US 20140271 940A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0271940 A1 Wurzer (43) Pub. Date: Sep. 18, 2014

(54) BIOACTIVE CONCENTRATES AND USES Publication Classification THEREOF (51) Int. Cl. (71) Applicant: SC LABORATORIES, INC., Capitola, A61E36/85 (2006.01) CA (US) (52) U.S. Cl. (72) Inventor: Joshua H. Wurzer, Boulder Creek, CA CPCSr...... 446 IK36/85K 185 (9.(2013.O1 (US) (73) Assignee: SC LABORATORIES, INC., Capitola, CA (US) (57) ABSTRACT (21) Appl. No.: 14/206,942 (22) Filed: Mar 12, 2014 The present invention relates to concentrates obtained from Related U.S. Application Data extraction from , preferably and/orter pene concentrates, and formulation of the concentrates, par (60) Provisional application No. 61/781,491, filed on Mar. ticularly for use for direct vaporization, infusion into edible 14, 2013, provisional application No. 61/781,479, matrices, in electronic inhalation devices, and as nutraceuti filed on Mar. 14, 2013. cals. US 2014/027 1940 A1 Sep. 18, 2014

BOACTIVE CONCENTRATES AND USES mind that THC and Cannabis are not synonymous for a THEREOF number of reasons. Firstly, THC does not exist as such in the plant material but rather it is found as a carboxylic acid CROSS-REFERENCE TO RELATED (THCA), as are other . While less studied, these APPLICATIONS carboxylic acid derivatives show pharmacological potential 0001. This application claims priority to pending U.S. as well. These acids (THCA and CBDA) decompose slowly Provisional Patent Application No. 61/781,491 filed Mar. 14, during storage to the corresponding chemically neutral but 2013 and to U.S. Provisional Patent Application No. 61/781, pharmacologically potent THC and CBD. This conversion is 479 filed Mar. 14, 2013, the contents of each of which are speeded up by the high temperatures involved in Smoking and incorporated by reference in their entirety. to a lesser extent by cooking or baking the drugs. Secondly, the THC/CBD ratio can markedly alter the effects of the FIELD OF THE INVENTION drugs. Thirdly, Some of the non-cannabinoid compounds from the plant may modulate the pharmacological effects of 0002 The present invention relates to concentrates the cannabinoids. Terpenoids, which are responsible for the obtained from extraction from Cannabis, preferably cannab characteristic smell and flavor of Cannabis, have been pos inoid and/or terpene concentrates, and formulation of the tulated as influencing the effects yet experimental evidence is concentrates, particularly for use for direct vaporization, scarce. Some 1% by weight of the plant is composed of a infusion into edible matrices, in electronic inhalation devices, mixture of 20 flavonoid compounds which are well known as and as nutraceuticals. antioxidants and which also scavenge damaging free radicals. 0008. There has been considerable research regarding the BACKGROUND OF THE INVENTION first cannabinoid discovered in the Cannabis plant, cannab 0003 Cannabinoids are a class of diverse chemical com inol (CBN). While generally considered an unwanted degra pounds that activate cannabinoid receptors. These include the dation product of A9 (THC), CBN is a endocannabinoids (produced naturally in the body by humans weakagonist of the CB1 and CB2 receptors. CBN is believed and animals), the phytocannabinoids (found in Cannabis and to cause drowsiness alone or when combined with CBD, Some other plants), and (produced THC, Cannagiberol (CBG), THCV, or chemically by humans). The most notable cannabinoid is the (CBC). As an isolated compound, CBN has shown moderate phytocannabinoid A9-tetrahydrocannabinol (THC), the pri toxicity in animal models. Combined with other cannab mary psychoactive compound of Cannabis. inoids, THC, CBD, CBG, or CBC, it is believed that the I0004. As mentioned, the main cannabinoid is A-tetrahy toxicity is reduced due to the mediating effects of the other drocannabinol (THC), which is recognized as the major psy cannabinoids. choactive euphoriant responsible for the characteristic intoxi 0009. As can be seen, most research around active com cation (high) which follows the Smoking or ingestion of ponents of Cannabis has centered on THC and CBD. To this Cannabis. High THC doses produce hallucinogenic effects. extract, there are many descriptions of processes making In addition to THC, several less potent metabolites and THC extracts and of products incorporating the extracts. related compounds, such as the also psychoactive A 8-THC However, there are relatively few reports of methods for and (CBN) are found in the Cannabis plant. extracting other bioactive compounds from Cannabis and the Another major compound is (CBD), which has use of Such bioactive extracts in a nutraceutical context. antagonistic effects to THC because it is a sedative com Accordingly, what is needed in the art are methods for pro pound. The ratio of THC to CBD in the plant is significant in ducing and formulating bioactive extracts from Cannabis that terms of psychoactivity and is genetically determined. contain desired compounds in addition to or other than THC. 0005. A number of chemotypes exist within Cannabis. These are plants which are visually and botanically identical SUMMARY OF THE INVENTION but which are chemically dissimilar. One type referred to as 0010. The present invention relates to concentrates the fiber- or hemp-type contains predominantly CBD and obtained from extraction from Cannabis, preferably cannab only trace amounts of THC. Conversely, drug-type plants inoid and/or terpene concentrates, and formulation of the produce predominantly THC with trace quantities of CBD. concentrates, particularly for use for direct vaporization, 0006. The issue is further complicated by the existence of infusion into edible matrices, in electronic inhalation devices, an intermediate plant which contains approximately equal and as nutraceuticals. amounts of both THC and CBD. The concentrations of these 0011. In some embodiments, the present invention pro and other cannabinoids vary enormously in practice depend vides processes for preparing cannabinoid and/or terpenoid ing on plant breeding and cultivation techniques and on post extracts for human consumption comprising: (a) concentrat harvest handling. THC is a highly unstable compound, break ing glandular trichomes from Cannabis plant material; (b) ing down in air and light to a number of inactive molecules, passing a solvent though the plant material to produce a one of which, cannabinol (CBN), is commonly found in Can cannabinoid/terpenoid-containing eluate; (c) filtering Solids nabis products as they age. Other relatively abundant, and in from the eluate; (d) refining the eluate to remove undesirable certain rare chemotypes, predominant cannabinoids include impurities; and (e) processing the eluate into a consumable (CBG), cannabichromene (CBC), tetrahydro form. In some embodiments, the refining comprises: (i) dis (THCV), and (CBDV) but in tilling the eluate; (ii) resuspending eluate in polar solvent; and general little is known about the biological activities of these (iii) cooling resuspended eluate to precipitate out undesirable and the remaining less frequently occurring molecules. impurities. In some embodiments, the refining comprises: (i) 0007 Most pharmacological research has focused on adding eluate to non-polar solvent; (ii) adding concentrated THC and CBD. However, while THC is responsible for many brine Solution; (iii) agitating vigorously; (iv) draining off of the drugs, it is important to bear in brine Solution; and (v) treating the eluate with desiccant. In US 2014/027 1940 A1 Sep. 18, 2014

some embodiments, the methods further comprise the step of (-)-6a, 7.10a-Trihydroxy-A9-tetrahydrocannabinol (-)-Can fractionating the eluate into fractions enriched for one or nabitetrol, 10-Oxo-A6a(10a)tetrahydrocannabinol OTHC); more cannabinoids and/or terpenoids. In some embodiments, (5aS,6S,9R,9aR)- CBE-C5, (5aS,6S.9R, the fractionating comprises passing the eluate over a column 9aR) C3-Cannabielsoin CBE-C3, (5aS,6S,9R,9aR)-Can in the presence of solvents of progressively different polari nabielsoic acid A CBEA-C5A, (5aS,6S,9R,9aR)-Cannabiel ties, and collecting fractions as they exit the column. In some soic acid B CBEA-C5 B; (5aS,6S,9R,9aR) C3 embodiments, the fractionating comprises: (i) concentrating Cannabielsoic acid B CBEA-C3 B, Cannabiglendol-C3 the eluate in a non-polar solvent; (ii) cooling the eluate solu OH-iso-HHCV-C3, Dehydrocannabifuran DCBF-C5, Can tion to 20 to -200 C; and (iii) filtering crystals according to nabifuran CBF-C5), (-)-A7-trans-(1R,3R,6R)-Isotetrahy composition. In some embodiments, the refining comprises drocannabinol, (+)-A7-12-cis-(1R,3R,6S/1S,3S,6R)-Isotet exposing eluate to UV light for at least 30 minutes to degrade rahydrocannabivarin, (-)-A7-trans-(1R,3R,6R)- chlorophyll. In some embodiments, the refining comprises: Isotetrahydrocannabivarin); (+)-(1aS,3aR,8bR,8cR)- (i) adding solvent and activated charcoal to eluate; (ii) mix CBL-C5, (+)-(1aS,3aR,8bR,8cR)- ing; (iii) filtering out activated charcoal; and (iv) removing Cannabicyclolic acid A CBLA-C5 A, (+)-(1aS.3aR.8bR. Solvent. In some embodiments, processing the eluate into a 8cR)-Cannabicyclovarin CBLV-C3: Cannabicitran CBT consumable form comprises spray drying the eluate to pro C5); Cannabichromanone CBCN-C5, Cannabichromanone duce a crystalline extract. In some embodiments, processing C3 CBCN-C3, and Cannabicoumaronone CBCON-C5); and the eluate into a consumable form comprises thin film evapo at least 0.1% w/w of at least one terpenoid selected from the ration. In some embodiments, processing the eluate into a group consisting of Alloaromadendrene, allyl hexanoate, consumable form comprises continuously stirring the eluate benzaldehyde, (Z)-C-cis-bergamotene, (Z)-O-trans-berga with a whisk or auger until eluate is dried into a wax. motene, B-bisabolol, epi-C.-bisabolol, B-bisabolene, borneol 0012. In some embodiments, the present invention pro (camphol), cis-y-bisabolene, borneol acetate (bornyl acetate), vides a concentrate produced by the foregoing methods. C-cadinene, camphene, , cis-carveol, (B-caryophyllene), C-humulene (C-caryophyllene), 0013. In some embodiments, the present invention pro Y-cadinene, A-3-carene, caryophyllene oxide, 1,8-cineole, vides a concentrate comprising at least 1% w/w of at least one citral A, citral B, cinnameldehyde, C-copaene (aglaiene), cannabinoid compound selected from the group consisting of Y-curcumene, B-cymene, B-elemene, y-elemene, ethyl decdi Cannabigerol (E)-CBG-C5, Cannabigerol monomethyl ether enoate, ethyl maltol, ethylpropionate, ethylvanillin, eucalyp (E)-CBGM-C5A, A (Z)-CBGA-C5A, tol, C-eudesmol, B-eudesmol, Y-eudesmol, , cis-B- Cannabigerovarin (E)-CBGV-C3, Cannabigerolic acid A(E)- farnesene ((Z)-3-farnesene), trans-C-farnesene, trans-B- CBGA-C5A, Cannabigerolic acid A monomethyl ether (E)- farnesene, trans-y bisabolene, fenchone, fenchol CBGAM-C5A and Cannabigerovarinic acid A(E)-CBGVA (norbornanol, B-fenchol), , C.-guaiene, guaiol, C3 A); (t)-Cannabichromene CBC-C5, (t)- methyl anthranilate, , 2-methyl-4-hep Cannabichromenic acid A CBCA-C5 A, (+)- tanone, 3-methyl-4-heptanone, hexyl acetate, ipsdienol, Cannabivarichromene, (+)- CBCV-C3, isoamyl acetate, lemenol, limonene, d-limonene (limonene), (+)-Cannabichromevarinic acid A CBCVA-C3A): (-)-Can linolool (linallyl alcohol, B-linolool), C.-longipinene, , nabidiol CBD-C5, Cannabidiol momomethyl ether CBDM Y-muurolene, myrcene (B-myrcene), nerolidol, trans-neroli C5, Cannabidiol-C4 CBD-C4, (-)-Cannabidivarin CBDV dol, nerol, B-Ocimene (cis-ocimene), octyl acetate, C.-phel C3, Cannabidiorcol CBD-C1, Cannabidiolic acid CBDA-C5, landrene, phytol, C-pinene (2-pinene), B-pinene, pulegone, Cannabidivarinic acid CBDVA-C3): CBND C5, Cannabinodivarin CBND-C3); A9-Tetrahydrocannab Sabinene, cis-Sabinene hydrate (cis-thujanol), B-selinene, inol A9-THC-C5. A9-Tetrahydrocannabinol-C4 A9-THC C-selinene, Y-terpinene, terpinolene (isoterpine), terpineol (a C4, A9- A9-THCV-C3, terpineol), terpineol-4-ol, C-terpinene (terpilene), C-thujene A9-, A9-THCO-Cl, A9-Tetrahydro (origanene), , viridiflorene (ledene), and C-ylange. cannabinolic acid AA9-THCA-C5A, A9-Tetrahydrocannab 0014. In some embodiments, the concentrate comprises at inolic acid B. A9-THCA-C5 B, A9-Tetrahydrocannabinolic least 1%, 2%. 5%, or 10% w/w of two or more of the cannab acid-C4A and/or B A9-THCA-C4A and/or B. A9-Tetrahy inoid compounds. In some embodiments, the concentrate dro-cannabivarinic acid AA9-THCVA-C3A, A9-Tetrahydro comprises at least 1%, 2%. 5%, or 10% w/w of three or more cannabiorcolic acid A and/or BA9-THCOA-C1A and/or B), of the cannabinoid compounds. In some embodiments, the (-)-A8-trans-(6aR.10aR)-A8-Tetrahydrocannabinol concentrate comprises at least 1%, 2%. 5%, or 10% w/w of A8-THC-C5, (-)-A8-trans-(6aR.10aR)-Tetrahydrocannabin four or more of the cannabinoid compounds. In some embodi olic acid AA8-THCA-C5A, (-)-(6aS,10aR)-A9-Tetrahydro ments, the concentrate comprises at least 1%, 2%. 5%, or 10% cannabinol (-)-cis-A9-THC-C5); Cannabinol CBN-C5, Can w/w of five of the cannabinoid compounds. In some embodi nabinol-C4 CBN-C4, Cannabivarin CBN-C3, Cannabinol ments, the concentrate comprises at least 0.01%, 0.05%, C2 CBN-C2, Cannabiorcol CBN-C1, Cannabinolic acid A 0.1%, 0.5%, 1%, 2%, 3%, 4%, or 5% w/w of two or more of CBNA-C5A, Cannabinol methyl ether CBNM-C5, (-)-(9R, the terpenoids. In some embodiments, the concentrate com 1OR)-trans-Cannabitriol (-)-trans-CBT-C5, (+)-(9S.10S)- prises at least 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, Cannabitriol (+)-trans-CBT-C5, (+)-(9R,10S/9S,10R) ); or 5% w/w of three or more of the terpenoids. In some Cannabitriol (+)-cis-CBT-C5, (-)-(9R. 10R)-trans-10-O- embodiments, the concentrate comprises at least 0.01%. Ethyl-cannabitriol (-)-trans-CBT-OEt-C5, (+)-(9R,10R/9S, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, or 5% of four of the 10S)-Cannabitriol-C3(+)-trans-CBT-C3, 8.9-Dihydroxy terpenoids. In some embodiments, the concentrate comprises A6a(10a)-tetrahydrocannabinol 8,9-Di-OH-CBT-C5, at least 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, or 5% Cannabidiolic acid A cannabitriol ester CBDA-C5 9-OH w/w of five or more of the terpenoids. In some embodiments, CBT-C5 ester, (-)-(6aR.9S,10S,10aR)-9,10-Dihydroxy the concentrate comprises at least 0.01%, 0.05%, 0.1%, 0.5%, hexahydrocannabinol, Cannabiripsol. Cannabiripsol-C5. 1%, 2%. 3%, 4%, or 5% w/w often or more of the terpenoids. US 2014/027 1940 A1 Sep. 18, 2014

0.015. In some embodiments, the concentrate is substan 0021. In some embodiments, the present invention pro tially free of THC-type compounds. In some embodiments, vides a thin film delivery vehicle comprising a concentrate as the concentrate is substantially free of CBN-type compounds. described above. 0016. In some embodiments, the concentrate comprise a 0022. In some embodiments, the present invention pro total cannabinoid fraction of from about 45% to 98% w/w vides a chewing gum composition comprising: (a) one or (calculated as a weight percentage of the total weight of the more cannabinoids, wherein the cannabinoids are present at concentrate), most preferably about 65% to 95% w/w total less than 15% by weight; and (b) greater that 85% by weight cannabinoid compounds (e.g., as listed above) and a total gum base. In some embodiments, the gum further comprises terpenoid fraction of from about 0.1% to 5% w/w total terpe a shell, wherein the shell encompasses the gum base. In some noids (e.g., as listed above; calculated as a weight percentage embodiments, the shell comprises cannabinoids. In some of the total weight of the concentrate). In some embodiments, embodiments, the cannabinoids are complexed with an addi the total cannabinoid fraction contains from about 62% to tional agent to enhance one or more of Solubility or absorp about 92% w/w or from about 75% to 92% w/w TCHA and tion. In some embodiments the cannabinoids are complexed THC combined (calculated as a weight percentage of the total with a cyclodexrin compound. In some embodiments, the one weight of the concentrate). In other embodiments, the total or more cannabinoids comprise a concentrate as provided cannabinoid fraction comprises from about 40% to 95% w/w above. In some embodiments, concentrate comprises one or or from about 60% to 92% w/w of a combination of CBG, more terpenoids as described above. CBC and THCV (calculated as a weight percentage of the 0023. In some embodiments, the present invention pro total weight of the concentrate). As described above, the total vides a cannabinoid delivery system comprising one or more cannabinoid fraction may additionally comprise at least 1%, cannabinoid compounds embedded in a polymer-based thin 2%. 5%, or 10% w/w of three or more of the cannabinoid film, wherein the polymer-based thin film is configured to compounds (calculated as a weight percentage of the total dissolve upon contacting oral mucosa. In some embodiments, weight of the concentrate). In some embodiments, the con the cannabinoid compounds are complexed with a cyclodex centrate comprises at least 1%, 2%. 5%, or 10% w/w of four trin compound. In some embodiments, a base polymer, com or more of the cannabinoid compounds (calculated as a prising one or more of hydroxy propyl methyl cellulose, weight percentage of the total weight of the concentrate). In hydroxy propyl cellulose, starch, pullulan, pectin, and gelatin Some embodiments, the concentrate comprises at least 1%, comprises at least 35% of the thin film. In some embodiments, 2%. 5%, or 10% w/w of five or more of the cannabinoid the delivery systems further comprise one or more additional compounds. Likewise, the total terpenoid fraction may addi components alter the mucoadhesion, flexibility, or rate of tionally comprise at least 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% dissolving of the thin film. In some embodiments, the one or w/w of two or more of the terpenoids (calculated as a weight more cannabinoids comprise a concentrate as provided percentage of the total weight of the concentrate). In some above. In some embodiments, concentrate comprises one or embodiments, the total terpenoid fraction may additionally more terpenoids as described above. comprise at least 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w of 0024. In some embodiments, the present invention pro three or more of the terpenoids (calculated as a weight per vides methods of rapidly delivering a dose of cannabinoid to centage of the total weight of the concentrate). In some the bloodstream of a Subject comprising: (a) placing a can embodiments, the total terpenoid fraction may additionally nabinoid delivery system as described above on the oral comprise at least 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w of mucosa of the subject; and (b) allowing the thin film of the four or more of the terpenoids (calculated as a weight per delivery system to dissolve, thereby releasing a dose on can centage of the total weight of the concentrate). In some nabinoid onto the oral mucosa. In some embodiments, the embodiments, the total terpenoid fraction may additionally dose comprises 2-200 mg of cannabinoid. comprise at least 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w of 0025. In some embodiments, the present invention pro five or more of the terpenoids (calculated as a weight percent vides for use of a concentrate, cannabinoid delivery system, age of the total weight of the concentrate). In some embodi oral delivery vehicle, topical skin care product, dietary ments, the total terpenoid fraction may additionally comprise Supplement, chewing gum or food product as described above at least 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w of ten or to reduce inflammation, reduce pain, reduce nausea, enhance more of the terpenoids (calculated as a weight percentage of mood, produce a calm feeling, induce drowsiness or sleep, the total weight of the concentrate). It should be noted that in reduce anxiety, Support joint health, Support mental health, defining the concentrates in weight percentage terms, the Support anti-inflammatory response by the body, Support weight percentage of the combined components will not brain function, Support feelings of wellbeing, Support healthy exceed 100%. skin and reduce blemishes. 0026. In some embodiments, the present invention pro 0017. In some embodiments, the present invention pro vides methods of reducing inflammation, reducing pain, vides an oral delivery vehicle comprising a concentrate as reducing nausea, enhancing mood, producing a calm feeling, described above. inducing drowsiness or sleep, reducing anxiety, Supporting 0018. In some embodiments, the present invention pro joint health, Supporting mental health, Supporting anti-in vides a chewing gum comprising a concentrate as described flammatory response by the body, Support braining function, above. Supporting feelings of wellbeing, Supporting healthy skin or reduce blemishes in a subject comprising administering an 0019. In some embodiments, the present invention pro effective amount of a concentrate, cannabinoid delivery sys vides a dietary Supplement as described above. tem, oral delivery vehicle, dietary Supplement, chewing gum 0020. In some embodiments, the present invention pro or food product as described above. vides a food product comprising a concentrate as described 0027. The present invention further relates to extracts con above. centrates obtained from extraction from cannabis, preferably US 2014/027 1940 A1 Sep. 18, 2014

cannabinoid and/or terpene concentrates, wherein THC is pinene, terpinolene (isoterpine), terpineol (a terpineol), ter converted to one or more natural CBN-type cannabinoids by pineol-4-ol, C-terpinene (terpilene), C-thujene (origanene), an oxidizing treatment. The extracts and concentrates find use Vanillin, viridiflorene (ledene), C-ylangene. for direct vaporization, infusion into edible matrices, infusion 0031. In some embodiments, the methods further com into topical skin care products, in electronic inhalation prise the step of formulating the CBN-converted extract with devices, and as nutraceuticals. The present invention relates a nutraceutically or pharmaceutically acceptable carrier. In to extracts concentrates obtained from extraction from Can Some embodiments, the methods further comprise combining nabis, preferably cannabinoid and/or terpene concentrates, the CBN-converted extract with one or more bioactive agents, wherein THC is converted to one or more natural CBN-type nutraceutical agents, or phytonutrients. In some embodi cannabinoids by an oxidizing treatment. The extracts and ments, the one or more bioactive agents, nutraceutical agents, concentrates find use for direct vaporization, infusion into or phytonutrients is from a source other than cannabis. In edible matrices, in electronic inhalation devices, and as nutra Some embodiments, the methods further comprise incorpo ceuticals. rating the CBN-converted extract into an oral delivery vehicle 0028. In some embodiments, the present invention pro selected from the group consisting of a tablet, capsule, chew vides methods of converting THC in a THC extract to CBN able matrix, dissolvable film, and chewing gum. In some comprising: (a) contacting the THC extract with an oxidizing embodiments, the methods further comprise incorporating agent under conditions such that THC is oxidized to CBN; the CBN-converted extract into a vaporizable formulation. and (b) allowing sufficient time for the oxidizing agent to 0032. In some embodiments, the present invention pro react with the THC extract such that THC is converted to one vides a converted-CBN concentrate produced by the pro or more CBN-type cannabinoids to provide a converted-CBN cesses described above. extract. In some embodiments, the THC is in an organic 0033. In some embodiments, the present invention pro solvent. In some embodiments, the methods further comprise vides a converted CBN-concentrate comprising at least 20% a step between steps (a) and (b) of decarboxylating THC(a) of one or more CBN-type cannabinoids selected from the present in the THC-rich extract to yield additional THC. In group consisting of Cannabinol CBN-C5, Cannabinol-C4 Some embodiments, step (c) is performed under exposure to CBN-C4, Cannabivarin CBN-C3, Cannabinol-C2 CBN-C2, UV light and in the presence of an oxygen Source. In some Cannabiorcol CBN-C1, Cannabinolic acid A CBNA-C5A, embodiments, the oxidizing agent is selected from the group and Cannabinol methyl ether CBNM-C5. In some embodi consisting of , oZone, halogens, Sulfuric ments, the concentrate comprises at least 30% of one or more acid, peroxydisulfuric acid, permamnganate compounds, and CBN-type cannabinoids selected from the group consisting nitrous oxide. In some embodiments, from about 10 to about of Cannabinol CBN-C5, Cannabinol-C4 CBN-C4, Cannabi 95% of THC in the THC extract is converted to a CBN-type varin CBN-C3, Cannabinol-C2 CBN-C2, Cannabiorcol cannabinoid. CBN-C1, Cannabinolic acid ACBNA-C5A, and Cannabinol 0029. In some embodiments, the THC extract is a THC methyl ether CBNM-C5. In some embodiments, the concen concentrate. In some embodiments, the THC concentrate is trate comprises at least 50% of one or more CBN-type can prepared by: (a) concentrating glandular trichomes from Can nabinoids selected from the group consisting of Cannabinol nabis plant material; (b) passing a solvent though the plant CBN-C5, Cannabino1-C4 CBN-C4, Cannabivarin CBN-C3, material to produce a cannabinoid/terpenoid-containing elu Cannabinol-C2CBN-C2, Cannabiorcol CBN-C1, Cannabin ate; (c) filtering Solids from the eluate; and (d) refining the olic acid A CBNA-C5 A, and Cannabinol methyl ether eluate to remove undesirable impurities. CBNM-C5. In some embodiments, the concentrate com 0030. In some embodiments, the THC extract is co-en prises at least 70% of one or more CBN-type cannabinoids riched for one or more terpenoids. In some embodiments, the selected from the group consisting of Cannabinol CBN-C5. one or more terpenoids are selected from the group consisting Cannabinol-C4 CBN-C4, Cannabivarin CBN-C3, Cannab of Alloaromadendrene, allyl hexanoate, benzaldehyde, (Z)- inol-C2CBN-C2, Cannabiorcol CBN-C1, Cannabinolic acid C-cis-bergamotene, (Z)-O-trans-bergamotene, B-bisabolol. A CBNA-C5A, and Cannabinol methyl ether CBNM-C5. In epi-C.-bisabolol, B-bisabolene, borneol (camphol), cis-y-bis some embodiments, the concentrate comprises at least 90% abolene, borneol acetate (bornyl acetate), C-cadinene, cam of one or more CBN-type cannabinoids selected from the phene, camphor, cis-carveol, caryophyllene (B-caryophyl group consisting of Cannabinol CBN-C5, Cannabinol-C4 lene), C.-humulene (C-caryophyllene), Y-cadinene, A-3- CBN-C4, Cannabivarin CBN-C3, Cannabinol-C2 CBN-C2, carene, caryophyllene oxide, 1,8-cineole, citral A, citral B. Cannabiorcol CBN-C1, Cannabinolic acid A CBNA-C5A, cinnameldehyde, C-copaene (aglaiene), Y-curcumene, and Cannabinol methyl ether CBNM-C5. O-cymene, B-elemene, y-elemene, ethyl decdienoate, ethyl 0034. In some embodiments, the concentrate further com maltol, ethyl propionate, ethylvanillin, , C-eudes prises at least 1% of at least a second cannabinoid selected mol, B-eudesmol, Y-eudesmol, eugenol, cis-B-farnesene (Z)- from the group consisting of Cannabigerol (E)-CBG-C5. B-farnesene), trans-C-farnesene, trans-B-farnesene, trans-Y Cannabigerol monomethyl ether (E)-CBGM-C5 A, Can bisabolene, fenchone, fenchol (norbornanol, B-fenchol), nabigerolic acid A (Z)-CBGA-C5A, Cannabigerovarin (E)- geraniol, C.-guaiene, guaiol, methyl anthranilate, methyl sali CBGV-C3, Cannabigerolic acid A (E)-CBGA-C5 A, Can cylate, 2-methyl-4-heptanone, 3-methyl-4-heptanone, hexyl nabigerolic acid A monomethyl ether (E)-CBGAM-C5A and acetate, ipsdienol, isoamyl acetate, lemenol, limonene, d-li Cannabigerovarinic acid A(E)-CBGVA-C3A); (+)-Cannab monene (limonene), linolool (linallyl alcohol, B-linolool), ichromene CBC-C5, (+)-Cannabichromenic acid A CBCA C.-longipinene, menthol, Y-muurolene, myrcene C5 A, (+)-Cannabivarichromene, (+)-Cannabichromevarin (B-myrcene), nerolidol, trans-nerolidol, nerol, B-Ocimene CBCV-C3, (+)-Cannabichromevarinic acid A CBCVA-C3 (cis-ocimene), octyl acetate, C.-phellandrene, phytol, A): (-)-Cannabidiol CBD-C5, Cannabidiol momomethyl C-pinene (2-pinene), B-pinene, pulegone, Sabinene, cis-sab ether CBDM-C5, Cannabidiol-C4 CBD-C4, (-)-Cannabidi inene hydrate (cis-thujanol), B-selinene, C-Selinene, Y-ter varin CBDV-C3, Cannabidiorcol CBD-C1, Cannabidiolic US 2014/027 1940 A1 Sep. 18, 2014

acid CBDA-C5, Cannabidivarinic acid CBDVA-C3): Can trate comprises at least 0.1% of three of the terpenoids. In nabinodiol CBND-C5, Cannabinodivarin CBND-C3), (-)- Some embodiments, the concentrate comprises at least 0.1% (9R,10R)-trans-Cannabitriol (-)-trans-CBT-C5, (+)-(9S. of four of the terpenoids. In some embodiments, the concen 10S)-Cannabitriol (+)-trans-CBT-C5, (+)-(9R,10S/9S, trate comprises at least 0.1% of five of the terpenoids. 1OR)—); Cannabitriol (+)-cis-CBT-C5, (-)-(9R,1OR)-trans 0036. In some embodiments, the concentrates comprise a 10-O-Ethyl-cannabitriol (-)-trans-CBT-OEt-C5, (+)-(9R, total cannabinoid fraction of from about 45% to 98% w/w 10R/9S,10S)-Cannabitriol-C3(+)-trans-CBT-C3,8.9- (calculated as a weight percentage of the total weight of the Dihydroxy-A6a(10a)-tetrahydrocannabinol 8,9-Di-OH concentrate), most preferably about 65% to 95% w/w total CBT-C5, Cannabidiolic acid A cannabitriol ester CBDA-C5 CBN-type compounds (e.g., as listed above) and a total ter 9-OH-CBT-C5 ester, (-)-(6aR.9S,10S,10aR)-9,10-Dihy penoid fraction of from about 0.1% to 5% w/w total terpe droxy-hexahydrocannabinol, Cannabiripsol. Cannabiripsol noids (e.g., as listed above; calculated as a weight percentage C5, (-)-6a, 7.10a-Trihydroxy-A9-tetrahydrocannabinol (-)- of the total weight of the concentrate). In some embodiments, Cannabitetrol, 10-Oxo-A6a(10a) tetrahydrocannabinol the total cannabinoid fraction contains from about 62% to OTHC); (5aS,6S,9R,9aR)-Cannabielsoin CBE-C5, (5aS,6S, about 92% w/w or from about 75% to 92% w/w CBN-type 9R.9aR) C3-Cannabielsoin CBE-C3, (5aS,6S,9R,9aR)- compounds (calculated as a weight percentage of the total Cannabielsoic acid A CBEA-C5A, (5aS,6S-9R.9aR)-Canna weight of the concentrate). As described above, the total bielsoic acid B CBEA-C5 B; (5aS,6S,9R,9aR) C3 cannabinoid fraction may additionally comprise at least 1%, Cannabielsoic acid B CBEA-C3 B, Cannabiglendol-C30H 2%. 5%, or 10% w/w of three or more of the cannabinoid iso-HHCV-C3, Dehydrocannabifuran DCBF-C5, compounds (calculated as a weight percentage of the total Cannabifuran CBF-C5), (-)-A7-trans-(1R,3R,6R)-Isotet weight of the concentrate). In some embodiments, the con rahydrocannabinol, (+)-A7-12-cis-(1R,3R,6S/1S.3S,6R)- centrate comprises at least 1%, 2%. 5%, or 10% w/w of four Isotetrahydrocannabivarin, (-)-A7-trans-(1R,3R,6R)-Isotet or more of the cannabinoid compounds (calculated as a rahydrocannabivarin); (+)-(1aS.3aR,8bR,8cR)- weight percentage of the total weight of the concentrate). In Cannabicyclol CBL-C5, (+)-(1aS.3aR,8bR,8cR)- Some embodiments, the concentrate comprises at least 1%, Cannabicyclolic acid A CBLA-C5 A, (+)-(1aS.3aR,8bR. 2%. 5%, or 10% w/w of five or more of the cannabinoid 8cR)-Cannabicyclovarin CBLV-C3: Cannabicitran CBT compounds. Likewise, the total terpenoid fraction may addi C5); Cannabichromanone CBCN-C5, Cannabichromanone tionally comprise at least 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% C3 CBCN-C3, and Cannabicoumaronone CBCON-C5). In w/w of two or more of the terpenoids (calculated as a weight some embodiments, the concentrate comprises at least 1% percentage of the total weight of the concentrate). In some w/w of two of the cannabinoid compounds. In some embodi embodiments, the total terpenoid fraction may additionally ments, the concentrate comprises at least 1% w/w of three of comprise at least 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w of the cannabinoid compounds. In some embodiments, the con three or more of the terpenoids (calculated as a weight per centrate comprises at least 1% w/w of four of the cannabinoid centage of the total weight of the concentrate). In some compounds. In some embodiments, the concentrate com embodiments, the total terpenoid fraction may additionally prises at least 1% w/w of five of the cannabinoid compounds. comprise at least 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w of 0035. In some embodiments, the concentrate is further four or more of the terpenoids (calculated as a weight per co-enriched for at least 0.1% w/w of at least one terpenoid centage of the total weight of the concentrate). In some selected from the group consisting of Alloaromadendrene, embodiments, the total terpenoid fraction may additionally allyl hexanoate, benzaldehyde, (Z)-O-cis-bergamotene, (Z)- comprise at least 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w of C-trans-bergamotene, B-bisabolol, epi-C.-bisabolol, B-bisab five or more of the terpenoids (calculated as a weight percent olene, borneol (camphol), cis-y-bisabolene, borneol acetate age of the total weight of the concentrate). In some embodi (bornyl acetate), C-cadinene, camphene, camphor, cis-car ments, the total terpenoid fraction may additionally comprise Veol, caryophyllene (B-caryophyllene), C-humulene at least 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w of ten or (C-caryophyllene), Y-cadinene, A-3-carene, caryophyllene more of the terpenoids (calculated as a weight percentage of oxide, 1,8-cineole, citral A, citral B, cinnameldehyde, C-co the total weight of the concentrate). It should be noted that in paene (aglaiene), Y-curcumene, B-cymene, B-elemene, y-el defining the concentrates in weight percentage terms, the emene, ethyl decdienoate, ethyl maltol, ethylpropionate, eth weight percentage of the combined components will not ylvanillin, eucalyptol, C.-eudesmol, 3-eudesmol, Y-eudesmol. exceed 100%. It should be noted that in defining the concen eugenol, cis-3-farnesene (Z)-3-farnesene), trans-C.-farne trates in weight percentage terms, the weight percentage of sene, trans-3-farnesene, trans-y bisabolene, fenchone, fen the combined components will not exceed 100%. chol (norbornanol, B-fenchol), geraniol, C-guaiene, guaiol, 0037. In some embodiments, the concentrate is substan methyl anthranilate, methyl salicylate, 2-methyl-4-hep tially free of THC-type compounds. tanone, 3-methyl-4-heptanone, hexyl acetate, ipsdienol, 0038. In some embodiments, the present invention pro isoamyl acetate, lemenol, limonene, d-limonene (limonene), vides an oral delivery vehicle comprising a concentrate as linolool (linallyl alcohol, B-linolool), C.-longipinene, menthol, described above. Y-muurolene, myrcene (B-myrcene), nerolidol, trans-neroli 0039. In some embodiments, the present invention pro dol, nerol, B-ocimene (cis-ocimene), octyl acetate, C.-phel vides a chewing gum comprising a concentrate as described landrene, phytol, C-pinene (2-pinene), B-pinene, pulegone, above. Sabinene, cis-Sabinene hydrate (cis-thujanol), B-selinene, 0040. In some embodiments, the present invention pro C-selinene, Y-terpinene, terpinolene (isoterpine), terpineol (C. vides an oral delivery vehicle comprising a concentrate as terpineol), terpineol-4-ol, C-terpinene (terpilene), C-thujene described above. (origanene), Vanillin, viridiflorene (ledene), C-ylangene. In 0041. In some embodiments, the present invention pro Some embodiments, the concentrate comprises at least 0.1% vides a dietary Supplement comprising a concentrate as of two of the terpenoids. In some embodiments, the concen described above. US 2014/027 1940 A1 Sep. 18, 2014

0042. In some embodiments, the present invention pro vides a food product comprising a concentrate as described OH above.

0043. In some embodiments, the present invention pro (E) vides a thin film delivery vehicle comprising a concentrate as described above. 2 0044. In some embodiments, the present invention pro vides a composition comprising a concentrate as described in combination with one or more bioactive agents, nutraceutical Cannabigerol agents, phytonutrients, or pharmaceutically acceptable carri OH ers and combinations thereof. 0045. In some embodiments, the present invention pro vides for use of a concentrate, cannabinoid delivery system, oral delivery vehicle, dietary Supplement, chewing gum, food product or composition as described above to ameliorate the psychoactive responses produced by other cannabinoids, reduce inflammation, reduce pain, reduce pain associated with cancer, reduce neuropathic pain, reduce nausea, enhance Cannabigerol monomethyl ether mood, produce a calm feeling, induce drowsiness or sleep, OH O reduce anxiety, Support joint health, Support mental health, Support anti-inflammatory response by the body, Support S OH brain function, Support feelings of wellbeing, Support healthy skin and reduce blemishes. O 0046. In some embodiments, the present invention pro H vides methods of ameliorating psychoactive responses pro duced by other cannabinoids, reducing inflammation, reduc ing pain, reducing nausea, enhancing mood, producing a calm Cannabigerolic acid A feeling, inducing drowsiness or sleep, reducing anxiety, Sup OH porting joint health, Supporting mental health, Supporting anti-inflammatory response by the body, Supporting brain N function, Supporting feelings of wellbeing, Supporting (E) healthy skin or reducing blemishes in a subject comprising O administering an effective amount of a concentrate, cannab H inoid delivery system, oral delivery vehicle, dietary supple ment, chewing gum or food product as described above. Cannabigerovarin DEFINITIONS OH O 0047. As used herein the term “Cannabis” is used to refer S OH to plants of the genus Cannabis, including , Cannabis indica, and Cannabis ruderalis. 0048. As used herein, the terms “trichome” and “glandular trichome” are used interchangeably to refer to plant epider mal structures that comprise secretions produced by the plant. Cannabigerolic acid A 0049. As used herein, the term “cannabinoid” refers to a chemical compound that shows director indirect activity at a (E)-CBGA-Cs. A cannabinoid . There are two main cannabinoid recep OH O tors, CB and CB2. Other receptors that research Suggests have cannabinoid activity include the GPR55 and GPR18 receptors. The term “phytocannabinoid’ refers to cannab inoids that occur in a plant species or are derived from can nabinoids occurring in a plant species. Examples of cannab inoids include, but are not limited to, Tetrahydrocannabinol (THC), Cannabidiol (CBD), Cannabinol (CBN), Cannabig erol (CBG), Cannabichromene (CBC), Cannabicyclol Cannabigerolic acid A (CBL), Cannabivarin (CBV), Tetrahydrocannabivarin monomethyl ether (THCV), Cannabidivarin (CBDV), Cannabichromevarin (E)-CBGAM-Cs. A (CBCV), Cannabigerovarin (CBGV), Cannabigerol Monom ethyl Ether (CBGM). Examples of structures of cannabinoids include, but are not limited to: US 2014/027 1940 A1 Sep. 18, 2014

-continued -continued OH O

S OH OH

H 8(H O H \ O H Cannabigerovarinic acid A

(E)-CBGVA-C.o -u A (-)-Cannabidiol CBD-Cs (RS) 21 O OH V H H s HO \ O (-)-Cannabichromene H CBC-Cs Cannabidiol momomethyl ether (RS) 21 CBDM-Cs O

OH

H 8.(wH

O OH O H (-)-Cannabichromenic acid A Cannabidiol-C4 CBCA-C5. A CBD-C (RS) 21 O

OH (w H HO H (-)-Cannabivarichromene, (-)-Cannabichromewarin O CBCV-C. H (-)-Cannabidivarin CBDV-C, (RS) 21 O

O H

O OH (-)-Cannabichromevarinic acid A Cannabidiorcol CBCVA-C. A CBD-C US 2014/027 1940 A1 Sep. 18, 2014

-continued -continued

OH

H 8 (H

O H A-Tetrahydrocannabinol-C4 Cannabidiolic acid CBDA-Cs A-THC-C,9

OH H

H

O A-Tetrahydrocannabivarin Cannabidivarinic acid 9 A-THCV-C, CBDVA-C

OH H OH H

O A-Tetrahydrocannabiorcol 2 A-THCO-C

Cannabinodiol CBND-Cs

OH A-Tetrahydro cannabinolic acid A A-THCA-Cs. A O H Cannabinodivarin CBND-C

HO O A-Tetrahydro cannabinolic acid B A-THCA-Cs B A-Tetrahydrocannabinol

US 2014/027 1940 A1 Sep. 18, 2014 13

-continued solvent extract may preferably have the solvent substantially removed from the extract, for example by evaporation. 0053 As used herein, the term “enriched for when used in reference to a composition means that one or more speci fied compounds are present in a higher concentration, com monly expressed as a weight/weight percentage, as compared to a starting material. Such as Cannabis plant material or trichomes. 0054 As used herein the term “concentrate' when used in Cannabicitran reference to a composition containing one or more com CBT-Cs pounds means that the one or more compounds are concen O HO trated in the composition on a weight/weight basis as com pared to a starting material. Such as Cannabis plant material or trichomes. 0055 As used herein, the term “substantially free of THC type compounds’ refers to extracts, fractions or other prepa O rations from a Cannabis plant that contain less than 2%, Cannabichromanone preferably less than 1%, more preferably less than 0.5%, and CBCN-Cs most preferably less than 0.1% Tetrahydrocannabinol-type O HO (THC) compounds (e.g., A-Tetrahydrocannabinol A-THC Cs, A-Tetrahydrocannabinol-C, A-THC-C, A-Tetrahy drocannabivarin A-THCV-C, A-Tetrahydrocannabiorcol A-THCO-C, A-Tetrahydrocannabinolic acid AA-THCA Cs A, A-Tetrahydrocannabinolic acid B, A-THCA-C, B, O A-Tetrahydrocannabinolic acid-CA and/or BA-THCA-C, Cannabichromanone-C3 A and/or B, A-Tetrahydro-cannabivarinic acid A A-TH CBCN-C CVA-C, A, A-Tetrahydrocannabiorcolic acid A and/or B A-THCOA-C, A and/or B), (-)-A-trans-(6aR.10aR)-A- | O Tetrahydrocannabinol A-THC-Cs, (-)-A-trans-(6aR, 10aR)-Tetrahydrocannabinolic acid A A-THCA-Cs A, (-)- (6aS.10aR)-A-Tetrahydrocannabinol (-)-cis-A-THC-C). 0056. As used herein, the term “phytonutrient” refers to O organic compounds isolated from plants that have a biologi Cannabicoumaronone cal effect, and includes, but is not limited to, compounds of CBCON-Cs the following classes: cannabinoids, isoflavonoids, oligo meric proanthcyanidins, indol-3-carbinol, Sulforaphone, fibrous ligands, plant phytosterols, ferulic acid, anthocyano 0050. As used herein, the term “terpene” refers to hydro cides, triterpenes, omega 3/6 fatty acids, polyacetylene, carbons of biological origin having carbon skeletons formally quinones, terpenes, cathechins, gallates, and quercitin. derived from isoprene CH2=C(CH3)CH=CH2. This class 0057. As used herein, the term “functional foods’ refers to is subdivided into the C5 hemiterpenes, C10 monoterpenes, food products that include biologically active nutraceutical C15 sesquiterpenes, C20 diterpenes, C25 sesterterpenes, C30 agents. triterpenes, C40 tetraterpenes (carotenoids), and C5n poly 0.058 As used herein, the terms “nutraceutical agent, and terpenes. related terms, refer to natural, bioactive chemical compounds that have health promoting, disease preventing or medicinal 0051. As used herein, the term “terpenoid refers to hydro properties. Examples of nutraceutical agents include, but are carbons of biological origin having carbon skeletons formally not limited to, extracts from Allium Cepa, Allium Sativum, derived from isoprene CH2=C(CH3)CH=CH2 and differ Aloe Vera, Angelica Species, Naturally Occurring Antioxi ing from terpenes in that one or more methyl groups have dants, Aspergillus Oryzae Enzyme Therapy, barley grass, been moved or added, or an oxygen added compared to the Bromelain, Carnitine, Carotenoids and Flavonoids, , terpene. Terpenoids are classified as follows: Hemiterpe Centella Asiatica (Gotu kola), Coenzyme Q10, Chinese Pre noids, 1 isoprene unit (5 carbons); Monoterpenoids, 2 iso pared Medicines, Coleus Forskohlii, Commiphora Mukul, prene units (10C); Sesquiterpenoids, 3 isoprene units (15C); Crataegus Oxyacantha (Hawthorne), Curcuma Longa (Tur Diterpenoids, 4 isoprene units (20C) (e.g. ginkgolides); Ses meric), Echinacea Species (Purple Coneflower), Eleuthero terterpenoids, 5 isoprene units (25C); Triterpenoids, 6 iso coccus Senticosus (Siberian Ginseng), Ephedra Species, prene units (30C) (e.g. sterols); Tetraterpenoids, 8 isoprene Dietary Fish Oil Consumption and Fish Oil Supplementation, units (40C) (e.g. carotenoids); and Polyterpenoids (larger , Ginkgo Biloba, Glycyrrhiza (Licorice), Hyperi number of isoprene units). Examples of terpenoids found in cum Perforatum (St. John's Wort), Hydrastis (Goldenseal) Cannabis include, but are not limited to, Limonene, and Other Berberine-Containing Plants, Lactobacillus, Lobe C.-Pinene, B-Myrcene, Linolool, B-Caryophyllene, Carophyl lia (Indian ), Melaleuca Alternifolia, Pip lene oxide, Nerolidol, and Phytol. erita, NGNA, Panax Ginseng, Pancreatic Enzymes, Piper 0.052 As used herein, the term “solvent extract” refers to a Mythisticum, Procyanidolic Oligomers, Pygeum Africanum, composition provided by solvent extraction of a starting Quercetin, Sarsaparilla Species, Serenoa Repens (Saw pal material Such as Cannabis plant material or trichomes. The metto, Sabal serrulata), Silybum Marianum (Milk Thistle), US 2014/027 1940 A1 Sep. 18, 2014

Rosemary/Lemon balm, Selenite, Tabebuia Avellanedae obtain a much larger amount of finished extract from each (LaPacho), Taraxacum Officinale, Tanacetum Parthenium Solvent extraction pass. The final extracts are of a higher (Feverfew), Taxol. Uva Ursi (Bearberry), Vaccinium Myrtil quality containing less water, chlorophyll, and other lus (Blueberry), Valerian Officinalis, Viscum Album (Mistle unwanted contaminants found in solvent extracts made toe), Vitamin A, Beta-Carotene and Other Carotenoids, and directly from plant materials. The final extracts are also more Zingiber Officinale (). visually appealing because of their lighter color. Another 0059. As used herein, the terms “subject” and “patient” advantage is to allow for the first extraction to take place on refer to any animal. Such as a mammal like a dog, cat, bird, fresh or freshly dried Cannabis after which the crude extract livestock, and preferably a human. Specific examples of “sub can be stored for great lengths of time before a solvent extrac jects” and “patients’ include, but are not limited to, individu tion takes place. Other methods produce a lower quality als suffering from viral obesity. extract when significant time passes between the harvesting 0060. As used herein, the term “physiologically accept of the plant material and when it is processed. able carrier” refers to any carrier or excipient commonly used 0068. The present invention further relates to extracts con with oily pharmaceuticals. Such carriers or excipients centrates obtained from extraction from cannabis, preferably include, but are not limited to, oils, starch, and lac cannabinoid and/or terpene concentrates, wherein THC is tOSe. converted to one or more natural CBN-type cannabinoids by 0061. As used herein, the term “oral delivery vehicle' an oxidizing treatment. The extracts and concentrates find use refers to any means of delivering a pharmaceutical orally, for direct vaporization, infusion into edible matrices, in elec including, but not limited to, capsules, pills, tablets and Syr tronic inhalation devices, and as nutraceuticals. The present ups. invention relates to extracts concentrates obtained from 0062. As used herein, the term “food product” refers to extraction from cannabis, preferably cannabinoid and/orter any food or feed suitable for consumption by humans, non pene concentrates, wherein THC is converted to one or more ruminant animals, or ruminant animals. The “food product’ natural CBN-type cannabinoids by an oxidizing treatment. may be a prepared and packaged food (e.g., mayonnaise, The extracts and concentrates find use for direct vaporization, salad dressing, bread, or cheese food) or an animal feed (e.g., infusion into edible matrices, in electronic inhalation devices, extruded and pelleted animal feed or coarse mixed feed). and as nutraceuticals. The concentrates described herein may "Prepared food product” means any pre-packaged food preferably be produced from either drug or industrial can approved for human consumption. nabis species. The concentrates are preferably enriched for 0063 As used herein, the term “foodstuff refers to any one or more cannabinoids, preferably CBN-type cannab Substance fit for human or animal consumption. inoids, and/or terpenes as described in more detail below. The 0064. As used herein, the term "dietary supplement' concentrates may be formulated in a variety of ways, with or refers to a small amount of a compound for Supplementation without other phytonutrients or nutraceutical agents as also of a human or animal diet packaged in single or multiple dose described in more detail below. units. Dietary Supplements do not generally provide signifi 0069 Disclosed herein are efficient methods to produce cant amounts of calories but may contain other micronutri cannabis extracts with unique chemical properties using ents (e.g., vitamins or minerals). mechanical extraction followed by a solvent extraction and 0065. As used herein, the term “nutritional supplement' oxidation process. The extracts are then optionally processed refers to a composition comprising a "dietary Supplement in by a whipping procedure to produce a finished extract with combination with a source of calories. In some embodiments, unique chemical and physical properties. The two-step nutritional Supplements are meal replacements or Supple extraction has many advantages over other techniques. The ments (e.g., nutrient or energy bars or nutrient beverages or process allows for a higher throughput with less solvent waste concentrates). because of the ability to obtain a much larger amount of finished extract from each solvent extraction pass. The final DETAILED DESCRIPTION OF THE INVENTION extracts are of a higher quality containing less water, chloro 0066. The present invention relates to extracts and concen phyll, and other unwanted contaminants found in Solvent trates obtained from extraction from Cannabis, preferably extracts made directly from plant materials. The final extracts cannabinoid and/or terpene concentrates, and formulation of are also more visually appealing because of their lighter color. the concentrates, particularly for use for direct vaporization, Another advantage is to allow for the first extraction to take infusion into edible matrices, in electronic inhalation devices, place on fresh or freshly dried cannabis after which the crude and as nutraceuticals. The concentrates described herein may extract can be stored for great lengths of time before a solvent preferably be produced from either drug or industrial Can extraction takes place. Other methods produce a lower quality nabis species. The concentrates are preferably enriched for extract when significant time passes between the harvesting one or more cannabinoids and/or terpenes as described in of the plant material and when it is processed. more detail below. The concentrates may be formulated in a 0070 Cannabis produces the majority of its active ingre variety of ways, with or without other phytonutrients or nutra dients (cannabinoids and terpenoids) in glandular trichomes ceutical agents as also described in more detail below. found on the flowers, buds, leaves, and stalks of the plants. In 0067. Disclosed herein are efficient methods to produce preferred embodiments of the present invention, Cannabis cannabis extracts with unique chemical properties using plant material (e.g., flowers and leaves, either fresh or dried) mechanical extraction followed by a solvent extraction. The containing glandular trichomes are processed mechanically extracts are then optionally processed by a whipping proce to remove and concentrate the majority of these trichomes. dure to produce a finished extract with unique chemical and Preferred processes separate the trichomes from the plant physical properties. The two-step extraction has many advan material by passing the trichomes through a mesh of appro tages over other techniques. The process allows for a higher priate size to allow the trichomes to pass through and exclude throughput with less solvent waste because of the ability to as much unwanted plant material as possible. The mesh may US 2014/027 1940 A1 Sep. 18, 2014

be made of any suitable material, e.g., stainless steel, alumi a wide range of pore sizes. Preferred filters include, but are num, nylon, etc. Different varieties of Cannabis produce tri not limited to, Teflon filters, sintered glass, paper, metal mesh, chome heads of varying size, thus the optimal mesh size and the like. depends on the average size of the trichome heads being 0076. Additional bioactive compounds, phytonutrients, collected. In preferred embodiments, the processes of the nutraceutical agents, flavoring agents and the like may be present invention utilize mesh sizes ranging from 1 to 1000 added to the Cannabis solvent extract either before or after microns in diameter, most preferably from 1 to 350 microns in Solvent removal and concentration. Examples of additives diameter. One or multiple layers of mesh may be utilized. The include, but are not limited to, terpene/terpenoid compounds, use of multiple layers of mesh can help to further separate the other essential oils, natural or artificial flavorings, edible or desired trichomes from unwanted particles of plant material food grade carrier solvents such as propylene glycol, glyc that are either slightly Smaller or slightly larger. erin, triacetin, food oils, topical oils and butters, etc. Additives 0071. In some embodiments, the mechanical trichome are described in more detail below. Solubilizers, suspension concentration processes utilize a cylindrical mesh drum agents, and uptake promoters such as beta-cyclodextrins may driven by a belt and motor. The plant material is placed in the also be added before or after solvent removal. drum, the drum is rotated, and the trichomes are expelled 0077. In preferred embodiments, solvent is removed from from the drum through the mesh pores. In some embodi the solvent extract to provide a concentrate. Suitable pro ments, the plant material is frozen (i.e., at -20C to -70 C) cesses for solvent removal include, but are not limited to, prior to tumbling. In some embodiments, the plant material is Solvent exchange, vacuum distillation, vacuum desiccation, tumbled in the presence of ice, preferably dry ice. In some TFE, or crystallization of active ingredients. Solvent removal embodiments, the mesh drum is rotated in an ice water bath. may take place at a wide range of temperatures consistent Both the dry and wet method yield trichome concentrates with the process used. with high levels of bioactive compounds. When a wet process 0078. The extracts can optionally be further processed to is used, excess liquid is preferably pressed from the trichome concentrate desired bioactive agents or remove undesired concentrate followed by drying. compounds (e.g., contaminants). In some embodiments, the 0072 The second step in the extraction process comprises extract or eluate is passed through a preparatory or industrial solvent extraction of the trichome concentrate. Extracts are scale column with stationary phases, for example, silica, alu preferably produced using a solvent recovery apparatus. For mina, C8, or C 18 stationary phases. A number of solvent gaseous organic solvent mixtures, a pressurized closed matrices may be utilized. Gradients may optionally be used to botanical extraction system is preferred. For carbon dioxide alter the polarity of mobile phases to facilitate this step. extraction, a Supercritical or Subcritical botanical extraction Examples of preferred systems include mixtures of hexane apparatus is preferred. For liquid organic solvent extraction, (S), heptane(s), pentane(s), ethyl acetate, and/or ethanol. spray dryers and/or common vacuum distillation apparatuses Fractions can be collected containing desired compounds, are preferred. In preferred embodiments, the apparatus allows and combined if desired. The solvent is then removed as for as low temperature removal of solvents as possible to described above. avoid unwanted decarboxylation and/or removal of terpene 0079. In some embodiments, target compounds (either compounds from the extract. desired or undesired) are removed from solution by crystal lization. Crystallization comprises concentrating the eluate 0073. In all methods, the solvent passes through the tri (with an additional optional solvent exchange) to a preferably chome concentrate either in a column packed with the tri non polar solvent (e.g., heptane(s), hexane(s), pentane(s)). chome concentrate (as part of the solvent recovery apparatus The concentrated solvent/extract mixture can be cooled to or with a discrete step) or the trichome concentrate can be -20 to -200 C to facilitate crystallization. Optional crystal saturated with solvent for a defined amount of time followed lization initiators may be incorporated into the process. Once by filtration. Optionally, the extraction can be assisted crystallization has occurred, the crystals are filtered and through the use of Sonication, microwave assistance, depending on whether the eluate or crystal products are mechanical mixing, or other similar processes. desired, one or the other can be discarded and desired product 0074 Examples of useful extraction solvents include gas can be passed through to additional steps for further process eous solvents, in a liquid state, either neat or as a mixture, ing or used as a final product. Such as propane, in butane, isobutylene and/or isobutane. 0080. In some embodiments, the extract or extract is fur Examples of preferred solvent mixtures include 40-80% ther refined prior to final processing. In some embodiments, isobutane, 60-10% propane, and 20-5% in butane. Other mix the extractis vacuum distilled to near dryness then taken up in tures can reverse these ratios. Examples of preferred liquid ethanol or another alcohol or polar solvent (the solvent solu (normal Tand P) extraction solvents include pentane, isopen tion may be optionally heated). The ethanol solution is cooled tane, hexanes (all structural isomers), ethyl acetate, ethanol, overnight to -20C+/-20 degrees after which undesirable fats, isopropanol, and heptanes (all structural isomers). Carbon lipids and waxes will precipitate out of the solution and can be dioxide in a Supercritical or Subcritical state is also a preferred filtered using common methods. In some embodiments, chlo solvent for the processes of the present invention. Other pre rophyll which provides a slight greenish to black hue, is ferred solvent extraction mixtures include mixtures of isobu removed from the extract. In these embodiments, the extract tane and/or pentane with liquid nitrogen passed through the is taken up in a solvent then exposed to UV light for 30 plant material followed by an optional sieve with pore diam minutes to 24 hours to break down remaining chlorophyll. eters from 50 to 1000 microns. which will turn from green to amber colors. If the color is still 0075. After the solvent has been passed through the plant not desirable, activated carbon may be added to the ethanol material, a filter or several filter steps can optionally be per solution. Additional solvents may also be utilized. In these formed to avoid passing plant material from the crude extract embodiments, the extract and activated carbon are agitated into the final elute. The filter(s) can take many forms and have together for several hours or days then the extract is filtered US 2014/027 1940 A1 Sep. 18, 2014

out of the activated carbon. The solvent may then be removed. ichromenic acid A CBCA-Cs A, (+)-Cannabivarichromene, In some embodiments, a final washing step is beneficial to (+)-Cannabichromevarin CBCV-C., (+)-Cannabichrom remove any remaining impurities. In some embodiments, a evarinic acid A CBCVA-C A); Cannabidiol-type (CBD) highly concentrated extract (regardless of the solvent it is compounds (e.g., (-)-Cannabidiol CBD-Cs, Cannabidiol dissolved in) is mixed with a non-polar solvent Such as pen momomethyl ether CBDM-Cs, Cannabidiol-C, CBD-C, tane, hexane, or heptane. Equal amounts of a concentrated (-)-Cannabidivarin CBDV-C, Cannabidiorcol CBD-C, brine solution are then added. The solution is agitated vigor Cannabidiolic acid CBDA-Cs, Cannabidivarinic acid ously then the brine Solution is decanted. This process may CBDVA-C); Cannabinodiol-type (CBND) compounds (e.g., preferably be repeated several times. This step may be fol Cannabinodiol CBND-Cs, Cannabinodivarin CBND-C); lowed with an optional water wash. The extract may then be Tetrahydrocannabinol-type (THC) compounds (e.g., g-Tet treated with sodium sulfate or another suitable desiccant to rahydrocannabinol A-THC-Cs, A-Tetrahydrocannabinol remove Water. C, A-THC-C, A-Tetrahydrocannabivarin A-THCV-C, 0081. In some embodiments, the extract or concentrate A-Tetrahydrocannabiorcol, A-THCO-C, A-Tetrahydro obtained as described above may be further processed, for cannabinolic acid AA-THCA-Cs A, A-Tetrahydrocannab example by adding one or more bioactive compounds or inolic acid B, A-THCA-Cs B, A-Tetrahydrocannabinolic nutraceutical agents or by further concentrating a target com acid-CA and/or BA-THCA-CA and/or B, A-Tetrahydro pound in the Cannabis extract. Further concentration may be cannabivarinic acid A A-THCVA-C, A, A-Tetrahydrocan preferably accomplished by column chromatography or crys nabiorcolic acid A and/or B A-THCOA-C, A and/or B). tallization as described above. In some preferred embodi (-)-A-trans-(6aR.10aR)-A-Tetrahydrocannabinol ments, the extracts are mechanically processed to provide a A-THC-Cs. (-)-A-trans-(6aR.10aR)-Tetrahydrocannabin composition with desired physiochemical properties. In some olic acid A A-THCA-Cs A, (-)-(6aS,10aR)-A-Tetrahydro embodiments, extracts are homogenized by shear force mix cannabinol (-)-cis-A-THC-Cs); Cannabinol-type (CBN) ing. Suitable mixing devices include, but are not limited to, type compounds (e.g., Cannabinol CBN-Cs, Cannabinol-C magnetic stir bar apparatuses, wire whisk devices, augers, CBN-C, Cannabivarin CBN-C, Cannabinol-C, CBN-C, and the like. Preferably, the extract is mixed (e.g., whisked or Cannabiorcol CBN-C, Cannabinolic acid A CBNA-C. A. whipped) until dry. The final product preferably has a wax or Cannabinol methyl ether CBNM-Cs. (-)-(9R,10R)-trans clay-like consistency, is white to slightly yellow in color, and Cannabitriol (-)-trans-CBT-Cs, (+)-(9S.10S)-Cannabitriol is opaque. (+)-trans-CBT-Cs, (+)-(9R, 10S/9S. 10R)—); Cannabitriol 0082 In other embodiments, spray drying is used to pro type (CBT) compounds (e.g., Cannabitriol (+)-cis-CBT-Cs. vide a fluffy crystalline extract of white to yellow or amber (-)-(9R,1OR)-trans-10-O-Ethyl-cannabitriol (-)-trans-CBT color. In this process, the Cannabis extract is sprayed into a OEt-Cs. (+)-(9R,10R/9S. 10S)-Cannabitriol-C (+)-trans fine mist inside of a vacuum chamber. The system is prefer CBT-C, 8.9-Dihydroxy-A'-tetrahydrocannabino 8.9- ably configured to facilitate the evaporation of solvent from Di-OH-CBT-Cs, Cannabidiolic acid A cannabitriol ester the fine mist leaving behind very fine crystalline cannabinoid CBDA-C 9-OH-CBT-C ester, (-)-(6aR,9S,10S,10aR)-9, extract that can be collected in final form containing from 10-Dihydroxy-hexahydrocannabinol, Cannabiripsol, Canna 30-99% cannabinoids, preferably from about 55% to 99% biripsol-Cs. (-)-6a, 7.10a-Trihydroxy-A-tetrahydrocannab cannabinoids, and most preferably from about 65% to 99% inol (-)-Cannabitetrol, 10-Oxo-As(10) cannabinoids. In other embodiments, thin film evaporation tetrahydrocannabinol OTHC); Cannabielsoin-type (CBE) techniques are utilized. In some embodiments, these methods compounds (e.g., (5 aS,6S,9R,9aR)-Cannabielsoin CBE-Cs. comprise spreading a thin layer of concentrated extract on a (5 aS,6S,9R,9aR)-C-Cannabielsoin CBE-C (5aS,6S.9R, Surface and placing the Surface inside of a vacuum oven 9aR)-Cannabielsoic acid A CBEA-Cs A, (5 aS,6S-9R.9aR)- and/or desiccator. Once the solventhas been removed, a white Cannabielsoic acid B CBEA-C B; (5 aS,6S,9R.9aR) C to yellow or amber or dark colored extract remains. This Cannabielsoic acid B CBEA-C B, Cannabiglendol-CH extract preferably has a semicrystalline consistency. This iso-HHCV-C, Dehydrocannabifuran DCBF-C, product can be milled (preferably cryogenically milled) to Cannabifuran CBF-Cs) Isocannabinoids compounds (e.g., produce a powder or divided into portions for easy handling. (-)-A-trans-(1R,3R,6R)-Isotetrahydrocannabinol, (+)-A7-1, I0083. The extracts described above can preferably be 2-cis-(1R,3R,6S/1S.3S,6R)-Isotetrahydrocannabivarin, (-)- pressed into standardized pellets through compaction, with or A-trans-(1R,3R,6R)-Isotetrahydrocannabivarin); Cannabi without heat. These pellets preferably provide a standardized cyclol-type (CBL) compounds (e.g., (+)-(1aS.3aR.8bR. size, weight of cannabinoid extract. The pellets can be pack 8cR)-CannabicyclolcBL-Cs. (+)-(1aS,3aR,8bR,8cR)- aged in blister pack, plastic jar, or a glass jar. Cannabicyclolic acid A CBLA-C, A, (+)-(1aS,3aR.8bR, 0084. The concentrates of the present invention are pref 8cR)-Cannabicyclovarin CBLV-C; Cannabicitran-type erably enriched for one or more bioactive compounds from (CBT) compounds (e.g., Cannabicitran CBT-C); or Cannab Cannabis. In some embodiments, the concentrates of the ichromanone-type (CBCN) compounds (e.g., Cannabichro present invention are preferably enriched for one or more manone CBCN-Cs, Cannabichromanone-C3 CBCN-C, cannabinoids. Preferred cannabinoid compounds include, but Cannabicoumaronone CBCON-Cs). In some embodiments, are not limited to: Cannabigerol-type (CBG) compounds the composition comprise greater than about 0.5%, 1%, 2%, (e.g., Cannabigerol (E)-CBG-Cs, Cannabigerol monomethyl 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% ether (E)-CBGM-CSA, Cannabigerolic acidA (Z)-CBGA-Cs or 99% w/w of one of the foregoing compounds. In some A, Cannabigerovarin (E)-CBGV-C, Cannabigerolic acid A embodiments, the compositions comprise from 0.5%, 1%, (E)-CBGA-Cs A, Cannabigerolic acid A monomethyl ether 2%. 5%, 10% or 20% w/w to about 25%, 30%, 40% or 50% (E)-CBGAM-Cs A and Cannabigerovarinic acid A (E)-CB W/w of one of the foregoing compounds. In some embodi GVA-CA); Cannabichromene-type (CBC) type compounds ments, the concentrates of the present invention are co-en (e.g., (t)-Cannabichromene CBC-Cs, (t)-Cannab riched for one or more of the foregoing compounds, for US 2014/027 1940 A1 Sep. 18, 2014

example, 2, 3, 4, 5, 6, 7, 8, 9 or 10 of the compounds. For chone, fenchol (norbornanol, 3-fenchol), geraniol, example, in some embodiments, the concentrates comprise C-guaiene, guaiol, methyl anthranilate, methyl salicylate, from about 0.5%, 1%, 2%, or 5% w/w to about 10% or 20% 2-methyl-4-heptanone, 3-methyl-4-heptanone, hexyl acetate, W/w of a combination of the foregoing compounds. In some ipsodienol, isoamyl acetate, lemenol, limonene, d-limonene embodiments, the compositions are essentially free of THC (limonene), linolool (linallyl alcohol, 3-linolool), C.-lon type cannabinoid compounds. In some embodiments, the gipinene, menthol, Y-muurolene, myrcene (B-myrcene), ner compositions are essentially free of CBN-type compounds. olidol, trans-nerolidol, nerol, B-ocimene (cis-ocimene), octyl Thus, in Some embodiments, the concentrates of the present acetate, C-phellandrene, phytol, C-pinene (2-pinene), invention are enriched (as specified by the percentages above) B-pinene, pulegone, Sabinene, cis-Sabinene hydrate (cis-thu for one or more cannabinoids as described, with the proviso janol), B-selinene, C-Selinene, Y-terpinene, terpinolene that the cannabinoids are not THC-type cannabinoid or CBN (isoterpine), terpineol (a terpineol), terpineol-4-ol, C-ter type cannabinoid. In some embodiments, the concentrates are pinene (terpilene), C-thujene (origanene), Vanillin, viridiflo enriched for one or more Cannabigerol-type (CBG) com rene (ledene), and C-ylange. pounds; Cannabichromene-type (CBC) type compounds; I0086. In some embodiments, the present invention pro Cannabidiol-type (CBD) compounds; Cannabinodiol-type vides concentrates and extracts that are treated to convert (CBND) compounds; Cannabielsoin-type (CBE) com THC-type cannabinoids into CBN-type cannabinoids. The pounds; Isocannabinoids compounds; Cannabicyclol-type concentrates and extracts are preferably produced as (CBL) compounds; Cannabicitran-type (CBT) compounds; described above. In preferred embodiments, the concentrates or Cannabichromanone-type (CBCN) compounds. and extracts are substantially free of THC-type cannabinoids. 0085. In some embodiments, the concentrates of the In some embodiments, the extracts and concentrates com present invention are co-enriched for one or more cannab prise less than 5%, 4%. 3%, 2%, 1%, 0.5% or 0.1% w/w inoid compounds (in the combinations and W/w percentages THC-type cannabinoids. In some embodiments, the extracts described above) and one or more terpenoids. The terpenoids and concentrates are enriched for one or more CBN-type are preferably elected from one or more of alloaromaden cannabinoids. In some embodiments, the CBN-type cannab drene, allyl hexanoate, benzaldehyde, (Z)-C-cis-bergamo inoids are selected from Cannabinol CBN-Cs, Cannabinol tene, (Z)-O-trans-bergamotene, B-bisabolol, epi-O-bisabolol. C. CBN-C, Cannabivarin CBN-C, Cannabinol-C, CBN B-bisabolene, borneol (camphol), cis-y-bisabolene, borneol C., Cannabiorcol CBN-C, Cannabinolic acid A CBNA-Cs acetate (bornyl acetate), C-cadinene, camphene, camphor, A, and Cannabinol methyl ether CBNM-Cs. In some embodi cis-carveol, caryophylene (B-caryophyllene), C-humulene ments, the concentrates comprise greater than 20%, 30%, (C-caryophyllene), Y-cadinene, A-3-carene, caryophyllene 40%, 50%, 60%, 70%, 80%, 90% or 95% w/w of one or more oxide, 1,8-cineole, citral A, citral B, cinnameldehyde, C-co (e.g., 2, 3, 4, or 5) CBN-type cannabinoids. In some embodi paene (aglaiene), Y-curcumene, B-cymene, B-elemene, y-el ments, the concentrates are co-enriched for one or more ter emene, ethyl decdienoate, ethyl maltol, ethylpropionate, eth penoids. The terpenoids are preferably selected from one or ylvanillin, eucalyptol, C.-eudesmol, 3-eudesmol, Y-eudesmol. more of Alloaromadendrene, allylhexanoate, benzaldehyde, eugenol, cis-3-farnesene (O-B-farnesene), trans-C.-farnesene, (Z)-C-cis-bergamotene, (Z)-O-trans-bergamotene, B-bisab trans-B-farnesene, trans-y bisabolene, fenchone, fenchol olol, epi-C.-bisabolol, B-bisabolene, borneol (camphol), cis (norbornanol, B-fenchol), geraniol, C.-guaiene, guaiol, Y-bisabolene, borneol acetate (bornyl acetate), C-cadinene, methyl anthranilate, methyl salicylate, 2-methyl-4-hep camphene, camphor, cis-carveol, caryophyllene (B-caryo tanone, 3-methyl-4-heptanone, hexyl acetate, ipsdienol, phyllene), C-humulene (C-caryophyllene), Y-cadinene, A-3- isoamyl acetate, lemenol, limonene, d-limonene (limonene), carene, caryophyllene oxide, 1,8-cineole, citral A, citral B. linolool (linallyl alcohol, B-linolool), C.-longipinene, menthol, cinnameldehyde, C-copaene (aglaiene), Y-curcumene, Y-muurolene, myrcene (B-myrcene), nerolidol, trans-neroli B-cymene, B-elemene, y-elemene, ethyl decdienoate, ethyl dol, nerol, B-ocimene (cis-ocimene), octyl acetate, C.-phel maltol, ethyl propionate, ethylvanillin, eucalyptol, C.-eudes landrene, phytol, C-pinene (2-pinene), B-pinene, pulegone, mol, B-eudesmol, Y-eudesmol, eugenol, cis-B-farnesene (Z)- Sabinene, cis-Sabinene hydrate (cis-thujanol), B-selinene, B-farnesene), trans-C-farnesene, trans-B-farnesene, trans-Y C-selinene, Y-terpinene, terpinolene (isoterpine), terpineol (a bisabolene, fenchone, fenchol (norbornanol, B-fenchol), terpineol), terpineol-4-ol, C-terpinene (terpilene), C-thujene geraniol, C.-guaiene, guaiol, methyl anthranilate, methyl sali (origanene), Vanillin, viridiflorene (ledene), and C-ylange. In cylate, 2-methyl-4-heptanone, 3-methyl-4-heptanone, hexyl Some embodiments, the concentrates one or more cannab acetate, ipsdienol, isoamyl acetate, lemenol, limonene, d-li inoid compounds (in the combinations and W/w percentages monene (limonene), linolool (linallyl alcohol, B-linolool), described above) in combination with from 0.1%, 0.5%, 1%, C.-longipinene, menthol, Y-muurolene, myrcene 2%, 3% to about 5% or 10% of one or more of Alloaroma (B-myrcene), nerolidol, trans-nerolidol, nerol, B-ocimene dendrene, allyl hexanoate, benzaldehyde, (Z)-C-cis-berga (cis-ocimene), octyl acetate, C-phellandrene, phytol, motene, (Z)-O-trans-bergamotene, B-bisabolol, epi-C.-bisab C-pinene (2-pinene), B-pinene, pulegone, Sabinene, cis-sab olol, B-bisabolene, borneol (camphol), cis-y-bisabolene, inene hydrate (cis-thujanol), B-selinene, C-Selinene, Y-ter borneol acetate (bornyl acetate), C-cadinene, camphene, pinene, terpinolene (isoterpine), terpineol (a terpineol), ter camphor, cis-carveol, caryophyllene (B-caryophyllene), pineol-4-ol, C-terpinene (terpilene), C-thujene (origanene), C-humulene (C-caryophyllene), Y-cadinene, A-3-carene, Vanillin, viridiflorene (ledene), C.-ylangene. In some embodi caryophyllene oxide, 1,8-cineole, citral A, citral B, cinnamel ments, the concentrates one or more cannabinoid compounds dehyde, C-copaene (aglaiene), Y-curcumene, 3-cymene, B-el (in the combinations and W/w percentages described above) emene, y-elemene, ethyl decdienoate, ethyl maltol, ethyl pro in combination with from 0.1%, 0.5%, 1%, 2%, 3% to about pionate, ethylvanillin, eucalyptol, C.-eudesmol, B-eudesmol. 5% or 10% of one or more of the terpenoids. In some embodi Y-eudesmol, eugenol, cis-B-farnesene (Z)-3-farnesene), ments, the concentrate comprise a total cannabinoid fraction trans-C.-farnesene, trans-B-farnesene, trans-y bisabolene, fen of from about 45% to 98% w/w (calculated as a weight US 2014/027 1940 A1 Sep. 18, 2014

percentage of the total weight of the concentrate), most pref embodiments, the total cannabinoid fraction contains from erably about 65% to 95% w/w total cannabinoid compounds about 62% to about 92% w/w or from about 75% to 92% w/w and a total terpenoid fraction of from about 0.1% to 5% w/w CBN-type compounds (calculated as a weight percentage of total terpenoids (calculated as a weight percentage of the total the total weight of the concentrate). As described above, the weight of the concentrate). In some embodiments, the total total cannabinoid fraction may additionally comprise at least cannabinoid fraction contains from about 62% to about 92% 1%, 2%. 5%, or 10% w/w of three or more of the cannabinoid w/w or from about 75% to 92% w/w TCHA and THC com compounds (calculated as a weight percentage of the total bined (calculated as a weight percentage of the total weight of weight of the concentrate). In some embodiments, the con the concentrate). In other embodiments, the total cannabinoid centrate comprises at least 1%, 2%. 5%, or 10% w/w of four fraction comprises from about 40% to 95% w/w or from about or more of the cannabinoid compounds (calculated as a 60% to 92% w/w of a combination of CBG, CBC and THCV weight percentage of the total weight of the concentrate). In (calculated as a weight percentage of the total weight of the Some embodiments, the concentrate comprises at least 1%, concentrate). As described above, the total cannabinoid frac 2%. 5%, or 10% w/w of five or more of the cannabinoid tion may additionally comprise at least 1%, 2%. 5%, or 10% compounds. Likewise, the total terpenoid fraction may addi W/w of three of the cannabinoid compounds (calculated as a tionally comprise at least 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% weight percentage of the total weight of the concentrate). In w/w of two or more of the terpenoids (calculated as a weight Some embodiments, the concentrate comprises at least 1%, percentage of the total weight of the concentrate). In some 2%. 5%, or 10% w/w of four of the cannabinoid compounds embodiments, the total terpenoid fraction may additionally (calculated as a weight percentage of the total weight of the comprise at least 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w of concentrate). In some embodiments, the concentrate com three or more of the terpenoids (calculated as a weight per prises at least 1%, 2%. 5%, or 10% w/w of five of the can centage of the total weight of the concentrate). In some nabinoid compounds. Likewise, the total terpenoid fraction embodiments, the total terpenoid fraction may additionally may additionally comprise at least 0.05%, 0.1%, 0.2%, or comprise at least 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w of 0.5% w/w of two of the terpenoids (calculated as a weight four or more of the terpenoids (calculated as a weight per percentage of the total weight of the concentrate). In some centage of the total weight of the concentrate). In some embodiments, the total terpenoid fraction may additionally embodiments, the total terpenoid fraction may additionally comprise at least 0.05%, 0.1%, 0.2%, or 0.5% w/w of three of comprise at least 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w of the terpenoids (calculated as a weight percentage of the total five or more of the terpenoids (calculated as a weight percent weight of the concentrate). In some embodiments, the total age of the total weight of the concentrate). In some embodi terpenoid fraction may additionally comprise at least 0.05%, ments, the total terpenoid fraction may additionally comprise 0.1%, 0.2%, or 0.5% w/w of four of the terpenoids (calculated at least 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w of ten or as a weight percentage of the total weight of the concentrate). more of the terpenoids (calculated as a weight percentage of In some embodiments, the total terpenoid fraction may addi the total weight of the concentrate). It should be noted that in tionally comprise at least 0.05%, 0.1%, 0.2%, or 0.5% w/w of defining the concentrates in weight percentage terms, the five of the terpenoids (calculated as a weight percentage of the weight percentage of the combined components will not total weight of the concentrate). exceed 100%. It should be noted that in defining the concen 0087. In some preferred embodiments, the processes of trates in weight percentage terms, the weight percentage of the present invention utilize natural or pharmaceutically the combined components will not exceed 100%. acceptable oxidizing agents to quickly oxidize a high THC I0089. In some embodiments, dry cannabis extracts or con cannabinoid extract to contain high levels of cannabinol. The centrates may be treated with ozone to effect oxidation. oxidation procedure may be conducted at any time during the OZone is a beneficial agent for processes where water is extraction or concentration process steps described above. In undesirable in the final product. Extracts or concentrates can some embodiments, a high THC(a) extract is utilized in the likewise be treated with UV or visible light in the presence of process with or without an optional decarboxylation step oxygen. This is a slower process, less predictable, with lower (heating or chemical) to convert the THC(a) to THC before efficiency. However, the advantage of this process is that there the oxidation step. In some preferred embodiments, the are no added chemicals or reagents and it can also be per extract or concentrate is dissolved in a solvent (e.g., ethanol). formed on dry cannabis extracts. Next, an oxidizing agent is added. Preferred oxidizing agents 0090. The concentrates, extracts and converted extracts of include hydrogen peroxide and oZone, which can be prefer the present invention may be formulated in a variety of ways. ably used without heating. Other Suitable oxidizing agents In some embodiments, the concentrates may be used either include, but are not limited to halogens, Sulfuric acid, peroxy for Smoking or in a vaporization system. In some embodi disulfuric acid, permanganate compounds, nitrous oxide, and ments, the mechanically mixed (e.g., whipped) products are the like. In some embodiments, more than 10%, 20, 30%, particularly suitable for these uses. There are numerous 40%, 50%, 60%, 70%, 80%, 90% or 95% of the THC in the devices on the market designed to vaporize Cannabis extracts extract or concentrate is converted to a CBN-type cannab for inhalation. The composition of the mechanically mixed inoid. product is such that it is easy to handle, visually unique and 0088. In some embodiments, the converted concentrates appealing due to the clay or wax-like consistency and light comprise a total cannabinoid fraction of from about 45% to color. The concentrates also preferably are enriched for ter 98% w/w (calculated as a weight percentage of the total penoids that add the characteristic aroma of Cannabis flowers weight of the concentrate), most preferably about 65% to that is favored by consumers of these types of extracts. 95% w/w total CBN-type compounds (e.g., as listed above) 0091. In some embodiments, the concentrates are utilized and a total terpenoid fraction of from about 0.1% to 5% w/w as an active ingredient in a thin film delivery device for use as total terpenoids (e.g., as listed above; calculated as a weight a sublingual or buccal delivery system. In preferred embodi percentage of the total weight of the concentrate). In some ments, the thin films are designed to be quick dissolving to US 2014/027 1940 A1 Sep. 18, 2014

administer a dose of 2 to 200 mg of the concentrates per and solubility/bioavailability enhancers. The shell optionally application directly to the blood stream via adsorption contains cannabinoids. In preferred embodiments, the gum through the buccal or oral mucosa. The thin films are prefer contains greater than 40% gum base. In some embodiments, ably formed using standard solvent casting or heat extrusion the gum includes an optional solubilizer, for example, one or techniques. The thin films optionally include a solubilizer, more of the cyclodextrin compounds (including, but not lim including one or more of the cyclodextrin compounds (in ited to, B-cyclodextrin, C.-cyclodextrin, Y-cyclodextrin, cluding, but not limited to, B-cyclodextrin, C.-cyclodextrin, hydroxypropyl B-cyclodextrin, and randomly methylated Y-cyclodextrin, hydroxypropyl B-cyclodextrin, and randomly B-cyclodextrin), one or more types of cyclodextrin polymers, methylated B-cyclodextrin), one or more types of cyclodex liposomes, micelles, dendrimers, etc. In preferred embodi trin polymers, liposomes, micelles, dendrimers, etc. In pre ments, the increased solubility provided by the compound ferred embodiments, the increased solubility provided by the increases the bio-availability of the active ingredients. compound increases the bio-availability of the active ingre 0096. The present invention also encompasses other for dients. In preferred embodiments, the excipients used for mulations of the concentrates. The concentrates may further construction of the film include a base polymer consisting of be formulated with acceptable excipients and/or carriers for at least 35% w/v of the final products. For the base polymer oral consumption. The carrier may be a liquid, gel, gelcap. one or more of the following common quick dissolving edible capsule, powder, Solid tablet (coated or non-coated), tea, or polymers is preferably used: hydroxylpropyl methyl cellu the like. Suitable excipient and/or carriers include maltodex lose (hypromellose, HPMC, Methocel, Metolose, Benecel), trin, calcium carbonate, dicalcium phosphate, tricalcium hydroxy propyl cellulose (hyprolose, Klucel, Nisso HPC), phosphate, microcrystalline cellulose, dextrose, rice flour, starch and modified starch (Amido, amylum, PharmCiel, magnesium Stearate, Stearic acid, croScarmellose Sodium, Fluftex W. Instant pure-Cote, Melogel.), pullulan (Pullulane, Sodium starch glycolate, crospovidone. Sucrose, vegetable 1.6 C. linked maltotriose), pectin (Citrus pectin, Methopectin, gums, lactose, methylcellulose, povidone, carboxymethyl pectin, pectinic acid), gelatin (Byco, cryogel, Instagel, Solu cellulose, corn starch, and the like (including mixtures gel), and carboxy methyl cellulose (Akulell, Blanose, Aqua thereof). Preferred carriers further include calcium carbonate, sorb, CMC sodium). magnesium Stearate, maltodextrin, and mixtures thereof. The 0092. In some embodiments, additional polymers are used various ingredients and the excipient and/or carrier are mixed to improve the properties of the thin film. Polymers that alter and formed into the desired form using conventional tech the disintegration properties of the film are used to make the niques. The tablet or capsule of the present invention may be thin film dissolve faster or more slowly. In some embodi coated with an enteric coating that dissolves at a pH of about ments, mucoadhesive/bioadhesive polymers are optionally 6.0 to 7.0. A suitable enteric coating that dissolves in the small used to promote adhesion of the strip. These include Xanthan intestine but not in the stomach is cellulose acetate phthalate. gum, guar gum, locust bean gum, polycarbophil, cellulose Further details on techniques for formulation for and admin derivatives, polyacyrlic acid, polycarbophil, and thiolated istration may be found in the latest edition of Remington's polymers. In some embodiments, plasticizers are used to Pharmaceutical Sciences (Maack Publishing Co., Easton, reduce cracking or brittleness of the thin film by improving Pa.). Such formulations may preferably comprise from about flexibility. Suitable plasticizers include maltodextrin, sorbi 1 to 200 mg of the concentrate. Where the formulation is an tol, mannitol, glycerol, glycerine, propylene glycol, polyeth oral delivery vehicle such as a capsule or tablet, the oral ylene glycols, triethyl citrate, tributyl citrate, acetyl citrate, delivery vehicle may preferably comprise from about 1 to 200 triacetin, dimethyl phthalate, diethyl phthalate, dibutyl phtha mg of the concentrate, 10 to 200 mg of the concentrate to 10 late, castor oil, etc. In preferred embodiments, plasticizers are to 100 mg of the concentrate. A daily dosage may comprise 1, included from 5% to 30% w/v of the total formulation. 2, 3, 4 or 5 of the oral delivery vehicles. 0093. The thin film can preferably be designed for quick 0097. In other embodiments, the concentrates are pro dissolution, or can comprise a polymer backing to slow the vided as a powder or liquid suitable for adding by the con rate of dissolution. This allows for a more slow release into Sumer to a food or beverage. For example, in Some embodi the target mucosal Surface and discourages oral ingestion of ments, the concentrate can be administered to an individual in the active ingredients. the form of a powder, for instance to be used by mixing into 0094. The thin film may optionally include additional a beverage, or by stirring into a semi-solid food such as a additives and excipients, such as -masking agents, fla pudding, topping, sauce, puree, cooked cereal, or salad dress Voring agents, Sweeteners, saliva stimulators, and hardening ing, for instance, or by otherwise adding to a food. and thickening agents. These additives and excipients will 0098. The concentrates of the present invention may be generally be included in an amount of about 1% to 15% w/v. combined with one or more additional bioactive agents, phy of the thin film. tonutrients, or nutraceutical agents to provide a dietary 0095. In some preferred embodiments, the present inven Supplement. In some embodiments, the one or more addi tion provides a chewing gum comprising a concentrate as tional bioactive agents, phytonutrients, or nutraceutical described in detail above. The chewing gum may preferably agents is from a source other than Cannabis. The dietary be used as a health aid, natural treatment for medical Symp Supplement may comprise one or more inert ingredients, toms, or for an intended psychoactive effect on the user and especially if it is desirable to limit the number of calories would be beneficial as a slow release oral mucosal or buccal added to the diet by the dietary supplement. For example, the delivery vehicle. In preferred embodiments, the chewing gum dietary Supplement of the present invention may also contain comprises from about 0.01 to 35% of a concentrate as optional ingredients including, for example, herbs, Vitamins, described above. The chewing gum may preferably contain a minerals, enhancers, colorants, Sweeteners, flavorants, inert sweetener (artificial or natural) as well as artificial and/or ingredients, and the like. For example, the dietary Supplement natural flavors. Optionally, the chewing gum can be coated of the present invention may contain one or more of the with a shell consisting of Sweetener, flavors, wetting agents, following: ascorbates (ascorbic acid, mineralascorbate salts, US 2014/027 1940 A1 Sep. 18, 2014 20 rose hips, acerola, and the like), dehydroepiandosterone or heat processed since the heat will break down the complex (DHEA), Fo-Ti or Ho Shu Wu (herb common to traditional carbohydrate into simple carbohydrates, wherein simple car Asian treatments), Cat's Claw (ancient herbal ingredient), bohydrates are mono- or disaccharides. The nutritional green tea (polyphenols), inositol, kelp, dulse, bioflavinoids, Supplement contains, in one embodiment, combinations of maltodextrin, nettles, niacin, niacinamide, , sele sources of carbohydrate of three levels of chain length nium, silica (silicon dioxide, silica gel, horsetail, shavegrass, (simple, medium and complex; e.g., Sucrose, maltodextrins, and the like), Spirulina, Zinc, and the like. Such optional and uncooked cornstarch). ingredients may be either naturally occurring or concentrated 0101 Sources of protein to be incorporated into the nutri forms. Nutraceutical agents are natural, bioactive chemical tional Supplement of the invention can be any suitable protein compounds that have health promoting, disease preventing or utilized in nutritional formulations and can include whey medicinal properties. Examples of nutraceutical agents that protein, whey protein concentrate, whey powder, egg, Soy may be combined with the concentrates of the present inven flour, Soy milk soy protein, soy protein isolate, caseinate (e.g., tion include, but are not limited to, resveratrol, fucoidan, Sodium caseinate, Sodium calcium caseinate, calcium casein Allium cepa, Allium sativum, Aloe vera, Angelica Species, ate, potassium caseinate), animal and vegetable protein and Naturally Occurring Antioxidants, Aspergillus Oryzae, barley mixtures thereof. When choosing a protein source, the bio grass, Bromelain, Carnitine, carotenoids and flavonoids, Cat logical value of the protein should be considered first, with the echin, Centella asiatica (Gotu kola), Coenzyme Q10, Chi highest biological values being found in caseinate, whey, nese Prepared Medicines, Coleus forskohlii, Commiphora lactalbumin, egg albumin and whole egg proteins. In a pre mukul. Conjugated Linoleic Acids (CLAS), Crataegus Oxya ferred embodiment, the protein is a combination of whey cantha (Hawthorne), Curcuna longa (), Echinacea protein concentrate and calcium caseinate. These proteins Species (Purple Coneflower), Eleutherococcus senticosus have high biological value; that is, they have a high proportion (Siberian Ginseng), Ephedra Species, Dietary Fish Oil, of the essential amino acids. See Modern Nutrition in Health Genistein, Ginkgo biloba, Glycyrrhiza (Licorice), Hyperi and Disease, eighth edition, Lea & Febiger, publishers, 1986, cum perforatum (St. John's Wort), Hydrastis (Goldenseal) especially Volume 1, pages 30-32. and other Berberine-containing plants, Lactobacillus, Lobe 0102 The nutritional supplement can also contain other lia (Indian Tobacco), Melaleuca alternifolia, Menaquinone, ingredients, such as one or a combination of other vitamins, Mentha piperita, n-glycolylneuraminic acid (NGNA), Panax minerals, antioxidants, fiber and other dietary Supplements Ginseng, Pancreatic Enzymes, Piper mythisticum, Procyani (e.g., protein, amino acids, choline, lecithin, omega-3 fatty dolic Oligomers, Pygeum africanum, Quercetin, Sarsaparilla acids). Selection of one or several of these ingredients is a species, Serenoa repens (Saw palmetto, Sabal serrulata), Silly matter of formulation, design, consumer preference and end bum marianum (Milk Thistle), Rosemary/Lemon balm, user. The amounts of these ingredients added to the dietary Selenite, Tabebuia avellanedae (LaPacho), Taraxacum offi supplements of this invention are readily known to the skilled cinale, Tanacetum parthenium (Feverfew), Taxol. Uva ursi artisan. Guidance to such amounts can be provided by the (Bearberry), Vaccinium myrtillus (Blueberry), Valerian offi U.S. RDA doses for children and adults. Further vitamins and cinalis, Viscum album (Mistletoe), Vitamin A, Beta-Carotene minerals that can be added include, but are not limited to, and other carotenoids, and Zingiber officinale (Ginger). calcium phosphate or acetate, tribasic; potassium phosphate, 0099. In some embodiments, the dietary supplements fur dibasic; magnesium sulfate or oxide; salt (sodium chloride); ther comprise vitamins and minerals including, but not lim potassium chloride or acetate; ascorbic acid; ferric ortho ited to, calcium phosphate or acetate, tribasic; potassium phosphate, niacinamide, Zinc sulfate or oxide; calcium pan phosphate, dibasic; magnesium sulfate or oxide; salt (sodium tothenate; copper gluconate; riboflavin; beta-carotene; pyri chloride); potassium chloride or acetate; ascorbic acid; ferric doxine hydrochloride; thiamin mononitrate; folic acid; orthophosphate, niacinamide; Zinc sulfate or oxide; calcium biotin; chromium chloride or picolonate; potassium iodide; pantothenate; copper gluconate; riboflavin; beta-carotene; Sodium selenate; sodium molybdate; phylloquinone; vitamin pyridoxine hydrochloride; thiamin mononitrate; folic acid; D., cyanocobalamin; sodium selenite; copper Sulfate; Vita biotin; chromium chloride or picolonate; potassium iodide; min A; Vitamin C; inositol; potassium iodide. Sodium selenate; sodium molybdate; phylloquinone; vitamin 0103) Flavors, coloring agents, spices, nuts and the like D., cyanocobalamin; Sodium selenite; copper Sulfate; Vita can be incorporated into the product. Flavorings can be in the min A; Vitamin C; inositol; potassium iodide. Suitable dos form of flavored extracts, volatile oils, chocolate flavorings, ages for vitamins and minerals may be obtained, for example, peanut butter flavoring, cookie crumbs, crisp rice, or by consulting the U.S. RDA guideline any commercially available flavoring. Examples of useful 0100. In other embodiments, the present invention pro flavoring include, but are not limited to, pure anise extract, vides nutritional Supplements (e.g., energy bars or meal imitation banana extract, imitation cherry extract, chocolate replacement bars or beverages) comprising a concentrate as extract, pure lemon extract, pure orange extract, pure pepper described above. The nutritional supplement may serve as mint extract, imitation pineapple extract, imitation rum meal or Snack replacement and generally provide nutrient extract, imitation Strawberry extract, or pure Vanilla extract; calories. Preferably, the nutritional supplements provide car or Volatile oils, such as balm oil, bay oil, bergamot oil, cedar bohydrates, proteins, and fats in balanced amounts. The nutri wood oil, walnut oil, cherry oil, oil, oil, or tional Supplement can further comprise carbohydrate, simple, peppermint oil; peanut butter, chocolate flavoring, Vanilla medium chain length, or polysaccharides, or a combination cookie crumb, butterscotch or toffee. In one embodiment, the thereof. A simple Sugar can be chosen for desirable organo dietary Supplement contains cocoa or chocolate. leptic properties. Uncooked cornstarch is one example of a 0104 Emulsifiers may be added for stability of the final complex carbohydrate. If it is desired that it should maintain product. Examples of suitable emulsifiers include, but are not its high molecular weight structure, it should be included only limited to, lecithin (e.g., from egg or Soy), and/or mono- and in food formulations orportions thereof which are not cooked di-glycerides. Other emulsifiers are readily apparent to the US 2014/027 1940 A1 Sep. 18, 2014

skilled artisan and selection of suitable emulsifier(s) will lies horizontally and is belt driven by an electric motor. The depend, in part, upon the formulation and final product. barrel portion is placed inside of a box with a collection pan 0105 Preservatives may also be added to the nutritional at the bottom. supplement to extend product shelf life. Preferably, preserva 0112 Methods: tives Such as potassium Sorbate, Sodium Sorbate, potassium 0113 200 g of dried Cannabis plant material from clones benzoate, sodium benzoate or calcium disodium EDTA are of the same variety of a drug strain of Cannabis sativa con used. sisting of Small flowers and trichome laden leaves was placed 0106. In addition to the carbohydrates described above, inside the tumbler and the motor turned on for differing the nutritional Supplement can contain natural or artificial lengths of time. The duration of extraction included 5 min (preferably low calorie) Sweeteners, e.g., Saccharides, cycla utes, 15 minutes, one hour, and 6 hours. After the extraction, mates, aspartamine, aspartame, acesulfame K, and/or Sorbi the trichome heads were collected as a dry powder in the tol. Such artificial Sweeteners can be desirable if the nutri bottom pan of the collection box. tional Supplement is intended to be consumed by an overweight or obese individual, or an individual with type II 0114. This method can be extended to any process which diabetes who is prone to hyperglycemia. agitates the plant material over a mesh screen to allow the 0107 The nutritional supplement can be provided in a trichome heads to fall through while catching the majority of variety of forms, and by a variety of production methods. In a plant material. Also, an optional step to freeze the plant mate preferred embodiment, to manufacture a food bar, the liquid rial at -20 C to -70 C to cause the trichomes to be brittle ingredients are cooked; the dry ingredients are added with the before being placed in the tumbler was found to increase yield liquid ingredients in a mixer and mixed until the dough phase and improve quality of the extract. Dry ice was found to be a is reached; the dough is put into an extruder, and extruded; the very suitable method for freezing the plant material because it extruded dough is cut into appropriate lengths; and the prod prevented moisture buildup on the plant material. Pieces of uct is cooled. The bars may contain other nutrients and fillers dry ice can also be placed inside of the extraction tumbler to to enhance taste, in addition to the ingredients specifically keep the plant material cold throughout the process and assist listed herein. in agitation of the plant material were also found to be useful. 0108. In still further embodiments, the present invention 0115 Results: provides functional foods, including food products, prepared 0116. The longer the duration of the extraction, the greater food products, or foodstuffs comprising a concentrate as the yield of trichome heads. Yields per 200 g were from 11 g described above. For example, in some embodiments, bever (5.5%) for the 5 minute extraction, 18 g (9%) for the 15 ages and solid or semi-solid foods comprising Sulfated minute extraction, 22 g (11%) for the 1 hour extraction, to 29 polysaccharides (e.g., fucoidan) are provided. These forms g (14.5%) for the 6 hour extraction. can include, but are not limited to, beverages (e.g., Softdrinks, 0117 The concentration of cannabinoids as measured milk and other dairy drinks, and diet drinks), baked goods, using HPLC/DAD decreased with increasing extraction puddings, dairy products, confections, Snack foods, or frozen times and yields. Total cannabinoids (THC+THCA--CBD+ confections or novelties (e.g., ice cream, milk shakes), pre CBDA+CBN) concentrations ranged from 49% for the 5 pared frozen meals, candy, Snack products (e.g., chips), minute extraction, 40% for the 15 minute extraction, 34% for Soups, spreads, sauces, salad dressings, prepared meat prod the 1 hour extraction, and 26% for the 6 hour extraction. ucts, cheese, yogurt and any other fat or oil containing foods, 0118. The color of the collected heads ranged from light and food ingredients (e.g., wheat flour). tan for the 5 minute extract to a darker, slightly greenish, 0109. In preferred embodiments, an effective amount of brown for the 6 hour extraction. the concentrate to cause the desired physiological response is provided to a subject, preferably in a once a day or twice a day Method 2A: dosage. In preferred embodiments, an effective amount of the concentrate is from 1-5000 mg of the concentrate, and most 0119 Materials: preferably from 100-2000 mg of the concentrate or 200 to 0.120. A large nylon cylinder was constructed of nylon 1000 mg of the concentrate daily. In some embodiments, the mesh with a 180 micron pore diameter. The cylinder was effective amount is the amount necessary to reduce inflam entirely enclosed and a Zipper was sewn in to allow access to mation, reduce pain, reduce nausea, enhance mood, produce the inside. A nylon bag large enough to fit the mesh cylinder a calm feeling, induce drowsiness or sleep, reduce anxiety, inside of it was also constructed with a zipper to allow for Support joint health, Support mental health, Support anti-in access to the inside. The nylon used to construct this bag flammatory response by the body, Support brain function, allowed water to penetrate but was woven tight enough to not Support feelings of wellbeing, Support healthy skin and allow any plant material or trichome heads to pass through. reduce blemishes. I0121 Equipment: I0122) A large drum driven by a belt was mounted inside of EXAMPLES a watertight container. The drum had several paddles Example 1 mounted to the inside of the cylinder to provide for agitation of the contents. The apparatus was constructed to allow for Preparation of Trichome Concentrate the drum to be rotated through the top of the container while Method 1 A it was filled with water. (0123 Method: Materials and Methods 0.124 400 g of plant material was placed inside the mesh 0110. Equipment: cylinder and it was Zipped shut. The cylinder was Zipped 0111. A mechanical tumbler with a cylindrical barrel inside the bag and the bag was placed in the drum. The drum made of a steel mesh containing 170 micron pores. The barrel apparatus was filled 34 of the way with ice water. The drum US 2014/027 1940 A1 Sep. 18, 2014 22 was rotated for 15 minutes, 30 minutes, and 1 hour. The bag umn packed with plant material or crude extract. The system was removed from the drum and allowed to drain of water. was pressurized to ensure the gases were in kept in a liquid The inner mesh bag was removed from the outer nylon bag. state while passing through the samples. The eluate was Inside the nylon bag, a medium light brown to dark, greenish mostly stripped of solvent using the mechanism designed into brown, sediment had collected. The sediment was collected the equipment. The remaining eluate was collected on glass on a glass plate and excess water was pressed out using a 5 petri dishes and placed in a vacuum desiccator. micron mesh nylon screen. The pressed trichome heads were 0.134 Data: placed on a glass plate and Vacuum desiccated for 24 hours. 0.135 The dried extracts were amorphous solids, slightly 0.125 Results: Sticky to touch, ranging from a translucent light yellow 0126 Trends for this process were similar to the dry orange color for the extract made from Material A, to a trans method, longer extraction times correlated to higher yields of lucent light amber color for Material B, to a darker translucent extract. The yield (after drying) for the 15 minute extraction amber color for material C. Material Ayielded 98.2 g of final was 52 g (12%), for the 30 minute extraction it was 72 g extract with 89.6% active cannabinoids. Material B yielded (18%), and for the 1 hour extraction it was 89 g (22.3%). 122.4 g of final extract with 87.4% active cannabinoids. 0127. The concentration of cannabinoids as measured Material C yielded 5.1 g of final extract that tested 79.0% using HPLC/DAD decreased with increasing extraction active cannabinoids. times and yields. Total cannabinoids (THC+THCA--CBD+ CBDA+CBN) concentrations ranged from 58% for the 15 Method 2B minute extraction, 52% for the 30 minute extraction, and 47% for the 1 hour extraction. Liquid Extraction Example 2 0.136. Materials and Equipment: 0.137 Avacuum distiller, n-Pentane, medium porosity sin Extraction from Trichome Concentrate tered glass Buchner funnel with filter flask equipment. Vari ous laboratory glassware was used. Three samples were used Method 1B for this extraction 100 grams of each of the crude extracts produced according to the methods in the previous descrip Gas Extraction tion were used as well as 100 grams of plant material (tri chome laden flower leaves and small flowers). Material A was 0128 Materials and Equipment: produced by tumbling freshly dried plant material in the 0129. A pressurized system was constructed with a sol cylinder from Method 1, for 30 minutes. It was a light brown vent reservoir mounted on top of the column and separated by color and tested 46% total active cannabinoids by HPLC/ a operator controlled valve. The column consisted of a stain DAD. Material B was produced by extracting freshly dried less steel cylinder with a valve pre-column leading to the plant material in the ice water extraction equipment from reservoir and filter followed by another operator controlled Method 2 for 30 minutes. It was a medium brown in color and valve post-column leading to a recovery chamber. The recov tested 59% total active cannabinoids. The crude extracts were ery chamber was outfitted with a heating mantle and an outlet made from the same plant material that was used for the valve to allow the solvent to be released back into the reser experiment. All of the plant material (Material C) consisted of Voir. All fitting and valves were airtight and explosion-proof. trichome dense Small leaves and Small Cannabis flowers and 0130. Additional materials included tanks of propane, it originated from the same strain of drug-type Cannabis isobutane, and n-butane. All solvents were ultra-high purity sativa. The homogenized plant material tested 14% total grade and purchased from a chemical Supplier. active cannabinoids. 0131 200 grams of each of the crude extracts produced according to the methods in the previous description were 0.138 Method: used as well as 50 grams of plant material (trichome laden 0.139. The samples were each placed in 2 L of n-Pentane flower leaves and small flowers). Material A was produced by and lightly stirred for 30 seconds. Much less solvent (-200 tumbling freshly dried plant material in the cylinder from ml) would have been needed for the pre-extracted samples, Method 1, for 30 minutes. It was a light brown color and but 2 L was used for each sample in the interest of uniformity. tested 46% total active cannabinoids by HPLC/DAD. Mate 2 L was the minimum solvent needed to ensure all of the plant rial B was produced by extracting freshly dried plant material material was Submerged in Solvent. This demonstrates the in the ice water extraction equipment from Method 2 for 30 inherent advantages of a two-step extraction with regard to minutes. It was a medium brown in color and tested 59% total minimizing solvent use and Volumes necessary to work with. active cannabinoids. The crude extracts were made from the The samples were stirred in the solvent for a short period of same plant material that was used for the experiment. All of time to avoid dissolving unwanted plant materials like chlo the plant material (Material C) consisted of trichome dense rophyll. Small leaves and Small Cannabis flowers and it originated 0140. The plant material was filtered out by pouring the from the same Strain of drug-type Cannabis sativa. The solution through the Buchner funnel. The eluate was then homogenized plant material tested 14% total active cannab stripped of n-Pentane using a rotary evaporator. inoids. 0141 Data: (0132 Methods: 0142. The dried extracts were amorphous solids at STP 0.133 Each of the samples was placed in the column. For slightly sticky to touch. With a slight warming, they become the fixed size of the column, 200g of the crude extract occu much more pliable and slightly runny. The extract produced pied approximately the same Volume as 50 g of the plant with material A was much more translucent and lighter amber material. Each extraction was carried out by passing 400 g of in color, the extract produced with material B was slightly a propane, iso-butane, and n-butane mixture through the col darker but still translucent, the extract produced with material US 2014/027 1940 A1 Sep. 18, 2014

C was opaque and almost black. When held to the light, it had fourth beaker and labeled D. A and B were placed in petri a green hue to it due to the increased chlorophyll content of dishes to maximize exposure to atop light Source. A, B, C, and this extract. D were equipped with magnetic stir bars and placed on a 0143. Material Ayielded 50.2 g of final extract with 88.9% stirring hotplate with the solution temperatures set to 40 C. A active cannabinoids. Material B yielded 63.0 g of final extract was placed in direct full spectrum sunlight for 12 hours at 40 with 84.9% active cannabinoids. Material C yielded 9.2 g of C with stirring. B was placed under UV light for 12 hours at final extract that tested 76.3% active cannabinoids. 40C with stirring. To C was added 5 ml of the 30% hydrogen peroxide and stirred for 12 hours at 40 C in a low light Example 3 environment. D was placed on a hot plate at 40C with stirring and placed in a low light environment. Processing of extracts to form a waxy base 0153. Results: 0144. Materials: 0154 Each sample other than D showed a marked increase 0145 Concentrated Cannabis extract eluate created from in CBN levels. Baseline CBN levels for the Stock Solution both Method 1A and Method 1B were utilized. Several whisk were 0.1 mg/ml. Sample A measured 4.6 mg/ml of CBN, attachments were constructed. Some acceptable designs Sample B measured 3.5 mg/ml of CBN. Sample C measured included magnetic stir bars, horizontal wires radiating from a 18.3 mg/ml of CBN, and Sample D measured 0.2 mg/ml of central point attached to the shaft, an aerated design, an auger CBN. type configuration, an auger with a flat blade at the bottom, 1. A concentrate comprising at least 1% w/w of at least one etc. The most successful design consisted of 6 wire “fish cannabinoid compound selected from the group consisting of hooks' radiating from the central hub attached to the shaft. Cannabigerol (E)-CBG-Cs, Cannabigerol monomethyl ether 0146 Methods: (E)-CBGM-Cs A, Cannabigerolic acid A (Z)-CBGA-C. A. 0147 The concentrated eluate is continuously stirred by Cannabigerovarin (E)-CBGV-C, Cannabigerolic acid A(E)- the whisk. This occurred in a fume hood with vacuum desic CBGA-Cs A, Cannabigerolic acid A monomethyl ether (E)- cation due to the volatile nature of the solvent system. The CBGAM-Cs A and Cannabigerovarinic acid A(E)-CBGVA eluate was placed in a Pyrex tray and the tray was maintained C A); (t)-Cannabichromene CBC-C, (t)- at 35C in a water batch. The eluate was continuously whipped Cannabichromenic acid A CBCA-Cs A, (+)- or whisked until dry. The whipped final product was a waxy or Cannabivarichromene, (+)-Cannabichromevarin CBCV-C, clay like consistency and had a white to yellow color. The (+)-Cannabichromevarinic acid A CBCVA-CA): (-)-Can product is opaque. The final product is not tacky to the touch nabidiol CBD-Cs, Cannabidiol momomethyl ether CBDM and is much easier to handle than the unwhipped extracts. Cs, Cannabidiol-CCBD-C (-)-Cannabidivarin CBDV-C, This waxy product base can optionally have additives mixed Cannabidiorcol CBD-C, Cannabidiolic acid CBDA-Cs. mechanically into the waxy base at this point. Cannabidivarinic acid CBDVA-C); Cannabinodiol CBND Cs, Cannabinodivarin CBND-CA); A-Tetrahydrocannabinol Example 4 A-THC-Cs, A-Tetrahydrocannabinol-C, A-THC-C, A-Tetrahydrocannabivarin A-THCV-C, A-Tetrahydro Oxidation of THC to CBN cannabiorcol, A-THCO-C, A-Tetrahydrocannabinolic 0148 Experiments using oZone, hydrogen peroxide, and acid A A-THCA-C A, A-Tetrahydrocannabinolic acid B, UV/visible light exposure in the presence of oxygen have A-THCA-Cs B, A-Tetrahydrocannabinolic acid-CA and/ been able to produce significant amounts of cannabinol from or BA-THCA-CA and/or B, A-Tetrahydro-cannabivarinic THC or THCa in plant material (H2O2, light) and extracts acid A A-THCVA-C, A, A-Tetrahydrocannabiorcolic acid (O3, H2O2, and light). A and/or B A-THCOA-C, A and/or B), (-)-A-trans-(6aR, 0149 Materials and Equipment: 10aR)-A-Tetrahydrocannabinol A-THC-Cs. (-)-A-trans 0150. Absolute ethanol, 30% concentrated hydrogen per (6aR.10aR)-Tetrahydrocannabinolic acid AA-THCA-C.s A. oxide, several different pieces of common laboratory glass (-)-(6aS, 10aR)-A-Tetrahydrocannabinol (-)-cis-A-THC ware and tools, temperature probe controlled magnetically Cs); Cannabinol CBN-Cs, Cannabinol-C, CBN-C Can stirred hot plates, common laboratory grade UV light used for nabivarin CBN-C, Cannabinol-C, CBN-C, Cannabiorcol reading TLC stains, analytical instruments for analysis (in CBN-C, Cannabinolic acid A CBNA-Cs A, Cannabinol cluding balances, HPLC-DAD, and assorted volumetric mea methyl ether CBNM-Cs. (-)-(9R. 10R)-trans-Cannabitriol Suring instruments) and cannabis extract produced using the (-)-trans-CBT-C (+)-(9S.10S)-Cannabitriol (+)-trans-CBT above methods. The cannabis extract was decarboxylated Cs, (+)-(9R, 10S/9S. 10R)—); Cannabitriol (+)-cis-CBT-Cs. using heat and measured for cannabinoid content. The extract (-)-(9R,1OR)-trans-10-O-Ethyl-cannabitriol (-)-trans-CBT measured 70.1% THC, 0.2% THCA, 0.2% CBN, 0.7% CBD, OEt-Cs. (+)-(9R,10R/ 19S.10S)-Cannabitriol-C (+)-trans and 0.4% CBDA w/w. Analysis were performed using HPLC CBT-C, 8.9-Dihydroxy-A'-tetrahydrocannabinol 8.9- with a DAD detector, with an isocratic gradient of acetonitrile Di-OH-CBT-Cs, Cannabidiolic acid A cannabitriol ester and water with formic acid, on a reverse phase C18 hplc CBDA-C 9-OH-CBT-C ester, (-)-(6aR,9S,10S,10aR)-9, column. All standards were purchased from Restek corpora 10-Dihydroxy-hexahydrocannabinol, Cannabiripsol, Canna tion. biripsol-Cs. (-)-6as7.10a-Trihydroxy-A-tetrahydrocannab 0151. Procedures: inol (-)-Cannabitetrol, 10-Oxo-As(10) 0152 200 ml of an ~50 mg/ml THC in ethanol solution tetrahydrocannabinol OTHC); (5 aS,6S,9R.9aR)- was prepared by dissolving 14.27g of the extract in 200 ml of Cannabielsoin CBE-C, (5 aS,6S,9R,9aR) C absolute ethanol. 50 ml of the solution was measured and Cannabielsoin CBE-C (5 aS,6S.9R,9aR)-Cannabielsoic poured into two large, petri dishes which were labeled A and acid A CBEA-Cs A, (5 aS,6S-9R.9aR)-Cannabielsoic acid B B. 50 ml of solution was measured and poured into a beaker CBEA-Cs B: (5 aS,6S,9R,9aR) C-Cannabielsoic acid B and labeled C. The final 50 ml of solution was placed in a CBEA-C B, Cannabiglendol-CH-iso-HHCV-C. Dehy US 2014/027 1940 A1 Sep. 18, 2014 24 drocannabifuran DCBF-Cs, Cannabifuran CBF-Cs), (-)-A- (a) concentrating glandular trichomes from Cannabis plant trans-(1R,3R,6R)-Isotetrahydrocannabinol, (+)-A7-12-cis material; (1R,3R,6S/1S.3S,6R)-Isotetrahydrocannabivarin, (-)-A- (b) passing a solvent though said plant material to produce trans-(1R,3R,6R)-Isotetrahydrocannabivarin); (+)-(1aS.3aR, a cannabinoid/terpenoid-containing eluate; 8bR,8cR)-Cannabicyclol CBL-Cs, (+)-(1aS.3aR,8bR,8cR)- (c) filtering solids from the eluate Cannabicyclolic acid A CBLA-C, A, (+)-(1aS.3aR.8bR, (d) refining the eluate to remove undesirable impurities; 8cR)-Cannabicyclovarin CBLV-C; Cannabicitran CBT-C); (e) processing the eluate into a consumable form. Cannabichromanone CBCN-Cs, Cannabichromanone-C3 9. The process of claim8, wherein said refining comprises: CBCN-C, and Cannabicoumaronone CBCON-Cs); and (i) distilling said eluate; at least 0.1% w/w of at least one terpenoid selected from the (ii) resuspending eluate in solvent; and group consisting of Alloaromadendrene, allyl hex (iii) cooling resuspended eluate to precipitate out undesir anoate, benzaldehyde, (Z)-C-cis-bergamotene, (Z)-C.- able impurities. trans-bergamotene, 3-bisabolol, epi-C.-bisabolol, B-bis 10. The process of claim 8, wherein said refining com abolene, borneol (camphol), cis-y-bisabolene, borneol prises: acetate (bornyl acetate), C-cadinene, camphene, cam (i) adding eluate to non-polar solvent; phor, cis-carveol, caryophylene (B-caryophylene), (ii) adding concentrated brine solution; C-humulene (C-caryophyllene), Y-cadinene, A-3- (iii) agitating vigorously; carene, caryophyllene oxide, 1,8-cineole, citral A, citral (iv) draining off brine solution; and B, cinnameldehyde, C-copaene (aglaiene), Y-cur (v) treating eluate with desiccant. cumene, B-cymene, B-elemene, y-elemene, ethyl decdi 11. The process of claim 8, further comprising a step of enoate, ethyl maltol, ethyl propionate, ethylvanillin, fractionating the eluate into fractions enriched for one or eucalyptol, C.-eudesmol, B-eudesmol, Y-eudesmol, more cannabinoids and/or terpenoids. eugenol, cis-B-farnesene (O-B-farnesene), trans-C.-far 12. The process of claim 11, wherein fractionating com nesene, trans-B-farnesene, trans-y bisabolene, fenchone, prises passing the eluate over a column in the presence of fenchol (norbornanol, B-fenchol), geraniol, C-guaiene, Solvents of progressively different polarities, and collecting guaiol, methyl anthranilate, methyl salicylate, 2-methyl fractions as they exit the column. 4-heptanone, 3-methyl-4-heptanone, hexyl acetate, ips 13. The process of claim 11, wherein fractionating com dienol, isoamyl acetate, lemenol, limonene, d-limonene prises: (limonene), linolool (linallyl alcohol, B-linolool), C.-lon (i) concentrating the eluate in a non-polar solvent; gipinene, menthol, Y-muurolene, myrcene (B-myrcene), (ii) cooling the eluate solution to 20 to -200 C; and nerolidol, trans-nerolidol, nerol, B-ocimene (cis (iii) filtering crystals according to composition. ocimene), octyl acetate, C-phellandrene, phytol, 14. The process of claim8, wherein said refining comprises C-pinene (2-pinene), B-pinene, pulegone, Sabinene, cis exposing eluate to UV light for at least 30 minutes to degrade Sabinene hydrate (cis-thujanol), B-selinene, C.-selinene, chlorophyll. Y-terpinene, terpinolene (isoterpine), terpineol (a terpi 15. The process of claim 14, wherein said refining com neol), terpineol-4-ol, C-terpinene (terpilene), C-thujene prises: (origanene), Vanillin, viridiflorene (ledene), and (i) adding solvent and activated charcoal to eluate; C-ylange. (ii) mixing: 2. The concentrate of claim 1, wherein said concentrate (iii) filtering out activated charcoal; and comprises at least 1% w/w of two of said cannabinoid com (iv) removing solvent. pounds. 16. The process of claim 8, wherein processing the eluate 3. The concentrate of claim 1, wherein said concentrate into a consumable form comprises spray drying the eluate to comprises at least 1% w/w of three of said cannabinoid com pounds. produce a crystalline extract. 4. The concentrate of claim 1, wherein said concentrate 17. The process of claim 8, wherein processing the eluate comprises at least 0.1% of two of said terpenoids. into a consumable form comprises thin film evaporation. 5. The concentrate of claim 1, wherein said concentrate 18. The process of claim 8, wherein processing the eluate comprises at least 0.1% of three of said terpenoids. into a consumable form comprises continuously stirring the 6. The concentrate of claim 1, wherein said concentrate is eluate with a whisk or auger until eluate is dried into a wax. substantially free of THC-type compounds. 19. An oral delivery vehicle, chewing gum, dietary Supple 7. The concentrate of claim 1, wherein said concentrate is ment, or food product comprising the concentrate of claim 1. substantially free of CBN-type compounds. 20. A thin film delivery vehicle comprising the concentrate 8. A process for preparing cannabinoid and/or terpenoid of claim 1. extracts for human consumption comprising: