WO2022192473A2

Movatterモバイル変換

Info

Publication number: WO2022192473A2
Application number: PCT/US2022/019650
Authority: WO
Inventors: Dylan FOOTEN; Matt LIMON; Daniel BARRERA; Thomas Martin; Matt FINLEY
Original assignee: Central Coast Agriculture Inc
Current assignee: Central Coast Agriculture Inc
Priority date: 2021-03-09
Filing date: 2022-03-09
Publication date: 2022-09-15
Anticipated expiration: 2023-09-09
Also published as: WO2022192473A3

Abstract

Provided herein are methods for preparing cannabinoid isolate and solid particles of tetrahydrocannabinolic acid.

Description

SYSTEMS AND METHODS FOR ISOLATING MATERIALS

CROSS-REFERENCE

[0001] This application claims priority to U.S. Provisional Patent Application No.

63/158,805, filed March 9, 2021, which is incorporated herein by reference in its entirety.

TECHNICAL FIELD

[0002] The present disclosure generally relates to crystalline cannabinoid compounds and methods of isolating and/or crystallizing cannabinoid compounds.

BACKGROUND

[0003] In recent years, the use of Cannabis and Cannabis extracts for medicinal and recreational purposes has increased. Many medicinal and recreational cannabinoid products feature tetrahydrocannabinolic acid (THCA). Current methods for purification of THCA from other components obtained from Cannabis extraction involve expensive and/or time intensive methods. Thus, there exists a need to develop new methods for isolating THCA with high purity and efficiency that are robust as to be suitable for scaled production. The present disclosure is directed towards this end.

SUMMARY

[0004] The disclosure provides, in part, solid particles (e.g., crystalline solid particles) comprising delta-9-tetrahydrocannabinolic acid (THCA) and methods of producing solid particles (e.g., crystalline solid particles) comprising THCA from Cannabis extracts (e.g., oil comprising a plurality of cannabinoids, terpenoids, and other components extracted from a feedstock comprising a plant of the genus Cannabis).

[0005] In an aspect, provided herein is a method for producing solid particles comprising THCA, the method comprising: (a) contacting an oil comprising a plurality of cannabinoids with a solvent to produce a mixture; (b) warming the mixture of step (a) to about 30 °C to form a homogenous solution; (c) cooling the homogenous solution of step (b) to precipitate THCA from the solution to form a THCA isolate and a mother liquor; (d) separating the THCA isolate from the mother liquor; and (e) optionally, washing the THCA isolate with a solvent to produce solid particles comprising THCA. [0006] In another aspect, provided herein is a method of producing crystalline solid particles comprising THCA, the method comprising: (i) contacting solid particles produced by the methods described herein with a solvent to produce a mixture; (ii) evaporating the mixture of step (i) to produce a saturated solution; (iii) incubating the saturated solution of step (ii) to produce crystalline solid particles comprising THCA and a mother liquor; and (iv) separating the crystalline solid particles from the mother liquor.

[0007] In another aspect, the present disclosure provides a method of producing crystalline solid particles comprising THCA, the method comprising: (i) contacting solid particles comprising at least 95% of THCA by weight with a solvent to produce a mixture;

(ii) evaporating the mixture of step (i) to produce a saturated solution; and (iii) incubating the saturated solution of step (ii) to produce crystalline solid particles comprising THCA and a mother liquor; and (iv) separating the crystalline solid particles from the mother liquor.

[0008] The present disclosure also provides for crystalline solid particles comprising tetrahydrocannabinolic acid (THCA) obtained from any of the methods described herein, wherein the crystalline solid particles comprises at least 99% of THCA by weight.

[0009] Other objects and advantages will become apparent to those skilled in the art from a consideration of the ensuing Detailed Description, Examples, and Claims.

BRIEF DESCRIPTION OF THE DRAWINGS

[00010] These and other features of the present disclosure will become more apparent in the following detailed description in which reference is made to the appended drawings. The appended drawings illustrate one or more embodiments of the present disclosure by way of example only and are not to be construed as limiting the scope of the present disclosure. [00011] FIG. 1 shows a flow diagram of an exemplary process, which may be employed in a method in accordance with the present disclosure.

[00012] FIG. 2 shows exemplary images of crystals obtained according to methods described herein (e.g., as described in Example 1).

[00013] FIG. 3 shows exemplary images of crystals obtained from crystallization from crude oil.

[00014] FIG. 4 shows comparative images of crystals obtained according to the methods described herein (e.g., as described in Example 1) (right) compared to crystals obtained from crystallization from crude oil (left). DETAILED DESCRIPTION

[00015] As generally described herein, the present disclosure provides for solid particles (e.g., crystalline solid particles) comprising delta-9-tetrahydrocannabinolic acid (THCA) and methods of producing solid particles (e.g., crystalline solid particles) comprising THCA from Cannabis extracts (e.g., oil comprising a plurality of cannabinoids extracted from a feedstock comprising a plant of the genus Cannabis).

[00016] As used herein the terms “crystal,” “crystallizing,” “crystalline” and the like are used broadly to refer to a spectrum of solid materials having a degree of microscopic order but not necessarily a highly ordered crystal lattice that extends in all directions. As will be appreciated by those skilled in the art who have benefitted from the teachings of the present disclosure, the degree of crystallinity of material can be evaluated by a variety of means such as but not limited to powder X-ray diffraction, single crystal X-ray diffraction, differential scanning calorimetry, and the like.

[00017] The term "substantially crystalline" refers to solid particles that may be at least a particular weight percent crystalline. Particular weight percentages are 70%, 75%, 80%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or any percentage between 75% and 100%. In certain embodiments, the particular weight percent of crystallinity is at least 90%. In certain other embodiments, the particular weight percent of crystallinity is at least 95%.

[00018] The term “substantially free” refers to solid particles that may be at least a particular weight percent free of impurities or contaminants such as a pesticide. Particular weight percentages of impurities or contaminants are, for example, about 30%, 25%, 20%, 15%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, 0.05, 0.01%, 0.001%, 0.0001%, 0.00001%, 0.000001%, or any percentage between 0% and 25% by weight with respect to the weight of solid particles. In some embodiments, impurities or contaminants are present in an amount of about 0.01 to 0.6 pg/g (ppm). In certain other embodiments, the amount of impurities or contaminants (e.g., a pesticide) is not detectable using conventional quantification techniques.

[00019] As used herein, the term “cannabinokl” refers to: (i) a chemical compound belonging to a class of secondary compounds commonly found in plants of genus Cannabis , (ii) synthetic cannabinoid s and any enantiomers thereof; and/or (iii) one of a class of diverse chemical compounds that may act on cannabinoid receptors such as CB! and CB2. [00020] Any and all isomeric, enantiomeric, or optically active derivatives are also encompassed. In particular, where appropriate, reference to a particular cannabinoid includes both the “A Form” and the “B Form”. For example, it is known that THCA has two isomers, THCA-A in which the carboxylic acid group is in the 1 position between the hydroxyl group and the carbon chain (A Form) and THCA-B in which the carboxylic acid group is in the 3 position following the carbon chain (B Form). As will be appreciated by those skilled in the art who have benefited from the teachings of the present discl osure, “cannabi noi d” may refer to: salts of acid forms, such as Na⁺ or Ca²⁺ salts of such acid forms; and/or ester forms, such as formed by hydroxyl -group esterification to form traditional esters, sulphonate esters, and/or phosphate esters.

[00021] Cannabinoids include delat-9-tetrahydrocannabinolic acid, delta-9- tetrahydrocannabinol, cannabigerol, cannabichromene, tetrahydrocannabivarin, cannabidiol, cannabinol, cannabigerivarin, tetrahydrocannabivarian, cannabidivarin, cannabichromevarin, and derivatives thereof. Examples of cannabinoids include, but are not limited to, Cannabigerolic Acid, (CBGA), Cannabigerolic Acid Monomethyl ether (CBGAM), Cannabigerol (CBG), Cannabigerol Monomethyl ether (CBGM), Cannabigerovarinic Acid (CBGVA), Cannabigerovarin (CBGV), Cannabichromenic Acid (CBCA), Cannabichromene (CBC), Cannabichromevarinic Acid (CBCVA), Cannabichromevarin (CBCV), Cannabidiolic Acid (CBD.A), Cannabidiol (CBD), A6-Cannabidiol (DQ-CBD), Cannabidiol Monomethyl ether (CBDM), Cannabidiol -C4 (CBD-C4), Cannabidivarinic Acid (CBDVA), Cannabidivarin (CBDV), Cannabidiorcol (CBD-C1), Tetrahydrocannabinolic Acid (e.g,, Tetrahydrocannabinol! c Acid A (THCA-A), Tetrahydrocannabinolic Acid B (THCA-B)), Tetrahydrocannabinol (THC or DQ-THC), Dd-tetrahydrocannabinol (Dd-THC), trans- A 10- tetrahydrocannabinol (trans-Al 0-THC), cis-Al 0-tetrahydrocannabinol (cis-Al 0-THC), Tetrahydrocannabinolic Acid C4 (THCA-C4), Tetrahydrocannabinol C4 (THC-C4), Tetrahydrocannabivarinic Acid (THCVA), Tetrahydrocannabivarin (THCV), Dd- Tetrahydrocannabivarin (Dd-THCV), A9-Tetrahydrocannabivarin (A9-THCV), Tetrahydrocannabiorcolic Acid (THCA-C1), Tetrahydrocannabiorcol (THC-C1), A7-cis-iso- tetrahydrocannabivarin, Dd-Tetrahydrocannabinolic Acid (Dd-THCA), A9- Tetrahydrocannabinolic Acid (DQ-THCA), Cannabicyclolic Acid (CB1 A), Cannabicyclol (CBL), Cannabicyclovarin (CBLV), Cannabielsoic Acid A (CBEA-A), Cannabielsoic Acid B (CBEA-B), Cannabielsoin (CBE), Cannabinolic Acid (CBNA), Cannabinol (CBN), Cannabinol Methyl ether (CBNM), Cannabinol-C4 (CBN-C4), Cannabivarin (CBV), Cannabino-C2 (CBN-C2), Cannabiorcol (CBN-Cl), Cannabinodiol (CBND), Cannabinodivarin (CBDV), Cannabitriol (CBT), 11 -hydroxy- A9-tetrahydrocannabinol (1 I- OH-THC), 11 nor 9-carboxy-A9-tetrahydrocannabinol, Ethoxy-cannabitriolvarin (CBTVE), 10-Ethoxy-9-hydroxy-A6a-tetrahydrocannabinol, Cannabitriolvarin (CBTV), 8,9 Dihydroxy - A6a(10a)-tetrahydrocannabinol (8,9-Di-OH-CBT-C5), Dehydrocannabifuran (DCBF), Cannbifuran (CBF), Cannabichromanon (CBCN), Cannabicitran, 10-Oxo-A6a(10a)~ tetrahydrocannabinol (OTHC), A9-cis-tetrahydrocannabinol (cis-THC), Cannabiripsol (CBR), 3,4,5,6-tetrahydro-7-hydroxy-alpha-alpha-2-trimethyl-9-n-propyl-2,6-methano-2H-l- benzoxocin-5-methanol (OH-iso-HHCV), Trihydroxy-delta-9-tetrahydrocannabinol (triOH- THC), Yangonin, Epigallocatechin gallate, Dodeca-2E, 4E, 8Z, lOZ-tetraenoic acid isobutyl amide, hexahydrocannibinol, and Dodeca-2E,4E-dienoic acid isobutyl amide.

[00022] Cannabis extracts comprising a plurality of cannabinoids may be a distillate, a resin, an extract, or the like. In some embodiments, the Cannabis extract is an oil comprising a plurality of cannabinoids. For example, the oil may be prepared by solvent extraction from a feedstock comprising a plant of the genus Cannabis and concentrating the extract (i.e., removing the extraction solvent(s)). In some embodiments, the feedstock is a fresh frozen biomass.

[00024] As used herein, “plurality of terpenoids” refers to a mixture of one or more terpenoids. As used herein, “plurality of cannabinoids” refers to a mixture of more than one cannabinoid.

[00025] "About" and "approximately" shall generally mean an acceptable degree of error for the quantity measured given the nature or precision of the measurements. Exemplary degrees of error are within 20 percent (%), typically, within 10%, and more typically, within 5% of a given value or range of values.

[00026] “Agitating” as used herein refers to the act of putting something (e.g., a solution or mixture comprising THCA and solvent) into motion through mechanical shaking or stirring. For example, in some embodiments, the solution or mixture comprising THCA and solvent are agitated when it is being warmed/heated or cooled.

[00027] “Separating” as used herein refers to the process of separating solid particles from a mixture of solid particles and solvent or mother liquor and removing the solid particles from the remainder of the mixture. Solid particles may be separated from and removed from a mixture by means including, but not limited to filtration, gravity separation, purification, isolation, or a combination thereof.

[00028] As used herein, the term “incubating” refers to the process of keeping a solution or a reaction mixture at a pre-determined temperature or pressure for a period of time to achieve a specific reaction, such as crystallization. The temperature, pressure, and the period of incubation are suitably selected such that the purpose of the incubation (e.g., crystalline growth) is achieved at the end of incubation.

[00029] As used herein, “sieving” or processing a material through a sieve refers to a separation process which is based on the difference in the size of particles of a material (e.g., solid particles comprising THCA). In some embodiments, the process uses a mechanical sieve or screen. For example, a sieve can be in the form of a regular or irregular mesh, a perforated solid surface, a three-dimensional matrix, or a column of differential porosity. The term encompasses a process separating a larger or coarser particle from a smaller or finer particle.

[00030] As used herein, “potency” refers to the sum of percentage by weight of THCA multiplied by 0.877 plus the percentage of weight of D-9-THC.

[00031] In an aspect, provided herein is a method for producing solid particles comprising tetrahydrocannabinolic acid (THCA), the method comprising: (a) contacting an oil comprising a plurality of cannabinoids with a solvent to produce a mixture; (b) warming the mixture of step (a) to about 30 °C to form a homogenous solution; (c) cooling the homogenous solution of step (b) to precipitate THCA from the solution to form a THCA isolate and a mother liquor; (d) separating the THCA isolate from the mother liquor; and (e) optionally, washing the THCA isolate with a solvent to produce solid particles comprising THCA.

[00032] In some embodiments, the cooling in step (c) occurs in a vessel comprising a circulation loop. In some embodiments, the cooling in step (c) further comprises agitating the solution.

[00035] In some embodiments, the solid particles are substantially crystalline.

[00036] In some embodiments, the solid particles comprises at least 75% of THCA by weight. In some embodiments, the solid particles comprises at least 80% of THCA by weight. In some embodiments, the solid particles comprises at least 85% of THCA by weight. In some embodiments, the solid particles comprises at least 90% of THCA by weight. In some embodiments, the solid particles comprises at least 95% of THCA by weight. In some embodiments, wherein the solid particles comprises at least 99% of THCA by weight. In some embodiments, the solid particles comprises 99% of THCA by weight. In some embodiments, the solid particles consist essentially of THCA.

[00037] In some embodiments, the methods further comprise collecting the mother liquor. In some embodiments, the methods further comprise collecting the solvent wash of step (e). In some embodiments, the washing step (e) is repeated at least once.

[00038] In some embodiments, the solvent has a polarity index range of 0.0 to 5.0, 0.0 to 4.0, 0.0 to 3.0, 0.0 to 2.0, or 0.0 to 1.0. For example, the solvent has a polarity index of 0.0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or 1.0. In some embodiments, the solvent has a polarity index below 1.0. In some embodiments, the solvent has a dielectric constant of 1.5 to 20.0, 1.5 to 15.0, 1.5 to 10.0, 1.5 to 5.0, or 1.5 to 2.0. For example, the solvent has a dielectric constant of about 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2,4, or 2.5. In some embodiments, the solvent has a boiling point of about 25 °C to about 100 °C, e.g., about 25^C'C to about 80 °C, about 25 °C to about 60 °C, about 25 °C to about 40 °C, about 30 °C to about 60 °C, or about 30 °C to 40 °C. Exemplary solvents include, but are not limited to, pentane, hexane, heptane, isopentane, isobutane, cyclopentane, cyclohexane, iso-octane, n-butylchloride, acetonitrile, methanol, ethanol, isopropanol, dimethyl sulfoxide, acetone, ethyl acetate, diethyl ether, tert-butyl methyl ether, water, acetic acid, anisole, 1 -butanol, 2-butanol, butane, butyl acetate, ethyl formate, formic acid, isobutyl acetate, isopropyl acetate, methyl acetate,

3 -methyl- 1 -butanol, methylethyl ketone, 2-methyl- 1 -propanol, l-pentano!, 1-propanol, propane, propyl acetate, trimethyl amine, dimethylacetamide, tetrahydrofuran, dimethylformamide, 1,1,2-trichlorotrifluoroethane, or a combination thereof. In some embodiments, the solvent is n-pentane. For example, n-pentane has a boiling point of about 36 °C, a dielectric constant of about 1.8, and a polarity index of 0.0. In some embodiments, the solvent may be a solvent or a combination of solvents that have a boiling point, a dielectric constant, or a polarity index about that of n-pentane.

[00039] In some embodiments, the solvent has a polarity index less than 1, including but not limited to hexane, heptane, petroleum ether, and 2,2,4-trimethylpentane. The present methods may comprise crystallization steps and washing steps. Exemplary solvents for crystallization steps described herein include, but are not limited to, pentane, hexane, heptane, isopentane, isobutane, cyclopentane, cyclohexane, iso-octane, n-butylchloride, or a combination thereof. In some embodiments, a solvent for a crystallization step described herein is a solvent having a polarity index less or equal to 1. Exemplary solvents for washing steps described herein include, but are not limited to acetonitrile, methanol, ethanol, isopropanol, dimethyl sulfoxide, acetone, ethyl acetate, diethyl ether, tert-butyl methyl ether, water, acetic acid, anisole, 1 -butanol, 2-butanol, butane, butyl acetate, ethyl formate, formic acid, isobutyl acetate, isopropyl acetate, methyl acetate, 3 -methyl- 1 -butanol, methylethyl ketone, 2-methyl- 1 -propanol, 1-pentanol, 1 -propanol, propane, propyl acetate, trim ethyl amine, dimethylacetamide, tetrahydrofuran, dimethylformamide, 1,1,2- trichlorotrifluoroethane, or a combination thereof.

[00040] In some embodiments, the solid particles are substantially free of a pesticide. In some embodiments, the pesticide is aldicarb, carbofuran, chlordane, chlorfenapyr, chlorpyrifos, coumaphos, daminozide, ddvp (dichlorvos), dimethoate, ethoprop(hos), etofenprox, fenoxycarb, fipronil, imazalil, methiocarb, methyl parathion, mevinphos, paclobutrazol, propoxur, spiroxamine, thiacloprid, abamectin, acephate, acequinocyl, acetamiprid, azoxystrobin, bifenazate, bifenthrin, boscalid, captan, carbaryl, chlorantraniliprole, clofentezine, cyfluthrin, cypermethrin, diazinon, dimethomorph, etoxazole, fenhexamid, fenpyroximate, flonicamid, fludioxonil, hexythiazox, imidacloprid, kresoxim-methyl, malathion, metalaxyl, methomyl, myclobutanil, naled, oxamyl, pentachloronitrobenzene, permethrin, phosmet, piperonylbutoxide, prallethrin, propiconazole, pyrethrins, pyridaben, spinetoram, spinosad, spiromesifen, spirotetramat, tebuconazole, thiamethoxam, or trifloxystrobin, or a combination thereof. In some embodiments, the pesticide is diazinon, myclobutanil, tebuconazole, or trifloxystrobin, or a combination thereof.

[00041] In some embodiments, the solid particles have a potency of greater than 75%. In some embodiments, the solid particles have a potency of greater than 80%. In some embodiments, the solid particles have a potency of greater than 85%.

[00042] In some embodiments, the method produces at least about 100 g of solid particles comprising THCA per kg of the oil. In some embodiments, the method produces at least about 200 g of solid particles comprising THCA per kg of the oil. In some embodiments, the method produces at least about 250 g of solid particles comprising THCA per kg of the oil. In some embodiments, the method produces at least about 300 g of solid particles comprising THCA per kg of the oil. In some embodiments, the method produces at least about 350 g of solid particles comprising THCA per kg of the oil. In some embodiments, the method produces at least about 400 g of solid particles comprising THCA per kg of the oil. In some embodiments, the method produces at least about 500 g of solid particles comprising THCA per kg of the oil.

[00043] In some embodiments the method produces about 20 to about 70% of the solid particles comprising THCA per weight of the oil. In some embodiments the method produces about 20 to about 50% of the solid particles comprising THCA per weight of the oil. In some embodiments the method produces about 20 to about 40% of the solid particles comprising THCA per weight of the oil. In some embodiments the method produces about 30 to about 40% of the solid particles comprising THCA per weight of the oil.

[00044] In some embodiments, the oil comprises about 50% of THCA by weight. In some embodiments, the oil comprises about 60% of THCA by weight. In some embodiments, the oil comprises about 70% of THCA by weight. In some embodiments, the oil comprises about 80% of THCA by weight.

[00045] In some embodiments, the method further comprises blending the solid particles comprising THCA. [00046] In some embodiments, the method further comprises processing the solid particles comprising THCA through a sieve.

[00047] In some embodiments, about 50% to about 90% of the solid particles are characterized as having a sieve size of about 0.6 mm to about 1.7 mm. In some embodiments, about 50% to about 80% of the solid particles are characterized as having a sieve size of about 0.6 mm to about 1.7 mm. In some embodiments, about 60% to about 90% of the solid particles are characterized as having a sieve size of about 0.6 mm to about 1.7 mm. In some embodiments, about 60% to about 80% of the solid particles are characterized as having a sieve size of about 0.6 mm to about 1.7 mm. In some embodiments, about 70% to about 80% of the solid particles are characterized as having a sieve size of about 0.6 mm to about 1.7 mm. In some embodiments, about 70% to about 90% of the solid particles are characterized as having a sieve size of about 0.6 mm to about 1.7 mm. In some embodiments, about 50% of the solid particles are characterized as having a sieve size of about 0.6 mm to about 1.7 mm.

In some embodiments, about 55% of the solid particles are characterized as having a sieve size of about 0.6 mm to about 1.7 mm. In some embodiments, about 60% of the solid particles are characterized as having a sieve size of about 0.6 mm to about 1.7 mm. In some embodiments, about 65% of the solid particles are characterized as having a sieve size of about 0.6 mm to about 1.7 mm. In some embodiments, about 70% of the solid particles are characterized as having a sieve size of about 0.6 mm to about 1.7 mm. In some embodiments, about 75% of the solid particles are characterized as having a sieve size of about 0.6 mm to about 1.7 mm. In some embodiments, about 80% of the solid particles are characterized as having a sieve size of about 0.6 mm to about 1.7 mm. In some embodiments, about 85% of the solid particles are characterized as having a sieve size of about 0.6 mm to about 1.7 mm.

In some embodiments, about 90% of the solid particles are characterized as having a sieve size of about 0.6 mm to about 1.7 mm.

[00049] In some embodiments, the solid particles are characterized as having a sieve size of about 0.4 mm to about 0.6 mm. In some embodiments, the solid particles are characterized as having a sieve size of about 0.3 mm to about 0.4 mm. In some embodiments, the solid particles are characterized as having a sieve size of less than or equal to about 0.3 mm.

[00052] In another aspect, provided herein is a method of producing crystalline solid particles comprising tetrahydrocannabinolic acid (THCA), the method comprising: (i) contacting solid particles produced by any of the methods described herein with a solvent to produce a mixture; (ii) evaporating the mixture of step (i) to produce a saturated solution; (iii) incubating the saturated solution of step (ii) to produce crystalline solid particles comprising THCA and a mother liquor; and (iv) separating the crystalline solid particles from the mother liquor.

[00053] In another aspect, provided herein is a method of producing crystalline solid particles comprising tetrahydrocannabinolic acid (THCA), the method comprising: (i) contacting solid particles comprising at least 80% of THCA by weight with a solvent to produce a mixture; (ii) evaporating the mixture of step (i) to produce a saturated solution; and (iii) incubating the saturated solution of step (ii) to produce crystalline solid particles comprising THCA and a mother liquor; and (iv) separating the crystalline solid particles from the mother liquor.

[00054] In another aspect, provided herein is a method of producing crystalline solid particles comprising tetrahydrocannabinolic acid (THCA), the method comprising: (i) contacting solid particles comprising at least 90% of THCA by weight with a solvent to produce a mixture; (ii) evaporating the mixture of step (i) to produce a saturated solution; and (iii) incubating the saturated solution of step (ii) to produce crystalline solid particles comprising THCA and a mother liquor; and (iv) separating the crystalline solid particles from the mother liquor.

[00055] In another aspect, provided herein is a method of producing crystalline solid particles comprising tetrahydrocannabinolic acid (THCA), the method comprising: (i) contacting solid particles comprising at least 95% of THCA by weight with a solvent to produce a mixture; (ii) evaporating the mixture of step (i) to produce a saturated solution; and (iii) incubating the saturated solution of step (ii) to produce crystalline solid particles comprising THCA and a mother liquor; and (iv) separating the crystalline solid particles from the mother liquor.

[00056] In some embodiments, the crystalline solid particles consist essentially of THCA. In some embodiments, the crystalline solid particles comprises at least 99% of THCA by weight. In some embodiments, the crystalline solid particles consist essentially of THCA.

[00057] In some embodiments, the crystalline solid particles are substantially free of a pesticide. In some embodiments, the pesticide is aldicarb, carbofuran, chlordane, chlorfenapyr, chlorpyrifos, coumaphos, daminozide, ddvp (dichlorvos), dimethoate, ethoprop(hos), etofenprox, fenoxycarb, fipronil, imazalil, methiocarb, methyl parathion, mevinphos, paclobutrazol, propoxur, spiroxamine, thiacloprid, abamectin, acephate, acequinocyl, acetamiprid, azoxystrobin, bifenazate, bifenthrin, boscalid, captan, carbaryl, chlorantraniliprole, clofentezine, cyfluthrin, cypermethrin, diazinon, dimethomorph, etoxazole, fenhexamid, fenpyroximate, flonicamid, fludioxonil, hexythiazox, imidacloprid, kresoxim-methyl, malathion, metalaxyl, methomyl, myclobutanil, naled, oxamyl, pentachloronitrobenzene, permethrin, phosmet, piperonylbutoxide, prallethrin, propiconazole, pyrethrins, pyridaben, spinetoram, spinosad, spiromesifen, spirotetramat, tebuconazole, thiamethoxam, or trifloxystrobin, or a combination thereof. In some embodiments, the pesticide is diazinon, myclobutanil, tebuconazole, or trifloxystrobin, or a combination thereof.

[00058] In some embodiments, the solid particles have a potency of greater than 75%. In some embodiments, the solid particles have a potency of greater than 80%. In some embodiments, the solid particles have a potency of greater than 85%.

[00059] In some embodiments, the methods further comprise modulating the temperature (e.g., warming or cooling) of the mixture of step (i). In some embodiments, the methods further comprise modulating the temperature (e.g., warming or cooling) of the saturated solution of step (ii). In some embodiments, modulating the temperature induces crystalline growth.

[00060] In some embodiments, the saturated solution is a super saturated solution. [00061] In certain embodiments, the methods further comprise adding a seed crystal of THCA to the saturated solution.

[00062] In some embodiments, the saturated solution is incubated for at least one week. In some embodiments, the saturated solution is incubated for at least two weeks. In some embodiments, the saturated solution is incubated for at least three weeks. In some embodiments, the saturated solution is incubated for about six weeks. In some embodiments, the saturated solution is incubated for more than six weeks.

[00063] In some embodiments, the solvent has a polarity index range of 0.0 to 5.0, 0.0 to 4.0, 0.0 to 3.0, 0.0 to 2.0, or 0.0 to 1.0. For example, the solvent has a polarity index of 0.0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or 1.0. In some embodiments, the solvent has a polarity index below 1.0. In some embodiments, the solvent has a dielectric constant of 1,5 to 20.0, 1.5 to 15.0, 1.5 to 10.0, 1.5 to 5.0, or 1.5 to 2.0. For example, the solvent has a dielectric constant of about 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, or 2.5. In some embodiments, the solvent has a boiling point of about 25 °C to about 100 °C, e.g., about 25 °C to about 80^C'C, about 25^C'C to about 60^C'C, about 25^C'C to about 40^C'C, about 30^C'C to about 60 °C, or about 30 °C to 40 °C. Exemplary solvents include, but are not limited to, pentane, hexane, heptane, isopentane, isobutane, cyclopentane, cyclohexane, iso-octane, n-butylchloride, acetonitrile, methanol, ethanol, isopropanol, dimethyl sulfoxide, acetone, ethyl acetate, diethyl ether, tert-butyl methyl ether, water, acetic acid, anisole, 1 -butanol, 2-butanol, butane, butyl acetate, ethyl formate, formic acid, isobutyl acetate, isopropyl acetate, methyl acetate,

3 -methyl- 1 -butanol, methylethyl ketone, 2-methyl-l -propanol, l-pentano!, 1-propanol, propane, propyl acetate, trimethylamine, dimethylacetamide, tetrahydrofuran, dimethylformamide, 1,1,2-trichlorotrifluoroethane, or a combination thereof. In some embodiments, the solvent is n-pentane. For example, n-pentane has a boiling point of about 36 °C, a dielectric constant of about 1.8, and a polarity index of 0.0. In some embodiments, the solvent may be a solvent or a combination of solvents that have a boiling point, a dielectric constant, or a polarity index about that of n-pentane,

[00064] In some embodiments, the solvent has a polarity index less than 1, including but not limited to hexane, heptane, petroleum ether, and 2,2,4-trimethylpentane. The present methods may comprise crystallization steps and washing steps. Exemplary solvents for crystallization steps described herein include, but are not limited to, pentane, hexane, heptane, isopentane, isobutane, cyclopentane, cyclohexane, iso-octane, n-butylchloride, or a combination thereof. In some embodiments, a solvent for a crystallization step described herein is a solvent having a polarity index less or equal to 1 . Exemplary solvents for washing steps described herein include, but are not limited to acetonitrile, methanol, ethanol, isopropanol, dimethyl sulfoxide, acetone, ethyl acetate, diethyl ether, tert-butyl methyl ether, water, acetic acid, anisole, I -butanol, 2-butanol, butane, butyl acetate, ethyl formate, formic acid, isobutyl acetate, isopropyl acetate, methyl acetate, 3 -methyl- 1 -butanol, methylethyl ketone, 2-methyl -1 -propanol, 1-pentanol, 1 -propanol, propane, propyl acetate, trimethylamine, dimethylacetamide, tetrahydrofuran, dimethylformamide, 1,1,2- trichlorotrifluoroethane, or a combination thereof.

[00065] In some embodiments, the methods further comprise crushing the crystalline solid particles by a mechanical force, e.g., to produce crystalline solid particles smaller in size.

[00066] In some embodiments, the methods further comprise blending the crystalline solid particles comprising THCA.

[00067] In some embodiments, the methods further comprise processing the crystalline solid particles comprising THCA through a sieve.

[00070] In some embodiments, the crystalline solid particles are characterized as having a sieve size of about 0.4 mm to about 0.6 mm. In some embodiments, the crystalline solid particles are characterized as having a sieve size of about 0.3 mm to about 0.4 mm. In some embodiments, the crystalline solid particles are characterized as having a sieve size of less than or equal to about 0.3 mm.

[00073] In some embodiments, the crystalline solid particles consist essentially of THCA. In some embodiments, the crystalline solid particles comprises at least 99% of THC A by weight.

[00074] In some embodiments, the crystalline solid particles are substantially free of a pesticide. In some embodiments, the pesticide is aldicarb, carbofuran, chlordane, chlorfenapyr, chlorpyrifos, coumaphos, daminozide, ddvp (dichlorvos), dimethoate, ethoprop(hos), etofenprox, fenoxycarb, fipronil, imazalil, methiocarb, methyl parathion, mevinphos, paclobutrazol, propoxur, spiroxamine, thiacloprid, abamectin, acephate, acequinocyl, acetamiprid, azoxystrobin, bifenazate, bifenthrin, boscalid, captan, carbaryl, chlorantraniliprole, clofentezine, cyfluthrin, cypermethrin, diazinon, dimethomorph, etoxazole, fenhexamid, fenpyroximate, flonicamid, fludioxonil, hexythiazox, imidacloprid, kresoxim-methyl, malathion, metalaxyl, methomyl, myclobutanil, naled, oxamyl, pentachloronitrobenzene, permethrin, phosmet, piperonylbutoxide, prallethrin, propiconazole, pyrethrins, pyridaben, spinetoram, spinosad, spiromesifen, spirotetramat, tebuconazole, thiamethoxam, or trifloxystrobin, or a combination thereof. In some embodiments, the pesticide is diazinon, myclobutanil, tebuconazole, or trifloxystrobin, or a combination thereof.

[00075] In some embodiments, the solid particles have a potency of greater than 75%. In some embodiments, the solid particles have a potency of greater than 80%. In some embodiments, the solid particles have a potency of greater than 85%.

[00076] In another aspect, provided herein is a method of producing crystalline solid particles comprising tetrahydrocannabinolic acid (THCA), the method comprising: (i) contacting solid particles produced by any of the methods described herein with a solvent to produce a first mixture; (ii) evaporating the first mixture of step (i) to produce a mixture of crystalline solid particles comprising THCA and a mother liquor; and (iii) separating the crystalline solid particles from the mother liquor.

[00077] In another aspect, provided herein is a method of producing crystalline solid particles comprising tetrahydrocannabinolic acid (THCA), the method comprising: (i) contacting solid particles comprising at least 80% of THCA by weight with a solvent to produce a first mixture; (ii) evaporating the first mixture of step (i) to produce a mixture of crystalline solid particles comprising THCA and a mother liquor; and (iii) separating the crystalline solid particles from the mother liquor.

[00078] In another aspect, provided herein is a method of producing crystalline solid particles comprising tetrahydrocannabinolic acid (THCA), the method comprising: (i) contacting solid particles comprising at least 85% of THCA by weight with a solvent to produce a first mixture; (ii) evaporating the first mixture of step (i) to produce a mixture of crystalline solid particles comprising THCA and a mother liquor; and (iii) separating the crystalline solid particles from the mother liquor.

[00079] In another aspect, provided herein is a method of producing crystalline solid particles comprising tetrahydrocannabinolic acid (THCA), the method comprising: (i) contacting solid particles comprising at least 90% of THCA by weight with a solvent to produce a first mixture; (ii) evaporating the first mixture of step (i) to produce a mixture of crystalline solid particles comprising THCA and a mother liquor; and (iii) separating the crystalline solid particles from the mother liquor.

[00080] In another aspect, provided herein is a method of producing crystalline solid particles comprising tetrahydrocannabinolic acid (THCA), the method comprising: (i) contacting solid particles comprising at least 95% of THCA by weight with a solvent to produce a first mixture; (ii) evaporating the first mixture of step (i) to produce a mixture of crystalline solid particles comprising THCA and a mother liquor; and (iii) separating the crystalline solid particles from the mother liquor.

[00081] In some embodiments, the method further comprises modulating the temperature of the first mixture of step (i). In some embodiments, the modulating comprises heating the first mixture of step (i) at a temperature of about 30 °C to about 40 °C and then cooling the mixture to a temperature less than 30 °C. In some embodiments, the modulating comprises heating the first mixture of step (i) at a temperature of about 25 °C to about 40 °C and then cooling the mixture to a temperature less than 25 °C. In some embodiments, the modulating comprises heating the first mixture of step (i) at a temperature of about 25 °C to about 35 °C and then cooling the mixture to a temperature less than 30 °C. In some embodiments, the modulating comprises heating the first mixture of step (i) at a temperature of about 30 °C to about 35 °C and then cooling the mixture to a temperature less than 30 °C. In some embodiments, the modulating of the temperature of the first mixture is achieved by modulating the temperature of a reactor jacket.

[00084] In some embodiments, the method further comprises further comprising agitating the second mixture of step (ii).

[00085] In some embodiments, the evaporating of step (ii) occurs over a time period of at least 1 day. In some embodiments, the evaporating of step (ii) occurs over a time period of at least 5 days. In some embodiments, the evaporating of step (ii) occurs over a time period of at least 10 days. In some embodiments, the evaporating of step (ii) occurs over a time period of about 15 days. In some embodiments, the evaporating of step (ii) occurs over a time period of about 17 days. In some embodiments, the evaporating of step (ii) occurs over a time period of about 20 days.

[00086] In some embodiments, the method further comprises washing the crystalline solid particles of step (iii) with a solvent. In some embodiments, the washing is repeated at least once.

[00089] In some embodiments, the solvent has a polarity index less than 1, including but not limited to hexane, heptane, petroleum ether, and 2,2,4-trimethylpentane. The present methods may comprise crystallization steps and washing steps. Exemplary solvents for crystallization steps described herein include, but are not limited to, pentane, hexane, heptane, isopentane, isobutane, cyclopentane, cyclohexane, iso-octane, n-butylchloride, or a combination thereof. In some embodiments, a solvent for a crystallization step described herein is a solvent having a polarity index less or equal to 1. Exemplary solvents for washing steps described herein include, but are not limited to acetonitrile, methanol, ethanol, isopropanol, dimethyl sulfoxide, acetone, ethyl acetate, diethyl ether, tert-butyl methyl ether, water, acetic acid, anisoie, 1 -butanol, 2-butanol, butane, butyl acetate, ethyl formate, formic acid, isobutyl acetate, isopropyl acetate, methyl acetate, 3-methyl-l -butanol, methylethyl ketone, 2-methyl -1 -propanol, 1-pentanol, l~propanol, propane, propyl acetate, trimethylamine, dimethylacetamide, tetrahydrofuran, dimethylformamide, 1,1,2- trichlorotrifluoroethane, or a combination thereof. [00090] In some embodiments, the solid particles are substantially free of a pesticide.

In some embodiments, the pesticide is aldicarb, carbofuran, chlordane, chlorfenapyr, chlorpyrifos, coumaphos, daminozide, ddvp (dichlorvos), dimethoate, ethoprop(hos), etofenprox, fenoxycarb, fipronil, imazalil, methiocarb, methyl parathion, mevinphos, paclobutrazol, propoxur, spiroxamine, thiacloprid, abamectin, acephate, acequinocyl, acetamiprid, azoxystrobin, bifenazate, bifenthrin, boscalid, captan, carbaryl, chlorantraniliprole, clofentezine, cyfluthrin, cypermethrin, diazinon, dimethomorph, etoxazole, fenhexamid, fenpyroximate, flonicamid, fludioxonil, hexythiazox, imidacloprid, kresoxim-methyl, malathion, metalaxyl, methomyl, myclobutanil, naled, oxamyl, pentachloronitrobenzene, permethrin, phosmet, piperonylbutoxide, prallethrin, propiconazole, pyrethrins, pyridaben, spinetoram, spinosad, spiromesifen, spirotetramat, tebuconazole, thiamethoxam, or trifloxystrobin, or a combination thereof. In some embodiments, the pesticide is diazinon, myclobutanil, tebuconazole, or trifloxystrobin, or a combination thereof.

[00091] In some embodiments, the methods further comprise crushing the crystalline solid particles by a mechanical force, e.g., to produce crystalline solid particles smaller in size,

[00092] In some embodiments, the methods further comprise blending the crystalline solid particles comprising THCA.

[00093] In some embodiments, the methods further comprise processing the crystalline solid particles comprising THCA through a sieve.

[00096] In some embodiments, the crystalline solid particles are characterized as having a sieve size of about 0.4 mm to about 0.6 mm. In some embodiments, the crystalline solid particles are characterized as having a sieve size of about 0.3 mm to about 0.4 mm. In some embodiments, the crystalline solid particles are characterized as having a sieve size of less than or equal to about 0.3 mm.

[000100] In some embodiments, the crystalline solid particles are substantially free of a pesticide. In some embodiments, the pesticide is aldicarb, carbofuran, chlordane, chlorfenapyr, chlorpyrifos, coumaphos, daminozide, ddvp (dichlorvos), dimethoate, ethoprop(hos), etofenprox, fenoxycarb, fipronil, imazalil, methiocarb, methyl parathion, mevinphos, paclobutrazol, propoxur, spiroxamine, thiacloprid, abamectin, acephate, acequinocyl, acetamiprid, azoxystrobin, bifenazate, bifenthrin, boscalid, captan, carbaryl, chlorantraniliprole, clofentezine, cyfluthrin, cypermethrin, diazinon, dimethomorph, etoxazole, fenhexamid, fenpyroximate, flonicamid, fludioxonil, hexythiazox, imidacloprid, kresoxim-methyl, malathion, metalaxyl, methomyl, myclobutanil, naled, oxamyl, pentachloronitrobenzene, permethrin, phosmet, piperonylbutoxide, prallethrin, propiconazole, pyrethrins, pyridaben, spinetoram, spinosad, spiromesifen, spirotetramat, tebuconazole, thiamethoxam, or trifloxystrobin, or a combination thereof. In some embodiments, the pesticide is diazinon, myclobutanil, tebuconazole, or trifloxystrobin, or a combination thereof.

[000101] In some embodiments, the solid particles have a potency of greater than 75%. In some embodiments, the solid particles have a potency of greater than 80%. In some embodiments, the solid particles have a potency of greater than 85%.

[000102] Embodiments of the present disclosure may be described by reference to FIG. 1

[000103] FIG. 1 shows a flow diagram for an exemplary method 100 for preparing THCA solid particles (e.g., substantially crystalline THCA solid particles). Method 100 comprises the following steps: contacting an oil comprising a plurality of cannabinoids with a solvent (e.g., n-pentane) to produce a mixture (step 101); warming the mixture of step 101 to about 30 °C to form a homogenous solution (step 102); cooling the homogenous solution of step 102 to precipitate THCA from the solution to form a THCA isolate and a mother liquor (step 103); separating the THCA isolate from the mother liquor (step 104); and washing the THCA isolate with a solvent (e.g., n-pentane) (step 105). The method may further comprise step 106 which comprises contacting (e.g., re-suspending) the THCA isolate with a solvent (e.g., n-pentane) for crystallization. [000104] In some embodiments, step 101 may occur inside a mixing vessel. In some embodiments, the solvent (e.g., n-pentane) is warmed to about 20 to about 40 °C, e.g., about 25 to about 35 °C, e.g,, about 30 °C.

[000105] In some embodiments, step 102 comprises mixing the mixture of step 101 for at least 8 hours (e.g., about 8 hours, about 9 hours, about 10 hours, about 11 hours, about 12 hours, about 13 hours, about 14 hours, about 15 hours, about 16 hours, about 17 hours, about 18 hours, about 20 hours, about 21 hours, about 22 hours, about 23 hours, about 24 hours). In some embodiments, step 102 comprises mixing the mixture of step 101 for about 12 hours. [000106] In some embodiments, step 102 further comprises bleeding air into the mixing vessel to eject any settled solids back into solution.

[000107] In some embodiments, step 103 may occur inside a reactor vessel. In some embodiments, the reactor vessel is equipped with a circulation loop and a heater. In some embodiments, the solution is cooled at a rate of about -1 to about -20 °C/hour (e.g., -1 ° C/hour, ~2 °C/hour, -3 °C/hour, -4 ° C/hour, -5 °C/hour, ~6 ° C/hour, -7 °C/hour, -8 ° C/hour, - 9 °C/hour, -10 °C/hour, -11 °C/hour, -12 °C/hour, -13 °C/hour, -14 °C/hour, -15 °C/hour). [000108] In some embodiments, step 103 further comprises agitating the solution,

[000109] In some embodiments, step 104 comprises pumping the mother liquor back to the mixing vessel (e.g., to retain the non-THCA fractions).

[000110] In some embodiments, step 105 comprises washing the THCA isolate with a solvent (e.g., n-pentane) in the reactor vessel. In some embodiments, the washing is repeated more than once. In some embodiments, the wash is pumped to the mixing vessel with the mother liquor.

[000111] In some embodiments, the method further compri ses heating the reactor vessel to about 30 °C thereby heating the solid particles to remove residual solvent (e.g., n-pentane). [000112] In some embodiments, step 106 comprises contacting (e.g., re-suspending) the THCA isolate with a solvent (e.g., n-pentane) for crystallization. In some embodiments, the THCA isolate is contacted with a solvent for at least one week (e.g., at least two weeks, at least 6 weeks, at least 1 month),

[000113] In some embodiments, the solvent has a polarity index range of 0.0 to 5.0, 0.0 to 4.0, 0.0 to 3.0, 0.0 to 2.0, or 0.0 to 1.0. For example, the solvent has a polarity index of 0.0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or 1.0. In some embodiments, the solvent has a polarity index below 1.0. In some embodiments, the solvent has a dielectric constant of 1.5 to 20,0, 1,5 to 15,0, 1.5 to 10.0, 1.5 to 5.0, or 1.5 to 2,0. For example, the solvent has a dielectric constant of about 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, or 2.5. In some embodiments, the solvent has a boiling point of about 25 °C to about 100 °C, e.g., about 25 °C to about 80^C'C, about 25^C'C to about 60^C'C, about 25^C'C to about 40^C'C, about 30^C'C to about 60 °C, or about 30 °C to 40 °C. Exemplary solvents include, but are not limited to, pentane, hexane, heptane, isopentane, isobutane, cyclopentane, cyclohexane, iso-octane, n-butylchloride, acetonitrile, methanol, ethanol, isopropanol, dimethyl sulfoxide, acetone, ethyl acetate, diethyl ether, tert-butyl methyl ether, water, acetic acid, anisole, 1 -butanol, 2-butanol, butane, butyl acetate, ethyl formate, formic acid, isobutyl acetate, isopropyl acetate, methyl acetate,

3 -methyl- 1 -butanol, methylethyl ketone, 2-methyl- 1 -propanol, 1-pentanol, 1-propanol, propane, propyl acetate, trimethylamine, dimethylacetamide, tetrahydrofuran, dimethylformamide, 1,1,2-trichlorotrifluoroethane, or a combination thereof. In some embodiments, the solvent is n-pentane. For example, n-pentane has a boiling point of about 36 °C, a dielectric constant of about 1.8, and a polarity index of 0.0. In some embodiments, the solvent may be a solvent or a combination of solvents that have a boiling point, a dielectric constant, or a polarity index about that of n-pentane.

[000114] In some embodiments, the solvent has a polarity index less than 1, including but not limited to hexane, heptane, petroleum ether, and 2,2,4-trimethylpentane. The present methods may comprise crystallization steps and washing steps. Exemplary solvents for crystallization steps described herein include, but are not limited to, pentane, hexane, heptane, isopentane, isobutane, cyclopentane, cyclohexane, iso-octane, n-butylchloride, or a combination thereof. In some embodiments, a solvent for a crystallization step described herein is a solvent having a polarity index less or equal to 1. Exemplary solvents for washing steps described herein include, but are not limited to acetonitrile, methanol, ethanol, isopropanol, dimethyl sulfoxide, acetone, ethyl acetate, diethyl ether, tert-butyl methyl ether, water, acetic acid, anisole, 1 -butanol, 2-butanol, butane, butyl acetate, ethyl formate, formic acid, isobutyl acetate, isopropyl acetate, methyl acetate, 3 -methyl- 1 -butanol, methylethyl ketone, 2-m ethyl -1 -propanol, 1-pentanol, 1-propanol, propane, propyl acetate, trimethylamine, dimethylacetamide, tetrahydrofuran, dimethylformamide, 1,1,2- trichlorotrifluoroethane, or a combination thereof.

[000115] In some embodiments, the methods described herein improves the stability of crystalline THCA (e.g,, preventing degradation of crystalline THCA) relative to crystalline THCA obtained from conventional extraction methods. In some embodiments, the method produces white, powdery solid particles (e.g., crystalline solid particles) comprising THCA, In some embodiments, the method produces solid particles uniform in size. Techniques used to determine particle size and particle size distribution include, but are not limited to, dynamic image analysis, static laser light scatering, dynamic light scattering, and sieve analysis.

[000118] In some embodiments, the solid particles have a potency of greater than 75%. In some embodiments, the solid particles have a potency of greater than 80%. In some embodiments, the solid particles have a potency of greater than 85%.

[000119] In an aspect, provided herein is a method of re-crystallizing solid particles comprising THCA (e g., crystalline solid particles ) in a solvent (e.g., n-pentane) to produce large, periodic crystals of THCA. Key advantages of this method includes using highly pure THCA isolates (e.g., crystalline solid particles) as a feedstock to create large, periodic crystals of THCA and reduces process time (e.g., re-crystallization time) compared to alternative feedstock (e.g., a crude oil comprising THCA).

[000120] In some embodiments, the methods further comprise modulating the temperature (e.g., warming or cooling) of the mixture produced by contacting (e.g., dissolving) solid particles comprising THCA (e.g., produced by any of the methods described herein) with a solvent. In some embodiments, the methods further comprise modulating the temperature (e.g., warming or cooling) of the saturated solution of THCA. In some embodiments, modulating the temperature of the saturated solution induces crystalline growth.

[000121] In some embodiments, the methods further comprise adding a seed crystal of THCA to the saturated solution.

[000122] In another aspect, provided herein are crystalline solid particles comprising tetrahydrocannabinolic acid (THCA) obtained from any of the methods described herein. In another aspect, provided herein are crystalline solid particles comprising tetrahydrocannabinolic acid (THCA) obtained from any of the methods described herein, wherein the crystalline solid particles comprises at least 90% of THCA by weight. In another aspect, provided herein are crystalline solid particles comprising tetrahydrocannabinolic acid (THCA) obtained from any of the methods described herein, wherein the crystalline solid particles comprises at least 95% of THCA by weight. In another aspect, provided herein are crystalline solid particles comprising tetrahydrocannabinolic acid (THCA) obtained from any of the methods described herein, wherein the crystalline solid particles comprises at least 99% of THCA by weight.

[000123] In some embodiments, the present disclosure, in part, is represented by embodiments (l)-(82):

[000124] (1): A method for producing solid particles comprising tetrahydrocannabinolic acid (THCA), the method comprising: (a) contacting an oil comprising a plurality of cannabinoids with a solvent to produce a mixture; (b) warming the mixture of step (a) to about 30 °C to form a homogenous solution; (c) cooling the homogenous solution of step (b) to precipitate THCA from the solution to form a THCA isolate and a mother liquor; (d) separating the THCA isolate from the mother liquor; and (e) optionally, washing the THCA isolate with a solvent to produce solid particles comprising THCA.

[000125] (2): The method of embodiment (1), wherein the cooling in step (c) occurs in a vessel comprising a circulation loop. [000126] (3): The method of embodiment (1) or (2), wherein the cooling in step (c) further comprises agitating the solution.

[000127] (4): The method of any one of embodiments (l)-(3), wherein the solution is cooled in step (c) at a rate of about -10 °C/hour.

[000128] (5): The method of any one of embodiments (l)-(4), wherein the solution is cooled to about -30 °C in step (c).

[000129] (6): The method of any one of embodiments (l)-(5), further comprising heating the solid particles of step (e) at about 30 °C to remove residual solvent.

[000130] (7): The method of any one of embodiments (l)-(6), wherein the solid particles are substantially crystalline.

[000131] (8): The method of any one of embodiments (l)-(7), wherein the solid particles comprises at least 85% of THCA by weight.

[000132] (9): The method of any one of embodiments (l)-(7), wherein the solid particles comprises at least 90% of THCA by weight

[000133] (10): The method of any one of embodiments (l)-(7), wherein the solid particles comprises at least 95% of THCA by weight.

[000134] (11): The method of any one of embodiments (l)-(7), wherein the solid particles comprises at least 99% of THCA by weight.

[000135] (12): The method of any one of embodiments (l)-(7), wherein the solid particles comprises 99% of THCA by weight.

[000136] (13): The method of any one of embodiments (1)-(12), wherein the oil further comprises a plurality of terpenoids.

[000137] (14): The method of embodiment (13), wherein the plurality of terpenoids comprises one or more terpenoids selected from the group consisting of alpha thujene, alpha pinene, camphene, beta pinene, beta myrcene, p-mentha- 1,5-diene, 3-carene, alpha terpinene, p-cymene, D-limonene, beta ocimene, terpinolene, linalool, fenchol, trans-2-pinanol, alpha terpineol, beta caryophyllene, gamma elemene, alpha bergamotene, humulene, caryophyllene oxide, 4,8,12-Tetradecatrienal, beta selinene, alpha selinene, alpha bulnesene, alpha famesene, beta maaliene, (4aR,8aS)-4a-Methyl-l-methylene-7-(propan-2- ylidene)decahydronaphthalene, cis nerolidol, trans nerolidol, Selina-3, 7(1 l)-diene, trans alpha bisabolene, beta guaiene, epi-gamma-eudesmol, longifolene, cis beta guaiene, aromandendrene, alpha eudesmol, alpha bulnesene, alpha bisabolol, juniper camphor, and beta bisabolene. [000138] (15): The method of embodiment (13) or (14), wherein the plurality of cannabinoids comprises one or more cannabinoids selected from the group consisting of tetrahydrocannabinolic acid, tetrahydrocannabinol, cannabigerol, cannabichromene, tetrahydrocannabivarin, cannabidiol, cannabinol, cannabigerivarin, tetrahydrocannabivarian, cannabidivarin, cannabichromevarin, and derivatives thereof.

[000139] (16): The method of any one of embodiments (l)-(l 5), wherein the oil is extracted from a feedstock comprising a plant of the genus Cannabis.

[000140] (17). The method of embodiment (16), wherein the plant of the genus

Cannabis is Cannabis sativa or Cannabis indica.

[000141] (18): The method of any one of embodiments (1)-(17), further comprising collecting the mother liquor.

[000142] (19): The method of any one of embodiments (l)-(l 8), further comprising collecting the solvent wash of step (e).

[000143] (20): The method of any one of embodiments (l)-(l 9), wherein the washing step (e) is repeated at least once.

[000144] (21): The method of any one of embodiments (l)-(20), further comprising recrystallizing the solid particles in a solvent.

[000145] (22): The method of any one of embodiments (1)-(21), wherein the solvent is n-pentane.

[000146] (23): The method of any one of embodiments (l)-(22), wherein the solid particles are substantially free of a pesticide.

[000147] (24): The method of embodiment (23), wherein the pesticide is diazinon, myclobutanil, tebuconazole, or trifloxystrobin, or a combination thereof.

[000148] (25): The method of any one of embodiments (l)-(24), wherein the method produces at least about 200 g of solid particles comprising THCA per kg of the oil.

[000149] (26): The method of any one of embodiments (l)-(24), wherein the method produces about 300 g of solid particles comprising THCA per kg of the oil.

[000150] (27): The method of any one of embodiments (l)-(24), wherein the method produces about 350 g of solid particles comprising THCA per kg of the oil.

[000151] (28): The method of any one of embodiments (l)-(27), wherein the oil comprises about 80% of THCA by weight.

[000152] (29): The method of any one of embodiments (l)-(28), further comprising blending the solid particles comprising THCA. [000153] (30): The method of any one of embodiments (l)-(29), further comprising processing the solid particles of THCA through a sieve.

[000154] (31): The method of any one of embodiments (l)-(30), wherein about 70% to about 80% of the solid particles are characterized as having a sieve size of about 0.6 mm to about 1.7 mm.

[000155] (32): The method of any one of embodiments (l)-(30), wherein about 20% to about 30% of the solid particles are characterized as having a sieve size of less than or equal to about 0.6 mm.

[000156] (33): The method of embodiment (32), wherein the solid particles are further characterized as having a sieve size of about 0.4 mm to about 0.6 mm.

[000157] (34): The method of embodiment (32), wherein the solid particles are further characterized as having a sieve size of about 0.3 mm to about 0.4 mm.

[000158] (35): The method of embodiment (32), wherein the solid particles are further characterized as having a sieve size of less than or equal to about 0.3 mm.

[000159] (36): The method of any one of embodiments (l)-(35), wherein the method produces about 15% to about 55% of solid particles characterized as having a sieve size of about 0.6 mm to about 1.7 mm per kg of total solid particles.

[000160] (37): The method of any one of embodiments (l)-(36), wherein the method produces about 30% of solid particles characterized as having a sieve size of about 0.6 mm to about 1.7 mm per kg of total solid particles.

[000161] (38): The method of any one of embodiments (l)-(37), wherein the method produces about 1% to about 70% of solid particles characterized as having a sieve size of less than or equal to about 0.6 mm per kg of total solid particles.

[000162] (39): The method of any one of embodiments (l)-(38), wherein the method produces about 30% of solid particles characterized as having a sieve size of less than or equal to about 0.6 mm per kg of total solid particles.

[000163] (40): A method of producing crystalline solid particles comprising tetrahydrocannabinolic acid (THCA), the method comprising: (i) contacting solid particles produced by any one of embodiments (l)-(39) with a solvent to produce a mixture; (ii) evaporating the mixture of step (i) to produce a saturated solution; (iii) incubating the saturated solution of step (ii) to produce crystalline solid particles comprising THCA and a mother liquor; and (iv) separating the crystalline solid particles from the mother liquor. [000164] (41): A method of producing crystalline solid particles comprising tetrahydrocannabinolic acid (THCA), the method comprising: (i) contacting solid particles comprising at least 95% of THCA by weight with a solvent to produce a mixture; (ii) evaporating the mixture of step (i) to produce a saturated solution; and (iii) incubating the saturated solution of step (ii) to produce crystalline solid particles comprising THCA and a mother liquor; and (iv) separating the crystalline solid particles from the mother liquor. [000165] (42): The method of embodiment (40) or (41), further comprising modulating the temperature of the mixture of step (i).

[000166] (43): The method of any one of embodiments (40)-(42), further comprising modulating the temperature of the saturated solution of step (ii).

[000167] (44): The method of embodiment (43), wherein the modulating the temperature induces crystalline growth.

[000168] (45): The method of any one of embodiments (40)-(44), wherein the saturated solution is a super saturated solution.

[000169] (46): The method of any one of embodiments (40)-(45), further comprising adding a seed crystal of THCA to the saturated solution.

[000170] (47): The method of any one of embodiments (40)-(46), wherein the saturated solution is incubated for at least three weeks.

[000171] (48): The method of any one of embodiments (40)-(47), wherein the saturated solution is incubated for about six weeks.

[000172] (49): The method of any one of embodiments (40)-(48), wherein the solid particles comprises at least 99% of THCA by weight.

[000173] (50): The method of any one of embodiments (40)-(49), wherein the solvent is n-pentane.

[000174] (51): The method of any one of embodiments (40)-(50), wherein the solid particles are substantially free of a pesticide.

[000175] (52): The method of embodiment (51), wherein the pesticide is diazinon, myclobutanil, tebuconazole, or trifloxystrobin, or a combination thereof.

[000176] (53): The method of any one of embodiments (40)-(52), further comprising crushing the solid particles by a mechanical force.

[000177] (54): The method of embodiment (53), further comprising processing the solid particles of THCA through a sieve.

[000178] (55): The method of embodiment (53) or (54), wherein about 70% to about

80% of the solid particles are characterized as having a sieve size of about 0.6 mm to about 1.7 mm. [000179] (56): The method of embodiment (53) or (54), wherein about 20% to about

30% of the solid particles are characterized as having a sieve size of less than or equal to about 0.6 mm.

[000180] (57): The method of embodiment (56), wherein the solid particles are further characterized as having a sieve size of about 0.4 mm to about 0.6 mm.

[000181] (58): The method of embodiment (56), wherein the solid particles are further characterized as having a sieve size of about 0.3 mm to about 0.4 mm.

[000182] (59): The method of embodiment (56), wherein the solid particles are further characterized as having a sieve size of less than or equal to about 0.3 mm.

[000183] (60): The method of any one of embodiments (53)-(59), wherein the method produces about 15% to about 55% of solid particles characterized as having a sieve size of about 0.6 mm to about 1.7 mm per kg of total solid particles.

[000184] (61): The method of any one of embodiments (53)-(60), wherein the method produces about 30% of solid particles characterized as having a sieve size of about 0.6 mm to about 1.7 mm per kg of total solid particles.

[000185] (62): The method of any one of embodiments (53)-(61), wherein the method produces about 1% to about 70% of solid particles characterized as having a sieve size of less than or equal to about 0.6 mm per kg of total solid particles.

[000186] (63): The method of any one of embodiments (53)-(62), wherein the method produces about 30% of solid particles characterized as having a sieve size of less than or equal to about 0.6 mm per kg of total solid particles.

[000187] (64): A method of producing crystalline solid particles comprising tetrahydrocannabinolic acid (THCA), the method comprising: (i) contacting solid particles produced by any one of embodiments (l)-(39) with a solvent to produce a first mixture; (ii) evaporating the first mixture of step (i) to produce a mixture of crystalline solid particles comprising THCA and a mother liquor; and (iii) separating the crystalline solid particles from the mother liquor.

[000188] (65): The method of embodiment (64), further comprising modulating the temperature of the first mixture of step (i).

[000189] (66): The method of embodiment (64) or (65), comprising heating the first mixture of step (i) at a temperature of about 30 °C to about 40 °C and then cooling the mixture to a temperature less than 30 °C.

[000190] (67): The method of any one of embodiments (64)-(66), further comprising stirring the first mixture of step (i). [000191] (68): The method of any one of embodiments (64)-(67), further comprising modulating the temperature of the second mixture of step (ii).

[000192] (69): The method of embodiment (68), comprising heating the second mixture of step (i) at a temperature of about 25 °C to about 35 °C and then cooling the mixture to a temperature less than 30 °C.

[000193] (70): The method of any one of embodiments (64)-(69), further comprising agitating the second mixture of step (ii).

[000194] (71): The method of any one of embodiments (64)-(70), wherein the evaporating of step (ii) occurs over a time period of about 15 days.

[000195] (72): The method of any one of embodiments (64)-(70), wherein the evaporating of step (ii) occurs over a time period of about 17 days.

[000196] (73): The method of any one of embodiments (64)-(70), wherein the evaporating of step (ii) occurs over a time period of at least 15 days.

[000197] (74): The method of any one of embodiments (64)-(73), further comprising washing the crystalline solid particles of step (iii) with a solvent.

[000198] (75): The method of any one of embodiments (64)-(74), further comprising contacting the crystalline solid particles with a solvent.

[000199] (76): The method of embodiment (75), comprising adding the solvent in a volume sufficient to cover and exceed the height of the crystalline solid particles and then separating the crystalline solid particles from the solvent.

[000200] (77): The method of any one of embodiments (64)-(76), wherein the solvent is n-pentane.

[000201] (78): The method of any one of embodiments (64)-(77), wherein the solid particles are substantially free of a pesticide.

[000202] (79): The method of embodiment (78), wherein the pesticide is diazinon, myclobutanil, tebuconazole, or trifloxystrobin, or a combination thereof.

[000203] (80): The method of any one of embodiments (64)-(79), further comprising crushing the solid particles by a mechanical force.

[000204] (81): The method of embodiment (80), further comprising processing the solid particles of THCA through a sieve.

[000205] (82): Crystalline solid particles comprising tetrahydrocannabinolic acid

(THCA) obtained from the method according to any one of embodiments (1)-(81), wherein the crystalline solid particles comprises at least 99% of THCA by weight. EXAMPLES

[000206] In order that the invention described herein may be more fully understood, the following examples are set forth. The examples described in this application are offered to illustrate the pharmaceutical compositions and methods provided herein and are not to be construed in any way as limiting their scope.

Example 1. Exemplary manufacturing process for THCA isolates and crystals

[000207] The mixing vessel for dissolving a crude oil comprising a mix of cannabinoids and terpenes was prepared. The pressure of the mixing vessel was maintained at 8 psi/hr. N- pentane was added to the mixing vessel. The amount of n-pentane was calculated based on the mass of the oil. The heater/chiller of the mixing vessel was set to 30°C and the solvent was stirred at 60-80 RPM. Crude oil was added and rinsed with fresh n-pentane. The mixture was agitated for 12 hours to create a homogenous solution. Any settled solids on the bottom of the vessel were ejected back into solution by bleeding air through a line into the mixing vessel. After, the homogenous solution was transferred to a reactor vessel equipped with a circulation loop. The temperature of the reactor vessel was set to -30 °C to cool at -10°C/hr (or at a rate between -l°C/hr to -10°C/hr). The circulation loop was run for about 12 hours. Agitation caused smaller crystals to form and isolate began to precipitate as the temperature dropped. After turning off circulation and allowing the solution to settle, the mother liquor was transferred back to mixing vessel to recover a brown-colored isolate in the reactor vessel. The isolate was washed with cold n-pentane in the reaction vessel to wash the isolate. Each wash was sent to the mixing vessel with the mother liquor. The reactor vessel was then heated to 30 °C for 12 hours to evaporate residual n-pentane from the isolate (the pentane vapor was sent to a cold trap for solvent recovery). The washes and mother liquor in the mixing vessel were concentrated to remove the solvent (solvent was recovered). The THCA isolate was resuspended in n-pentane for crystallization. This process involved status crystallization using evaporation rate to achieve saturation of THCA solution. Pure, uniform, and large crystalline structures of THCA were produced within 3 weeks or 6 weeks. FIG. 2 shows exemplary images of the crystals formed from the re-crystallization step after 2.5 weeks and 6 weeks. FIG. 3 shows exemplary images of crystals formed from crystallizing THCA from the crude oil mixture for 12-15 weeks. FIG. 4 shows side-by-side comparative images of the crystals formed from the new method described herein (right) compared to the crystals formed from crystallizing THCA from the crude oil mixture. The crystals formed from the new method described herein are white, large and uniform in size, indicating higher purity and improved crystalline structure. Such crystals were obtained in a short period of processing time.

[000208] Any crystals that are larger than about 0.5 g may be broken up (e.g., crushed) during post-processing and packaging.

Yields

[000209] The isolate process for producing solid particles comprising tetrahydrocannabinolic acid (THCA) is described above. For example, the method comprises: (a) contacting an oil comprising a plurality of cannabinoids with a solvent to produce a mixture; (b) warming the mixture of step (a) to about 30 °C to form a homogenous solution; (c) cooling the homogenous solution of step (b) to precipitate THCA from the solution to form a THCA isolate and a mother liquor; (d) separating the THCA isolate from the mother liquor; and (e) optionally, washing the THCA isolate with a solvent to produce solid particles comprising THCA.

[000210] This process produced an average yield (w/w) of approximately 350 g of THCA crystals per kilogram of THCA oil (also referred to as “bulk oil”). As an example, the bulk oil inputs for step (c) were approximately 80% THCA, or 800 g THCA per kilogram of oil. Isolate yield for diamonds ranged, for example, from 20%-70%. It is noted that total diamond/crush diamond yield excludes any THCA material that did not conform to specification and returned for further processing to the final crystalline product.

[000211] As an example, Table 1 below shows exemplary batches and yields of crystalline THCA. Extracts LB587 and LB596 were comprised of 81.61% and 77.52% THC- A respectively. The isolate production process described as above recovered 38.41% and 29.63% of that THC-A as crystals, respectively.

Table 1.

Example 2. Exemplary manufacturing process for THCA crystals

[000212] Described below is an exemplary manufacturing process for obtaining THCA crystals. [000213] To a 100 L jacketed glass reactor with mechanical stirring and a reflux condenser is added 50 L of pentane. With mechanical stirring set to 500 rpm 5 kg of THCA isolate powder is added to the reactor solution. Jacket heating is initiated with the target temperature set to 40° Celsius. Once it is noted that most of the THCA has dissolved an additional 5 kg of THCA is added. As stirring and heating continue the solution begins to reflux and the majority of the THCA is dissolved. A third and final 5 kg portion of THCA is added and then the solution is stirred and refluxed until the solution becomes clear with all THCA having been dissolved. Heating of the reactor jacket is discontinued and the solution is allowed to cool.

[000214] After the temperature has cooled to below 25° Celsius the solution is drained out of the glass reactor and transferred to a 150 L jacketed stainless steel reactor. Attached to the top of this stainless steel reactor is a bellow hose which connects to a vertical spiral condenser (solvent vapor trap) with a round bottom collection flask below (solvent collection flask). The chiller for this condenser/trap is turned on and set to -30° Celsius and serves to collect pentane vapor as it is slowly released from the solution in the reactor. The reactor jacket temperature is set to 25° Celsius. Over the course of 3 days the reactor solution loses approximately 1/4 of its total volume. The jacket temperature is lowered to 21° Celsius. Over the next 7 days crystalline THCA formations become visible against the walls of the vessel and the crystal formations continue to grow as the solution concentrates.

[000215] After the solution has reached about half its original volume large crystal formations are visible covering the bottom of the reactor as well as the lower portions of the walls. In order to avoid growing a large solid mass of crystalline THCA, which is difficult to remove from the reactor, it is advantageous to quickly warm the reactor jacket to 30° Celsius in order to weaken the crystal linkages. A large PTFE spatula is quickly used to break down any large masses of THCA crystals and free them from being stuck to the bottom and walls. Afterwards the jacket temperature is reduced to 23° Celsius for 24 hours and then reduced again back to 21° Celsius for the remainder of the evaporation/crystallization.

[000216] After another 7 days the solution has evaporated down to a thick liquid that barely covers the large crystalline formations. A large spatula is used to agitate and ensure that the crystals are not stuck to the vessel walls or stuck to each other in overly large formations. The thick pentane solution is either drained, decanted, or siphoned off. The remaining crystals are quickly washed with chilled pentane (0° Celsius) - a minimal amount such that the crystals are barely submerged in solvent and then briefly agitated with the spatula. This wash solution is then removed and the THCA crystals are transferred out of the reactor for drying.

[000217] In some batches, break up of large crystal chunks causes unwanted amorphous powder to form, and a final polishing step is applied. After removing the wash pentane solution another portion of pentane is added to cover and exceed the height of the crystals by about 1 cm. The reactor jacket is set to 25° Celsius. The bellow hose is removed and replaced with a sealed air-tight lid. After 24 hours the jacket temperature is set to 21°

Celsius. After another 24 hours has passed the bellow hose is reconnected for recovery of the solvent over the next 1-2 days. During this polishing process the amorphous THCA material preferentially dissolves and then redeposits onto the crystalline THCA, forming a more desirable shiny appearance with smooth faces. The crystalline product is quickly washed with chilled pentane (0° Celsius) and then the solvent is separated in order to remove any non-crystalline residue. The polished diamonds are removed from the reactor and laid out in glass pans which are placed in a fume hood to quickly dry.

Example 3. Isolation of THCA crystalline solid particles (crushed diamonds)

[000218] An exemplary isolation process for obtaining crystalline solid particles comprising THCA is described. Smaller (<) than sieve mesh 12 and larger (>) than sieve mesh 30 (e.g., BU5070) and smaller than sieve mesh 30 (e.g., BU5013) were used to isolate the solid particles. Sieve mesh 12 corresponds to sieve size (hole diameter) of 1.7 mm and opening of 0.0661 in and sieve mesh 30 corresponds to sieve size of 0.595 mm and opening of 0.0232 in. Crystalline solid particles comprised 90% of THCA and 10% terpene mixture by mass. Of the 90% by mass that was THCA, 75% was <12/>30 (larger rocks) and the remainder being <30 (smaller rocks).

[000219] Other sieve meshes and corresponding sieve sizes and openings are shown in Table 2 below.

Table 2.

[000220] In another exemplary isolation process, <12/>30 (e.g., BU5070), <30/>40 (e.g., BU5013, <40/>50 (e.g., BU5014), and <50 (e.g., BU5017) sieves were used to isolate the solid particles comprising THCA and subdivide solids <30 size, <30/>40, <40/>50, and <50. Sieve 40 corresponds to sieve size of 0.400 mm and opening of 0.0165 in, and sieve 50 corresponds to sieve size of 0.30 mm and opening size of 0.0117 in.

Yields

[000221] The production of crushed diamonds applies additional processing and sizing steps to the isolate produced per the processes described above, such as in Examples 1-2. Converting bulk oil THC-A to crystalline THC-A yielded a range of 20%-70% recovery of THC-A across 103 batches, with an average yield of 38%. [000222] Individual batches of crystalline THC-A is blended before conversion to Crushed Diamonds or processed separately. An exemplary processing comprises using a metal sieve to separate THC-A crystals by size. The Crushed Diamonds recipe is 90% THC- A and 10% terpene mixture. Of the 90% of the mass that is THC-A, 75% of that is <12/>30 (larger crystals (BU5070)) with the balance being <30 (smaller crystals (BU5013)).

[000223] Separating isolate by size yields approximately 30% crystals that are <12/>30 in size (larger crystals (BU5070)) and 30% <30 (smaller crystals (BU5013)) for a total yield of 60% suitable Crushed Diamond material per kilogram crystalline input (average of 20 batches, Table 3). The remainder of the crystalline input is recovered and recycled into the isolate process. It is noted that total diamond/crush diamond yield excludes any THCA material that did not conform to specification and returned for further processing to the final crystalline product.

Table 3.

Example 4. Removal of Pesticides during Isolation Process

[000224] The manufacturing and isolation processes as described in Examples 1-3 are particularly advantageous for removing pesticide contamination from the final solid particles comprising THCA. Pesticide-contaminated cannabis extracts are converted into high purity THCA crystals.

[000225] Table 4 below shows exemplary batches of crude oil and corresponding batches of crystalline solid particles and quantification of pesticides. In each example (examples A-C), the bulk oil contaminated with one or more pesticides were combined and processed to produce the isolates (solid crystalline particles).

Table 4.

LLOQ = lower limit of quantification

LOQ = limit of quantification ND = not detected NT = not tested EQUIVALENTS AND SCOPE

[000226] In the claims articles such as “a,” “an,” and “the” may mean one or more than one unless indicated to the contrary or otherwise evident from the context. Claims or descriptions that include “or” between one or more members of a group are considered satisfied if one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process unless indicated to the contrary or otherwise evident from the context. The invention includes embodiments in which exactly one member of the group is present in, employed in, or otherwise relevant to a given product or process. The invention includes embodiments in which more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process.

[000227] Furthermore, the invention encompasses all variations, combinations, and permutations in which one or more limitations, elements, clauses, and descriptive terms from one or more of the listed claims is introduced into another claim. For example, any claim that is dependent on another claim can be modified to include one or more limitations found in any other claim that is dependent on the same base claim. Where elements are presented as lists, e.g., in Markush group format, each subgroup of the elements is also disclosed, and any element(s) can be removed from the group. It should it be understood that, in general, where the invention, or aspects of the invention, is/are referred to as comprising particular elements and/or features, certain embodiments of the invention or aspects of the invention consist, or consist essentially of, such elements and/or features. For purposes of simplicity, those embodiments have not been specifically set forth in haec verba herein. It is also noted that the terms “comprising” and “containing” are intended to be open and permits the inclusion of additional elements or steps. Where ranges are given, endpoints are included. Furthermore, unless otherwise indicated or otherwise evident from the context and understanding of one of ordinary skill in the art, values that are expressed as ranges can assume any specific value or sub-range within the stated ranges in different embodiments of the invention, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise.

[000228] This application refers to various issued patents, published patent applications, journal articles, and other publications, all of which are incorporated herein by reference. If there is a conflict between any of the incorporated references and the instant specification, the specification shall control. In addition, any particular embodiment of the present invention that falls within the prior art may be explicitly excluded from any one or more of the claims. Because such embodiments are deemed to be known to one of ordinary skill in the art, they may be excluded even if the exclusion is not set forth explicitly herein. Any particular embodiment of the invention can be excluded from any claim, for any reason, whether or not related to the existence of prior art.

[000229] Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation many equivalents to the specific embodiments described herein. The scope of the present embodiments described herein is not intended to be limited to the above Description, but rather is as set forth in the appended claims. Those of ordinary skill in the art will appreciate that various changes and modifications to this description may be made without departing from the spirit or scope of the present invention, as defined in the following claims.

Claims

1. A method for producing solid particles comprising tetrahydrocannabinolic acid (THCA), the method comprising:

(a) contacting an oil comprising a plurality of cannabinoids with a solvent to produce a mixture;

(b) warming the mixture of step (a) to about 30 °C to form a homogenous solution;

(c) cooling the homogenous solution of step (b) to precipitate THCA from the solution to form a THCA isolate and a mother liquor;

(d) separating the THCA isolate from the mother liquor; and

(e) optionally, washing the THCA isolate with a solvent to produce solid particles comprising THCA.

2. The method of claim 1, wherein the cooling in step (c) occurs in a vessel comprising a circulation loop.

3. The method of claim 1, wherein the cooling in step (c) further comprises agitating the solution.

4. The method of claim 1, wherein the solution is cooled in step (c) at a rate of about -10 ° C/hour.

5. The method of claim 1, wherein the solution is cooled to about -30 °C in step (c).

6. The method of claim 1, further comprising heating the solid particles of step (e) at about 30 °C to remove residual solvent.

7. The method of claim 1, wherein the solid particles are substantially crystalline.

8. The method of claim 1, wherein the solid particles comprises at least 85% of THCA by weight.

9. The method of claim 1, wherein the solid particles comprises at least 90% of THCA by weight

10. The method of claim 1, wherein the solid particles comprises at least 95% of THCA by weight.

11. The method of claim 1, wherein the solid particles comprises at least 99% of THCA by weight.

12. The method of claim 1, wherein the solid particles comprises 99% of THCA by weight.

13. The method of claim 1, wherein the oil further comprises a plurality of terpenoids.

14. The method of claim 13, wherein the plurality of terpenoids comprises one or more terpenoids selected from the group consisting of alpha thujene, alpha pinene, camphene, beta pinene, beta myrcene, p-mentha- 1,5-diene, 3-carene, alpha terpinene, p-cymene, D-limonene, beta ocimene, terpinolene, linalool, fenchol, trans-2-pinanol, alpha terpineol, beta caryophyllene, gamma elemene, alpha bergamotene, humulene, caryophyllene oxide, 4,8,12- Tetradecatrienal, beta selinene, alpha selinene, alpha bulnesene, alpha farnesene, beta maaliene, (4aR,8aS)-4a-Methyl-l-methylene-7-(propan-2-ylidene)decahydronaphthalene, cis nerolidol, trans nerolidol, Selina-3, 7(1 l)-diene, trans alpha bisabolene, beta guaiene, epi- gamma-eudesmol, longifolene, cis beta guaiene, aromandendrene, alpha eudesmol, alpha bulnesene, alpha bisabolol, juniper camphor, and beta bisabolene.

15. The method of claim 13, wherein the plurality of cannabinoids comprises one or more cannabinoids selected from the group consisting of tetrahydrocannabinolic acid, tetrahydrocannabinol, cannabigerol, cannabichromene, tetrahydrocannabivarin, cannabidiol, cannabinol, cannabigerivarin, tetrahydrocannabivarian, cannabidivarin, cannabichromevarin, and derivatives thereof.

16. The method of claim 1, wherein the oil is extracted from a feedstock comprising a plant of the genus Cannabis.

17. The method of claim 16, wherein the plant of the genus Cannabis is Cannabis sativa or Cannabis indica.

18. The method of claim 1, further comprising collecting the mother liquor.

19. The method of claim 1, further comprising collecting the solvent wash of step (e).

20. The method of claim 1, wherein the washing step (e) is repeated at least once.

21. The method of claim 1, further comprising re-crystallizing the solid particles in a solvent.

22. The method of claim 1, wherein the solvent is n-pentane.

23. The method of claim 1, wherein the solid particles are substantially free of a pesticide.

24. The method of claim 23, wherein the pesticide is diazinon, myclobutanil, tebuconazole, or trifloxystrobin, or a combination thereof.

25. The method of claim 1, wherein the method produces at least about 200 g of solid particles comprising THCA per kg of the oil.

26. The method of claim 1, wherein the method produces about 300 g of solid particles comprising THCA per kg of the oil.

27. The method of claim 1, wherein the method produces about 350 g of solid particles comprising THCA per kg of the oil.

28. The method of claim 1, wherein the oil comprises about 80% of THCA by weight.

29. The method of claim 1, further comprising blending the solid particles comprising

THCA.

30. The method of claim 1, further comprising processing the solid particles of THCA through a sieve.

31. The method of claim 30, wherein about 70% to about 80% of the solid particles are characterized as having a sieve size of about 0.6 mm to about 1.7 mm.

32. The method of claim 30, wherein about 20% to about 30% of the solid particles are characterized as having a sieve size of less than or equal to about 0.6 mm.

33. The method of claim 32, wherein the solid particles are further characterized as having a sieve size of about 0.4 mm to about 0.6 mm.

34. The method of claim 32, wherein the solid particles are further characterized as having a sieve size of about 0.3 mm to about 0.4 mm.

35. The method of claim 32, wherein the solid particles are further characterized as having a sieve size of less than or equal to about 0.3 mm.

36. The method of claim 30, wherein the method produces about 15% to about 55% of solid particles characterized as having a sieve size of about 0.6 mm to about 1.7 mm per kg of total solid particles.

37. The method of claim 30, wherein the method produces about 30% of solid particles characterized as having a sieve size of about 0.6 mm to about 1.7 mm per kg of total solid particles.

38. The method of claim 30, wherein the method produces about 1% to about 70% of solid particles characterized as having a sieve size of less than or equal to about 0.6 mm per kg of total solid particles.

39. The method of claim 30, wherein the method produces about 30% of solid particles characterized as having a sieve size of less than or equal to about 0.6 mm per kg of total solid particles.

40. A method of producing crystalline solid particles comprising tetrahydrocannabinolic acid (THCA), the method comprising:

(i) contacting solid particles produced by any one of claims 1-39 with a solvent to produce a mixture;

(ii) evaporating the mixture of step (i) to produce a saturated solution;

(iii) incubating the saturated solution of step (ii) to produce crystalline solid particles comprising THCA and a mother liquor; and

(iv) separating the crystalline solid particles from the mother liquor.

41. The method of claim 40, further comprising modulating the temperature of the mixture of step (i).

42. The method of claim 40, further comprising modulating the temperature of the saturated solution of step (ii).

43. The method of claim 42, wherein the modulating the temperature induces crystalline growth.

44. The method of claim 40, wherein the saturated solution is a super saturated solution.

45. The method of claim 40, further comprising adding a seed crystal of THCA to the saturated solution.

46. The method of claim 40, wherein the saturated solution is incubated for at least three weeks.

47. The method of claim 40, wherein the saturated solution is incubated for about six weeks.

48. The method of claim 40, wherein the solid particles comprises at least 99% of THCA by weight.

49. The method of claim 40, wherein the solvent is n-pentane.

50. The method of claim 40, wherein the solid particles are substantially free of a pesticide.

51. The method of claim 50, wherein the pesticide is diazinon, myclobutanil, tebuconazole, or trifloxystrobin, or a combination thereof.

52. The method of claim 50, further comprising crushing the solid particles by a mechanical force.

53. The method of claim 52, further comprising processing the solid particles of THCA through a sieve.

54. The method of claim 53, wherein about 70% to about 80% of the solid particles are characterized as having a sieve size of about 0.6 mm to about 1.7 mm.

55. The method of claim 53, wherein about 20% to about 30% of the solid particles are characterized as having a sieve size of less than or equal to about 0.6 mm.

56. The method of claim 53, wherein the solid particles are further characterized as having a sieve size of about 0.4 mm to about 0.6 mm.

57. The method of claim 53, wherein the solid particles are further characterized as having a sieve size of about 0.3 mm to about 0.4 mm.

58. The method of claim 53, wherein the solid particles are further characterized as having a sieve size of less than or equal to about 0.3 mm.

59. The method of claim 53, wherein the method produces about 15% to about 55% of solid particles characterized as having a sieve size of about 0.6 mm to about 1.7 mm per kg of total solid particles.

60. The method of claim 53, wherein the method produces about 30% of solid particles characterized as having a sieve size of about 0.6 mm to about 1.7 mm per kg of total solid particles.

61. The method of claim 53, wherein the method produces about 1% to about 70% of solid particles characterized as having a sieve size of less than or equal to about 0.6 mm per kg of total solid particles.

62. The method of claim 53, wherein the method produces about 30% of solid particles characterized as having a sieve size of less than or equal to about 0.6 mm per kg of total solid particles.

63. A method of producing crystalline solid particles comprising tetrahydrocannabinolic acid (THCA), the method comprising:

(i) contacting solid particles comprising at least 95% of THCA by weight with a solvent to produce a mixture;

(ii) evaporating the mixture of step (i) to produce a saturated solution; and

(iv) separating the crystalline solid particles from the mother liquor.

64. The method of claim 63, further comprising modulating the temperature of the mixture of step (i).

65. The method of claim 63, further comprising modulating the temperature of the saturated solution of step (ii).

66. The method of claim 65, wherein the modulating the temperature induces crystalline growth.

67. The method of claim 63, wherein the saturated solution is a super saturated solution.

68. The method of claim 63, further comprising adding a seed crystal of THCA to the saturated solution.

69. The method of claim 63, wherein the saturated solution is incubated for at least three weeks.

70. The method of claim 63, wherein the saturated solution is incubated for about six weeks.

71. The method of claim 63, wherein the solid particles comprises at least 99% of THCA by weight.

72. The method of claim 63, wherein the solvent is n-pentane.

73. The method of claim 63, wherein the solid particles are substantially free of a pesticide.

74. The method of claim 73, wherein the pesticide is diazinon, myclobutanil, tebuconazole, or trifloxystrobin, or a combination thereof.

75. The method of claim 63, further comprising crushing the solid particles by a mechanical force.

76. The method of claim 75, further comprising processing the solid particles of THCA through a sieve.

77. The method of claim 76, wherein about 70% to about 80% of the solid particles are characterized as having a sieve size of about 0.6 mm to about 1.7 mm.

78. The method of claim 76, wherein about 20% to about 30% of the solid particles are characterized as having a sieve size of less than or equal to about 0.6 mm.

79. The method of claim 76, wherein the solid particles are further characterized as having a sieve size of about 0.4 mm to about 0.6 mm.

80. The method of claim 76, wherein the solid particles are further characterized as having a sieve size of about 0.3 mm to about 0.4 mm.

81. The method of claim 76, wherein the solid particles are further characterized as having a sieve size of less than or equal to about 0.3 mm.

82. The method of claim 76, wherein the method produces about 15% to about 55% of solid particles characterized as having a sieve size of about 0.6 mm to about 1.7 mm per kg of total solid particles.

83. The method of claim 76, wherein the method produces about 30% of solid particles characterized as having a sieve size of about 0.6 mm to about 1.7 mm per kg of total solid particles.

84. The method of claim 76, wherein the method produces about 1% to about 70% of solid particles characterized as having a sieve size of less than or equal to about 0.6 mm per kg of total solid particles.

85. The method of claim 76, wherein the method produces about 30% of solid particles characterized as having a sieve size of less than or equal to about 0.6 mm per kg of total solid particles.

86. A method of producing crystalline solid particles comprising tetrahydrocannabinolic acid (THCA), the method comprising:

(i) contacting solid particles produced by any one of claims 1-39 with a solvent to produce a first mixture;

(ii) evaporating the first mixture of step (i) to produce a mixture of crystalline solid particles comprising THCA and a mother liquor; and

(iii) separating the crystalline solid particles from the mother liquor.

87. The method of claim 86, further comprising modulating the temperature of the first mixture of step (i).

88. The method of claim 87, comprising heating the first mixture of step (i) at a temperature of about 30 °C to about 40 °C and then cooling the mixture to a temperature less than 30 °C.

89. The method of claim 86, further comprising stirring the first mixture of step (i).

90. The method of claim 86, further comprising modulating the temperature of the second mixture of step (ii).

91. The method of claim 90, comprising heating the second mixture of step (i) at a temperature of about 25 °C to about 35 °C and then cooling the mixture to a temperature less than 30 °C.

92. The method of claim 86, further comprising agitating the second mixture of step (ii).

93. The method of claim 86, wherein the evaporating of step (ii) occurs over a time period of about 15 days.

94. The method of claim 86, wherein the evaporating of step (ii) occurs over a time period of about 17 days.

95. The method of claim 86, wherein the evaporating of step (ii) occurs over a time period of at least 15 days.

96. The method of claim 86, further comprising washing the crystalline solid particles of step (iii) with a solvent.

97. The method of claim 86, further comprising contacting the crystalline solid particles with a solvent.

98. The method of claim 97, comprising adding the solvent in a volume sufficient to cover and exceed the height of the crystalline solid particles and then separating the crystalline solid particles from the solvent.

99. The method of claim 86, wherein the solvent is n-pentane.

100. The method of claim 86, wherein the solid particles are substantially free of a pesticide.

101. The method of claim 100, wherein the pesticide is diazinon, myclobutanil, tebuconazole, or trifloxystrobin, or a combination thereof.

102. The method of claim 86, further comprising crushing the solid particles by a mechanical force.

103. The method of claim 86, further comprising processing the solid particles of THCA through a sieve.

104. Crystalline solid particles comprising tetrahydrocannabinolic acid (THCA) obtained from the method according to any one of claims 1-103, wherein the crystalline solid particles comprises at least 99% of THCA by weight.