecia areata, Alzheimer's disease, amphetamine dependency, amyloidosis, amyotrophic lateral sclerosis (ALS), angina pectoris, ankylosis, ankylosing spondylitis, anorexia, anorexia nervosa, anxiety disorders, any chronic medical symptom that limits major life activities, any chronic medical symptom that limits major life activities, arteriosclerotic heart disease, arthritis, arthritis (rheumatoid), arthropathy, gout, asthma, attention deficit hyperactivity disorder (ADD/ADHD), autism, autoimmune disease, back pain, back sprain, Bell's palsy, bipolar disorder, brain tumor, malignant, bruxism, bulimia, cachexia, cancer, carpal tunnel syndrome, cerebral palsy, cervical disk disease, cervicobrachial syndrome, chemotherapy chronic fatigue syndrome, chronic pain, chronic renal failure, cocaine dependence, colitis, conjunctivitis, constipation, Crohn's disease, cystic fibrosis, damage to spinal cord nervous tissue, Darier's disease, degenerative arthritis, degenerative arthropathy, delirium tremens, dermatomyositis, diabetes, diabetic neuropathy, diabetic peripheral vascular disease, diarrhea, diverticulitis, dysthymic disorder, eczema, emphysema, emphysema, endometriosis, epidermolysis bullosa, epididymitis, epilepsy, Felty's syndrome, fibromyalgia, Friedreich's ataxia, gastritis, genital herpes, glaucoma, glioblastoma multiforme, Graves disease, cluster headaches, migraine headaches, tension headaches, hemophilia a, Henoch-Schonlein purpura, hepatitis C, hereditary spinal ataxia, HIV/AIDS, hospice patients, Huntington's disease, hypertension, hypertension, hyperventilation, hypoglycemia, impotence, inflammatory autoimmune-mediated arthritis, inflammatory bowel disease (IBD), insomnia, intermittent explosive disorder (IED), intractable pain, intractable vomiting, lipomatosis, Lou Gehrig's disease, lyme disease, lymphoma, major depression, malignant melanoma, mania, melorheostosis, Meniere's disease, motion sickness, mucopolysaccharidosis (MPS), multiple sclerosis (MS), muscle spasms, muscular dystrophy, myeloid leukemia, nail-patella syndrome, nightmares, obesity, obsessive compulsive disorder, opiate dependence, osteoarthritis, panic disorder, Parkinson's disease, peripheral neuropathy, peritoneal pain, persistent insomnia, porphyria, post-polio syndrome (PPS), post-traumatic arthritis, post-traumatic stress disorder (PTSD), premenstrual syndrome (PMS), prostatitis, psoriasis, pulmonary fibrosis, quadriplegia, radiation therapy, Raynaud's disease, Reiter's syndrome, restless legs syndrome (RLS), rheumatoid arthritis, rosacea, schizoaffective disorder, schizophrenia, scoliosis, sedative dependence, seizures, senile dementia, severe nausea, shingles (herpes zoster), sinusitis, skeletal muscular spasticity, sleep apnea, sleep disorders, spasticity, spinal stenosis, Sturge-Weber syndrome (SWS), stuttering, tardive dyskinesia (TD), temporomandibular joint disorder (TMJ), tenosynovitis, terminal illness, thyroiditis, tic douloureux, Tietze's syndrome, tinnitus, tobacco dependence, Tourette's syndrome, trichotillomania, viral hepatitis, wasting syndrome, whiplash, Wittmaack-Ekbom's syndrome, writers' cramp, nausea, vomiting, unintentional weight loss, insomnia, and lack of appetite, spasticity, painful conditions, especially neurogenic pain, movement disorders, asthma, glaucoma, adrenal disease, migraines, fibromyalgia, and related conditions, spinal cord injuries. The formulations disclosed herein can exhibit antispasmodic and muscle-relaxant properties as well as stimulates appetite, and may be useful in treating alcohol abuse, amyotrophic lateral sclerosis, collagen-induced arthritis, asthma, atherosclerosis, bipolar disorder, colorectal cancer, HIV-associated sensory neuropathy, depression, dystonia, epilepsy, digestive diseases, gliomas, hepatitis C, Huntington's disease, leukemia, skin tumors, methicillin-resistant Staphylococcus aureus (MRSA), Parkinson's disease, pruritus, posttraumatic stress disorder (PTSD), psoriasis, sickle-cell disease, sleep apnea, and anorexia nervosa. In other embodiments, the formulations as disclosed herein can be used for recreational purposes.

Anxiety is a common disorder experienced by many individuals. While the study behind the causes and effects of anxiety are ever changing, there have been several SNPs discovered that relate to the interaction of anxiety and cannabinoids. For example, the SNP rs1049353 for the CNR1 gene is associated with activation of specific brain areas (the insula and amygdala). The effect of this related to how one gauges visual, emotional, and social cues. Examples include facial expressions that change from anger to sadness or fear; happiness to sadness or fear; and neutral. Another example is the SNP rs324420 for the FAAH gene, which is associated with how an individual's endocannabinoid system (ECS) is related to specific neural mechanisms which may impact complex behavioral processes related to risk for addiction, dependence, and obesity. Yet another example is the SNP 5-HTTLPR for the SLC6A4 gene, which is associated with the development of anxiety for youth users of cannabis. By analyzing these SNPs, a subject at risk for anxiety or suffering from anxiety may be effectively treated with the formulations as disclosed herein.

Bipolar disorder, or manic depression, is a serious brain illness that causes unusual shifts in mood, energy, activity, and the ability to carry out daily activities. Individuals suffering from bipolar disorder experience periods of intense emotion, changes in sleep, and unusual behavior, known as episodes. Episodes can be categorized as either manic (more energetic and “up” than normal) or depressive (more low energy and “down” than normal). While research surrounding bipolar disorder is ever changing, researchers have identified a SNP associated with the risk for developing bipolar disorder. For example, the SNP rs41311993 for the CNR2 gene is associated with the risk for developing bipolar disorder. By analyzing these SNPs, a subject at risk for developing bipolar disorder or suffering from bipolar disorder may be effectively treated with the formulations as disclosed herein.

Cognitive function may, for example, relate to a user's ability of their brain to process information and knowledge. While this is a general trait, researchers have identified SNPs that indicate how cannabis may affect a user's cognitive function. In one example, the SNP rs1049353 for the CNR1 gene is associated with lower performance of executive function and sustained attention. Thus, depending on their endocannabinoid genotype, some users may experience an elevated risk of not being able to sustain attention when using cannabis. In another example, the SNP rs4680 for the COMT gene is associated with risk of structural brain changes following cannabis use. Users that have an at-risk genotype for this SNP (e.g., homozygous alleles, such as (A/A)), may want to consult with a specialist in cognitive function before using cannabis. In yet another example, the SNP rs12199654 for the MAPK14 gene is associated with a risk of decreased white matter brain volume from cannabis use, which may result in impairing a user's cognitive function. In another example, the SNP rs7834206 for the NRG1 gene is associated with auditory reception when using cannabis. Users with heterozygous alleles (C/A) may be more likely to have auditory discrepancies after using cannabis when compared to users with other genotypes. In yet another example, the SNP 5-HTTLPR for the SLC6A4 gene is associated with a user's focus, visual interpretation of their environment, and decision making. Users with homozygous alleles (L′/L′) might not experience a decrease in brain performance when using cannabis. By analyzing these SNPs, the cognitive function of a subject may be effectively treated and/or improved with the formulations as disclosed herein.

Depression may, for example, relate to how a user feels, thinks, and acts. Specifically, depression is a long-term mental degradation that can affect the way a user functions in daily life. Depression can further be characterized by feeling tearful, irritable, and having diminished interest or pleasure in activities every day; significant weight loss/decrease or increase in appetite; inability to get to sleep or difficulty staying asleep or sleeping too much; problems with sitting or a slowing of one's movements; talking very quietly with slowed speech; fatigue; tiredness; feelings of worthlessness; diminished ability to think or concentrate; recurrent thoughts of death (not just fear of dying); recurrent suicidal ideas without a specific plan; or a suicide attempt or creating a specific plan for committing suicide. Due to the severity of depression symptoms, it is beneficial to have an understanding of how cannabis may affect users that have a particular genotype. For example, the SNP rs1049353 for the CNR1 gene is associated with depression—specifically, how a user reacts to certain antidepressants such as citalopram. Users that have heterozygous alleles (C/T) may have a decrease likelihood of responding to antidepressants. In another example, the SNP rs2023239 for the CNR1 gene is associated with depression generally. Users that have homozygous alleles (T/T) may experience a higher likelihood of exacerbating pre-existing symptoms of depression when using cannabis. In yet another example, the SNP rs806377 for the CNR1 gene is associated with how a user responds to positive emotional stimuli. Users with homozygous alleles (T/T) may experience a higher amount of positive emotions after a positive event than people with heterozygous alleles. In yet another example, the SNP rs324420 for the FAAH gene is associated with white matter integrity in the brain and increased reports of depression and apathy in cannabis users. Users with homozygous alleles (CC) may experience decreased white matter in the brain and weakened brain structure when cannabis is used at a young age. By analyzing these SNPs, a subject at risk for developing depression or suffering from depression may be effectively treated with the formulations as disclosed herein.

Impulsive behavior may, for example, relate to making decisions without thinking of the results and/or consequences beforehand. Impulsive behavior has many causes, which can include mental disorders such as hyperactivity disorder or personality disorders, such as borderline personality disorder. Cannabis usage may also cause impulsivity for certain users. For example, the SNP rs1049353 for the CNR1 gene is associated with adolescent psychosocial adversity, which is how one responds and/or adapts to family or relationship problems, health problems, school and other structural worries, and how they relate to impulsive behavior. Users with a genotype containing heterozygous alleles (C/T) may have an elevated risk of impulsive behavior when using cannabis. In another example, the SNP rs806379 for the CNR1 gene is also associated with adolescent psychosocial adversity. Users with homozygous alleles (A/A) that experienced early psychosocial adversity may have a higher risk of impulsive behavior. In yet another example, the SNP rs1611115 for the DBH gene is associated with impulsivity after cannabis consumption. Users with homozygous alleles (C/C) might not have increased impulsivity after cannabis use, while users with heterozygous alleles may have increased impulsivity after cannabis use. In yet another example, the SNP rs221533 for the NRG1 gene is associated with lower inhibition and significantly riskier decision making. Users with heterozygous alleles (T/C) may have a lower risk of having behaviors associated with risky decision making when using cannabis. In yet another example, the SNP rs28363170 for the SLC6A3 gene is also associated with impulsivity when using cannabis. Users with homozygous alleles (10R/10R) may have a lower risk of impulsivity after consuming cannabis compared to users with heterozygous alleles. By analyzing these SNPs, a subject at risk for developing impulsive behavior or suffering from impulsive behavior may be effectively treated with the formulations as disclosed herein.

Memory impairment may, for example, relate to a person's ability to store information in their brain. For example, the SNP rs1049353 for the CNR1 gene is associated with varying brain awareness states, which is related to working memory ability and other cognitive functions. Users with heterozygous alleles (C/T) may have a normal state of awareness when compared to users with a different genotype. In another example, the SNP rs1406977 for the CNR1 gene is associated with performance on working memory tasks when using cannabis. Users with homozygous alleles (T/T) may be less likely to experience working memory impairments after use of THC. By analyzing these SNPs, a subject at risk for developing memory impairment or suffering from memory impairment may be effectively treated with the formulations as disclosed herein.

Metabolic function may, for example, relate to how a user's cells breaks down materials from food to energy. Metabolic function may vary in users that are consuming cannabis. For example, the SNP rs1045642 for the ABCB1 gene is associated with THC levels and THC metabolites in cannabis users. Users with homozygous alleles (T/T) may have two-fold lower blood THC levels after consuming THC relative to people with a different genotype. In another example, the SNP rs1057910 for the CYP2C9 gene is associated with how oral THC is processed or metabolized in the body. Users with homozygous alleles (A/A) are typically no more sensitive to oral THC. By analyzing these SNPs, the metabolic function of a subject may be effectively treated and/or improved with the formulations as disclosed herein.

Migraines may, for example, relate to severe headaches that occur on one side of the head. Migraines can cause extreme discomfort and symptoms such as nausea and oversensitivity to lights and sounds. Research indicates that cannabis usage may have an effect on migraines in certain individuals. For example, the SNP rs806366 for the CNR1 gene is associated with a user's susceptibility to migraines. Users with homozygous alleles (T/T) may be more likely to develop migraines after stressful events. This is beneficial information because a medical provider can prescribe an appropriate dose if the provider is aware that the user is more likely to develop migraines. By analyzing these SNPs, a subject at risk for developing migraines or suffering from migraines may be effectively treated with the formulations as disclosed herein.

Motor control may, for example, relate to the process of creating and sending purposeful, voluntary movements throughout the body. Research indicates that the consumption of cannabis may have profound effects on a user's motor control. For example, the SNP rs1130233 for the AKT1 gene is associated with the degree of impairment in a user's psychomotor control and/or motor coordination after consumption of THC. Users with heterozygous alleles (C/T) may develop impaired motor coordination and slowed down thinking after consuming THC. By analyzing these SNPs, motor control in subject may be effectively treated and/or improved with the formulations as disclosed herein.

Opioids are, for example, a class of drugs created from the opium poppy plant. The plants are harvested and used in various types of medications because they contain a chemical that relaxes the body, and helps to relieve pain. Examples of opioids include Hydrocodone, Oxycodone, Oxymorphone, Morphine, Fentanyl, and Codeine. Research indicates that particular genetic markers may affect how a user reacts to opioids. For example, the SNP rs324420 for the FAAH gene is associated with having adverse opioid effects when combined with how a user's endocannabinoid system modulates, by way of such cannabinoids such as anandamide. Users with homozygous alleles (C/C) may have a lower risk of experienced side effects from opioids relative to people with a different genotype. By analyzing these SNPs, a subject at risk for developing opioid dependence or suffering from opioid dependence may be effectively treated with the formulations as disclosed herein.

Pain may, for example, relate to the unpleasant and corresponding emotional reaction in response to injury or tissue damage. Pain is a signal sent through the spinal cord, to a user's brain, alerting her that something is wrong in her body. Pain can be difficult to diagnose as it can manifest itself in different ways for different people. For example, the SNP rs324420 for the FAAH gene is associated with pain sensitivity and use of postoperative analgesia. Users with homozygous alleles (C/C) may have higher pain sensitivity to cold temperatures and more need for analgesia during periods of acute pain, such as after an operation. This information is beneficial when a provider is prescribing cannabis after an operation. By analyzing these SNPs, a subject at risk for developing pain or suffering from pain may be effectively treated with the formulations as disclosed herein.

Psychosis may, for example, relate to a user's propensity for becoming disconnected from reality. Psychosis from cannabis can cause delusions, which are strong beliefs that don't make sense and/or are not consistent with the user's actual beliefs. Research indicates that cannabis may have a more profound effect on users with particular genetic markers. For example, the SNP rs1130233 for the AKT1 gene is associated with the risk of psychosis-like effects (e.g., include delusion, delirium and confusion) after consuming THC. Users with heterozygous alleles (C/T) may have an increased risk of experience acute psychosis-like effects after consuming THC. In another example, the SNP rs2494732 for the AKT1 gene is associated with the risk of psychotic episode in users that consume cannabis. Users with homozygous alleles (T/T) may have a lower risk of experiencing psychotic disorder effects after consuming THC. In yet another example, the SNP rs6265 for the BDNF gene is associated with the onset of a psychotic disorder at a young age. Users with homozygous alleles (G/G) may not be at risk for onset psychosis if the user is already predisposed to developing psychosis. In yet another example, the SNP rs4680 for the COMT gene is also associated with psychosis-like effects (e.g., delusion, delirium, and confusion) after consuming THC. Users with homozygous alleles (A/A) may be less likely to experience psychosis-like effects after consuming THC relative to people with different genotypes. In another example, the SNP rs1076560 for the DRD2 gene is associated with a greater risk of developing psychosis (e.g., having regular hallucinations and delusions) in cannabis users. In yet another example, the SNP rs2494732 for the AKT1 gene is associated with a risk of a psychotic disorder and cognitive disabilities, including verbal memory and sustained attention impairments. Users with homozygous alleles (T/T) may have a lower risk of psychotic disorder and a lower risk of memory and attention impairments after consuming THC than users with a different genotype. This information may be particularly beneficial as it may prevent a user that is predisposed to psychosis from overdosing on THC. By analyzing these SNPs, a subject at risk for developing psychosis or suffering from psychosis may be effectively treated with the formulations as disclosed herein.

Psychotic like effects may, for example, include delusions and delirium caused by cannabis usage. Research indicates that cannabis use can cause schizophrenia, an illness that can cause a person to feel as if they have lost touch with reality. Research also indicates that certain genetic markers can indicate whether an individual is more likely to experience psychotic like effects when consuming cannabis. For example, the SNP 5-HTTLPR for the gene SLC6A4 is associated with psychotic like effects in user with bipolar disorder when that user consumes cannabis. By analyzing these SNPs, a subject at risk for developing psychotic like effects or suffering from psychotic like effects may be effectively treated with the formulations as disclosed herein.

Sleep quality may, for example, relate to the amount of time a user sleeps, the amount of times a user wakes up during the night, and the amount of time it takes a user to fall asleep. Research indicates certain genetic markers are related to sleep quality. For example, the SNP rs324420 for the FAAH gene is associated with poorer sleep quality among young cannabis users who exhibit depression symptoms. Users with homozygous alleles (C/C) may have an increased risk of poor sleep quality while using certain cannabinoid formulations. By analyzing these SNPs, a subject's sleep quality may be effectively treated and/or improved with the formulations as disclosed herein.

In an embodiment of the methods disclosed herein, when the subject is determined to have heterozygous alleles (A/C) at the rs1057910 polymorphism of the CYP2C9 gene, the subject is administered a formulation wherein the primary terpene is linalool and the secondary terpene is beta-caryophyllene, and having a CBD:THC ratio of about 18:1 to about 4:1. This polymorphism was associated with metabolism and pharmacokinetics of oral THC. THC levels immediately after pulmonary administration (smoking, vaporizing) are not highly affected by the rate of metabolism, so this polymorphism probably has little effect with these methods. No effect on CBD levels is expected since it is not AC metabolized to a significant extent by CYP2C9. The subject may feel the effects of oral THC more strongly or find that the effects last longer relative to people with the most common genotype. It is recommended that the first time the subject uses oral THC, that the subject starts at 60% of the standard dose. No change in THC dose is needed for pulmonary administration.

In an embodiment of the methods disclosed herein, when the subject is determined to have heterozygous alleles (C/T) at the rs35599367 polymorphism of the CYP3A4 gene, the subject is administered subject is administered a formulation wherein the primary terpene is linalool and the secondary terpene is beta-caryophyllene, and having a CBD:THC ratio of about 18:1 to about 4:1. This polymorphism has not directly been associated with cannabinoid metabolism in a clinical study. However, it is associated with decreased expression and activity of the CYP3A4 enzyme. Clinical studies with the CYP3A4 inhibitor ketoconazole showed that it boosts both THC and CBD levels after oromucosal dosing by approximately 2-fold. Therefore, it is very likely that this polymorphism affects THC and CBD levels after oral dosing. A subject may feel the effects of oral THC more strongly or find that the effects last longer relative to other people. It is recommended that the first time a subject uses oral THC, that the subject start with a 1.5-fold lower dose. No change in THC dose is needed for pulmonary administration.

In an embodiment of the methods disclosed herein, when the subject is determined to have heterozygous alleles (C/T) at the rs1045642 polymorphism of the ABCB1 gene, the subject is administered subject is administered a formulation wherein the primary terpene is linalool and the secondary terpene is beta-caryophyllene, and having a CBD:THC ratio of about 18:1 to about 4:1. Genetic factors are known to influence cannabis dependence. ABCB1 polymorphisms are known to modify drug pharmacokinetics and research studies have indicated their role in generating and maintaining cannabis dependence. The biomarker rs1045642 has been identified and associated with the risk of cannabis dependence. Research studies suggest that a subject may have a higher risk of cannabis dependence relative to people with the TT genotype. Any subject should consult a specialist before titrating a dose of THC. Caution is warranted.

EXAMPLES

The Examples that follow are illustrative of specific embodiments of the invention, and various uses thereof. They are set forth for explanatory purposes only, and are not to be taken as limiting the invention.

Exemplary formulations:

1. 1:1 10 mg CBD, 10 mg THC (1 mg CBN, Myrcene 5%, Terpinolene 3%)

2. 4:1 40 mg CBD, 10 mg THC (α-Pinene 5%, Terpineol 3%)

3. 1:1 10 mg CBD, 10 mg THC (Limonene 5%, Linalool 3%, 1 mg Bisabolol)

4. 1:1 10 mg CBD, 10 mg THC (13-Caryophyllene 5%, Limonene 3%)

5. 4:1 40 mg CBD, 10 mg THC (Linalool 5%, β-Caryophyllene, 1% Bomeol, 1% Pinene)

6. 1:2 10 mg CBD, 20 mg THC (5% β-Caryophyllene, 3% Myrcene, 1% Humulene, 1% CBC)

7. 1:2 10 mg CBD, 20 mg THC (Limonene 5%, Pinene 3%, THCV 1%)

Additional exemplary formulations are shown in Tables 1-9.

For Tables 1-9, while the ratios and percentages remain constant, the number of milligrams for both Tetrahydrocannabinol (THC) and Cannabidiol (CBD) are variable. Because THC is the psychoactive component of these formulations, these models utilize the THC dose as the control. These models assume a defacto dose of 10 mg THC for THC-rich formulations and 1 mg THC for CBD-rich formulations. Defacto dose is assumed for individuals with normal metabolic function and without contraindications. Metabolic function can be indicated by pharmacogenomic testing and assessment of CYP-450 enzyme expression, for example. Dosing is incremental and can titrated up or down in these proportions.

TABLE 1

Exemplary formulations

FORMULA-
EXEMPLARY

TION
CONDITION(S)
COMPOSITION

UNWIND
Sleep apnea,
1:1 to 1:5 CBD:THC

Insomnia,
Myrcene 3.0-5.0%

waking up easy
Linalool 1.5-5.0%

Terpinolene 1.0-3.0%

0.04-0.1% Lavender

0.04-0.1% Chamomile

0.04-0.1% Sandalwood

FOCUS
ADHD, Autism,
4:1 to 20:1 CBD:THC

High energy,
alpha Pinene 3.0-5.0%

Anxiety,
Terpineol 2.0-3.0%

Hyperactivity
Eucalyptol 0.25-1.0%

0.04-0.1% Wild Orange

0.04-0.1% Peppermint

0.04-0.1% Pulegone

COGNITIVE
Stress,
1:1 to 20:1 - CBD:THC

Depression
Limonene 2.0-5.0%

Linalool 1.5-5.0%

0.5-1.5% Bisabolol

0.04-0.1% Juniper Berry

0.04-0.1% Lime

0.04-0.1% Lavender

IMMUNE
Auto-immune
1:1 to 1:10 - CBD:THC

disorders, Pain,
Beta Caryophyllene 1.0-5.0%

treatment of
Limonene 2.0-5.0%

inflammation
0.01-5.0% BCAA (branched chain

related symptoms
amino acids)

0.04-0.1% Glutamine

0.04-0.1% Marjoram

0.04-0.1% Ginger

0.04-0.1% Lemongrass

RESPONSE
Fatigue, Low
4:1 to 20:1 - CBD:THC

energy, Anxiety
Linalool 1.5-5.0%

Bomeol 0.5-2.0%

Beta Caryophyllene 1.0-5.0%

Pinene 3.0-5.0%

0.04-0.1% Geranium

0.04-0.1% Mint

0.04-0.1% Guava

0.04-0.1% Lavender

RELIEF
Cancer, Pain,
1:1 to 1:20 - CBD:THC

Inflammation
Beta Caryophyllene 1.0-5.0%

Myrcene 3.0-5.0%

Humulene 1.0-2.0%

CBC 0.5-2.0%

0.04-0.1% Lavender

0.04-0.1% Sandalwood

0.04-0.1% Cayenne

0.04-0.1% Peppermint

ACTIVATE/
Mood disorders,
1:1 to 1:20 - CBD:THC

WELLNESS
fatigue, low
Limonene 2.0-5.0%

energy
Pinene 3.0-5.0%

THCV 0.5-2.0%

0.04-0.1% Peppermint

0.04-0.1% Eucalyptol

0.04-0.1% Cedarwood

0.04-0.1% Rosemary

RECOVERY
Post-workout,
1:1 to 1:3 - CBD:THC

exercise
BCAA 500-1500 mg

L-glutamine 250-750 mg

Pipeline 1-10 mg

Magnesium stearate 5-15 mg

MCC (Endurance) 5-15 mg

Silicon dioxide 4-12 mg

OPTIONAL INGREDIENTS: Any of the above formulations may also further comprise: CBC, CBCV, CBD, CBDA, CBDV, CBG, CBGV, CBL, CBN, CBV, THC, THCA, THCV, Ocimene, Valencene, Geraniol, Theramine, Phytol, Sabinene, Isobomeol, Cedrene, Guaiol, Geranyl Acetate, Eucalyptol, Carene, Fenchol, Bisabolol, Camphene, Camphor, Menthol, Nerolidol, Isopulegol, Cymene, or Pulegone.

In certain embodiments, any of the above formulations may be essentially free of THC.

Formulation #4

Wellness 1:1-1:20

THC Dose (mg):

10
10
10
10
10
10
10
10
10
10

Ratio:
1:1
1:2
1:3
1:4
1:5
1:6
1:7
1:8
1:9
1:10

By Milligrams:

CBD (mg)
10.00
5.00
3.33
2.50
2.00
1.67
1.43
1.25
1.11
1.00

THC (mg)
10.00
10.00
10.00
10.00
10.00
10.00
10.00
10.00
10.00
10.00

By Percentage:

CBD (%)
50.0%
33.33%
25.00%
20.00%
16.67%
14.29%
12.50%
11.11%
10.00%
9.09%

THC (%)
50.0%
66.67%
75.00%
80.00%
83.33%
85.71%
87.50%
88.89%
90.00%
90.91%

Additional

Cannabinoids,

Terpenes &

Active

Ingedients

Beta
2.50%
2.50%
2.50%
2.50%
2.50%
2.50%
2.50%
2.50%
2.50%
2.50%

Caryophylene

Limonene
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%

Pinene
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%

Majoram
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Lemongrass
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Mint
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Ginger
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

THC Dose (mg):

10
10
10
10
10
10
10
10
10
10

Ratio:
1:11
1:12
1:13
1:14
1:15
1:16
1:17
1:18
1:19
1:20

By Milligrams:

CBD (mg)
0.91
0.83
0.77
0.71
0.67
0.63
0.59
0.56
0.53
0.50

THC (mg)
10.00
10.00
10.00
10.00
10.00
10.00
10.00
10.00
10.00
10.00

By Percentage:

CBD (%)
8.33%
7.69%
7.14%
6.67%
6.25%
5.88%
5.56%
5.26%
5.00%
4.76%

THC (%)
91.67%
92.31%
92.86%
93.33%
93.75%
94.12%
94.44%
94.74%
95.00%
95.24%

Additional

Cannabinoids,

Terpenes &

Active

Ingedients

Beta
2.50%
2.50%
2.50%
2.50%
2.50%
2.50%
2.50%
2.50%
2.50%
2.50%

Caryophylene

Limonene
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%

Pinene
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%

Majoram
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Lemongrass
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Mint
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Ginger
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Formulation #2

Focus 20:1-1:1

THC Dose (mg):

1
1
1
1
1
1
1
1
1
1

Ratio:
20:1
19:1
18:1
17:1
16:1
15:1
14:1
13:1
12:1
11:1

By Milligrams:

CBD (mg)
20.00
19.00
18.00
17.00
16.00
15.00
14.00
13.00
12.00
11.00

THC (mg)
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00

By Percentage:

CBD (%)
95.24%
95.00%
94.74%
94.44%
94.12%
93.75%
93.35%
92.86%
92.31%
91.67%

THC (%)
4.76%
5.00%
5.26%
5.56%
5.88%
6.25%
6.67%
7.14%
7.69%
8.33%

Additional

Cannabinoids,

Terpenes &

Active

Ingedients

Terpenelene
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%

Eucolyptol
0.50%
0.50%
0.50%
0.50%
0.50%
0.50%
0.50%
0.50%
0.50%
0.50%

Pinene
3.00%
3.00%
3.00%
3.00%
3.00%
3.00%
3.00%
3.00%
3.00%
3.00%

Wild Orange
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Pulegone
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Cayenne
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Peppermint
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

THC Dose (mg):

1
1
1
1
1
1
1
1
1
1

Ratio:
10:1
9:1
8:1
7:1
6:1
5:1
4:1
3:1
2:1
1:1

By Milligrams:

CBD (mg)
10.00
9.00
8.00
7.00
6.00
5.00
4.00
3.00
2.00
10.00

THC (mg)
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
10.00

By Percentage:

CBD (%)
90.91%
90.00%
88.89%
87.50%
85.71%
83.33%
80.00%
75.00%
66.67%
50.00%

THC (%)
9.09%
10.00%
11.11%
12.50%
14.29%
16.67%
20.00%
25.00%
33.33%
50.00%

Additional

Cannabinoids,

Terpenes &

Active

Ingedients

Terpenelene
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%

Eucolyptol
0.50%
0.50%
0.50%
0.50%
0.50%
0.50%
0.50%
0.50%
0.50%
0.50%

Pinene
3.00%
3.00%
3.00%
3.00%
3.00%
3.00%
3.00%
3.00%
3.00%
3.00%

Wild Orange
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Pulegone
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Cayenne
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Peppermint
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

TABLE 4

Formulation #1

Unwind 1:1-1:5

THC Dose (mg):
10
10
10
10
10

Ratio:
1:1
1:2
1:3
1:4
1:5

By Milligrams:

CBD (mg)
10.00
5.80
3.33
2.50
2.00

THC (mg)
10.00
10.00
10.00
10.00
10.00

By percentage:

CBD (%)
50.00%
33.33%
25.00%
20.00%
16.67%

THC (%)
50.00%
66.67%
75.00%
80.00%
83.33%

Additional Cannabinoids,

Terpenes & Active

Ingredients

Myecene
3.50%
3.50%
3.50%
3.50%
3.50%

Linalool
1.50%
1.50%
1.50%
1.50%
1.50%

Terpenolene
2.50%
2.50%
2.50%
2.50%
2.50%

Lavender
0.10%
0.10%
0.10%
0.10%
0.10%

Chamomile
0.10%
0.10%
0.10%
0.10%
0.10%

Sandlewood
0.10%
0.10%
0.10%
0.10%
0.10%

TABLE 5

Formulation #3

Cognitive 20:1-2:1

THC Dose (mg):

1
1
1
1
1
1
1
1
1
1

Ratio:
20:1
19:1
18:1
17:1
16:1
15:1
14:1
13:1
12:1
11:1

By Milligrams:

CBD (mg)
20.00
19.00
18.00
17.00
16.00
15.00
14.00
13.00
12.00
11.00

THC (mg)
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00

By Percentage:

CBD (%)
95.24%
95.00%
94.74%
94.44%
94.12%
93.75%
93.35%
92.86%
92.31%
91.67%

THC (%)
4.76%
5.00%
5.26%
5.56%
5.88%
6.25%
6.67%
7.14%
7.69%
8.33%

Additional

Cannabinoids,

Terpenes &

Active

Ingedients

Linalool
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%

Limocene
3.50%
3.50%
3.50%
3.50%
3.50%
3.50%
3.50%
3.50%
3.50%
3.50%

Bisabolol
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%

Lime
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Junniper
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Berry

Mint
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Guava
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Lavender
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

THC Dose (mg):

1
1
1
1
1
1
1
1
1

Ratio:
10:1
9:1
8:1
7:1
6:1
5:1
4:1
3:1
2:1

By Milligrams:

CBD (mg)
10.00
9.00
8.00
7.00
6.00
5.00
4.00
3.00
2.00

THC (mg)
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00

By Percentage:

CBD (%)
90.91%
90.00%
88.89%
87.50%
85.71%
83.33%
80.00%
75.00%
66.67%

THC (%)
9.09%
10.00%
11.11%
12.50%
14.29%
16.67%
20.00%
25.00%
33.33%

Additional

Cannabinoids,

Terpenes &

Active

Ingedients

Linalool
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%

Limocene
3.50%
3.50%
3.50%
3.50%
3.50%
3.50%
3.50%
3.50%
3.50%

Bisabolol
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%

Lime
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Junniper
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Berry

Mint
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Guava
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Lavender
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

TABLE 6

Formulation #6

Response 18:1-4:1

THC Dose (mg):

1
1
1
1
1
1
1
1

Ratio:
18:1
17:1
16:1
15:1
14:1
13:1
12:1
11:1

By Milligrams:

CBD (mg)
18.00
17.00
16.00
15.00
14.00
13.00
12.00
11.00

THC (mg)
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00

By Percentage:

CBD (%)
94.74%
94.44%
94.12%
93.75%
93.33%
92.86%
92.31%
91.67%

THC (%)
5.26%
5.56%
5.88%
6.25%
6.67%
7.14%
7.69%
8.33%

Additional

Cannabinoids,

Terpenes &

Active

Ingedients

Linalool
3.50%
3.50%
3.50%
3.50%
3.50%
3.50%
3.50%
3.50%

Terpenolene
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%

Borneol
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%

Mint
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Guarava
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Lavender
0.04%
0.04%
0.04%
0.04%
0.04%
0.04%
0.04%
0.04%

THC Dose (mg):

1
1
1
1
1
1
1

Ratio:
10:1
9:1
8:1
7:1
6:1
5:1
4:1

By Milligrams:

CBD (mg)
10.00
9.00
8.00
7.00
6.00
5.00
4.00

THC (mg)
1.00
1.00
1.00
1.00
1.00
1.00
1.00

By Percentage:

CBD (%)
90.91%
90.00%
88.89%
87.50%
85.71%
83.33%
80.00%

THC (%)
9.09%
10.00%
11.11%
12.50%
14.29%
16.67%
20.00%

Additional

Cannabinoids,

Terpenes &

Active

Ingedients

Linalool
3.50%
3.50%
3.50%
3.50%
3.50%
3.50%
3.50%

Terpenolene
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%

Borneol
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%

Mint
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Guarava
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Lavender
0.04%
0.04%
0.04%
0.04%
0.04%
0.04%
0.04%

TABLE 7

Formulation #7

Relief 1:1-1:6

THC Dose (mg):

10
10
10
10
10
10

Ratio:
1:1
1:2
1:3
1:4
1:5
1:6

By Milligrams:

CBD (mg)
10.00
5.00
3.33
2.50
2.00
1.67

THC (mg)
10.00
10.00
10.00
10.00
10.00
10.00

By Percentage:

CBD (%)
50.00%
33.33%
25.00%
20.00%
16.67%
14.29%

THC (%)
50.00%
66.67%
75.00%
80.00%
83.33%
85.71%

Additional

Cannabinoids,

Terpenes &

Active

Ingedients

Myrcene
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%

Beta
3.50%
3.50%
3.50%
3.50%
3.50%
3.50%

Caryophyllene

Humulene
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%

Lavender
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Sandlewood
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Pepperming
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Rosemary
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

TABLE 8

Formulation #5

IMMUNE 1:1-1:10

THC Dose (mg):

10
10
10
10
10
10
10
10
10
10

Ratio:
1:1
1:2
1:3
1:4
1:5
1:6
1:7
1:8
1:9
1:10

By Milligrams:

CBD (mg)
10.00
5.00
3.33
2.50
2.00
1.67
1.43
1.25
1.11
1.00

THC (mg)
10.00
10.00
10.00
10.00
10.00
10.00
10.00
10.00
10.00
10.00

By Percentage:

CBD (%)
50.00%
33.33%
25.00%
20.00%
16.67%
14.29%
12.50%
11.11%
10.00%
9.09%

THC (%)
50.00%
66.67%
75.00%
80.00%
83.33%
85.71%
87.50%
88.89%
90.00%
90.91%

Additional

Cannabinoids,

Terpenes &

Active

Ingedients

Beta
3.00%
3.00%
3.00%
3.00%
3.00%
3.00%
3.00%
3.00%
3.00%
3.00%

Caryophyllene

Humulene
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%
2.00%

Terpenolene
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%
1.00%

Lavender
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Chamomile
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

Sandlewood
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%
0.10%

TABLE 9

Formulation #8

Recovery (Capsules)

This product is a powder-based and encapsulated for oral administration

Vegan Branch Chain Amino Acids,
1,000
mg

(L-Leucine, L-Isoleuice, L-Valline)

L-Glutamine
500
mg

BioPerine
5
mg

Magnesium Stearate
10
mg

MCC (Endurance)
10
mg

Silicon Dioxide (Sipernat22S)
8
mg

CBD/THC dose/ratio:

Hemp Extract (CBD) 5.5 mg
5.5
mg

THC Isolate Powder 2.5 mg
2.5
mg

TABLE 10

Single-nucleotide polymorphisms (SNPs), endocannabinoid genotype, and potential formulation.

References

SNIP I.D.
Gene
rsID
Category
Formulation
Effect/Findings/Discussion
(PMID)

2-01-
ABCB1
rs1045642
Response to
RESPONSE
When consumed regularly,
28917442

AFMLG

Cannabinoids

THC can accumulate in your

body. If for example, you are

a T carrier, and you stop

consuming for a significant

period of time, you may have

higher levels of THC for an

extended period of time. You

may find withdrawal easier

than the other genotypes (C

carrier) because you may

excrete THC more slowly. It

is important to note that this

polymorphism is only one of

many contributing factors to

withdrawal experiences.

3-01-A
AKT1
rs1130233
Response to
COGNITIVE
This polymorphism is
22290123

Cannabinoids

associated with the risk of

psychotomimetic (psychosis-

like) effects after consuming

THC. The risk is especially

increased by an interaction

with the SLC6A3 3′UTR

VNTR polymorphism (9

repeat allele). It is important

to note that this

polymorphism is only one of

many contributing factors to

this side effect.

4-01-A
AKT1
rs1130233
Response to
COGNITIVE
Impaired motor control can
25065544

Cannabinoids

be caused by THC, but this

effect is modulated by this

polymorphism. It is

important to note that this

polymorphism is only one of

many contributing factors to

this profile.

5-01-2AL
AKT1
rs2494732
Response to
COGNITIVE
This polymorphism may
22831980

Cannabinoids

confer a significantly

elevated risk of a psychotic

disorder for those who use

cannabis -- and when some

previous psychosis of some

sort is present, cannabis may

dramatically increase further

psychotic experiences.

However, this polymorphism

is only one of many

contributing factors to this

profile.

6-01-2AL
AKT1
rs2494732
Response to
COGNITIVE
Cognitive functioning,
21775978

Cannabinoids

including attention and

accuracy, are adversely

affected by THC. This effect

may be modified by this

AKT1 polymorphisms and

by interactions with

psychosis. It is important to

note that polymorphism is

only one of many

contributing factors to this

profile.

7-01-2AL
AKT1
rs2494732
Response to
COGNITIVE
THC can cause acute
26882038

Cannabinoids

psychotomimetic (psychosis-

like) effects in some people

and this response is

modulated by this AKT1

polymorphism. It is

important to note that this

polymorphism is only one of

many contributing factors to

this profile.

8-01-2AL
AKT1
rs2494732
Response to
COGNITIVE
This polymorphism was
27336035;

Cannabinoids

associated with greater risk
PMC4849451

of developing psychosis in

cannabis risers. It is

important to note that this

polymorphism is only one of

many contributing factors to

this profile.

9-01-ALG
BDNF
rs6265
Response to
RESPONSE
Cannabis use was associated
21305693

Cannabinoids

with earlier age of onset of a

psychotic disorder. In one

study, this effect was

stronger with a higher

frequency of cannabis use

and earlier age at first use. In

males, this effect occured

independent of BDNF

genotype. In females, the

effect of cannabis use on age

of onset of psychosis was

highly dependent on this

polymorphism. It is

important to note that this

polymorphism is only one of

many contributing factors to

this profile.

CNR1
(rs202329,
Response to
COGNITIVE
Based on your TAG
24445906

rs1535255,
Cannabinoids

haplotype of ACA, you may

rs806379)

have a higher risk of

experiencing acute

psychomimetic effects after

consumption of THC.

[In exploring CNR1, AKT1,

BDNF and COMT genes

with psychotomimetic effects

when first using cannabis

(PEFU), Reserchers found a

significant association with a

functional haplotype block in

CNR1], (Overall

reccomendation include not

consuming alcohol and other

substances in parallel with

THC use). Consult a

specialist for a dose titration/

adjustment. It is important

to note that this

polymorphism is only one of

many contributing factors to

this profile.

16-01-
CNR1
rs1O49353
Response to
COGNITIVE
This polymorphism was
roar.uel.ac.uk/4985/1/

2AFML

Cannabinoids

associated with performance
Stephanie%20Marie%20Lynch.pdf

on a test of executive

function (mental skills that

help you set and accomplish

goals) and sustained

attention in a combined

group of cannabis users and

non-users. It is important to

note that this is only one of

many factors determining on

how you sustain attention

and focus on activities.

17-01-
CNR1
rs1406977
Response to
COGNITIVE
This polymorphism was
25139064;

AFM

Cannabinoids

associated with performance
27261878

on a working memory task in

cannabis users, but not in

non-cannabis users. It is

important to note that this is

only one of many factors

determining your working

memory profile.

26-01-2
COMT
rs4680
Response to
COGNITIVE
This polymorphism was
21947654;

Cannabinoids

associated with the onset of
23445265;

psychotomimetic (psychosis-
26464454;

like) effects after consuming
16936704

THC. However, this was not

confirmed by all studies.

Other studies found an

interacting effect of

childhood abuse or

psychosis-related cognitive

changes. It is important to

note that this polymorphism

is only one of many

contributing factors to this

profile.

27-01-2
COMT
rs4680
Response to
COGNITIVE
This polymorphism was
23311613

Cannabinoids

associated with the volume/

neuroanatomical changes of

specific brain regions in

young males who are chronic

cannabis users. These

include the ventral caudate

nucleus (involved in

memory), the left amygdala

(involved in emotions such

as anxiety), prefrontal cortex,

neostriatum (caudate-

putamen), ACC and the

hippocampus-amygdala

complex (respectively tied

into short-term memory

emotions, moods, and other

functions related to

depression and anxiety). It is

important to note that this is

only one of many factors that

could be linked to anxiety

and other emotions.

28-01-2
COMT
rs4680
Response to
COGNITIVE
This polymorphism was
26882038;

Cannabinoids

associated with memory and
16936704;

other cognitive impairments
26464454;

after consuming THC. It is
23449176

important to note that this

polymorphism is only one of

many contributing factors to

this profile.

29-01-2
COMT
rs4680
Response to
RESPONSE
Individuals who carried high
26950642

Cannabinoids

function COMT and low-

function DRD4 7R alleles (a

combination expected to be

associated with higher risk)

showed more lifetime

cannabis abuse in a cohort of

women with binge-purge

eating disorders.

30-01-
CYP2C9
rs1057910
Response to
RESPONSE
This polymorphism was
19005461

2AFMLG

Cannabinoids

associated with metabolism

and pharmacokinetics of oral

THC. THC levels

immediately after pulmonary

administration (smoking,

vaporizing) are not highly

affected by the rate of

metabolism, so this

polymorphism probably has

little effect with these

methods. No effect on CBD

levels is expected since it is

not metabolized to a

significant extent by

CYP2C9.

31-01
CYP3A4
rs35599367
Response to
RESPONSE
This polymorphism was
23750331

Cannabinoids

associated with activity of

the CYP3A4 enzyme, which

can metabolize both THC

and CBD. Although this

polymorphism has not

directly been associated with

cannabinoid metabolism,

clinical studies of the

CYP3A4 inhibitor

ketoconazole showed that it

boosts both THC and CBD

levels after oronmcosal

dosing by approximately 2-

fold. Therefore, it is likely

that this polymorphism

affects THC and CBD levels

after oral dosing.

32-01
DAT1
VNTR
Response to
COGNITIVE
Genetic Factors are a key
29404409

Cannabinoids

component in how your body

responds to THC and CBD

by way of absorption,

distribution, metabolism, and

excretion. The hippocampus

is a brain region associated

with learning, memory, and

emotions. Although cannabis

use was associated with a

decreased volume of the

hippocampus, the effect was

highly dependent on this

polymorphism. It is

important to note that this

polymorphism is only one of

many contributing factors to

this profile.

33-01
DBH
rs1611115
Response to
COGNITIVE
This polymorphism was
26667034

Cannabinoids

associated with impulsivity

after cannabis consumption

in a group of people that

regularly used cannabis and

cocaine. It is important to

note that this polymorphism

is only one of many

contributing factors to this

profile.

34-01-
DRD2
rs1076560
Response to
COGNITIVE
This polymorphism was
27336035

2AFMLG

Cannabinoids

associated with greater risk

of developing psychosis in

cannabis users. It is

important to note that this

polymorphism is only one of

many contributing factors to

this profile.

41-01
FAAH
rs324420
Response to
RESPONSE
This polymorphism was
26106535

Cannabinoids

associated with brain white

matter integrity in young

cannabis users. Lower white

matter integrity was linked to

apathy and depression. It is

important to note that this

polymorphism is only one of

many contributing factors to

this profile.

42-01
MAPK14
rs12199654
Response to
COGNITIVE
This polymorphism was
22850347

Cannabinoids

associated with white matter

volume reduction in

cannabis-dependent

schizophrenic patients.

White matter is important for

cognition and executive

control (e.g. attention and

planning). It is important to

note that this polymorphism

is only one of many

contributing factors to this

profile.

46-01
NRG1
rs22153 3
Response to
COGNITIVE
This polymorphism was
roar.uel.ac.uk/4985/1/

Cannabinoids

associated with some
Stephanie%20Marie%20Lynch.pdf

symptoms of schizotypal

personality. It is important to

note that this polymorphism

is only one of many

contributing factors to this

profile.

47-01
NRG1
rs7834206
Response to
COGNITIVE
This polymorphism was
20582876

Cannabinoids

associated with deficits in

auditory information

processing after cannabis

consumption. Auditor

information processing

deficits are associated with

schizophrenia. It is important

to note that this

polymorphism is only one of

many contributing factors to

this profile.

50-01
SLC6A3
rs28363170
Response to
COGNITIVE
This polymorphism was
22290123

Cannabinoids

associated with the risk of

psychotomimetic (psychosis-

like) effects after consuming

THC. The risk was

especially increased by an

interaction with the AKT1

rs1130233 polymorphism. It

is important to note that this

polymorphism is only one of

many contributing factors to

this profile.

51-01
SLC6A3
rs28363170
Response to
COGNITIVE
This polymorphism was
22290123

Cannabinoids

associated with the risk of

psychotomimetic (psvchosis-

like) effects after consuming

THC. There was a further

interaction of this

polymorphisms with the

AKT1 rs130233

polymorphism. The

psychotomimetic effects of

THC may be especially

increased in subjects who

carry both the risk alleles.

Furthermore, this effect

involves an alteration in the

neural response to THC in

the dopamine-rich regions of

striatum and midbrain,

consistent w ith independent

evidence that the

psychotomimetic effects of

cannabis are mediated by

dopamine. It is important to

note that this polymorphism

is only one of many

contributing factors to this

profile.

52-01
SLC6A4
5-HTTLPR
Response to
COGNITIVE
This polymorphism is
26860734

Cannabinoids

associated with the

development of anxiety

following cannabis use in

adolescents. Research

indicates that cannabis use is

associated with an increase

in symptoms of anxiety but

only in carriers of the short

allele of the 5-HTTLPR

polymorphism. It is

important to note that this

polymorphism is only one of

many contributing factors to

this profile.

53-01
SLC6A4
5-HTTLPR
Response to
COGNITIVE
This polymorphism was
20434316

Cannabinoids

associated with psychotic

symptoms in patients with

bipolar disorder. The short

allele of the 5-HTTLPR

polymorphism of the 5-HTT

gene was associated with

psychotic symptoms when

when there was a

dependence or abuse of

cannabis. It is important to

note that this polymorphism

is only one of many

contributing factors to this

profile.

54-01
SLC6A4
5-HTTLPR
Response to
COGNITIVE
This polymorphism was
23449176

Cannabinoids

associated with decision

making abilities in a manner

dependence on both

genotype and cannabis use.

Among youth with two

“short” alleles of the 5-

HTTLPR polymorphism,

decision making abilities

were significantly worse in

cannabis users. Decision

making ability was similar in

cannabis users and non-users

of other genotypes. It is

important to note that this

polymorphism is only one of

many contributing factors to

this profile.

CNR1
(AAT)n
Physical
IMMUNE
This polymorphism was
23306084;

microsatellite
Health &

associated with Irritable
24444427

Wellness

Bowel Syndrome (IBS) and

severity of symptoms in

patients with IBS. Hence,

research supports the

hypothesis that cannabinoid

receptors may play a role in

control of colonic transit and

sensation in humans. It is

important to note that this

polymorphism is only one of

many contributing factors to

this profile.

20-01-
CNR1
rs806366
Physical
RELIEF
Migraines and its symptoms
27762084

AFM

Health &

may be exacerbated by

Wellness

recent stressful life events.

Tliis polymorphism was

associated with headache

with nausea only in those

people who had experienced

recent stressful events. It is

important to note that this is

only one of many factors

determining whether and

how you may experience

migraine symptoms.

39-01
FAAH
rs324420
Physical
RESPONSE
This polymorphism was
26808012

Health &

associated with cold pain

Wellness

sensitivity and use of

postoperative analgesia. It is

important to note that this

polymorphism is only one of

many contributing factors to

this profile.

40-01
FAAH
rs324420
Physical
RESPONSE
Some opioid effects are
25558980;

Health &

potentiated by cannabinoids,
27977335

Wellness

including the

endocannabinoid

anandamidc. This

polymorphism lias been

linked to the severity of

morphine side effects, such

as respiratory depression and

nausea/vomiting. in children

and adolescents following

surgery. It is important to

note that this polymorphism

is only one of many

contributing factors to this

profile.

11-01-
CNR1
rs1049353
Mental
COGNITIVE
This polymorphism was
26717543

2AFML

Health &

associated with signs of post-

Wellness

traumatic threat symptoms.

In particular, minor An allele

carrier w ho also scored high

on a measure of early child

hood trauma reported greater

threat symptoms and

hypervigilance reactions.

The association depends on

the level of childhood

physical abuse experienced.

It is important to note that

this polymorphism is only

one of many factors

contributing to the

development these kind of

symptoms.

12-01-
CNR1
rs1049353
Mental
COGNITIVE
A polymorphism in the
22826533

2AFML

Health &

endocannabinoid system was

Wellness

linked to the antidepressant

responses for a class of

antidepressants called

selective serotonin reuptake

inhibitors (SSRIs).

Specifically, the C/C

genotype of this CNR1

polymorphism was

associated with a better

response to the

antidepressant citalopram/

Celexa* in males. It is

important to note that this

polymorphism is only one of

many contributing factors to

this profile.

13-01-
CNR1
rs1049353
Mental
COGNITIVE
The endocannabinoid
24980155

2AFML

Health &

signaling system (ECS) helps

Wellness

controls neural development,

particularly during

adolescence. The ECS is

vulnerable to disturbances

during this time (including

exposure to exogenous

cannabinoids) and

disturbances may lead to

impairments in self

control. In one study of

communities at risk for extra

stressors, this polymorphism

was linked to adolescent

impulsivity following early

psychosocial adversity. In

particular, early adversity is

linked to enhanced

impulsivity among

homozygous carriers of the

rs806379 A and the

rslO49353 T allele when

compared to homozygous

carriers of the respective

major allele. It is important

to note that this

polymorphism is only one of

many contributing factors to

this profile.

14-01-
CNR1
rs1049353
Mental
COGNITIVE
The theta wave is a type of
25116250

2AFML

Health &

brain wave measured by

Wellness

EEG that is correlated with

working memory

performance. This

polymorphism was

associated with the

magnitude of the theta wave.

It is important to note that

this polymorphism is only

one of many contributing

factors to tlris profile.

15-01-
CNR1
rs1049353
Mental
COGNITIVE
Tliis polymorphism was
26527537

2AFML

Health &

associated with the

Wellness

recognition of negative

emotions in adolescents and

the activation of associated

brain areas that process

emotional recognition. These

brain areas include the insula

and amygdala. Specifically,

adolescent C/C carriers of

this polymorphism had

greater insula and amygdala

activation of viewing angry

faces.This is part of a larger

body of research on how

complex social cues are

learned. Researchers note

that this overlaps with the

endocannabinoid system

modulating the mesolimbic

dopaminergic system. It is

important to note that this

polymorphism is only one of

many contributing factors to

tliis profile.

19-01-
CNR1
rs2023239
Mental
COGNITIVE
This polymorphism was
26331953

AFMG

Health &

associated with depression in

Wellness

a population of patients on

methadone maintenance. For

those with the C allele there

are some indications of a

protective role against major

depressive disorder (MDD).

This polymorphism is only

one of many factors

contributing to the

development of depression.

21-01-
CNR1
rs806377
Mental
COGNITIVE
In one study, it was found
24690898

AFLG

Health &

that C allele carriers of this

Wellness

CNR1 polymorphism have

an increased subjective

happiness levels, including

experiencing more overall

happiness in life and

experiencing greater positive

emotions after a positive

event. It is important to note

that this polymorphism is

only one of many factors

contributing to the

development of these kind of

outlooks/experiences.

23-01
CNR1
rs806379
Mental
COGNITIVE
The endocannabinoid
24980155

Health &

signaling system (ECS) helps

Wellness

control neural development,

particularly during

adolescence. The ECS is

vulnerable to disturbances

during this time (including

exposure to exogenous

cannabinoids) and

disturbances may lead to

impairments in self

control. In one study of

communities at risk for extra

stressors, this polymorphism

was linked to adolescent

impulsivity following early

psychosocial adversity. In

particular, early adversity is

linked to enhanced

impulsivity among

homozygous carriers of the

rs806379 A and the

rsl049353 T allele when

compared to homozygous

carriers of the respective

major allele. It is important

to note that this

polymorphism is only one of

many contributing factors to

this profile.

24-01
CNR2
rs2501432
Mental
COGNITIVE
In a Japanese study that
18991891

Health &

compared both humans, this

Wellness

polymorphism was

associated with higher

vulnerability to depression. It

is important to note that this

is only one of many factors if

and how you may experience

depressive behaviors.

25-01
CNR2
rs41311993
Mental
COGNITIVE
Tliis polymorphism was
21658778

Health &

significantly associated with

Wellness

the risk for developing

bipolar disorder (BD). It is

important to note that this is

only one of many factors

linked to tliis profile.

37-01
FAAH
rs324420
Mental
COGNITIVE
This polymorphism was
19103437

Health &

associated with threat-related

Wellness

anxiety, reward-related

impulsivity, and activation of

associated brain areas (the

amygdala and ventral

striatum, respectively). It is

important to note that this

polymorphism is only one of

many contributing factors to

tliis profile.

38-01
FAAH
rs324420
Mental
REST
This polymorphism was
27074158

Health &

associated with poorer sleep

Wellness

quality among young

cannabis users. Depressive

symptoms were identified as

a possible link between this

polymorphism and poor

sleep quality. It is important

to note that this

polymorphism is only one of

many contributing factors to

this profile.

1-01-
ABCB1
rs1045642
Drug
RESPONSE
This polymorphism was
19625010

AFMLG

Dependence

associated with the risk of

cannabis dependence. This

may be due to effects on

brain penetration of THC or

effects on elimination of

THC from the body. It is

important to note that this

polymorphism is only one of

many contributing factors to

developing cannabis

dependence.

10-01-
CNR1
rs1049353
Drug
RESPONSE
This polymorphism had a
19443135

2AFML

Dependence

weak trend towards

association with cannabis

dependence symptoms in

young adults. This research

was also carried out in a

specific population of youth

with polysubstance

dependence and conduct

problems, and thus the

results may not be

generalizable to other groups

of youth or adults. It is

important to note that this is

only one of many factors

determining whether and

how cannabis dependence

occur.

18-01-
CNR1
rs2023239
Drug
RESPONSE
One research study linked
18705688

AFMG

Dependence

this polymorphism to craving

for cannabis after 5 days of

abstinence in daily cannabis

smokers. Craving for a drug

is a warning sign for

psychological dependence. It

is important to note that this

polymorphism is only one of

many contributing factors to

dependency issues.

22-01
CNR1
rs806379
Drag
COGNITIVE
Nicotine withdrawal can
27453054

Dependence

cause cognitive disruption,

which is partially mediated

by the endocannabinoid

system. This polymorphism

was associated with the

degree of cognitive

disruption during nicotine

withdrawal. Current research

suggests potential efficacy of

a pharmacotherapy approach

for smoking cessation among

individuals who exhibit

greater nicotine withdrawal-

related cognitive disruption.

35-01
DRD2
rsl800497
Drug
COGNITIVE
Tliis polymorphism was
26833047;

Dependence

associated with the risk of
22536882

cannabis dependence. There

was also an interaction noted

with the CNR1 rs1049353

polymorphism. It is

important to note that this

polymorphism is only one of

many contributing factors to

this profile.

36-01
FAAH
rs324420
Drug
RESPONSE
This polymorphism was
24407958

Dependence

associated with risky alcohol

use. which is a precursor to

more significant dependence

on alcohol. It is important to

note that this polymorphism

is only one of many

contributing factors to this

profile.

43-01
MGLL
rs604300
Drug
RESPONSE
This polymorphism was
26595473

Dependence

associated with cannabis

dependence in a maimer that

depended on the presence of

early childhood abuse. It is

important to note that this

polymorphism is only one of

many contributing factors to

this profile.

44-01
NCAM1
rs4471463
Drug
RESPONSE
This polymorphism was
27023175

Dependence

associated with lifetime use

of cannabis. The specific

outcome of this study was

whether the subjects had ever

tried cannabis or had never

tried it. Although further

study is needed, this

polymorphism could also be

associated with cannabis

dependence. It is important

to note that this

polymorphism is only one of

many contributing factors to

this profile.

45-01
NRG1
rsl7664708
Drug
RESPONSE
This polymorphism was
22520967

Dependence

associated with the risk of

cannabis dependence in a

group of African Americans.

This finding was not

replicated in European

Americans. It is important to

note that this polymorphism

is only one of many

contributing factors to this

profile.

48-01
OPRM1
rs1799971
Drug
RESPONSE
This polymorphism was
26392368

Dependence

associated with a general risk

of substance abuse, including

cannabis dependence. It is

important to note that this

polymorphism is only one of

many contributing factors to

this profile.

49-01
PENK
rs2609997
Drug
RESPONSE
This polymorphism was
22745721

Dependence

associated with cannabis

dependence. This risk was

modified by the neuroticism

personality trait, which

describes a person's

propensity for experiencing

negative emotions.

(Limitations of the research

include that the sample was

drawn from a population

without significant

psychiatric comorbidity). It

is important to note that this

polymorphism is only one of

many contributing factors to

this profile.

Suggestion -

Suggestion -

Major
Minor
Homozygous MAJOR
Suggestion -
Homozygous MINOR

SNIP I.D.
Gene
Allele
Allele
Allele
Heterozygous
Allele

2-01-
ABCB1
C
T
Homozygous MAJOR
Heterozygous
Homozygous MINOR

AFMLG

Alleles (C/C)
Alleles (C/T)
Alleles (T/T)

Research indicates you
Research indicates
Research indicates you

may have higher THC
you may have 2-fold
may have 2-fold lower

levels in your blood
lower THC levels in
blood THC levels after

after consuming THC
your blood after
consuming THC

relative to other
consuming THC
relative to people with

genotypes.
relative to people
the most common

with the most
genotype.

common genotype.

3-01-A
AKT1
C
T
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (C/C)Research
Alleles
Alleles (T/T)Research

indicates you may have
(C/T)Research
indicates you may have

an increased risk of
indicates you may
a lower risk of

experiencing acute
have a lower risk of
experiencing acute

psychotomimetic effects
experiencing acute
psychotomimetic effects

after consuming THC.
psychotomimetic
after consuming THC.

Your risk is highest if
effects after

you also carry an
consuming THC.

SLCA6 3′ UTR VNTR

9R allele. Caution and

consultation with a

licensed medical

professional who

focuses on THC/CBD

titration/adjustments

and cessation.is

recommended to assess

your risks.

4-01-A
AKT1
C
T
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (C/C)
Alleles (C/T)
Alleles (T/T)

Research indicates you
Research indicates
Research indicates you

may be less likely to
you may be less
may develop

develop coordination
likely to develop
coordination

impairment after
coordination
impairment after

consuming THC.
impairment after
consuming THC. Avoid

consuming THC.
using alcohol when

consuming THC.

Careful titration of dose

under supervision a

licensed medical

professional who

focuses on THC/CBD

titration/adjustments

and cessation.

5-01-2AL
AKT1
T
C
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (T/T)You may
Alleles (T/C)You
Alleles (C/C)You may

have a lower risk of
may have an
have an increased

developing a psychotic
increased likelihood
likelihood of a

disorder with cannabis
of a psychotic
psychotic disorder with

use relative to people
disorder with
cannabis use. This risk

with other genotypes.
cannabis use. This
may be especially

risk is especially
elevated in daily

elevated in daily
cannabis users. Caution

cannabis users.
is warranted.

Caution is warranted.
Consultation with a

Consultation with a
licensed medical

licensed medical
professional who

professional who
focuses on THC/CBD

focuses on THC &
titration is

CBD titration is
recommended.

recommended.

6-01-2AL
AKT1
T
C
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (T/T)
Alleles (T/C)
Alleles (C/C)

You may have a lower
You may have a
You may be at a higher

risk of memory and
lower risk of memory
risk of impairments in

attention impairments
and attention
memory and attention

after consuming THC.
impairments after
after consuming THC

consuming THC.
relative to people with

other genotypes.

Responsible use is

warranted.

7-01-2AL
AKT1
T
C
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (T/T)Research
Alleles (TC)You may
Alleles (C/C)You may

indicates you may have
have an increased
have an increased risk

a lower risk of
risk of experiencing
of experiencing acute

experiencing acute
acute
psychotomimetic effects

psychotomimetic effects
psychotomimetic
(psychosis-like) after

(psychosis-like) after
effects after
consuming THC.

consuming THC.
consuming THC.
Caution and

Caution and
consultation with a

consultation with a
specialist are

specialist are
recommended to assess

recommended to
your risks.

assess your risks.

8-01-2AL
AKT1
T
C
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (T/T)
Alleles (T/C)
Alleles (C/C)

Research indicates that
If you are
If you are predisposed

THC may not increase
predisposed to
to developing

your risk of developing
developing psychosis,
psychosis, THC may

psychosis relative to
THC may increase
increase your risk. The

other genotypes.
your risk. The risk is
risk is highest with

highest with more
more frequent use of

frequent use of THC
THC and in those who

and in those who also
also carry a DRD2

carry a DRD2
rs107650 A allele.

rs107650 A allele.
Caution and

Caution and
consultation with a

consultation with a
licensed medical

licensed medical
professional who

professional who
focuses on THC & CBD

focuses on THC &
titration is

CBD titration is
recommended to assess

recommended to
your risks.

assess your risks.

9-01-ALG
BDNF
G
A
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (G/G)Research
Alleles (G/A)If you
Alleles (A/A)If you are

indicates If you are
are female who is
female who is

female who is
predisposed to
predisposed to

predisposed to
developing psychosis,
developing psychosis,

developing psychosis,
cannabis use may
cannabis use may result

cannabis use may not
result in a
in a significantly earlier

result in an earlier age
significantly earlier
age of onset of

of onset of psychosis.
age of onset of
psychosis. The effect of

psychosis. The effect
cannabis depends on the

of cannabis depends
extent of cannabis use

on the extent of
and the age at which

cannabis use and the
you start using it. Use

age at which you start
with caution and consult

using it. Use with
a specialist for a dose

caution and consult a
titration.

specialist for a dose

titration.

CNR1

Based on your TAG
Based on your TAG

haplotype of ACA, you
haplotype of AAA,

may have a higher risk
you may have a lower

of experiencing acute
risk of experiencing

psychomimetic effects
acute psychomimetic

after consumption of
effects after

THC. Do not consume
consumption of THC.

alcohol and other

substances in parallel

with THC use. Consult

a specialist for a dose

titration.

16-01-
CNR1
C
T
Homozygous MAJOR
Heterozygous
Homozygous MINOR

2AFML

Alleles (C/C)You may
Alleles (C/T)You
Alleles (T/T)You may

have greater ability in
may have an elevated
have an elevated risk of

sustained attention
risk of impairments
impairments in

relative to people with
in sustained attention
sustained attention with

other genotypes.
with cannabis use
cannabis use relative to

relative to people
people with the most

with the most
common genotype.

common genotype.
Consume responsibly.

Consume

responsibly.

17-01-
CNR1
T
C
Homozygous MAJOR
Heterozygous
Homozygous MINOR

AFM

Alleles (T/T)
Alleles (T/C)
Alleles (C/C)

You may be less likely
You may be more
You may be more likely

to experience working
likely to experience
to experience working

memory impairments
working memory
memory impairments

after use of THC.
impairments after use
after use of THC.

of THC. Careful dose
Careful dose titration is

titration is warranted.
warranted. Please

Please consult a
consult a specialist.

specialist.

26-01-2
COMT
G
A
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (G/G)
Alleles (G/A)
Alleles (A/A)

You may be more likely
You may be more
You may be less likely

to experience
likely to experience
to experience

psychotomimetic effects
psychotomimetic
psychotomimetic effects

after consuming THC.
effects after
after consuming THC

Although there are other
consuming THC.
relative to people with

predisposing factors,
Although there are
other genotypes.

caution is warranted
other predisposing
However, there are

upon THC
factors, caution is
other predisposing

consumption.
warranted upon THC
factors.

consumption.

27-01-2
COMT
G
A
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (G/G)You may
Alleles (G/A)You
Alleles (AA)You may

be at increased risk of
may be at increased
have a decreased risk of

brain volume changes
risk of brain volume
brain volume changes

following cannabis use
changes following
following cannabis use

that are linked to
cannabis use that are
that are linked to

alterations in emotions
linked to alterations
alterations in emotions

and memory.
in emotions and
and memory.

memory.

28-01-2
COMT
G
A
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (G/G)
Alleles (G/A)
Alleles (A/A)

You may experience
You may experience
You may experience

greater cognitive
greater cognitive
less cognitive

impairment after
impairment after
impairment after

consuming THC
consuming THC
consuming THC

relative to people with
relative to people
relative to people with

other genotypes.
with the AA
other genotypes.

Caution and careful
genotype. Caution
Caution and careful

titration of THC is
and careful titration
titration of THC is still

highly recommended.
of THC is highly
recommended.

recommended.

29-01-2
COMT
G
A
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (G/G)You may
Alleles (G/A)You
Alleles (A/A)You may

have a higher risk for
may have a relatively
have a relatively lower

dependence on cannabis
lower risk to develop
risk to develop

and associated cravings
dependence on
dependence on cannabis

relative to other
cannabis relative to
relative to people with

genoty pes. Caution and
people with the most
the most common

consultation with a
common genotype.
genotype.

specialist is

recommended.

30-01-
CYP2C9
A
C
Homozy gous MAJOR
Heterozygous
Homozygous MINOR

2AFMLG

Alleles (A/A)
Alleles (A/C)
Alleles (C/C)

As you do not have a
You may feel the
You may feel the effects

version of CYP2C9
effects of oral THC
of oral THC more

with reduced activity,
more strongly or find
strongly or find that the

you can start oral THC
that the effects last
effects last longer

at a typical dose.
longer relative to
relative to people with

However, this is not the
people with the most
the most common

only factor affecting
common genotype. It
genotype. It is

sensitivity to THC and
is recommended that
recommended that the

careful dose titration is
the first time you use
first time you use oral

still recommended.
oral THC, you start at
THC, you start at 30%

60% of the standard
of the standard dose. No

dose. No change in
change in THC dose is

THC dose is needed
needed for pulmonary

for pulmonary
administration.

administration.

31-01
CYP3A4
C
T
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (C/C)As you
Alleles (C/T)You
Alleles (T/T)You may

have the ty pical version
may feel the effects
feel the effects of oral

of CYP3A4, you may
of oral THC more
THC more strongly or

start oral THC or CBD
strongly or find that
find that the effects last

at a normal dose.
the effects last longer
longer relative to other

However, this is not the
relative to other
people. It is

only factor affecting
people. It is
recommended that the

sensitivitity to THC.
recommended that
first time you use oral

the first time you use
THC. you start at 50%

oral THC. you start at
of the standard dose. No

75% of the standard
change in dose is

dose. No change in
needed for pulmonary

THC dose is needed
administration.

for pulmonary

administration.

32-01
DAT1

You may be at risk for
This genotype was
This genotype was not

reduced hippocampal
not associated with
associated with reduced

volume with cannabis
reduced hippocampal
hippocampal volume in

use. This could lead to
volume in cannabis
cannabis users.

long- and short-term
users.

memory impairments

and altered emotions.

Responsible use and

consultation with a

specialist is warranted.

33-01
DBH
C
T
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (C/C)This
Alleles (C/T)You
Alleles (T/T)You may

genotype was not
may be more likely to
be more likely to act

associated with
act impulsively after
impulsively after

increased impulsivity
consuming cannabis.
consuming cannabis.

after cannabis use.
Responsible use is
Responsible use is

warranted.
warranted.

34-01-
DRD2
C
A
Homozygous MAJOR
Heterozygous
Homozygous MINOR

2AFMLG

Alleles (C/C)
Alleles (A/C)
Alleles (A/A)

THC may not increase
If you are
If you are predisposed

your risk of developing
predisposed to
to developing

psychosis relative to
developing psychosis,
psychosis, THC may

other genotypes.
THC may increase
increase your risk. The

your risk. The risk is
risk is highest with

highest with more
more frequent use of

frequent use of THC
THC and in those who

and in those who also
also carry an AKT1

carry an AKT1
rs2494732 C allele.

rs2494732 C allele.
Caution and

Caution and
consultation with a

consultation with a
specialist are

specialist are
recommended to assess

recommended to
your risks.

assess your risks.

41-01
FAAH
C
A
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (C/C)
Alleles (C/A)
Alleles (A/A)

You may be more likely
You may have less
You may have less risk

relative to other
risk for decreased
for decreased white

genotypes to experience
white matter integrity
matter integrity with

decreased white matter
with cannabis use
cannabis use. Cautious

integrity with cannabis
relative. Cautious use
use is warranted.

use at a young age.
is warranted.

Careful dose titration is

warranted. Please

consult a specialist.

42-01
MAPK14
A
G
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (A/A)You may
Alleles (A/G)Your
Alleles (G/G)Your

have a higher risk of
genotype may not
genotype may not

decreased white matter
confer risk of
confer risk of decreased

brain volume from
decreased white
white matter volume

cannabis use. This could
matter volume from
from cannabis use.

impair your cognition.
cannabis use.
Cautious use is

Use with caution and
Cautious use is
warranted.

consult a specialist for a
warranted.

dose titration.

46-01
NRG1
T
C
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (T/T)
Alleles (T/C)
Alleles (C/C)

You may have a lower
You may have a
You may have a higher

risk of experiencing
lower risk of
risk of experiencing

psychomimetic effects
experiencing
psychomimetic effects

following cannabis use
psychomimetic
following cannabis use

relative to people with
effects following
relative to people with

the (T/T) genotype.
cannabis.
the other genotypes.

Consume responsibly

and consult a specialist

for guidance.

47-01
NRG1
C
A
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (C/C)
Alleles (C/A)
Alleles (A/A)

You may be less likely
You may be more
You may be more likely

to develop
likely to develop
to develop

psychomimetic effects
psychomimetic
psychomimetic effects

after cannabis
effects after cannabis
after cannabis

consumption relative to
consumption.
consumption.

people with other
Responsible
Responsible

genotypes. Responsible
consumption and a
consumption and a

consumption and a
titration with a help
titration with a help of a

titration with a help of a
of a specialist is
specialist is warranted.

specialist is warranted.
warranted.

50-01
SLC6A3
10R
9R
You may have a lower
You may have an
You may have an

risk of experiencing
increased risk of
increased risk of

acute psychotomimetic
experiencing acute
experiencing acute

effects after consuming
psychotomimetic
psychotomimetic effects

THC.
effects after
after consuming THC.

consuming THC.
Your risk is highest if

Your risk is highest if
you also have an AKT1

you also have an
C/C genotype. Caution

AKT1 C/C genotype.
and consultation with a

Caution and
specialist are

consultation with a
recommended to assess

specialist are
your risks and prevent

recommended to
them.

assess your risks and

prevent them.

51-01
SLC6A3
10R
9R
You may have a lower
You may have a
You may have a higher

risk of impulsivity after
higher risk of
risk of impulsivity after

consuming cannabis
impulsivity after
consuming cannabis

compared to other
consuming cannabis
relative to the most

genotypes.
relative to the most
common genotype.

common genotype.

52-01
SLC6A4
L′
S′
Adolescents may be at
Adolescents with this
Adolescents with this

increased risk of
genotype may be at
genotype may be at

developing anxiety
increased risk of
increased risk of

following cannabis use,
developing anxiety
developing anxiety

but this genotype was
following cannabis
following cannabis use.

not associated with
use. Cannabis should
Cannabis should only

extra risk. Cannabis
only be used
be used responsibly

should only be used
responsibly once
once legal age is

responsibly once legal
legal age is attained.
attained.

age is attained.

53-01
SLC6A4
L′
S′
Your genotype was not
Please be advised that
Please be advised that if

associated with
if you or your close
you or your close blood

heightened risk of
blood related
related relatives have

psychotomimetic
relatives have bipolar
bipolar disorder, you

symptoms in patients
disorder, you may be
may be at a higher risk

with bipolar disorder.
at a higher risk of
of psychotic effects

psychotic effects with
with cannabis

cannabis
consumption\. Careful

consumption\.
titration of THC dose

Careful titration of
and a consultation with

THC dose and a
a specialist is suggested.

consultation with a

specialist is

suggested.

54-01
SLC6A4
L′
S′
You may be less likely
You may be less
You may be more likely

to experience a decrease
likely to experience a
to experience a decrease

in decision making
decrease in decision
in decision making

ability as a result of
making ability as a
ability as a result of

using cannabis.
result of using
using cannabis

cannabis.
compared to people of

other genotypes.

Caution is warranted.

CNR1

Based on your genotype
Based on your
Based on your genotype

of <10/<10, you may
genotype of <10/>10,
of >10/>10, you may

have a lower risk of
you may have an
have an elevated risk of

developing IBS relative
elevated risk of
developing IBS. If you

to people of other
developing IBS. A
have IBS or develop it

genotypes.
specialist should be
in the future, you may

consulted for THC
have more severe

dose titration.
symptoms than patients

with a different

genotype. A specialist

should be consulted for

THC dose titration.

20-01-
CNR1
T
C
Homozygous MAJOR
Heterozygous
Homozygous MINOR

AFM

Alleles (T/T)You may
Alleles (T/C)This
Alleles (C/C)This

be more likely to
genotype does not
genotype does not

experience headache
appear to confer
appear to confer greater

with nausea after a
greater risk of
risk of experiencing

stressful event in vour
experiencing
headache with nausea

life. Use THC
headache with nausea
after recent stressful life

responsibly and consult
after recent stressful
events.

a specialist to titrate a
life events.

dose appropriately to

your condition.

39-01
FAAH
C
A
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (C/C)
Alleles (C/A)
Alleles (A/A)

You may have higher
You may have higher
You may have

cold pain sensitivity and
cold pain sensitivity
significantly lower cold

more need for analgesia
and more need for
pain sensitivity and less

during periods of acute
analgesia during
need for analgesia

pain, such as after an
periods of acute pain,
during periods of acute

operation.
such as after an
pain, such as after an

operation.
operation.

40-01
FAAH
C
A
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (C/C)
Alleles (C/A)
Alleles (A/A)

You may have a lower
You may have a
You may have a higher

risk experiencing side
higher risk of
risk of experiencing

effects from opioids
experiencing side
side effects from

relative to people with
effects from opioids
opioids relative to

other genotypes.
relative to people
people with the most

with the most
common genotype. If

common genotype. If
you will be receiving

you will be receiving
opioids, consider

opioids, consider
informing your

informing your
physician of a potential

physician of a
predisposition to

potential
respiratory depression

predisposition to
and nausea/vomiting.

respiratory

depression and

nausea/vomiting.

11-01-
CNR1
C
T
Homozygous MAJOR
Heterozygous
Homozygous MINOR

2AFML

Alleles (C/C)Research
Alleles (C/T)If you
Alleles (T/T)If you

indicates you that if you
have experienced
have experienced

have experienced
childhood physical
childhood physical

childhood physical
abuse, you may have
abuse, you may have a

abuse, you may have
a lower risk of
lower risk of

increased risk of
posttraumatic threat
posttraumatic threat

posttraumatic threat
symptoms relative to
symptoms relative to

symptoms relative to
people with the most
people with the most

people with other
common genotype.
common genotype.

genotypes. Please

consult a specialist if

symptoms are present.

12-01-
CNR1
C
T
Homozygous MAJOR
Heterozygous
Homozygous MINOR

2AFML

Alleles (C/C)
Alleles (C/T)
Alleles (T/T)

Research indicates that
Research indicates
Research indicates that

if you are a male patient
that if you are a male
if you are a male patient

with depression, you
patient with
with depression, you

may respond better to
depression, you may
may have decreased

treatment with
have a decreased
likelihood of responding

antidepressants such as
likelihood of
to antidepressants such

citalopram. Consult a
responding to
as citalopram/Celexa.

specialist prior to
antidepressants such
Consult a specialist

cannabinoid use or
as citalopram/
prior to cannabinoid use

making any change in
Celexa*. Consult a
or making any change

antidepressant
specialist prior to
in antidepressant

treatment.
cannabinoid use or
treatment.

making any change in

antidepressant

treatment.

13-01-
CNR1
C
T
Homozygous MAJOR
Heterozygous
Homozygous MINOR

2AFML

Alleles (C/C)Research
Alleles
Alleles (T/T)Research

indicates adolescents
(C/T)Research
indicates that

who experienced early
indicates adolescents
adolescents who

psychosocial adversity
who experienced
experienced early

may not have an
early psychosocial
psychosocial adversity

elevated risk of
adversity may have a
may have a higher of

impulsive behavior.
slightly higher of risk
risk of impulsive

of impulsive
behavior. Consult a

behavior. Consult a
specialist for

specialist for
cannabinoid dose

cannabinoid dose
titration.

titration.

14-01-
CNR1
C
T
Homozygous MAJOR
Heterozygous
Homozygous MINOR

2AFML

Alleles (C/C)
Alleles (C/T)
Alleles (T/T)

You may have lower
Research indicates
Research indicates you

resting state EEG theta
you may have a
may have a higher

power. This may be
higher resting state
resting state EEG theta

correlated with lower
EEG theta power
power relative to the

working memory
relative to the most
most common

performance.
common genotype.
genotype. This may be

This may be
correlated with better

correlated with better
working memory.

working memory.

15-01-
CNR1
C
T
Homozygous MAJOR
Heterozygous
Homozygous MINOR

2AFML

Alleles (C/C)You may
Alleles (C/T)You
Alleles (T/T)You may

have greater amygdala
may have less
have less amygdala

and insula activation
amygdala and insula
activation upon viewing

upon viewing angry
activation upon
angry faces similar

faces or similar stimuli.
viewing angry faces
stimuli.

or similar stimuli.

19-01-
CNR1
T
c
Homozygous MAJOR
Heterozygous
Homozygous MINOR

AFMG

Alleles (T/T)
Alleles (T/C)
Alleles (C/C)

You may be more likely
You may be less
You may be less likely

to experience
likely to experience
to experience

depression. Use THC
depression relative to
depression relative to

with caution as it could
people with the most
people with the most

potentiate your
common genotype.
common genotype.

symptoms Consult a
Caution with use of
Caution with use of

specialist for a careful
THC is still
THC is still

dose titration /
recommended.
recommended.

adjustment.

21-01-
CNR1
T
C
Homozygous MAJOR
Heterozygous
Homozygous MINOR

AFLG

Alleles (T/T)Rcscarch
Alleles
Alleles (C/C)Research

indicates that you may
(T/C)Research
indicates you may

experience more overall
indicates that you
experience more overall

happiness in life and
may experience more
happiness in life and

experience greater
overall happiness in
experience greater

positive emotions after
life and experience
positive emotions after

a positive event. In one
greater positive
a positive event, noting

study, C allele of CNR1
emotions after a
that long term

was significantly
positive event, noting
sociological factors

associated with an
that long term
affect the momentary

increased subjective
sociological factors
emotional state.

happiness level noting
affect the momentary

that long term
emotional state.

sociological factors

affect the momentary

emotional state.

23-01
CNR1
A
T
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (A/A)Research
Alleles
Alleles (T/T)Research

indicates that
(A/T)Research
indicates that

adolescents who
indicates that
adolescents who

experienced early
adolescents who have
experienced early

psychosocial adversity
experienced early
psychosocial adversity

may have a higher risk
psychosocial
may not have an

of impulsive behavior.
adversity may have a
elevated risk of

Consult a specialist for
slightly higher of risk
impulsive behavior.

cannabinoid dose
of impulsive

titration.
behavior. Consult a

specialist for

cannabinoid dose

titration.

24-01
CNR2
C
T
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (C/C)
Alleles (C/T)
Alleles (T/T)

Your risk of depression
You may have a
You may have a higher

may be lower relative to
higher than average
than average risk of

people with other
risk of developing
developing depression.

genotypes. This
depression. Watch for
Watch for symptoms of

polymorphism is only
symptoms of
depression and consider

factor in the risk for
depression and
consulting with a

developing depression.
consider consulting
specialist if these

with a specialist if
symptoms are

these symptoms are
interfering with your

interfering with your
daily life.

daily life.

25-01
CNR2
G
T
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (G/G)You may
Alleles (G/T)You
Alleles (T/T)You may

have a lower risk of
may have a higher
have a higher risk of

developing bipolar
risk of developing
developing bipolar

disorder relative to
bipolar disorder
disorder relative to

people of other
relative to people of
people of the most

genotypes.
the most common
common genotype.

genotype.

37-01
FAAH
C
A
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (C/C)
Alleles (C/A)
Alleles (A/A)

You may have greater
You may have
You may have reduced

anxiety (and associated
reduced anxiety (and
anxiety (and associated

activation of the
associated activation
activation of the

amygdala) in a
of the amygdala) in a
amygdala) in a

threatening situation
threatening situation
threatening situation

relative to other
relative to the most
relative to the most

genotypes. However,
common genotype.
common genotype.

you may have decreased
Hoyvever, you may
Hoyvever, you may have

reward-related
have increased
increased reward-

impulsivity.
reyvard-related
related impulsivity (and

impulsivity (and
associated activation of

associated activation
the ventral striatum).

of the ventral

striatum).

38-01
FAAH
C
A
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (C/C)
Alleles (C/A)
Alleles (A/A)

You may be at
This polymorphism
This polymorphism

increased risk of poor
does not appear to
does not appear to

sleep quality. Consume
increase your risk of
increase your risk of

THC responsibly and
poor sleep.
poor sleep.

consult a specialist for

an optimal dose

titration.

1-01-
ABCB1
C
T
Homozygous MAJOR
Heterozygous
Homozygous MINOR

AFMLG

Alleles (C/C)Research
Alleles
Alleles (T/T) Research

indicates you may have
(C/T)Research
indicates you may have

a higher risk of cannabis
indicates you may
an even less cannabis

dependence. Consider
have a higher risk of
dependence relative to

consulting with a
cannabis dependence.
other genotypes

medical professional
Consider consulting
combinations. Your

with experience in THC
with a medical
genotype at this

& CBD dose titration.
professional with
polymorphism does not

experience in THC &
suggest a specific type

CBD dose titration.
of cannabis product you

should consume. Your

choice of cannabis

product can be driven

by any symptoms you

may have. However,

thoroughly check all

polymorphisms in this

report for areas where

you may have

heightened risks.

10-01-
CNR1
C
T
Homozygous MAJOR
Heterozygous
Homozygous MINOR

2AFML

Alleles (C/C)
Alleles (C/T)
Alleles (T/T)

You may have a higher
You may have a
You may have a lower

risk of developing
higher risk of
risk of developing

symptoms of cannabis
developing symptoms
symptoms of cannabis

dependence. Please
of cannabis
dependence relative to

consume responsibly
dependence. Please
people with the most

and consult with a
consume responsibly
common genotype.

specialist for guidance.
and consult with a

specialist for

guidance.

18-01-
CNR1
T
C
Homozygous MAJOR
Heterozygous
Homozygous MINOR

AFMG

Alleles (T/T)Research
Alleles
Alleles (C/C)Research

indicates you that if you
(T/C)Research
indicates you that if you

are a regular cannabis
indicates you if you
are a regular cannabis

user, you may
are a regular cannabis
user, you may

experience less cravings
user, you may
experience stronger

and withdrawal after
experience stronger
cravings and withdrawal

stopping relative to the
cravings and
after stopping relative to

other genotypes. If there
withdrawal after
people with the most

are indications you are
stopping relative to
common genotype. If

dependent on cannabis
people with the most
you feel that you are

and have trouble
common genotype. If
dependent on cannabis

stopping, it is
you feel that you are
and have trouble

recommended that you
dependent on
stopping, it is

consult with a licensed
cannabis and have
recommended that you

medical professional
trouble stopping, it is
consult with a licensed

who focuses on THC/
recommended that
medical professional

CBD titration and
you consult with a
who focuses on THC &

cessation.
licensed medical
CBD titration and

professional who
cessation.

focuses on THC/

CBD titration/

adjustments and

cessation.

22-01
CNR1
A
T
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (A/A)
Alleles (A/T)
Alleles (T/T)

Research indicates that
Research indicates
Research indicates that

based on your genotype,
that based on your
based on your genotype,

you may exhibit greater
genotype, you may
you may exhibit less

nicotine withdrawal-
exhibit less nicotine
nicotine withdrawal-

related cognitive
withdrawal-related
related cognitive

dismption.
cognitive dismption.
dismption.

35-01
DRD2
G
A
Homozy gous MAJOR
Heterozygous
Homozygous MINOR

Alleles (G/G)You may
Alleles (G/A)You
Alleles (A/A)You may

have decreased
may have decreased
have a greater

likelihood of developing
likelihood of
likelihood of developing

cannabis dependence.
developing cannabis
cannabis dependence,

dependence.
with associated cravings

and mood changes.

Avoid mixing alcohol

and cannabis. Consult a

specialist for dose

titration.

36-01
FAAH
C
A
Homozy gous MAJOR
Heterozygous
Homozygous MINOR

Alleles (C/C)
Alleles (C/A)
Alleles (A/A)

You may be
You may have a
You may have a lower

significantly more likely
lower risk of
risk of engaging in risky

to use alcohol in a risky
engaging in risky
alcohol use.

fashion. Use THC
alcohol use.

responsibly and don't

combine with alcohol

use.

43-01
MGLL
G
A
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (G/G)
Alleles (G/A)
Alleles (A/A)

Although vour genotype
You may have
You may have

may be protective
increased risk of
increased risk of

against cannabis
cannabis dependence
cannabis dependence

dependence, this
independent of early
independent of early

protective effect appears
childhood stress or
childhood stress or

to be absent if you have
abuse. Caution and
abuse. Caution and

experienced early
responsible use is
responsible use is

childhood stress or
warranted.
warranted.

abuse. Cautious use is

warranted. Consult a

specialist for a dose

titration.

44-01
NCAM1
T
C
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (T/T)You may
Alleles (T/C)You
Alleles (C/C)You may

be less likely to ever
may have a greater
have a greater

consume cannabis
likelihood of using
likelihood of using

relative to people with
cannabis relative to
cannabis relative to

other genotypes.
people with the most
people with the most

common genotype.
common genotype.

Although not yet
Although not yet

directly studied, this
directly studied, this

may extend to a
may extend to a greater

greater likelihood of
likelihood of cannabis

cannabis dependence.
dependence. Consume

Consume
responsibly.

responsibly.

45-01
NRG1
C
T
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (C/C)
Alleles (C/T)
Alleles (T/T)

If you are African
If you are African
If you are African

American, you may
American, you may
American, you may

have a lower risk of
have a higher risk of
have a higher risk of

cannabis dependence in
cannabis dependence
cannabis dependence

comparison to the other
relative to the most
relative to the most

genotypes.
common genotype.
common genotype.

48-01
OPRM1
A
G
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (A/A)
Alleles (A/G)
Alleles (G/G)

You may have a slightly
You may have a
You may have a slightly

higher risk of substance
slightly lower risk of
lower risk of substance

abuse, including
substance abuse,
abuse, including

cannabis dependence,
including cannabis
cannabis dependence,

relative to the other
dependence, relative
relative to the most

genotypes.
to the most common
common genotype.

genotype.

49-01
PENK
T
C
Homozygous MAJOR
Heterozygous
Homozygous MINOR

Alleles (T/T)You may
Alleles (T/C)You
Alleles (C/C)You may

be less likely to develop
may be more likely to
be more likely to

symptoms of cannabis
develop symptoms of
develop symptoms of

dependence relative to
cannabis dependence
cannabis dependence

people with other
relative to people
relative to people with

genotypes.
with the most
the most common

common genotype.
genotype. This risk may

This risk may be
be increased further if

increased further if
you have high levels of

you have high levels
neuroticism. Consume

of neuroticism.
THC responsibly and

Consume THC
consult a specialist for

responsibly and
guidance.

consult a specialist

for guidance.

All-allele disclaimer: Your choice of cannabis product can be driven by any symptoms you may have. However, thoroughly check all polymorphisms in this report for areas where you may have heightened risks.

Non-risk Allele disclaimer: Your genotype at this polymorphism does not suggest a specific type of cannabis.

Number	Name	Date	Kind
20110064720	Amato	Mar 2011	A1
20140295040	Milici	Oct 2014	A1
20160250270	Wendschuh et al.	Sep 2016	A1
20160279073	Donsky et al.	Sep 2016	A1
20170172977	Kleidon et al.	Jun 2017	A1

Number	Date	Country
2014100231	Jun 2014	WO
2017158539	Sep 2017	WO
2017182950	Oct 2017	WO

Number	Date	Country
62721294	Aug 2018	US
62680885	Jun 2018	US
62707300	Oct 2017	US

Cannabinoid formulations

Information

Patent Number

Date Filed

Date Issued

Inventors

Original Assignees

Examiners

Agents

CPC

Field of Search

CPC

International Classifications

Term Extension

Abstract

Description

Claims

RELATED APPLICATIONS

PCT Information

US Referenced Citations (5)

Foreign Referenced Citations (3)

Non-Patent Literature Citations (3)

Related Publications (1)

Provisional Applications (3)

Entry
PCT International Search Report and Written Opinion, PCT International Application No. PCT/US2018/058199, dated Jan. 7, 2019, 23 pages.
Crippa, Jose Alexandre S. et al. “Neural Basis of Anxiolytic Effects of Cannabidiol (CBD) in Generalized Social Anxiety Disorder: A Preliminary Report”, Journal of Psychopharmacology vol. 25, Jan. 2011, pp. 121-130.
EP Partial Supplementary Search Report, EP Application No. 18872736.6, dated Jul. 27, 2021, 16 pages.