WO2023126934A1

WO2023126934A1 - Cannabis compositions for treating pain and inflammation related disorders

Info

Publication number: WO2023126934A1
Application number: PCT/IL2022/051403
Authority: WO
Inventors: Inbal Nurith DANGOOR; Yaacov Micha BROG
Original assignee: Canonic Ltd.
Priority date: 2021-12-29
Filing date: 2022-12-28
Publication date: 2023-07-06

Abstract

The application relates to a composition comprising a Cannabis derived extract for use in the treatment of inflammation and/or pain related disorders. The composition comprising a Cannabis derived extract comprising: (a) Tetrahydrocannabinol (THC) or a derivative thereof in an amount of about 35% to about 70% by weight, and Cannabidiol (CBD) in an amount of less than 1% by weight; or (b) THC or a derivative thereof in an amount of about 15% to about 35% by weight, and CBD in an amount of 25% to 35% by weight.

Description

CANNABIS COMPOSITIONS FOR TREATING PAIN AND INFLAMMATION RELATED DISORDERS

TECHNICAL FIELD

[0001] The invention relates generally to the field of methods and compositions for treating pain and inflammation related disorders, and in particular to compositions comprising extract of a Cannabis plant for relief of pain and inflammation symptoms.

BACKGROUND

[0002] In recent years, there has been a rapid increase in the medical use of Cannabis (Marijuana). While Cannabis is not registered as a drug or a medical product, the potential of Cannabis-based medicines for the treatment of various conditions has led to authorize the clinical use of such treatments, in many countries. However, the basic and medical research dedicated to medical Cannabis is currently limited. Pharmacologically, the principal psychoactive constituent of Cannabis is tetrahydrocannabinol (THC) representing one of hundreds of known compounds in the plant, including many other cannabinoids, such as cannabidiol (CBD), cannabinol (CBN), tetrahydrocannabivarin (THCV) and cannabigerol (CBG). The use of both neutral and acid forms of the cannabinoids, results in distinctly different therapeutic endpoints.

[0003] As US states legalize the medicinal use of Cannabis and Cannabis products, there is a need to develop Cannabis products for the efficient and effective treatment of various medical conditions.

[0004] One of the challenges for health care professionals is management of patient's pain management, as pain often can negatively affect individuals in their day- to-day functioning and productivity. However, as pain has many causes, some of which are poorly understood, it can be a difficult problem to treat. There are no truly effective medicines for certain types of pain, and sometimes relief comes only at the expense of undesirable side effects. Physicians are often reluctant to administer large doses of analgesic drugs. The same holds true for currently available opioid -based drug therapies which can produce undesirable side effects such as hallucinations, constipation, sedation, nausea and dysphoria. Thus, the search for new and better pain relievers, is highly relevant. [0005] Since the Institute of Medicine (IOM) determined that Cannabis appears to be a source of analgesic medications, medical Cannabis is increasingly used to manage chronic pain, particularly in jurisdictions that have enacted policies to reduce use of opioids.

[0006] Cannabinoids have shown significant promise in basic experiments on pain and appear to block peripheral nerve pain in experimental animals. However, there are conflicting evidence on whether higher doses provide superior pain relief. Some clinical studies not only have failed to demonstrate that THC relieves pain but have also found that the drug has the opposite effect (see for example, A selective review of medical Cannabis in cancer pain management. Alexia Blake 1, Bo Angela Wan, Leila Malek, Carlo DeAngelis, Patrick Diaz, Nicholas Lao, Edward Chow, Shannon O’Hearn, Vol 6, Supplement 2 (December 2017): Annals of Palliative Medicine; Initial experiences with medicinal extracts of Cannabis for chronic pain: Results from 34 ‘N of 1 ’ studies. William Notcutt, Mario Price, Roy Miller, Samantha Newport, Cheryl Phillips, Susan Simmons and Cathy Sansom, Anaesthesia, 2004, 59, pages 440-452).

[0007] Inflammation is the body’s immune system’s response to an irritant. The irritant might be a pathogen (bacteria, viruses, and other organisms, which cause infections) or any other foreign object. Types of inflammation include acute inflammation and chronic inflammation. It is believed by experts that inflammation may contribute to a wide range of chronic diseases. Examples of such diseases are metabolic syndrome, which includes type 2 diabetes, heart disease, and obesity.

[0008] The correlation between immune response and Cannabis use has been explored. Cannabinoids has been reported as potent anti-inflammatory agents which might exert their effects through induction of apoptosis, inhibition of cell proliferation, suppression of cytokine production and induction of T-regulatory cells.

[0009] Although it was reported that Cannabis use can produce immune inflammatory suppression in healthy people, this effect is not robust enough to change inflammatory mediators’ levels in situations of highly dysfunctional inflammatory activation. Thus, the literature about medical potential of Cannabis extracts, including its anti-inflammatory properties, remains inconclusive (see for example Cannabidiol (CBD) and its analogs: A review of their effects on inflammation. Sumner Burstein, Bioorganic & Medicinal Chemistry, Volume 23, Issue 7, 1 April 2015, Pages 1377- 1385; The effects of D9-tetrahydrocannabinol and cannabidiol alone and in combination on damage, inflammation and in vitro motility disturbances in rat colitis. JM Jamontt, A Molleman, RG Pertwee and ME Parsons, British Journal of Pharmacology (2010), 160, 712-723).

[0010] Many Cannabis-based products contain harmful preservatives and stabilizers, artificial flavorings, colors, mycotoxins, as well as toxic byproducts and/or trigger side effects and fail to provide effective relief for the subject medical condition.

In view of the above, there is still a long felt need for effective Cannabis preparations with reduced adverse effects for treating pain and inflammation related disorders.

SUMMARY OF THE INVENTION

[0011] Accordingly, it is a principal object of the present invention to overcome disadvantages of prior art Cannabis based compositions. This is accomplished in one embodiment by a composition comprising a Cannabis derived extract for use in the treatment of inflammation and/or pain related disorders. The composition comprising a Cannabis derived extract for use in the treatment of inflammation and/or pain related disorders, the extract comprising: a. Tetrahydrocannabinol (THC) or a derivative thereof in an amount of about 35% to about 70% by weight, and Cannabidiol (CBD) in an amount of less than 1% by weight; or b. THC or a derivative thereof in an amount of about 15% to about 35% by weight, and CBD in an amount of 25% to 35% by weight.

[0012] It is another object of the present application to di sclose the composition according to the above, wherein the Cannabis derived extract comprises THC or a derivative thereof in an amount of about 40% to about 65% by weight, and CBD in an amount of less than 0.5%, such as less than 0.2 %, by weight.

[0013] It is another object of the present application to disclose the composition according to any of the above, wherein the Cannabis derived extract comprises THC to CBD ratio, by weight, of 1:1.66 to 1.4:1.

[0014] It is another object of the present application to disclose the composition according to the above, wherein the composition comprises one or more cannabinoids selected from: THCVA, THCV THCOA, THCO, THC-C7 (THCP), THC-C6, THC-C4 (THCB), THCA-OAc, THCA-C7 (THCPA), THCA-C6, THCA-C4 (THCBA), Sesqui- CBGA, Sesqui-CBG, OH-CBNA, OH-CBN, d9-THCMA, d9-THCM, d9-THCA, d9- THC, d8-THC, CNF-B, CNF-A, CBTV-3, CBTV-1, CBTA-3, CBTA-1, CBT-3, CBT- 2, CBT-1, CBNVA, CBNV, CBNOA, CBNO, CBNM, CBNDVA, CBNDA, CBND, CBN-C6, CBN-C4 (CBNB), CBNA-C4 (CBNBA), CBNA-8-OH, CBNA, CBN-8-OH, CBN, CBL, CBGVA, CBGV, CBG-OAc, CBGOA, CBGO, CBGMA, CBGM, CBG- C7 (CBGP), CBG-C6, CBG-C4 (CBGB), CBGA-OAc, CBGA-C7 (CBGPA), CBGA- C6, CBGA-C4 (CBGAB), CBGA, CBG, CBEVA, CBEV, CBEA, CBE, CBDVM, CBDVA, CBDV, CBD-OAc, CBDOA, CBDO, CBDMA, CBDM, CBD-C7 (CBDP), CBD-C6, CBD-C4 (CBDB), CBDA-Oac, CBDA-C7 (CBDPA), CBDA-C6, CBDA- C4 (CBDAB), CBDA, CBD, CBCVA, CBCV, CBCOA, CBCO, CBC-C4 (CBCB), CBCA-C4 (CBCBA), CBCA, CBC, Cannabicitran, CA-5992 , 417-15a , 375-19c , 375- 19b , 375-19a , 373-15c, 373-15b, 373-12d, 373-12c, 373-12b, 373-12a, 371-14b, 371- 14a, 361-17b, 361-17a, 357-16a, 331-18d, 331-18c, 331-18b, 331-18a, 329-l le, 329- 1 Id, 329-11c, 329-1 lb, 329-1 la, 327-13c, 327-13b, 327-13a, 313- 16b and any mixtures or combination thereof.

[0015] It is another object of the present application to disclose the composition according to the above, wherein the composition comprises one or more noncannabinoid components selected from terpenes, terpenoids, phenylpropanoids, amino acids, polyamines, hydrocarbons, sugars and related compounds, nitrogenous compounds, non-cannabinoid phenols, fatty acids, flavonoids, sterols, triglycerides, alkanes, squalene, tocopherol, carotenoids, chlorophyll, glycosides, alkaloids, anthocyanins, vitamins, minerals, macronutrients and any combination thereof.

[0016] It is another object of the present application to di sclose the composition according to the above, wherein the non-cannabinoid components are further selected from flavonols such as catechin, epicatechin, flavanone, naringenin, lignanamides, cannabisin a, cannabisin b and cannabisin c; phenolic amides such as n- transcaffeoyltyramine, rutin, quercetin-3-glucoside, kaempferol-3-oglucoside, quercetin and kaempferol; flavones such as cannflavin a, cannflavin b, luteolin-7- oglucoside, apigenin-7-oglucoside, luteolin and apigenin; phenolic acids such as hydroxycinnamic acids, chlorogenic acid, caffeic acid, p-coumaric acid, ferulic acid, and isoflavonoid. [0017] It is another object of the present application to disclose the composition according to the above, wherein the terpene and/or flavonoids include for example, 1,8- cineole, P-myrcene, P-caryophyllene, cannflavin A, apigenin, quercetin, pulegone, a- Pinene, Camphene, b-Pinene, Sabinene, -(-)b-Myrcene, 3d-Carene, a-Terpinene, D/L- Limonene, p-Cymene, cis-Ocimene, Eucalyptol, trans-Ocimene, D/L-Fenchone, Terpinolene, Linalool, Fenchol, -(-)Camphor, -(-)Isopulegol, D/L-Bomeol, Isobomeol, D/L-Menthol, a-Terpineol, Geraniol, Nerol, a-Pulegone, b-Caryophyllene, trans-b- Farnesene, a-Humulene, -(+)Ledene, Valencene, trans-Nerolidol, Caryophyllene oxide, -(+)Cedrol, -(-)Guaiol, (-)a-Bisabolol, cis-Nerolidol, a-Phellandrene, m-Cymene, g- Terpinene, cis-Linalool oxide, trans-Linalool oxide, -(-/+)Terpinen-4-ol, -(-)Bomyl acetate, -(+)Longipinene, a-Curcumene, b-Citronellol, trans-2-pinanol, a-Bulnesol, Selina 4 diene or Selina 3,7 diene and any mixtures or combination thereof.

[0018] It is another object of the present application to disclose the composition according to the above, wherein the extract comprises Sesqui-CBG 82-637 ppm, CBCOA 0-4 ppm, (-)a-Bisabolol 514-968 ppm, (+)-Ledene 307-1175, Linalool 121- 2317 ppm, trans-Nerolidol 179-483 and CBG-OAc 10-13 ppm.

[0019] It is another object of the present application to disclose the composition according to the above, wherein the composition is useful in pain management.

[0020] It is another object of the present application to disclose the composition according to the above, wherein the extract comprises (-)a-Bisabolol 18-968 ppm, (+)- Ledene 307-1175 ppm, Linalool 121-1538, trans-Nerolidol 179-483 ppm, trans-b- Farnesene 96-214 ppm and CBG-OAc 10-13 ppm.

[0021] It is another object of the present application to disclose the composition according to the above, wherein the composition is useful in conferring antiinflammatory effect pain.

[0022] It is another object of the present application to disclose the composition according to the above, wherein the extract is derived from one or more Cannabis species or variety or strain.

[0023] It is another object of the present application to disclose the composition according to the above, wherein the Cannabis species or variety or strain belongs to at least one of Cannabis sativa, Cannabis indica, Cannabis ruderalis and any hybrid or cultivated variety of the genus Cannabis. [0024] It is another object of the present application to disclose the composition according to the above, wherein the inflorescence of the Cannabis species or variety or strain is characterized as comprising 0.11-0.33% CBCA, <0.1% CBDA, <0.1% CBDVA, 0.03-0.41% CBG, 0.09-0.4% CBGA, <0.1%CBN, <0.1% CBNA, 0.4-0.6% THC, 9.29-15.93% THCA and <0.1% CBD by weight.

[0025] It is another object of the present application to disclose the composition according to the above, wherein the composition is in a dosage form selected from a tablet, a capsule, an inhalant, a parenteral, a transdermal, a sublingual, a rectal, a vaginal, a suppository, a liquid, an aerosol spray, a pastille, a gel, a capsule, a powder or a vaporizer.

[0026] It is another object of the present application to disclose the composition according to the above, wherein the composition is a liquid solution, a Cannabis-based oil preparation, or a liquid suspension.

[0027] It is another object of the present application to disclose the composition according to the above, wherein the composition is used for treating inflammation and/or pain related disorder symptoms.

[0028] It is another object of the present application to disclose the composition according to the above, wherein the composition is useful for treating symptoms associated with diseases or disorders selected from acute inflammation, chronic inflammation, pain associated with inflammation, acute pain, chronic pain, nociceptive pain, referred pain, cancer pain, neuropathic pain, psychogenic pain and visceral pain.

[0029] It is another object of the present application to disclose the composition according to the above, wherein the diseases or disorders are selected from autoimmune diseases and disorders, motor neuron diseases and disorders, neurodegenerative diseases and disorders, diabetes, cardiovascular disease (CVD), arthritis and other joint diseases, allergies, chronic obstructive pulmonary disease (COPD), psoriasis, rheumatoid arthritis, Cancer, Chemotherapy-induced peripheral neuropathy (CIPN), Opioid Use Disorder/ Addiction, Carpal Tunnel Syndrome, Osteoarthritis, CRPS/RSD, Osteoporosis, Diabetic Neuropathy, Plantar Fasciitis, Ehlers-Danlos Syndrome (EDS), Postherpetic Neuralgia, Fibromyalgia, Insomnia, Gout, Pelvic Pain, hATTR Amyloidosis, Psoriatic Arthritis, Low Back Pain, Rheumatoid Arthritis, Lupus, Sickle Cell Disease, Lyme Disease, Thigh Pain, Migraine and Headaches, Traumatic Brain Injuries, Neck Pain and TMJ Disorders, Crohn's Disease, inflammatory bowel disorders (IBS and IBD).

[0030] It is another object of the present application to disclose the composition according to the above, for use as a medicament.

[0031] It is another object of the present application to disclose the composition according to the above, for use as anti-inflammatory therapy.

[0032] It is another object of the present application to disclose the composition according to the above, wherein the composition comprises at least one pharmacologically inactive substance.

[0033] It is another object of the present application to disclose the composition according to the above, wherein the pharmacologically inactive substance is selected from pharmaceutically acceptable carriers, diluents, adjuvants, excipients or any combination thereof.

[0034] It is another object of the present application to disclose the composition according to the above, wherein the composition provides a therapeutic effect selected from an anti-inflammatory effect and a pain relief effect.

[0035] It is another object of the present application to di sclose the composition according to the above, wherein the anti-inflammatory effect confers inhibition of immune system cells such as macrophage and lymphocyte cells.

[0036] It is another object of the present application to disclose the composition according to the above, wherein the anti-inflammatory effect confers inhibition of activated immune system cells such as macrophage activated cells by at least 30%.

[0037] It is another object of the present application to di sclose the composition according to the above, wherein the anti-inflammatory effect confers reduced proliferation of activated immune system cells such as lymphocyte activated cells by at least 40%.

[0038] It is another object of the present application to di sclose the composition according to the above, wherein the pain relief effect confers inhibition, reduction or prevention of nociceptive pain symptoms by at least 20%. [0039] It is another object of the present application to disclose the composition according to the above, wherein the effect is additive or synergistic relative to the effect conferred by THC or CBD, administered separately in a similar concentration.

[0040] It is another object of the present application to disclose the composition according to the above, wherein the THC ,CBD or any other cannabinoid compound or non- cannabinoid compound or a derivative thereof, is one or more of: (i) natural cannabinoids or non- cannabinoids; (ii) synthetically derived cannabinoids or noncannabinoids; (iii) semi-synthetic cannabinoids or non- cannabinoids; (iv) active metabolites of any of the foregoing, (vi) pro-drugs of any of the foregoing; and (vii) mixtures thereof.

[0041] It is another object of the present application to disclose the composition according to the above, wherein the composition contains a synthetic analogue of one or more of the cannabinoids or non-cannabinoids compounds.

[0042] It is the object of the present application to disclose a medicament comprising an effective amount of a composition according to any of the above.

[0043] It is the object of the present application to disclose the use of a Cannabis extract in the preparation of a medicament for treating an inflammation or pain disorder, wherein the Cannabis extract is as defined in any of the above.

[0044] It is the object of the present application to disclose a Cannabis based preparation for inhalation, for use in the treatment of inflammation and/or pain related disorders, comprising the composition according to any of the above.

[0045] It is another object of the present application to disclose the Cannabis based preparation according to the above, wherein the preparation is in a dosage form selected from a tablet, a capsule, an inhalant, a parenteral, a transdermal, a sublingual, a rectal, a vaginal, a suppository, a liquid, an aerosol spray, a pastille, a gel, a capsule, a powder or a vaporizer.

[0046] It is the object of the present application to disclose the a method for treating pain and/or inflammation related disorders, the method comprising administering to a patient in need thereof an effective amount of the composition according to any of the above, or a medicament according to the above or a Cannabis based preparation according to any of the above. [0047] It is another object of the present application to disclose the method according to the above, wherein the composition is administered to the patient in combination with one or more other medicinal substances used in the treatment of pain and inflammation related disorders.

[0048] It is the object of the present application to disclose a composition comprising a Cannabis derived extract for use in the treatment of inflammation and/or pain related disorders, produced according to a method comprising steps of: a. obtaining at least one part of a Cannabis plant variety selected from 'Precise- A', 'Precise-B', 'Precise-C, 'Precise-D' or 'Precise-E'; b. generating an extract from the Cannabis plant part; wherein the composition comprises: i. tetrahydrocannabinol (THC) or a derivative thereof in an amount of 40% to 65% by weight, and Cannabidiol (CBD) in an amount of less than 1%; or ii. THC or a derivative thereof in an amount of 15% to 35% by weight, and CBD in an amount of 25% to 35% by weight.

[0049] It is another object of the present application to disclose the composition according to the above, wherein the Cannabis plant part is characterized as inflorescences.

[0050] It is another object of the present application to disclose the method according to the above, wherein the composition is administered to the patient in combination with one or more other medicinal substances used in the treatment of pain and inflammation related disorders.

[0051] It is another object of the present application to di sclose the composition according to the above, wherein the inflorescence is characterized as comprising 0.11- 0.33% CBCA, <0.1% CBDA, <0.1% CBDVA, 0.03-0.41% CBG, 0.09-0.4% CBGA, <0.1%CBN, <0.1% CBNA, 0.4-0.6% THC, 9.29-15.93% THCA and <0.1% CBD.

[0052] It is another object of the present application to disclose the composition according to the above, wherein the step of generating an extract comprises at least one step of suspending the part of the Cannabis plant in a solvent, gas or any combination thereof. [0053] It is another object of the present application to disclose the composition according to the above, wherein the gas is carbon dioxide, or other gases in isolation or combination.

[0054] It is another object of the present application to disclose the composition according to the above, wherein the carbon dioxide is characterized as being supercritical.

[0055] It is another object of the present application to disclose the composition according to the above, wherein the solvent is selected from the group consisting of ethanol, propanol, butanol, hexane, chloroform, dichloromethane, acetone, water and any mixture thereof.

[0056] It is another object of the present application to di sclose the composition according to the above, wherein the step of extraction compromises steps of proving the solvent and the plant at a ratio of 1 part Cannabis to 5-10 parts of solvent, by weight.

[0057] It is another object of the present application to disclose the composition according to the above, wherein the step of generating an extract comprises at least one step, selected from the group consisting of Soxhlet extraction, solvent-extraction, solvent-free-extraction, super-critical fluid extraction, the application of pressure and/or heat, or combinations thereof.

[0058] It is another object of the present application to disclose the composition according to the above, wherein the method additionally comprising a step of preparing a plant sample, comprising at least one step selected from the group consisting of tearing, crushing, cutting, shredding, milling and pulverizing.

[0059] It is another object of the present application to disclose the composition according to the above, wherein the method additionally comprising at least one step of separating liquid and solid phases.

[0060] It is another object of the present application to di sclose the composition according to the above, wherein the step of separating the liquid and solid phases is conducted by at least one method selected from the group consisting of decanting, centrifugation, rotary evaporation, benchtop evaporation via the application of heat, evaporation under a stream of inert gas, evaporation under reduced pressure, filtration. [0061] It is another object of the present application to disclose the composition according to the above, wherein the method additionally comprising a step of decarboxylation.

[0062] It is another object of the present application to disclose the composition according to the above, comprising THC to CBD at a ratio of 1 : 1.66 to 1.4: 1 , by weight.

[0063] It is another object of the present application to di sclose the composition according to the above, additionally comprising at least one other cannabinoids selected from the group consisting of THCVA, THCV THCOA, THCO, THC-C7 (THCP), THC-C6, THC-C4 (THCB), THCA-OAc, THCA-C7 (THCPA), THCA-C6, THCA-C4 (THCBA), Sesqui-CBGA, Sesqui-CBG, OH-CBNA, OH-CBN, d9-THCMA, d9- THCM, d9-THCA, d9-THC, d8-THC, CNF-B, CNF-A, CBTV-3, CBTV-1, CBTA-3, CBTA-1, CBT-3, CBT-2, CBT-1, CBNVA, CBNV, CBNOA, CBNO, CBNM, CBNDVA, CBNDA, CBND, CBN-C6, CBN-C4 (CBNB), CBNA-C4 (CBNBA), CBNA-8-OH, CBNA, CBN-8-OH, CBN, CBL, CBGVA, CBGV, CBG-OAc, CBGOA, CBGO, CBGMA, CBGM, CBG-C7 (CBGP), CBG-C6, CBG-C4 (CBGB), CBGA-OAc, CBGA-C7 (CBGPA), CBGA-C6, CBGA-C4 (CBGAB), CBGA, CBG, CBEVA, CBEV, CBEA, CBE, CBDVM, CBDVA, CBDV, CBD-OAc, CBDOA, CBDO, CBDMA, CBDM, CBD-C7 (CBDP), CBD-C6, CBD-C4 (CBDB), CBDA- Oac, CBDA-C7 (CBDPA), CBDA-C6, CBDA-C4 (CBDAB), CBDA, CBD, CBCVA, CBCV, CBCOA, CBCO, CBC-C4 (CBCB), CBCA-C4 (CBCBA), CBCA, CBC, Cannabicitran, CA-5992 , 417-15a , 375-19c , 375-19b , 375-19a , 373-15c, 373-15b, 373-12d, 373-12c, 373-12b, 373-12a, 371-14b, 371-14a, 361-17b, 361-17a, 357-16a, 331-18d, 331-18C, 331-18b, 331-18a, 329-l le, 329-l ld, 329-l lc, 329-l lb, 329-l la, 327-13c, 327-13b, 327-13a, 313- 16b and any mixtures or combination thereof.

[0064] It is another object of the present application to disclose the composition according to the above, additionally comprising at least one other non-cannabinoid components selected from terpenes, terpenoids, phenylpropanoids, amino acids, polyamines, hydrocarbons, sugars and related compounds, nitrogenous compounds, non-cannabinoid phenols, fatty acids, flavonoids, sterols, triglycerides, alkanes, squalene, tocopherol, carotenoids, chlorophyll, glycosides, alkaloids, anthocyanins, vitamins, minerals, macronutrients, flavonols, phenolic amides, flavones, phenolic acids and any combination thereof. [0065] It is another object of the present application to disclose the composition according to the above, wherein the flavonol is selected from the group consisting of catechin, epicatechin, flavanone, naringenin, lignanamides, cannabisin a, cannabisin b and cannabisin c;

[0066] It is another object of the present application to di sclose the composition according to the above, wherein the phenolic amide is selected from the group consisting of n-transcaffeoyltyramine, rutin, quercetin-3 -glucoside, kaempferol-3- oglucoside, quercetin and kaempferol;

[0067] It is another object of the present application to disclose the composition according to the above, wherein the flavone is selected from the group consisting of cannflavin a, cannflavin b, luteolin-7-oglucoside, apigenin-7-oglucoside, luteolin and apigenin;

[0068] It is another object of the present application to disclose the composition according to the above, wherein the phenolic acid is selected from the group consisting of hydroxycinnamic acids, chlorogenic acid, caffeic acid, p-coumaric acid, ferulic acid, and isoflavonoid.

[0069] It is another object of the present application to disclose the composition according to the above, wherein the terpene and/or flavonoids are selected from the groups consisting of 1,8-cineole, P-myrcene, P-caryophyllene, cannflavin A, apigenin, quercetin, pulegone, a-Pinene, Camphene, b-Pinene, Sabinene, -(-)b-Myrcene, 3d- Carene, a-Terpinene, D/L-Limonene, p-Cymene, cis-Ocimene, Eucalyptol, trans- Ocimene, D/L-Fenchone, Terpinolene, Linalool, Fenchol, -(-)Camphor, -(-)Isopulegol, D/L-Borneol, Isoborneol, D/L-Menthol, a-Terpineol, Geraniol, Nerol, a-Pulegone, b- Caryophyllene, trans-b-Farnesene, a-Humulene, -(+)Ledene, Valencene, trans- Nerolidol, Caryophyllene oxide, -(+)Cedrol, -(-)Guaiol, (-)a-Bisabolol, cis-Nerolidol, a-Phellandrene, m-Cymene, g-Terpinene, cis-Linalool oxide, trans-Linalool oxide, -/+) -(Terpinen-4-ol, -(-)Bornyl acetate, -(+)Longipinene, a-Curcumene, b-Citronellol, trans-2-pinanol, a-Bulnesol, Selina 4 diene or Selina 3,7 diene.

[0070] It is another object of the present application to disclose the composition according to any of the above, wherein the extraction comprises Sesqui-CBG 82-637 ppm, CBCOA 0-4 ppm, (-)a-Bisabolol 514-968 ppm, (+)-Ledene 307-1175, Linalool 121-2317 ppm, trans-Nerolidol 179-483 and CBG-OAc 10-13 ppm. [0071] It is another object of the present application to disclose the composition according to any of the above, wherein the extraction comprises (-)a-Bisabolol 18-968 ppm, (+)-Ledene 307-1175 ppm, Linalool 121-1538, trans-Nerolidol 179-483 ppm, trans-b-Farnesene 96-214 ppm and CBG-OAc 10-13 ppm.

[0072] It is another object of the present application to di sclose the composition according to the above, for use as a medicament.

[0073] It is another object of the present application to disclose the composition according to the above, for use as anti-inflammatory therapy and/or for pain management.

[0074] It is another object of the present application to disclose the composition according to the above, wherein the composition is used for treating symptoms associated with diseases or disorders selected from acute inflammation, chronic inflammation, pain associated with inflammation, acute pain, chronic pain, nociceptive pain, referred pain, cancer pain, neuropathic pain, psychogenic pain and visceral pain.

[0075] It is another object of the present application to disclose the composition according to the above, wherein the diseases or disorders are selected from autoimmune diseases and disorders, motor neuron diseases and disorders, neurodegenerative diseases and disorders, diabetes, cardiovascular disease (CVD), arthritis and other joint diseases, allergies, chronic obstructive pulmonary disease (COPD), psoriasis, rheumatoid arthritis, Cancer, Chemotherapy-induced peripheral neuropathy (CIPN), Opioid Use Disorder/ Addiction, Carpal Tunnel Syndrome, Osteoarthritis, CRPS/RSD, Osteoporosis, Diabetic Neuropathy, Plantar Fasciitis, Ehlers-Danlos Syndrome (EDS), Postherpetic Neuralgia, Fibromyalgia, Insomnia, Gout, Pelvic Pain, hATTR Amyloidosis, Psoriatic Arthritis, Low Back Pain, Rheumatoid Arthritis, Lupus, Sickle Cell Disease, Lyme Disease, Thigh Pain, Migraine and Headaches, Traumatic Brain Injuries, Neck Pain and TMJ Disorders, Crohn's Disease, inflammatory bowel disorders (IBS and IBD).

[0076] It is another object of the present application to disclose the composition according to the above, wherein the method additionally comprises a step of adding at least one pharmacologically inactive substance.

[0077] It is another object of the present application to disclose the composition according to the above, wherein the pharmacologically inactive substance is selected from pharmaceutically acceptable carriers, diluents, adjuvants, excipients or any combination thereof.

[0078] It is another object of the present application to disclose the composition according to the above, wherein the composition provides a therapeutic effect selected from an anti-inflammatory effect and a pain relief effect.

[0079] It is another object of the present application to di sclose the composition according to the above, wherein the anti-inflammatory effect confers inhibition of immune system cells such as macrophage and lymphocyte cells.

[0080] It is another object of the present application to disclose the composition according to the above, wherein the anti-inflammatory effect confers inhibition of activated immune system cells such as macrophage activated cells by at least 30%.

[0081] It is another object of the present application to disclose the composition according to the above, wherein the anti-inflammatory effect confers reduced proliferation of activated immune system cells such as lymphocyte activated cells by at least 40%.

[0082] It is another object of the present application to di sclose the composition according to the above, wherein the pain relief effect confers inhibition, reduction or prevention of nociceptive pain symptoms by at least 20%.

[0083] It is the object of the present application to disclose a method of producing a composition for the management of pain and inflammation, comprising steps of: a. obtaining at least one Cannabis plant variety selected from 'Precise-A', 'Precise- B', 'Precise-C, 'Precise-D' or 'Precise-E', or from any part of the Cannabis plant thereof; and b. generating an extract from the Cannabis plant; wherein the composition comprises: i. tetrahydrocannabinol (THC) or a derivative thereof in an amount of 40% to 65% by weight, and Cannabidio (CBD) in an amount of less than 1%; or ii. THC or a derivative thereof in an amount of 15% to 35% by weight, and CBD in an amount of 25% to 35% by weight.

[0084] It is another object of the present application to disclose the method according to the above, wherein the Cannabis plant part is characterized as inflorescences.

[0085] It is another object of the present application to disclose the method according to the above, wherein the inflorescences comprises 0.11-0.33% CBCA, <0.1% CBDA, <0.1% CBDVA, 0.03-0.41% CBG, 0.09-0.4% CBGA, <0.1%CBN, <0.1% CBNA, 0.4-0.6% THC, 9.29-15.93% THCA and <0.1% CBD.

[0086] It is another object of the present application to disclose the method according to the above, wherein the step of generating an extract comprises at least one step of suspending the part of the Cannabis plant in a solvent, gas or any combination thereof.

[0087] It is another object of the present application to disclose the method according to the above, wherein the gas is carbon dioxide.

[0088] It is another object of the present application to disclose the method according to the above, wherein the carbon dioxide is characterized as being supercritical.

[0089] It is another object of the present application to disclose the method according to the above, wherein the solvent is selected from the group consisting of ethanol, propanol, butanol, hexane, chloroform, dichloromethane, acetone, water and any mixture thereof.

[0090] It is another object of the present application to disclose the method according to the above, wherein the step of extraction comprising steps of providing the solvent and the plant at a ratio of 1 part Cannabis to 5-10 parts of solvent, by weight.

[0091] It is another object of the present application to disclose the method according to the above, wherein the step of generating an extract comprises at least one step, selected from the group consisting of Soxhlet extraction, solvent-extraction, solvent-free-extraction, super-critical fluid extraction, the application of pressure and/or heat, or combinations thereof. [0092] It is another object of the present application to disclose the method according to the above, additionally comprising a step of preparing a plant sample, comprising at least one step selected from the group consisting of tearing, crushing, cutting, shredding, milling and pulverizing.

[0093] It is another object of the present application to disclose the method according to the above, additionally comprising at least one step of separating liquid and solid phases.

[0094] It is another object of the present application to disclose the method according to the above, wherein the step of separating the liquid and solid phases is conducted by at least one method selected from the group consisting of decanting, centrifugation, rotary evaporation, benchtop evaporation via the application of heat, evaporation under a stream of inert gas, evaporation under reduced pressure, filtration.

[0095] It is another object of the present application to disclose the method according to the above, additionally comprising a step of de-carboxylation.

[0096] It is another object of the present application to disclose the method according to the above, wherein the composition comprises THC to CBD at a ratio of 1:1.66 to 1.4:1, by weight.

[0097] It is another object of the present application to disclose the method according to the above, wherein the composition additionally comprising at least one other cannabinoids selected from the group consisting of THCVA, THCV THCOA, THCO, THC-C7 (THCP), THC-C6, THC-C4 (THCB), THCA-OAc, THCA-C7 (THCPA), THCA-C6, THCA-C4 (THCB A), Sesqui-CBGA, Sesqui-CBG, OH-CBNA, OH-CBN, d9-THCMA, d9-THCM, d9-THCA, d9-THC, d8-THC, CNF-B, CNF- A, CBTV-3, CBTV-1, CBTA-3, CBTA-1, CBT-3, CBT-2, CBT-1, CBNVA, CBNV, CBNOA, CBNO, CBNM, CBNDVA, CBNDA, CBND, CBN-C6, CBN-C4 (CBNB), CBNA-C4 (CBNBA), CBNA-8-OH, CBNA, CBN-8-OH, CBN, CBL, CBGVA, CBGV, CBG-OAc, CBGOA, CBGO, CBGMA, CBGM, CBG-C7 (CBGP), CBG-C6, CBG-C4 (CBGB), CBGA-OAc, CBGA-C7 (CBGPA), CBGA-C6, CBGA-C4 (CBGAB), CBGA, CBG, CBEVA, CBEV, CBEA, CBE, CBDVM, CBDVA, CBDV, CBD-OAc, CBDOA, CBDO, CBDMA, CBDM, CBD-C7 (CBDP), CBD-C6, CBD-C4 (CBDB), CBDA-Oac, CBDA-C7 (CBDPA), CBDA-C6, CBDA-C4 (CBDAB), CBDA, CBD, CBCVA, CBCV, CBCOA, CBCO, CBC-C4 (CBCB), CBCA-C4 (CBCBA), CBCA, CBC, Cannabicitran, CA-5992 , 417-15a , 375-19c , 375-19b , 375- 19a , 373-15c, 373-15b, 373-12d, 373-12c, 373-12b, 373-12a, 371-14b, 371-14a, 361- 17b, 361-17a, 357-16a, 331-18d, 331-18c, 331-18b, 331-18a, 329-l le, 329-l ld, 329- 11c, 329-1 lb, 329-1 la, 327-13c, 327-13b, 327-13a, 313-16b and any mixtures or combination thereof.

[0098] It is another object of the present application to disclose the method according to the above, wherein the composition additionally comprising at least one other non-cannabinoid components selected from terpenes, terpenoids, phenylpropanoids, amino acids, polyamines, hydrocarbons, sugars and related compounds, nitrogenous compounds, non-cannabinoid phenols, fatty acids, flavonoids, sterols, triglycerides, alkanes, squalene, tocopherol, carotenoids, chlorophyll, glycosides, alkaloids, anthocyanins, vitamins, minerals, macronutrients, flavonols, phenolic amides, flavones and phenolic acids any combination thereof.

[0099] It is another object of the present application to disclose the method according to the above, wherein the flavonol is selected from the group consisting of catechin, epicatechin, flavanone, naringenin, lignanamides, cannabisin a, cannabisin b and cannabisin c.

[00100] It is another object of the present application to disclose the method according to the above, wherein the phenolic amide is selected from the group consisting of n-transcaffeoyltyramine, rutin, quercetin-3 -glucoside, kaempferol-3- oglucoside, quercetin and kaempferol.

[00101] It is another object of the present application to disclose the method according to the above, wherein the flavone is selected from the group consisting of cannflavin a, cannflavin b, luteolin-7-oglucoside, apigenin-7-oglucoside, luteolin and apigenin;

[00102] It is another object of the present application to disclose the method according to the above, wherein the phenolic acid is selected from the group consisting of hydroxycinnamic acids, chlorogenic acid, caffeic acid, p-coumaric acid, ferulic acid, and isoflavonoid.

[00103] It is another object of the present application to disclose the method according to the above, wherein the terpene and/or flavonoids are selected from the groups consisting of 1,8-cineole, P-myrcene, P-caryophyllene, cannflavin A, apigenin, quercetin, pulegone, a-Pinene, Camphene, b-Pinene, Sabinene, -(-)b-Myrcene, 3d- Carene, a-Terpinene, D/L-Limonene, p-Cymene, cis-Ocimene, Eucalyptol, trans- Ocimene, D/L-Fenchone, Terpinolene, Linalool, Fenchol, -(-)Camphor, -(-)Isopulegol, D/L-Borneol, Isoborneol, D/L-Menthol, a-Terpineol, Geraniol, Nerol, a-Pulegone, b- Caryophyllene, trans-b-Farnesene, a-Humulene, -(+)Ledene, Valencene, trans- Nerolidol, Caryophyllene oxide, -(+)Cedrol, -(-)Guaiol, (-)a-Bisabolol, cis-Nerolidol, a-Phellandrene, m-Cymene, g-Terpinene, cis-Linalool oxide, trans-Linalool oxide, -/+) -(Terpinen-4-ol, -(-)Bornyl acetate, -(+)Longipinene, a-Curcumene, b-Citronellol, trans-2-pinanol, a-Bulnesol, Selina 4 diene or Selina 3,7 diene.

[00104] It is another object of the present application to disclose the method according to any of the above, wherein the extract comprises Sesqui-CBG 82-637 ppm, CBCOA 0-4 ppm, (-)a-Bisabolol 514-968 ppm, (+)-Ledene 307-1175, Linalool 121- 2317 ppm, trans-Nerolidol 179-483 and CBG-OAc 10-13 ppm.

[00105] It is another object of the present application to disclose the method according to any of the above, wherein the extract comprises (-)a-Bisabolol 18-968 ppm, (+)-Ledene 307-1175 ppm, Linalool 121-1538, trans-Nerolidol 179-483 ppm, trans-b-Farnesene 96-214 ppm and CBG-OAc 10-13 ppm.

[00106] It is the object of the present application to disclose method of treating a disorder associated with inflammation and/or pain, comprising steps of: a. obtaining the composition or preparation of any one of the above; and b. administering a pharmacologically active dose of the composition or preparation to a subject;

[00107] It is another object of the present application to disclose the method according to the above, wherein the pain or inflammation is selected from acute inflammation, chronic inflammation, pain associated with inflammation, acute pain, chronic pain, nociceptive pain, referred pain, cancer pain, neuropathic pain, psychogenic pain and visceral pain.

[00108] Additional features and advantages of the invention will become apparent from the following drawings and description. BRIEF DESCRIPTION OF THE DRAWINGS

[00109] For a better understanding of the invention and to show how the same may be carried into effect, reference will now be made, purely by way of example, to the accompanying drawings in which like numerals designate corresponding elements or sections throughout.

[00110] With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of the preferred embodiments of the present invention only, and are presented in the cause of providing what is believed to be the most useful and readily understood description of the principles and conceptual aspects of the invention. In this regard, no attempt is made to show structural details of the invention in more detail than is necessary for a fundamental understanding of the invention, the description taken with the drawings making apparent to those skilled in the art how the several forms of the invention may be embodied in practice. In the accompanying drawings:

[00111] FIGs 1A - 1C graphically illustrate the effect of extracts of different Cannabis varieties on NO production of activated RAW cells, as compared to negative and positive controls;

[00112] FIG. 2 graphically illustrate viability (%) of RAW cells treated with different Cannabis extracts as compared to non-treated control cells;

[00113] FIG. 3 graphically illustrate the inhibitory effect of extracts from different Cannabis varieties on proliferation of lymphocyte immune system cells;

[00114] FIGs 4A-4B graphically illustrate movement reduction of zebrafish larvae exposed to Cannabis extract (Fig. 4A- variety 'Precise-C and 'Precise-E' extracts, Fig. 4B-variety 'Precise-A', 'Precise-B' and 'Precise-D' extracts) as compared to positive and negative controls;

[00115] FIGs 5A-C show representative photographs of the new variety 'Precise- A' grown under controlled greenhouse conditions. FIG. 5 A shows an overall view of variety 'Precise-A' at a reproductive stage (about 6 to 8 weeks post flowering), FIG. 5B shows a close view of an inflorescence of variety 'Precise-A' at a reproductive stage (about 6 to 8 weeks post flowering), and FIG. 5C shows an overall view of variety 'Precise-A' at a vegetative stage (about 4 to 5 weeks post planting); [00116] FIGs 6A-C show representative photographs of the new variety 'Precise- B' grown under controlled greenhouse conditions. FIG. 6A shows an overall view of variety 'Precise-B' at a reproductive stage (about 6 to 8 weeks post flowering); FIG. 6B shows a close view of top parts, including inflorescence of variety 'Precise-B' at a reproductive stage (about 6 to 8 weeks post flowering), and FIG. 6C shows an overall view of variety 'Precise-B' at a vegetative stage (about 5 to 6 weeks post planting);

[00117] FIGs 7A-C show representative photographs of the new variety 'Precise- C' grown under controlled greenhouse conditions. FIG. 7A shows top parts (including inflorescence) of variety 'Precise-C' at a reproductive stage (about 6 to 8 weeks post flowering), FIG. 7B shows close view of flowers of variety 'Precise-C' at a reproductive stage (about 6 to 8 weeks post flowering), and FIG. 7C shows an overall view of variety 'Precise-C at a vegetative stage (about 4 to 5 weeks post planting);

[00118] FIGs 8A-C show representative photographs of the new variety 'Precise- D' grown under controlled greenhouse conditions. FIG. 8 A shows top parts (including inflorescence and foliage) of variety 'Precise-D' at a reproductive stage (about 6 to 8 weeks post flowering), FIG. 8B shows a close view of flowers of variety 'Precise-D' at a reproductive stage (about 6 to 8 weeks post flowering), and FIG. 8C shows an overall view of variety 'Precise-D' at a vegetative stage (about 4 to 5 weeks post planting); and

[00119] FIGs 9A-B show representative photographs of the new variety 'Precise- E' grown under controlled greenhouse conditions. FIG. 9A shows an overall view of variety 'Precise-E' at a vegetative stage (about 2 weeks post planting), and FIG. 9B shows an overall view of variety 'Precise-E' at a vegetative stage (about 5 to 6 weeks post planting).

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[00120] Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details of construction and the arrangement of the components set forth in the following description or illustrated in the drawings. The invention is applicable to other embodiments or of being practiced or carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting. [00121] In one embodiment, the present invention provides Cannabis derived compositions or preparations in various dosage forms, effective in treatment or reduction of inflammation and/or pain related indications, disorders, conditions or symptoms.

[00122] It is also within the scope to provide a composition comprising a Cannabis derived extract for use in the treatment of inflammation and/or pain related disorders. The aforementioned extract comprising: Tetrahydrocannabinol (THC) or a derivative thereof in an amount of about 35% to about 70% by weight, and Cannabidiol (CBD) in an amount of less than 1% by weight; or THC or a derivative thereof in an amount of about 15% to about 35% by weight, and CBD in an amount of 25% to 35% by weight.

[00123] According to a further embodiment, the present invention provides a medicament comprising an effective amount of a composition as defined in any of the above.

[00124] It is further within the scope to disclose use of a Cannabis extract in the preparation of a medicament for treating an inflammation or pain disorder, wherein the Cannabis extract is as defined in any one of the above.

[00125] According to a further embodiment, the present invention provides a Cannabis based preparation for inhalation, for use in the treatment of inflammation and/or pain related disorders, comprising the composition as defined in any of the above.

[00126] It is also within the scope of the present invention to provide a method for treating pain and/or inflammation related disorders, the method comprising administering to a patient in need thereof an effective amount of the composition as defined in any of the above, or a medicament as defined in any of the above or a Cannabis based preparation as defined in any of the above.

[00127] According to a further embodiment, the present invention provides a composition comprising a Cannabis derived extract for use in the treatment of inflammation and/or pain related disorders, produced according to a method comprising steps of:

[00128] obtaining at least one part of a Cannabis plant variety selected from 'Precise- A', 'Precise-B', 'Precise-C, 'Precise-D' or 'Precise-E'; [00129] generating an extract from said Cannabis plant part;

[00130] wherein the composition comprises:

[00131] tetrahydrocannabinol (THC) or a derivative thereof in an amount of 40% to 65% by weight, and Cannabidiol (CBD) in an amount of less than 1%; or

[00132] THC or a derivative thereof in an amount of 15% to 35% by weight, and CBD in an amount of 25% to 35% by weight.

[00133] In another embodiment, the present invention provides a method of producing a composition for the management of pain and inflammation, comprising steps of:

[00134] obtaining at least one Cannabis plant variety selected from 'Precise-A', 'Precise-B', 'Precise-C, 'Precise-D' or 'Precise-E', or from any part of the Cannabis plant thereof; and

[00135] generating an extract from said Cannabis plant;

[00136] wherein the composition comprises:

[00137] tetrahydrocannabinol (THC) or a derivative thereof in an amount of 40% to 65% by weight, and Cannabidio (CBD) in an amount of less than 1%; or

[00138] THC or a derivative thereof in an amount of 15% to 35% by weight, and CBD in an amount of 25% to 35% by weight.

[00139] According to a further embodiment, the present invention provides a method of treating a disorder associated with inflammation and/or pain, comprising steps of:

[00140] obtaining the composition or preparation of any one of claim 1-31, 34- 45 and 38-71; and

[00141] administering a pharmacologically active dose of said composition or preparation to a subject.

[00142] It is within the scope of the present invention to disclose a composition comprising a Cannabis derived extract for use in the treatment of inflammation and/or pain related disorders, the extract comprising tetrahydrocannabinol (THC) or a derivative thereof in an amount of about 15% to about 70% by weight. [00143] According to a further embodiment, the present invention provides a medicament comprising an effective amount of a Cannabis- based composition comprising tetrahydrocannabinol (THC) or a derivative thereof in an amount of about 15% to about 70% by weight.

[00144] The present invention further discloses the use of a Cannabis extract as defined in any of the above, in the preparation of a medicament for treating an inflammation or pain related disorder or condition.

[00145] It is also within the scope of the present invention to provide a new and distinct variety selected from a Cannabis plant variety named 'Precise-A', 'Precise-B', 'Precise-C, 'Precise-D' or 'Precise-E', substantially as illustrated and described herein.

[00146] It is further within the scope to disclose a Cannabis based preparation derived from a variety selected from Cannabis plant variety named 'Precise-A', 'Precise-B', 'Precise-C, 'Precise-D' or 'Precise-E', or any plant part thereof, such as inflorescence.

[00147] According to a further embodiment, the present invention provides a Cannabis based preparation for inhalation, for use in the treatment of inflammation and/or pain related disorders, comprising THC or a derivative thereof in an amount of 5% to 25% by weight.

[00148] In further aspects of the current invention, a method for treating pain and inflammation related disorders is disclosed. The method comprising administering to a patient in need thereof an effective amount of the composition, or a medicament, or a Cannabis based preparation as defined in any of the above.

[00149] In another embodiment, the present invention provides a composition or Cannabis preparation as defined in any of the above, for use in the treatment of inflammation and pain related disorders or conditions.

[00150] The inventors of the present invention developed medical Cannabis products that provide users with pain relief and anti-inflammatory properties.

[00151] The present invention reports positive pre-clinical/clinical results of preparations from Cannabis developed genetic lines showing anti-inflammatory and pain relief properties. These studies were repeated with Cannabis from independent cultivation cycles, and several developed varieties consistently exhibited positive results. The compositions and preparations of the present invention were produced based on the best preforming developed screened varieties. Thus, the Cannabis based compositions and preparations of the present invention provides a potential solution for specific, difficult to treat, medical conditions, such as pain or inflammatory diseases, for which ideal treatments are lacking.

[00152] It is further within the scope that the medical Cannabis varieties of the present invention are impressively effective in reducing pain and inflammation. It is emphasized that, breeding whole Cannabis plants such that they contained specific compounds in specific quantities and tailored ratios in order to be effective in treating specific disease targets, with minimal adverse events, is, according to some embodiments, what is aimed and achieved by the current invention.

[00153] Thus, in some aspects, the present invention provides medical Cannabis products that specifically target pain and inflammation.

[00154] Medical Cannabis is typically provided in the form of the dried, unfertilized, female flowers prepared so that it is suitable for smoking.

[00155] Furthermore, the effects of Cannabis preparations are not limited to the cannabinoids present, as terpene contents can also be relevant. Therefore, as will be described herein, there is a great, and presently unmet, potential of Cannabis-plant preparations or extracts, especially inflorescence enriched preparations, formulated in such a way as to provide a standardized dose of medically relevant ingredient. Such preparations may be derived from individual lines or varieties or multiple lines of Cannabis, or from one or more tissues of a given line or variety, or multiple varieties.

[00156] Described herein are compositions that approximate an inflorescence enriched Cannabis extract for administration to patients via many different routes. In typical aspects, the extracts are prepared from different parts of one or more Cannabis varieties, such as from the leaves or trimmed flowers. These extracts are typically diluted, for example with an oil, such as olive oil and/or soybean oil and/or coconut oil. The composition may be administered as-is, or it may be further formulated into, for example, a tablet, capsule, a lozenge, a mint, a chewing gum, an edible food or beverage product, a suppository, or a pessary, or modified for administration parenterally, such as via inhalation. [00157] According to further aspects, the Cannabis based compositions of the present invention are useful for treating or alleviating pain and inflammation related symptoms and disorders in a subject.

[00158] The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used in the description of the invention and the appended claims, the singular forms “a”, “an,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. Moreover, the term “or” is intended to mean an inclusive “or” rather than an exclusive “or.” It will also be understood that the term “and/or” as used herein refers to and encompasses any and all possible combinations of one or more of the associated listed items. It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof.

[00159] It will be understood that any aspects described as “comprising” certain components may also “consist of’ or “consist essentially of,” wherein “consisting of’ has a closed-ended or restrictive meaning and “consisting essentially of’ means including the components specified but excluding other components except for materials present as impurities, unavoidable materials present as a result of processes used to provide the components, and components added for a purpose other than achieving the technical effect of the invention. For example, a composition defined using the phrase “consisting essentially of’ encompasses any known pharmaceutically acceptable additive, excipient, diluent, carrier, and the like. A composition consisting essentially of a set of specified components may comprise less than 5% by weight, typically less than 3% by weight, more typically less than 1% by weight of nonspecified components.

[00160] It will be understood that any component defined herein as being included may be explicitly excluded from the claimed invention by way of proviso or negative limitation.

[00161] In addition, all ranges given herein include the end of the ranges and also any intermediate range points, whether explicitly stated or not. [00162] The terms “include”, “comprise” and “have” and their conjugates as used herein mean “including but not necessarily limited to”.

[00163] The term "essentially" as used herein is meant to be understood as at least partially comprising an indicated substance.

[00164] Finally, terms of degree such as “substantially”, “about” and “approximately” as used herein mean a reasonable amount of deviation of the modified term such that the end result is not significantly changed. These terms of degree should be construed as including a deviation of at least ±25% of the modified term if this deviation would not negate the meaning of the word it modifies.

[00165] Thus, as used herein the term "about" denotes ± 25% of the defined amount or measure or value.

[00166] As used herein the term "similar" denotes a correspondence or resemblance range of about ± 20%, particularly ± 15%, more particularly about ± 10% and even more particularly about ± 5%.

[00167] As used herein the term "corresponding" generally means similar, analogous, like, alike, akin, parallel, identical, resembling or comparable. In further aspects it means having or participating in the same relationship (such as type or species, kind, degree, position, correspondence, or function). It further means related or accompanying. In some embodiments of the present invention it refers to plants of the same Cannabis species or strain or variety or to sibling plant, or one or more individuals having one or both parents in common.

[00168] As used herein, the terms “related”, “in connection”, or “associated”, or “relevant”, and similar, depending on the context, means any association, whether direct or indirect, by any applicable criteria as the case may be.

[00169] The word “exemplary” is used herein to mean “serving as an example, instance, or illustration”. And no aspect of this disclosure shall be construed as preferred or advantageous over other aspects or designs unless expressly stated.

[00170] A "plant" as used herein refers to any plant at any stage of development, particularly a seed plant. The term "plant" includes the whole plant or any parts or derivatives thereof, such as plant cells, seeds, plant protoplasts, plant cell tissue culture from which Cannabis plants can be regenerated, plant callus or calli, meristematic cells, microspores, embryos, immature embryos, pollen, ovules, anthers, fruit, inflorescence, flowers, leaves, cotyledons, pistil, seeds, seed coat, roots, root tips and the like.

[00171] The term "plant cell" used herein refers to a structural and physiological unit of a plant, comprising a protoplast and a cell wall. The plant cell may be in a form of an isolated single cell or a cultured cell, or as a part of higher organized unit such as, for example, plant tissue, a plant organ, or a whole plant.

[00172] The term "plant material" or "plant part" used herein refers to leaves, stems, roots, root tips, inflorescences, flowers or flower parts, fruits, pollen, egg cells, zygotes, seeds, seed coat, cuttings, cell or tissue cultures, or any other part or product of a plant or a combination thereof.

[00173] A "plant organ" as used herein means a distinct and visibly structured and differentiated part of a plant such as a root, stem, leaf, inflorescence, flower, flower bud, or embryo.

[00174] The term "plant tissue" as used herein means a group of plant cells organized into a structural and functional unit. Any tissue of a plant in planta or in culture is included. This term includes, but is not limited to, whole plants, plant organs, plant seeds, tissue culture, protoplasts, meristematic cells, calli and any group of plant cells organized into structural and/or functional units. The use of this term in conjunction with, or in the absence of, any specific type of plant tissue as listed above or otherwise embraced by this definition is not intended to be exclusive of any other type of plant tissue.

[00175] As used herein, the term "progeny" or "progenies" refers in a nonlimiting manner to offspring or descendant plants. According to certain embodiments, the term "progeny" or "progenies" refers to plants developed or grown or produced from the disclosed or deposited seeds as detailed inter alia. The grown plants preferably have the desired traits of the disclosed or deposited plant material.

[00176] The term “Cannabis” refers hereinafter to a genus of flowering plants in the family Cannabaceae. Cannabis is an annual, dioecious, flowering herb that includes, any member of the genus Cannabis, including but not limited to three different species, Cannabis sativa, Cannabis indica, and Cannabis ruderalis, as well as any strains, lines, varieties or hybrids thereof. The term also refers to hemp. It is noted that any reference to Cannabis sativa includes any Cannabis sub-species or hybrid thereof. The term “Cannabis” also includes whole Cannabis plants as well as portions and tissues of Cannabis plants, especially Cannabis inflorescence. Cannabis plants produce a group of chemicals called cannabinoids. Cannabinoids, terpenoids, and other compounds are secreted by glandular trichomes that occur most abundantly on the floral calyxes and bracts of female Cannabis plants. Different Cannabis varieties significantly vary in their chemical compositions. The concentration of Cannabis’s compounds depends on the plant’ s tissue-type, age, variety, growth conditions (for example nutrition, humidity and light levels), harvest time, and storage conditions.

[00177] The term “trichome” refers to fine glandular outgrowths on sinsemilla that secrete cannabinoids and terpenes.

[00178] The term “trim” refers to the leafy parts of a Cannabis plant, particularly those found near sinsemilla, which therefore also tend to be enriched in trichomes.

[00179] The term “cannabinoid” refers to any one or more of the over 144known members of the phytocannabinoid family, including, for example, A9- tetrahydrocannabinol (THC), A9-tetrahydrocannabivarin (THCV), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), and cannabichromene (CBC). An exemplary list of known phytocannabinoids in Cannabis, included within the scope of the current invention may be derived from the publication "A new ESI-LC/MS approach for comprehensive metabolic profiling of phytocannabinoids in Cannabis, Paula Berman, et al. Scientific Reports (2018) 8:14280 and the Supporting Information for Publication A new ESI-LC/MS approach for comprehensive metabolic profiling of phytocannabinoids in Cannabis, including in its entirety by reference. Cannabinoids are compounds usually derived from Cannabis saliva. an annual plant in the Cannabaceae family. The plant contains more than hundreds of different components, with above 144 compounds of these belonging to the class of cannabinoids. The most active naturally occurring cannabinoids are (-)-A9-trans-tetrahydrocannabinol (A9-THC) and cannabidiol (CBD).

[00180] According to further aspects of the present invention, the term "cannabinoid" refers hereinafter to a class of diverse chemical compounds that act on cannabinoid receptors on cells that repress neurotransmitter release in the brain. These cannabinoids include the endocannabinoids (produced naturally in the body by humans and animals), the phytocannabinoids (found in Cannabis and some other plants), and synthetic cannabinoids.

[00181] In the context of the current invention, cannabinoids are naturally occurring compounds found in the Cannabis sativa plant. Few hundred different active compounds present in the plant, only around 144 are termed cannabinoids. The most well known among these compounds is the delta-9-tetrahydrocannabinol (A9-THC), which is the main psychoactive ingredient in Cannabis. Cannabidiol (CBD) is another important component, which encompass about 50% or more of the plant resin extract, in certain varieties. Cannabinoids exert their effects by interacting with specific cannabinoid receptors present on the surface of cells. These receptors are found in different parts of the central nervous system and the two main known types of cannabinoid receptors in the body are CB1 and CB2. The effects of cannabinoids depends on the brain area involved. Effects on the limbic system may alter the memory, cognition and psychomotor performance; effects on the mesolimbic pathway may affect the reward and pleasure responses and pain perception may also be altered.

[00182] The main classes of cannabinoids include: Cannabigerols (CBG), Cannabichromenes (CBC), Cannabidiol (CBD), Tetrahydrocannabinol (THC), Cannabinol (CBN), Cannabinodiol (CBDL) and other cannabinoids including cannabicyclol (CBL), cannabielsoin (CBE) and cannabitriol (CBT), and their acid forms.

[00183] The main cannabinoids are concentrated in a viscous resin produced in structures known as glandular trichomes.

[00184] According to further aspects, the following cannabinoids are included, in a non-limiting manner, within the scope of the current invention: Cannabichromenes, Cannabichromene (CBC), Cannabichromenic acid (CBCA), Cannabichromevarin (CBCV), Cannabichromevarinic acid (CBCVA), Cannabicyclols, Cannabicyclol (CBL), Cannabicyclolic acid (CBLA), Cannabicyclovarin (CBLV), Cannabidiols, Cannabidiol (CBD), Cannabidiol monomethylether (CBDM), Cannabidiolic acid (CBDA), Cannabidiorcol (CBD-C1), Cannabidivarin (CBDV), Cannabidivarinic acid (CBDVA), Cannabielsoins, Cannabielsoic acid B (CBEA-B), Cannabielsoin (CBE), Cannabielsoin acid A (CBEA-A), Cannabigerols, Cannabigerol (CBG), Cannabigerol monomethylether (CBGM), Cannabigerolic acid (CBGA), Cannabigerolic acid monomethylether (CBGAM), Cannabigerovarin (CBGV), Cannabigerovarinic acid (CBGVA), Cannabinols and cannabinodiols, Cannabinodiol (CBND), Cannabinodivarin (CBVD), Cannabinol (CBN), Cannabinol methylether (CBNM), Cannabinol-C2 (CBN-C2), Cannabinol-C4 (CBN-C4), Cannabinolic acid (CBNA), Cannabiorcool (CBN-C1), Cannabivarin (CBV), Cannabitriols, 10-Ethoxy-9-hydroxy- delta-6a-tetrahydrocannabinol, 8,9-Dihydroxy-delta-6a-tetrahydrocannabinol,

Cannabitriol (CBT), Cannabitriolvarin (CBTV), Delta-8-tetrahydrocannabinols, Delta- 8-tetrahydrocannabinol (A8-THC), Delta-8-tetrahydrocannabinolic acid (A8-THCA), Delta-9-tetrahydrocannabinols, Delta-9-tetrahydrocannabinol (THC), Delta-9- tetrahydrocannabinol-C4 (THC-C4), Delta-9-tetrahydrocannabinolic acid A (THCA- A), Delta-9-tetrahydrocannabinolic acid B (THCA-B), Delta-9-tetrahydrocannabinolic acid-C4 (THCA-C4), Delta-9-tetrahydrocannabiorcol (THC-C1), Delta-9- tetrahydrocannabior colic acid (THCA-C1), Delta-9-tetrahydrocannabivarin (THCV), Delta-9-tetrahydrocannabivarinic acid (THCVA), Miscellaneous cannabinoids, 10- Oxo-delta-6a-tetrahydrocannabinol (OTHC), Cannabichromanon (CBCF), Cannabifuran (CBF), Cannabiglendol, Cannabiripsol (CBR), Cannbicitran (CBT), Dehydrocannabifuran (DCBF), Delta-9-cis-tetrahydrocannabinol (cis-THC), Tryhydroxy-delta-9-tetrahydrocannabinol (triOH-THC) and any mixtures or combination thereof.

[00185] According to further aspects of the present invention, non-limiting examples of cannabinoid compounds included within the compositions or preparations of the present invention are selected from THCVA, THCV THCOA, THCO, THC-C7 (THCP), THC-C6, THC-C4 (THCB), THCA-OAc, THCA-C7 (THCPA), THCA-C6, THCA-C4 (THCBA), Sesqui-CBGA, Sesqui-CBG, OH-CBNA, OH-CBN, d9- THCMA, d9-THCM, d9-THCA, d9-THC, d8-THC, CNF-B, CNF-A, CBTV-3, CBTV- 1, CBTA-3, CBTA-1, CBT-3, CBT-2, CBT-1, CBNVA, CBNV, CBNOA, CBNO, CBNM, CBNDVA, CBNDA, CBND, CBN-C6, CBN-C4 (CBNB), CBNA-C4 (CBNBA), CBNA-8-OH, CBNA, CBN-8-OH, CBN, CBF, CBGVA, CBGV, CBG- OAc, CBGOA, CBGO, CBGMA, CBGM, CBG-C7 (CBGP), CBG-C6, CBG-C4 (CBGB), CBGA-OAc, CBGA-C7 (CBGPA), CBGA-C6, CBGA-C4 (CBGAB), CBGA, CBG, CBEVA, CBEV, CBEA, CBE, CBDVM, CBDVA, CBDV, CBD-OAc, CBDOA, CBDO, CBDMA, CBDM, CBD-C7 (CBDP), CBD-C6, CBD-C4 (CBDB), CBDA-Oac, CBDA-C7 (CBDPA), CBDA-C6, CBDA-C4 (CBDAB), CBDA, CBD, CBCVA, CBCV, CBCOA, CBCO, CBC-C4 (CBCB), CBCA-C4 (CBCBA), CBCA, CBC, Cannabicitran, CA-5992 , 417-15a , 375-19c , 375-19b , 375-19a , 373-15c, 373- 15b, 373-12d, 373-12c, 373-12b, 373-12a, 371-14b, 371-14a, 361-17b, 361-17a, 357- 16a, 331-18d, 331-18c, 331-18b, 331-18a, 329-l le, 329-l ld, 329-l lc, 329-l lb, 329- 11a, 327-13c, 327-13b, 327-13a, 313- 16b and any mixtures or combination thereof.

[00186] Reference is now made to Tetrahydrocannabinol (THC), the primary psychoactive component of the Cannabis plant. Delta-9-tetrahydrocannabinol or (-)- A9-trans-tetrahydrocannabinol (A9-THC) or tetrahydrocannabinol (THC) are herein used interchangeably. A9-THC and delta-8-tetrahydrocannabinol (A8-THC), through intracellular CB 1 activation, induce anandamide and 2-arachidonoylglycerol synthesis produced naturally in the body and brain. These cannabinoids produce the effects associated with Cannabis by binding to the CB1 cannabinoid receptors in the brain.

[00187] The term total THC is herein meant to include the acid (carboxylated) form THC A and/or THC.

[00188] Reference is now made to Cannabidiol (CBD) which is considered as non-psychotropic. Cannabidiol has little affinity for CB1 and CB2 receptors but acts as an indirect antagonist of cannabinoid agonists. It is further acknowledged herein that it is an antagonist at the putative cannabinoid receptor, GPR55, a GPCR expressed in the caudate nucleus and putamen. Cannabidiol has also been shown to act as a 5-HT1A receptor agonist. The term total CBD is herein meant to include the acid (carboxylated) form CBDA and/or CBD.

[00189] CBD shares a precursor with THC and is the main cannabinoid in CBD- dominant Cannabis strains or varieties.

[00190] The term "cannabinoid receptor" refers hereinafter to a class of cell membrane receptors, for example receptors under the G protein-coupled receptor superfamily. There are main two known subtypes of cannabinoid receptors, termed CB 1 and CB2. The CB 1 receptor is expressed mainly in the brain, but also in the lungs, liver and kidneys. The CB2 receptor is expressed mainly in the immune system and in hematopoietic cells.

[00191] The term "Cannabinoid receptor type 1 (CB1)" refers hereinafter to a G protein-coupled cannabinoid receptor located primarily in the central and peripheral nervous system. It is activated by the endocannabinoid neurotransmitters anandamide and 2-arachidonoyl glyceride (2-AG); by plant cannabinoids, such as the compound THC, an active ingredient of the psychoactive drug Cannabis; and by synthetic analogues of THC.

[00192] The term "Cannabinoid receptor type 2 (CB2)" refers hereinafter to a G protein-coupled receptor from the cannabinoid receptor family that in humans is encoded by the CNR2 gene. It is closely related to the cannabinoid receptor type 1, which is largely responsible for the efficacy of endocannabinoid-mediated presynaptic- inhibition, the psychoactive properties of Tetrahydrocannabinol, the active agent in marijuana, and other phytocannabinoids (natural cannabinoids). The principal endogenous ligand for the CB2 receptor is 2-arachidonoylglycerol (2-AG).

[00193] The term "nonpsychoactive" refers hereinafter to products or compositions or elements or components of Cannabis not significantly affecting the mind or mental processes.

[00194] The natural cannabinoid compounds are readily obtained from plant tissue by suspending the tissue in an appropriate solvent to extract cannabinoid compounds and other tissue components. Analytical purification of such an extract provides pharmaceutical grade cannabinoid compounds. Alternatively, cannabinoid compounds are extracted from plant tissue under carbon dioxide, or other gases in isolation or combination with or without solvent modifiers, selected from ethanol, propanol, butanol, hexane, chloroform, dichloromethane, acetone, or any organic solvent capable of extracting cannabinoids, and alcohol-water mixtures, for instance, water-ethanol or water-butanol mixtures, etc.

[00195] The present invention, in one embodiment, involves producing an extract from Cannabis plant matter, containing tetrahydrocannabinol, cannabidiol and optionally the carboxylic acids thereof. In one embodiment, the dried plant matter is ground and subjected to ethanol extraction and the primary extract obtained may be diluted and/or separated and/or de-carboxylated.

[00196] The term "Cannabis extract" refers hereinafter to any preparation, extract or concentrate or fraction derived from the Cannabis plant. The term “Cannabis extract or a derivative thereof’ refers hereinafter to Cannabis extract or Cannabis concentrates or fractions or compounds (including isolated compounds) thereof that are used as components of the composition of the present invention. Such an extract or a derivative thereof may include cannabinoid-type compounds or fractions, non- cannabinoid-type compounds or fractions and combinations thereof. It further refers to any extract or concentrate derived from the Cannabis plant which contains at least one cannabinoid. The cannabinoids may be extracted from the Cannabis plant using any one of the many known extraction methods, such as non-hydrocarbons extraction methods and hydrocarbons extraction methods. It is also within the scope that the Cannabis extract may be treated by separation or purification or fractionation processes. It further refers to purified or partially purified Cannabis extract containing cannabinoid-type portions or elements. In alternative embodiments, cannabinoid extract or derivative thereof may contain synthetic cannabinoids.

[00197] According to further aspects of the present invention, a Cannabis extract is a concentrate produced with the use of a solvent. “Extract” and “concentrate” are herein used interchangeably. The most common solvents used to make a Cannabis extract include butane, propane, ethanol, and supercritical carbon dioxide (CO2).

[00198] A Cannabis extract or concentrates can be made through the use of both various mechanical processes and the use of a solvent. The extraction process differ slightly based on the specific solvent being used. In general, the process involves combining Cannabis plant materials with another chemical or substance in such a way that all the cannabinoids and other chemical constituents, or fractions thereof, are extracted or removed from the plant matter. The plant matter is then separated from the cannabinoid-infused solvent, and the solvent is evaporated or removed through a predefined mechanism. A mass of concentrated cannabinoids and other chemical compounds is obtained.

[00199] It will be understood that extracts of any portions or tissues of Cannabis plants are included herein. Such portions or tissues include the flowers, inflorescence, leaves, stems, roots, and seeds. More typically, extracts are taken from flowers (e.g., sinsemilla) and leaves (e.g., trim) or may be combined together to approximate a wholeplant Cannabis extract. Different tissues of Cannabis plants contain different concentrations of cannabinoids, terpenes, and other active agents. The tissues used for extraction may be fresh, meaning they have not been dried and/or cured, or they may be dried and/or cured tissues. Combinations of fresh and dried tissues are contemplated for use herein. [00200] The extracts may be obtained through any known extraction method. In some aspects, the extraction method may be Soxhlet extraction, solvent-extraction, solventless-extraction, super-critical fluid extraction, the application of pressure and/or heat, or combinations thereof. Different extraction methods may be used to obtain different extract profiles and/or purity levels, as would be understood by a skilled person.

[00201] In typical aspects, the extracts are prepared through a solvent extraction method. Briefly, the plant tissues are provided whole (e.g. plant inflorescence), torn, crushed, cut, shredded, milled, pulverized, or otherwise mechanically treated and are mixed with a solvent (e.g. ethanol) in any desired ratio. In a typical aspect, about 1 part by weight of Cannabis is mixed with about 8-10 parts by volume of solvent.

[00202] The solvent may be any desired aqueous or non-aqueous liquid, chosen based upon the Cannabis plant tissue being extracted and the desired end-profile of the extract. For example, the solvent may be selected from the group consisting of methanol, ethanol, isopropanol, acetone, acetonitrile, butane, pentane, hexane, cyclohexane, super- or sub-critical carbon dioxide, chloroform, carbon tetrachloride, tetrahydrofuran, turpentine, benzene, toluene, and other organic solvents known to persons skilled in the art, water (which may or may not contain mineral or organic acids, inorganic or organic bases, buffering agents, lipids, fatty acids, and fatty alcohols, or combinations thereof), hemp seed oil, olive oil, soybean oil, coconut oil or other plant or animal derived oils, fats, or waxes, or combinations thereof.

[00203] Once the extraction is completed, the liquid and solid phases are separated by any known method, such as decanting, centrifugation, rotary evaporation, benchtop evaporation via the application of heat, evaporation under a stream of inert gas, evaporation under reduced pressure, filtration, including the use of more than one filtration step, and/or more than one size of filtration membrane, and/or combinations of two or more of any of these means.

[00204] Optionally, the resulting liquid phase may be extracted a second time, for example, by using different solvent, and/or a solvent immiscible with the first solvent. If so, subsequent phase separation may be carried out by the use of separatory funnels, centrifugation, aspiration, cannulation, or combinations thereof. [00205] Optionally, resulting liquid may then be modified in many ways, including, for example, dilution, adjustment of pH, cooling, heating, mixing and subsequent separation from an immiscible co-solvent, or combinations thereof.

[00206] Solvent may be removed from the extract by any known method, such as decanting, centrifugation, rotary evaporation, benchtop evaporation at room temperature or via the application of heat, evaporation under a stream of inert gas, evaporation under reduced pressure, filtration, including the use of more than one filtration step, and/or more than one size of filtration membrane, and/or combinations of two or more of any of these means.

[00207] The Cannabis extracts described herein, may be, in some aspects, formulated into compositions. In typical aspects, the compositions comprise an extract from a Cannabis plant tissue, such as flower tissue. However, extracts from the same type of tissue from two or more different Cannabis varieties may be combined. Furthermore, more than two extracts may be combined, from two or more different varieties. In yet other aspects, the ratio of the two or more extracts is specifically selected to provide the desired chemical profile.

[00208] According to some embodiments, the compositions described herein can be prepared by known methods for the preparation of pharmaceutically acceptable compositions that can be administered to subjects, such that an effective quantity of the active substance is combined in a mixture with a pharmaceutically acceptable vehicle.

[00209] The term "vehicle" generally refers hereinafter to pharmaceutical vehicles or placebo or control group or control treatment which for example include carrier or inert medium used as a solvent (or diluent) in which the medicinally active agent is formulated and or administered. In the context of the present invention, a control or control treatment may include a vehicle only or a combination of ingredients which is used as a control or reference to an experimental group or treatment.

[00210] Thus, the compositions may include, in a non- limited manner, the Cannabis extract(s) in association with one or more pharmaceutically acceptable vehicles or diluents, and may be contained in buffered solutions with a suitable pH to physiological fluids.

[00211] According to one embodiment of the present invention, the Cannabis extract may contain at least one cannabinoid. The cannabinoids may be extracted from the Cannabis plant using any one of the many known extraction methods, such as nonhydrocarbons extraction methods and hydrocarbons extraction methods.

[00212] Over 100 different terpenes have been identified in the Cannabis plant, and every variety tends toward a unique terpene type and composition. It is herein acknowledged that the terpenes act synergistically with the cannabinoids to provide a therapeutic effect. Non limiting examples of some common terpenes found in Cannabis include: Borneol, Caryophyllene, Eucalyptol, Delta3Carene, Limonene, Linalool, Myrcene, Pinene- and Pulegone, including D/L and/or alpha/betta isomers of these terpenes.

[00213] According to further embodiments, examples of terpenes and/or flavonoids included within the compositions or preparations of the present invention may be selected from, 1,8-cineole, P-myrcene, P-caryophyllene, cannflavin A, apigenin, quercetin, pulegone, a-Pinene, Camphene, b-Pinene, Sabinene, -(-)b- Myrcene, 3d-Carene, a-Terpinene, D/L-Limonene, p-Cymene, cis-Ocimene, Eucalyptol, trans-Ocimene, D/L-Fenchone, Terpinolene, Linalool, Fenchol, -(-) Camphor, -(-)Isopulegol, D/L-Bomeol, Isoborneol, D/L-Menthol, a-Terpineol, Geraniol, Nerol, a-Pulegone, b-Caryophyllene, trans-b-Farnesene, a-Humulene, -(+) Ledene, Valencene, trans-Nerolidol, Caryophyllene oxide, -(+)Cedrol, -(-)Guaiol, (-)a- Bisabolol, cis-Nerolidol, a-Phellandrene, m-Cymene, g-Terpinene, cis-Linalool oxide, trans-Linalool oxide, -(-/+)Terpinen-4-ol, -(-)Bornyl acetate, -(+)Longipinene, a- Curcumene, b-Citronellol, trans-2-pinanol, a-Bulnesol, Selina 4 diene or Selina 3,7 diene.

[00214] In various aspects, the invention provides Cannabis extracts with predefined ratios of cannabinoids. Standard conditions for cannabinoid assays, and methods of calculating cannabinoid content (as %) are well known in the art.

[00215] According to some embodiments of the present invention, the Cannabis based extracts or preparations of the present invention contain compounds such as terpenes, terpenoids, phenylpropanoids, hydrocarbons, sugars, essential oil derived from Cannabis, nitrogen-containing compounds, carbohydrates, amino acids, polyamines, flavonoids, fatty acids, noncannabinoid phenols, simple alcohols, aldehydes, ketones, acids, esters, lactones, phytosterols such as campesterol, ergosterol, E-sitosterol, and stigmasterol, vitamin K, pigments such as carotene and xanthophylls, elements such as Na, K, Ca, Mg, Fe, Cu, Mn, Zn and Hg and any combination thereof.

[00216] According to further aspects, the extracts are mixture of cannabinoids and include at least terpenes and/or flavonoids. In one embodiment, the extracts contain a mixture of at least cannabinoids such as cannabinoid types selected from tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol (CBD), cannabichromene (CBC) and Cannabigerol (CBG).

[00217] In one embodiment, the terpenes and/or flavonoids in the extract include for example, linalool, 1,8-cineole (eucalyptol), a-Humulene, Ledene, borneol, P-myrcene, P-caryophyllene, limonene, cannflavin A, apigenin, quercetin or pulegone or any mixture thereof.

[00218] The extracts of the invention may be formulated with one or more pharmaceutically acceptable carriers, diluents or excipients or deposited on a pharmaceutically acceptable surface for vaporisation in order to produce pharmaceutical formulations containing cannabinoids as the pharmaceutically active agents.

[00219] Therefore, in one embodiment, the invention provides a method of making a pharmaceutical composition comprising, as an active agent, a substance which is an extract from at least one Cannabis plant variety.

[00220] According to a further embodiment, the composition comprises a mixture of active compounds such as cannabinoids, terpenes and flavones, from a synthetic source, showing therapeutic effect on pain and/or inflammation.

[00221] Separate extracts may be prepared from single Cannabis plant varieties having differing cannabinoid content or ratios (e.g. high or rich THC and high or rich CBD plants). In some embodiments, the extracts may be then mixed or blended together prior to formulation to produce the final pharmaceutical composition. Alternatively, plant material from one or more Cannabis plant varieties of defined cannabinoid content may be mixed together prior to extraction of a single botanical drug substance having the desired cannabinoid content, which may then be formulated into a final pharmaceutical composition.

[00222] The extract may be formulated with any convenient pharmaceutically acceptable diluents, carriers or excipients to produce a pharmaceutical composition. The choice of diluents, carriers or excipients will depend on the desired dosage form, which may in turn be dependent on the intended route of administration to a patient. Preferred dosage forms include, liquid dosage forms for administration via pump-action or aerosol sprays, tablets, pastilles, gels, capsules, suppositories, powders, etc. and vaporizers. Such dosage forms may be prepared in accordance with standard principles of pharmaceutical formulation, known to those skilled in the art.

[00223] An exemplified formulation includes a composition comprising a Cannabis extract comprising a cannabinoid mixture where Total THC (THCa and/or THC) is in the range of 15 to 70% (w/w) and Total CBD (CBDa and/or CBD) is less than 35% (w/w). In some aspects, the composition of the present invention comprises a Cannabis extract where Total THC (THCa and/or THC) is in the range of 40 to 65% (w/w) and Total CBD (CBDa and/or CBD) is less than 0.5% (w/w), preferably less than 0.2% (w/w). In other aspects, the composition of the present invention comprises a Cannabis extract where Total THC (THCa and/or THC) is in the range of 15% to 35% (w/w), particularly 18% to 30% (w/w), and Total CBD (CBDa and/or CBD) is in the range of 25% to 35% (w/w).

[00224] The term "similar concentration" refers hereinafter to a concentration which is +/- 25% of the defined concentration value, preferably +/- 10% of the defined concentration value, more preferably +/- 5% of the defined concentration value.

[00225] The term "terpene" as used hereinafter refers to a large and diverse class of organic compounds, produced by a variety of plants, particularly the Cannabis plant. Terpenes are hydrocarbons, and they may be classified by the number of isoprene units in the molecule. Examples of terpenes within the scope of the present invention include:

[00226] Hemiterpenes: consist of a single isoprene unit. Isoprene itself is considered the only hemiterpene, but oxygen-containing derivatives such as prenol and isovaleric acid are hemiterpenoids.

[00227] Monoterpenes: consist of two isoprene units and have the molecular formula C10H16. Examples of monoterpenes and monoterpenoids include Eucalyptol, terpineol (present in lilacs), D/L-limonene (present in citrus fruits), myrcene (present in hops), linalool (present in lavender) or pinene (present in pine trees). Iridoids derive from monoterpenes. [00228] Sesquiterpenes: consist of three isoprene units and have the molecular formula C15H24. Examples of sesquiterpenes and sesquiterpenoids include humulene, farnesenes, b-Caryophyllene.

[00229] Diterpenes: composed of four isoprene units and have the molecular formula C20H32. They derive from geranylgeranyl pyrophosphate. Examples of diterpenes and diterpenoids are cafestol, kahweol, cembrene and taxadiene (precursor of taxol). Diterpenes also form the basis for biologically important compounds such as retinol, retinal, and phytol.

[00230] Sesterterpenes: are terpenes having 25 carbons and five isoprene units (significant fractions of sesterterpenes have a C20-core carbon skeleton possessing an extra Cs-head/Cs-tail unit). An example of a sesterterpenoid is geranylfamesol.

[00231] Triterpenes: consist of six isoprene units and have the molecular formula C30H48. The linear triterpene squalene, the major constituent of shark liver oil, is derived from the reductive coupling of two molecules of famesyl pyrophosphate. Squalene is then processed biosynthetically to generate either lanosterol or cycloartenol, the structural precursors to all the steroids.

[00232] Sesquarterpenes: are composed of seven isoprene units and have the molecular formula C35H56. Sesquarterpenes are typically microbial in their origin. Examples of sesquarterpenoids are ferrugicadiol and tetraprenylcurcumene.

[00233] Tetraterpenes: contain eight isoprene units and have the molecular formula C40H64. Examples of tetraterpenoids include the acyclic lycopene, the monocyclic gamma-carotene, and the bicyclic alpha- and beta-carotenes.

[00234] Polyterpenes: consist of long chains of many isoprene units. Some plants produce a polyisoprene with trans double bonds, known as gutta-percha.

[00235] Norisoprenoids: such as the C13-norisoprenoids 3-oxo-a-ionol present in Muscat of Alexandria leaves and 7,8-dihydroionone derivatives, such as megastigmane-3,9-diol and 3-oxo-7,8-dihydro-a-ionol found in Shiraz leaves (both grapes in the species Vitis vinifera) or wine (responsible for some of the spice notes in Chardonnay), can be produced by fungal peroxidases or glycosidases. [00236] It is further within the scope that the term terpenoids (or isoprenoids) refers to modified terpenes that contain additional functional groups, usually oxygencontaining.

[00237] It is herein acknowledged that terpenes and terpenoids are the primary constituents of the essential oils of many types of plants and flowers. Synthetic variations and derivatives of natural terpenes and terpenoids are also within the scope of the present invention.

[00238] Terpenes and terpenoids are compounds within the Cannabis plant that play important role as synergistic and/or entourage compounds. Some terpenes are known to bind and/ or affect cannabinoid receptors (e.g. b-caryophyllene can bind CB2). The terpenes/terpenoids compounds in mixture with cannabinoids are herein shown to have importance in medical treatment.

[00239] The term "fraction thereof" used hereinafter refers to a plant extract, preferably a Cannabis extract treated by separation or purification or fractionation processes. More particularly it refers to purified or partially purified plant extract containing chemical compounds or constituents or portions or the extract or elements thereof.

[00240] It is according to some aspects of the present invention that Cannabis extract contains cannabinoid-type portions or elements.

[00241] In alternative embodiments, Cannabis or cannabinoid fraction may contain synthetic cannabinoids.

[00242] The Cannabis extract or a fraction thereof may comprise noncannabinoid-type constituents selected from the group consisting of: terpenes, terpenoids, phenylpropanoids, hydrocarbons, sugars, essential oil derived from Cannabis, nitrogen-containing compounds, carbohydrates, amino acids, polyamines, flavonoids, fatty acids, noncannabinoid phenols, simple alcohols, aldehydes, ketones, acids, esters, lactones, phytosterols such as campesterol, ergosterol, E-sitosterol, and stigmasterol, vitamin K, pigments such as carotene and xanthophylls, elements such as Na, K, Ca, Mg, Fe, Cu, Mn, Zn and Hg and any combination thereof. It is further within the scope that there are about several hundred different identifiable chemical constituents known to exist in Cannabis. The most distinctive class of compounds are the cannabinoids. Other constituents of the Cannabis plant may encompass: nitrogenous compounds, amino acids, proteins, glycoproteins, enzymes, sugars and related compounds, hydrocarbons, simple alcohols, aldehydes, ketones, simple acids, fatty acids, simple esters, lactones, steroids, terpenes, non-cannabinoid phenols, flavonoids, vitamins (such as Vitamin A), pigments, and elements.

[00243] As used herein, the term "derivative thereof" refers to a cannabinoid compound or any compound of the Cannabis extract, which may be included in its free form, or in the form of a salt; an acid; an acid addition salt of an ester; an amide; an enantiomer; an isomer; a tautomer; a prodrug; a derivative of an active agent of the present invention; different isomeric forms (for example, enantiomers and diastereoisomers), analogue form, both in pure or synthetic form and in admixture, including racemic mixtures; enol forms.

[00244] Administration “in combination with” one or more further therapeutic agents includes simultaneous (concurrent) and consecutive administration in any order.

[00245] The term “pharmaceutically acceptable” means that the preparation or composition is compatible with the remaining ingredients of a formulation for pharmaceutical use, and that it is generally safe for administering to humans according to established governmental standards, including those established by the United States Food and Drug Administration.

[00246] The term “pharmaceutically acceptable carrier” includes, but is not limited to solvents, dispersion media, coatings, antibacterial agents, antifungal agents, isotonic and/or absorption delaying agents and the like. The use of pharmaceutically acceptable carriers is well known.

[00247] Suitable pharmaceutically acceptable carriers include essentially chemically inert and nontoxic compositions that do not interfere with the effectiveness of the biological activity of the pharmaceutical composition. Examples of suitable pharmaceutical carriers include, but are not limited to, water, saline solutions, glycerol solutions, ethanol, N-(l(2,3-dioleyloxy)propyl)N,N,N-trimethylammonium chloride (DOTMA), diolesylphosphotidyl-ethanolamine (DOPE), and liposomes. Such compositions should contain a therapeutically effective amount of the extracts, together with a suitable amount of carrier so as to provide the form for direct administration to the patient. [00248] The term "anti-inflammatory" refers herein after to a property of a substance or treatment that reduces inflammation or swelling. It is within the context of the present invention that the nutraceutical composition of the present invention comprising a Cannabis preparation or extract confers an anti-inflammatory effect with respect to immune system cells in a subject. Non limiting examples of antiinflammatory effect include inhibition of macrophage cells and inhibition or prevention of lymphocytes proliferation. It is noted that the composition of the present invention may be administered together with one or more anti-inflammatory drugs, analgesic compounds, remedying pain by reducing inflammation or with opioids, which affect the central nervous system to block pain signaling to the brain.

[00249] The term "inhibition of cancerous cells" or "cell proliferation inhibition" as used herein refers to a reduce in cell proliferation and/or survival, including an anticancer or tumor effect including decrease in survival rate of cancerous cells, cytotoxic effect on cancerous cells, tumor size reduction, reduced viability of cancerous cells, apoptosis, cell cycle arrest, cell signaling arrest, mitochondrial trans membrane potential arrest and ROS production arrest.

[00250] As used herein, “treatment” or “therapy” is an approach for obtaining beneficial or desired clinical results. For the purposes described herein, beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, diminishment of extent of disease, stabilized (i.e., not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total), whether detectable or undetectable. “Treatment” and “therapy” can also mean prolonging survival as compared to expected survival if not receiving treatment or therapy. Thus, “treatment” or “therapy” is an intervention performed with the intention of altering the pathology of a disorder. Specifically, the treatment or therapy may directly prevent, slow down or otherwise decrease the pathology of a disease or disorder.

[00251] The terms “therapeutically effective amount”, “effective amount” or “sufficient amount” or "therapeutically effective dose or dosage" refers hereinafter to the amount of an agent or agents present at a sufficient concentration to produce a therapeutic effect on a patient, cells, or any combination thereof. It further means a quantity sufficient, when administered to a subject, including a mammal, for example a human, to achieve a desired result, for example an amount effective to treat the symptoms of a specific disease or condition, such as, for example, inflammation or pain related medical conditions. Effective amounts of the preparations, extracts, compositions or compounds described herein may vary according to factors such as the disease state, age, sex, and weight of the subject. Dosage or treatment regimens may be adjusted to provide the optimum therapeutic response, as is understood by a skilled person.

[00252] Moreover, a treatment regime of a subject with a therapeutically effective amount may consist of a single administration, or alternatively comprise a series of applications. The length of the treatment period depends on a variety of factors, such as the severity of the disease, the age of the subject, the concentration of the agent, the responsiveness of the patient to the agent, or any combination thereof. It will also be appreciated that the effective dosage of the agent used for the treatment may increase or decrease over the course of a particular treatment regime. Changes in dosage may result and become apparent by standard diagnostic assays known in the art. The compositions described herein may, according to some aspects, be administered before, during or after treatment with conventional therapies for the disease or disorder in question, such as inflammation or nociceptive pain.

[00253] The term “subject” or "patient" as used herein refers to any animal, typically a mammal, including humans.

[00254] The compositions of the present invention are effective in treatment of the symptoms of medical conditions or diseases or ailments, such as, for example, pain (such as chronic pain or nociceptive or neuropathic pain), neuropathy, inflammation related diseases such as Crohn's Disease, inflammatory bowel disorders (IBS and IBD), autoimmune disorders, tumors, and cancer. In addition, nausea and vomiting that are unresponsive to other medications have been shown to be helped through the use of the Cannabis based compositions of the present invention. In some embodiments the subject receives both a formulation containing a Cannabis extract and raw Cannabis. In some aspects, raw Cannabis refers to the Cannabis plant or any part thereof (e.g. flowers or inflorescences, which might be processed).

[00255] Thus, pharmaceutical compositions include, without limitation, lyophilized powders or aqueous or non-aqueous solutions or suspensions (e.g. containing oils), which may further contain antioxidants, buffers, bacteriostats and solutes that render the compositions substantially compatible with the tissues or the blood of the subject. Other components that may be present in such compositions include water, surfactants (such as Tween), alcohols, polyols, glycerin and vegetable oils.

[00256] Pharmaceutical finished dosage forms of the extracts described herein may further include other ingredients, such as but not limited to pharmaceutically acceptable glidants, lubricants, opacifiers, colorants, and other commonly used excipients. The extracts described herein, or finished dosage forms, can further be optionally film coated, or enteric coated, or seal coated, or coated with substances to modify the release (slow, controlled or rapid release) of the active ingredient(s). The coating can be done by any technique known in the art or conventionally used in the pharmaceutical industry.

[00257] Solvents used in the context of the extracts described herein in the processes of preparation of, or coating of tablets, capsules, oils etc. prepared from the extracts described herein, include but are not limited to water, isopropyl alcohol, dichloromethane, acetone, ethanol, ethyl acetate, or combinations thereof in any ratio suitable for processing the compositions. Thus, the compositions described herein may be formulated in many different manners, such as for injection or infusion by intravenous, intraarterial, intradermal, intramuscular, intracerebral, intraperitoneal, intracerebro spinal, subcutaneous, intraocular, intraarticular, intrasynovial, or intrathecal routes, for oral, buccal, sublingual, nasal, topical, transdermal, ophthalmic, vaginal, rectal, intravesical, pulmonary administration, and/or by various controlled- release systems, such as immediate release, delayed release, or sustained release systems.

[00258] Additional agents such as adjuvants or further pharmaceutically active agents may be included in the compositions described herein, such as vitamins, antiinflammatory agents, analgesics, muscle relaxants, and so on. Such active agents may include drugs or pharmaceuticals or nutraceuticals having therapeutic and/or nutritional value and include, but are not limited to members of classes of actives including analgesics, anti-inflammatory agents, anthelminthics, anti-bacterial agents, anti-viral agents, anti-coagulants, anti-depressants, anti-diabetics, anti-fungal agents, nutritional agents, opioid analgesics, nutritional oils, essential fatty acids, non-essential fatty acids and the like. [00259] The compositions described herein may be useful in the form of an inhalable dry powder formulation based on the Cannabis plant, which may comprise a pharmaceutically acceptable carrier or excipient. It will be understood that “dry powder” refers to a fine particulate composition that is not suspended or dissolved in a propellant, carrier, or other liquid. It is not meant to necessarily imply a complete absence of all water or liquid molecules.

[00260] The inhalable dry powder formulation based on the Cannabis plant is, in aspects, provided to the patient by pulmonary inhalation using a dry powder inhalation system. In one aspect, the system comprises a dry powder inhaler with or without a container and a dry powder formulation.

[00261] In another aspect, the composition or preparation described herein is for pulmonary administration by inhalation using a breath powered, dry powder inhaler with or without a container, wherein the container can be a cartridge, such as a unit dosing cartridge for a reusable inhaler, or a single use inhaler. In this and other aspects, the dry powder inhaler system typically comprises a high resistance dry powder inhaler.

[00262] In one aspect, the formulation, composition or preparation described herein can be administered to a subject in a dry powder formulation by inhalation using a dry powder inhaler. Repeat inhalation of the dry powder formulation can also be administered once, twice, three, four, or more times a day as needed.

[00263] It has now been found that a Cannabis extract can be prepared from different Cannabis plant tissue sources and optionally mixing those with an oily carrier, such as hemp seed oil. In aspects, these extracts, may exert a synergistic effect in terms of symptom relief in various conditions such as inflammation and pain as compared to administering main cannabinoid such as THC and CBD separately, and can therefore be used to treat the symptoms of certain conditions, such as inflammation and pain associated conditions, with a synergistic effect.

[00264] The compositions of the invention can, in aspects, be administered for example, by parenteral, intravenous, subcutaneous, intradermal, intramuscular, intracranial, intraorbital, ophthalmic, intraventricular, intracapsular, intraspinal, intracisternal, intraperitoneal, intranasal, intrarectal, aerosol or oral administration. Typically, the compositions of the invention are administered orally or by inhalation. [00265] The compositions of the invention may, in aspects, be administered in combination, concurrently or sequentially, with conventional treatments for the condition in question, including with analgesics (e.g. metamizole, or dipyrone), antiinflammatories, or muscle relaxants, for example. The compositions of the invention may be formulated together with such conventional treatments when appropriate.

[00266] The compositions of the invention may be used in any suitable effective amount of active agent, e.g., THC, CBD, a particular terpene, or another active compound.

[00267] Additionally, treatment with the compositions described herein may occur once or may be repeated several times. For example, treatment may occur as needed, several times daily, weekly, monthly, yearly, or a combination thereof, depending upon the disease state. For example, a subject may be administered several doses per day to treat active and acute symptoms, depending on the recommended schedule.

[00268] While it has been stated above that the compositions described herein can be used to treat symptoms, it will be understood that they could also be used to prevent symptoms from occurring.

[00269] It is further within the scope to disclose the method as defined in any of the above, wherein the measurable effect on cells is selected from the group consisting of: anti proliferative, regenerative, anti-inflammatory, anti-mitotic, differentiative, anti- metastatic, anti-angiogenic, apoptotic, cytotoxic, cytopathic and any combination thereof.

[00270] The term "synergistic" or "synergy" refers hereinafter to an effect arising between two or more agents, compounds, entities, factors, or substances that produces an effect greater than the sum of their individual effects. It is opposite of antagonism. In general synergy is the creation of a whole that is greater than the simple sum of its parts. A synergistic effect can be beneficial or harmful.

[00271] It is within the scope of the present invention that the combination index (CI) analysis provides quantitative estimation of the extent of synergy.

[00272] Combination index (CI) = (D)l /(D_x)l + (D)2/(D_X)2. (D_x)l and (D_x)2 represent concentrations of each constituent alone to exert x% effect, while (D) 1 and (D)2 were concentrations of constituents in combination to elicit the same effect. CI < 1, = 1 and > 1 indicated synergism, additivity and antagonism, respectively.

[00273] According to one aspect of the present invention, CI value lower than 1 indicates synergism between the constituents of the composition of the present invention with respect to an anti-inflammatory and/or pain relief effects.

[00274] According to a further aspect of the present invention, a combination index (CI) value of 1 indicates an additive effect between the constituents of the composition of the present invention with respect to an anti inflammatory and/or pain relief effects.

[00275] According to core aspects, the present invention provides a composition comprising therapeutically effective amount of, or consisting essentially therapeutically effective amount of a Cannabis extract comprising tetrahydrocannabinol (THC) or a derivative thereof in an amount of about 15% to about 70% by weight for use in the treatment of inflammation and/or pain related disorders. According to further aspects, the composition comprises Cannabidiol (CBD) or a derivative thereof in an amount of less than 35% by weight.

[00276] According to further core aspects, the Cannabis extract comprises THC in the range of 40 to 65% by weight (w/w) and CBD in an amount of less than 0.5% (w/w), preferably less than 0.2% (w/w). In other aspects, the Cannabis extract comprising THC in the range of 15% to 35% (w/w), particularly 18% to 30% (w/w), and CBD in the range of 25% to 35% (w/w).

[00277] It is further within the scope to disclose a Cannabis derived extract comprising a predefined ratio of THC to CBD conferring a therapeutic effect with respect to inflammation and/or pain related disorders. In some embodiments, the Cannabis derived extract comprises THC to CBD ratio of 1:1 by weight, particularly 1:1.66 to 1.4:1 by weight.

[00278] As used herein the term "immune system cells" or immune cells" generally refers to white blood cells, also called leukocytes. There are two main types of leukocyte:

[00279] 1. Phagocytes, including, neutrophils, monocytes, macrophages and mast cells [00280] 2. Lymphocytes, including, B lymphocytes (B cells) and T lymphocytes

(T cells).

[00281] In general, the response to pathogens involves the complex interactions and activities of the large number of diverse cell types involved in the immune response. The innate immune response is the first line of defense and occurs soon after pathogen exposure. It is carried out by phagocytic cells such as neutrophils and macrophages, cytotoxic natural killer (NK) cells, and granulocytes. The subsequent adaptive immune response includes antigen-specific defense mechanisms and may take days to develop. Cell types with critical roles in adaptive immunity are antigen-presenting cells including macrophages and dendritic cells. Antigen-dependent stimulation of various cell types including T cell subsets, B cells, and macrophages play critical roles in host defense.

[00282] The stimulation of the immune system by increasing activity of any of its components may be excreted by two main categories of immuno stimulants:

[00283] Specific immuno stimulants that provide antigenic specificity in immune response, such as vaccines or any antigen.

[00284] Non-specific immuno stimulants that act irrespective of antigenic specificity to augment immune response of other antigen or stimulate components of the immune system without antigenic specificity.

[00285] According to further aspects of the present invention, activation of immune responses evokes the release of cytokines, such as IL-1, TNF-a, and IL-6, which initiate the acute-phase response of inflammation, aimed at fighting infection. It is herein acknowledged that the acute -phase response facilitate or enhances immune responsiveness and also inhibit the ability of some pathogens to multiply and inhibit or limit or reduce the spread of infection

[00286] Reference is now made to an inflammatory cytokines which is a type of cytokine that is secreted from immune cells and other cell types that promotes inflammation. Inflammatory cytokines are predominantly produced by T helper cells (Th) and macrophages and involved in the upregulation of inflammatory reactions.

[00287] It is further within the scope of the current invention that inflammatory cytokines play a role in initiating the inflammatory response and to regulate the host defense against pathogens mediating the innate immune response. Examples of pro- inflammatory cytokines include IL-ip, IL-6, and TNF-a. Excessive chronic production of inflammatory cytokines contribute to inflammatory diseases such as atherosclerosis and cancer. Dysregulation of proinflammatory cytokines have also been linked to depression and other neurological diseases. A balance between proinflammatory and anti-inflammatory cytokines is necessary to maintain health.

[00288] According to some aspects of the present invention, inflammatory cytokines include interleukin- 1 (IL-1), IL-12, and IL-18, tumor necrosis factor alpha (TNF-a), interferon gamma (IFNy), and granulocyte-macrophage colony stimulating factor (GM-CSF).

[00289] The term "Next-generation sequencing" or "NGS" as used herein refers hereinafter to massively, parallel, high- throughput or deep sequencing technology platforms that perform sequencing of millions of small fragments of DNA in parallel. Bioinformatics analyses are used to piece together these fragments by mapping the individual reads to the reference genome.

[00290] The term "variety" or "cultivar" or "strain" or "line" used herein means a group of similar plants that by structural features and performance can be identified from other varieties cultivars or strains within the same species.

[00291] As used herein, the term "locus" (loci plural) means a specific place or places or region or a site on a chromosome where for example a gene or genetic marker element or factor is found. In specific embodiments, such a genetic element is contributing to a trait.

[00292] As used herein, the term "homozygous" refers to a genetic condition or configuration existing when two identical or like alleles reside at a specific locus, but are positioned individually on corresponding pairs of homologous chromosomes in the cell of a diploid organism.

[00293] Conversely, as used herein, the term "heterozygous" means a genetic condition or configuration existing when two different or unlike alleles reside at a specific locus, but are positioned individually on corresponding pairs of homologous chromosomes in the cell of a diploid organism.

[00294] As used herein, the phrase "genetic marker" or "molecular marker" or "biomarker" refers to a feature in an individual's genome e.g., a nucleotide or a polynucleotide sequence that is associated with one or more loci or trait of interest. In some embodiments, a genetic marker is polymorphic in a population of interest, or the locus occupied by the polymorphism, depending on context. Genetic markers or molecular markers include, for example, single nucleotide polymorphisms (SNPs), indels (i.e. insertions deletions), simple sequence repeats (SSRs), restriction fragment length polymorphisms (RFLPs), random amplified polymorphic DNAs (RAFDs), cleaved amplified polymorphic sequence (CAPS) markers, Diversity Arrays Technology (DArT) markers, and amplified fragment length polymorphisms (AFLPs) or combinations thereof, among many other examples such as the DNA sequence per se. Genetic markers can, for example, be used to locate genetic loci containing alleles on a chromosome that contribute to variability of phenotypic traits. The phrase "genetic marker" or "molecular marker" or "biomarker" can also refer to a polynucleotide sequence complementary or corresponding to a genomic sequence, such as a sequence of a nucleic acid used as a probe or primer.

[00295] As used herein, the term "germplasm" refers to the totality of the genotypes of a population or other group of individuals (e.g., a species). The term "germplasm" can also refer to plant material; e.g., a group of plants that act as a repository for various alleles. Such germplasm genotypes or populations include plant materials of proven genetic superiority; e.g., for a given environment or geographical area, and plant materials of unknown or unproven genetic value; that are not part of an established breeding population and that do not have a known relationship to a member of the established breeding population.

[00296] The terms "hybrid", "hybrid plant" and "hybrid progeny" used herein refers to an individual produced from genetically different parents (e.g., a genetically heterozygous or mostly heterozygous individual).

[00297] As used herein, the terms "nucleic acid", "nucleic acid sequence", "nucleotide", "nucleic acid molecule" or "polynucleotide" are intended to include DNA molecules (e.g., cDNA or genomic DNA), RNA molecules (e.g., mRNA), natural occurring, mutated, synthetic DNA or RNA molecules, and analogs of the DNA or RNA generated using nucleotide analogs. It can be single-stranded or double-stranded. Such nucleic acids or polynucleotides include, but are not limited to, coding sequences of structural genes, anti-sense sequences, and non-coding regulatory sequences that do not encode mRNAs or protein products. These terms also encompass a gene. The term "gene", "allele" or "gene sequence" is used broadly to refer to a DNA nucleic acid associated with a biological function. Thus, genes may include introns and exons as in the genomic sequence, or may comprise only a coding sequence as in cDNAs, and/or may include cDNAs in combination with regulatory sequences. Thus, according to the various aspects of the invention, genomic DNA, cDNA or coding DNA may be used. In one embodiment, the nucleic acid is cDNA or coding DNA.

[00298] The terms "peptide", "polypeptide" and "protein" are used interchangeably herein and refer to amino acids in a polymeric form of any length, linked together by peptide bonds.

[00299] According to other aspects of the invention, a "modified" or a "mutant plant is a plant that has been altered compared to the naturally occurring wild type (WT) plant.

[00300] The composition of the present invention is used for treating symptoms associated with diseases or disorders selected from acute inflammation, chronic inflammation, autoimmune diseases and disorders, motor neuron diseases and disorders, neurodegenerative diseases and disorders, pain associated with inflammation, acute pain, chronic pain, referred pain, cancer pain, neuropathic pain, nociceptive pain, psychogenic pain and visceral pain.

[00301] In general, acute pain is experienced rapidly in response to disease or injury. Acute pain often resolves within a short time once the underlying condition is treated.

[00302] Chronic pain may be defined, in some aspects as lasting more than three months. Chronic pain often begins as acute pain that lingers beyond the natural course of healing or after steps have been taken to address the cause of pain.

[00303] Referred pain means pain that originates in one part of the body but is felt in another part of the body.

[00304] Cancer pain is associate with nerve irritation caused by malignancy.

[00305] Neuropathic pain is caused by damage to the nervous system.

[00306] Visceral pain is associated with the internal organs, such as the liver, gallbladder, kidney, heart or lungs.

[00307] Main types of pain include: acute pain, chronic pain, neuropathic pain, nociceptive pain, somatic pain, visceral pain and psychogenic pain. [00308] Acute pain refers to a pain which is short in duration (lasting from minutes to about three months, sometimes up to six months). Acute pain also tends to be related to an injury or a temporary illness, so it typically subsides after the injury or the illness reliefs. Acute pain from an injury may evolve into chronic pain if the injury doesn’t heal correctly or if the pain signals malfunction.

[00309] Chronic pain, is longer in duration. It can be constant or intermittent. For example, headaches can be considered chronic pain when they continue over many months or years, even if the pain isn’t always present. Chronic pain is often due to a health condition, like arthritis, fibromyalgia, or a spine condition.

[00310] Neuropathic pain, is the result of an injury or malfunction of the peripheral or the central nervous system. The pain may be triggered by an injury but not necessarily by an injury of the nervous system itself. Neuropathic pain is frequently chronic and is often refractory to treatment with opioids. Terminal illnesses are often accompanied by unbearable pain that is severe and difficult to treat.

[00311] Nociceptive pain, is a type of pain caused by damage to body tissue. It’s often caused by an external injury. In nociceptive pain, the stimulation of the sensory nerve endings called nociceptors cause the sensation of pain. Such pain often occurs after injury or surgery. The pain signals are transmitted by the nociceptors to the brain. Often the pain is localized, constant and has an aching or throbbing quality. Treatment with opioids often resolves nociceptive pain. It can be both acute and chronic.

[00312] In a somatic pain, a signal is sent by receptors located throughout the body. Somatic pain signals transfer to the brain via peripheral nerves, and are typically experienced as a constant ache in the injured region.

[00313] Visceral pain occurs when tissues or organs in the abdominal cavity become stretched or otherwise disturbed due to disease or injury. Pain signals issue from a specific class of receptors present in the gut, producing feelings of pressure deep within the abdomen. Visceral pain often seems to be coming from a different part of the body than its actual source, a phenomenon known as referred pain.

[00314] Psychogenic pain is a pain disorder that is associated with psychological factors. Some types of mental or emotional problems can cause pain. They can also increase or prolong pain. Headaches, muscle pains, back pain, and stomach pains are some of the most common types of psychogenic pain. [00315] According to further aspects, the composition or Cannabis preparation of the present invention is used for treating symptoms associated with diseases or disorders, wherein the diseases or disorders are selected from autoimmune diseases and disorders, motor neuron diseases and disorders, neurodegenerative diseases and disorders, diabetes, cardiovascular disease (CVD), arthritis and other joint diseases, allergies, chronic obstructive pulmonary disease (COPD), psoriasis, rheumatoid arthritis, Cancer, Chemotherapy-induced peripheral neuropathy (CIPN), Opioid Use Disorder/Addiction, Carpal Tunnel Syndrome, Osteoarthritis, CRPS/RSD, Osteoporosis, Diabetic Neuropathy, Plantar Fasciitis, Ehlers-Danlos Syndrome (EDS), Postherpetic Neuralgia, Fibromyalgia, Insomnia, Gout, Pelvic Pain, hATTR Amyloidosis, Psoriatic Arthritis, Low Back Pain, Rheumatoid Arthritis, Lupus, Sickle Cell Disease, Lyme Disease, Thigh Pain, Migraine and Headaches, Traumatic Brain Injuries, Neck Pain and TMJ Disorders, Crohn's Disease, inflammatory bowel disorders (IBS and IBD).

[00316] It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination.

[00317] EXAMPLES

[00318] EXAMPLE 1

[00319] Cannabis extract preparation and characterization

[00320] Cannabis extract was produced from selected Cannabis varieties (e.g.

Cannabis varieties 'Precise- A', 'Precise-B', 'Precise-C, 'Precise-D' and 'Precise-E',) to be tested for providing anti-inflammatory and pain relief therapeutic effects. The Cannabis extracts were prepared from inflorescences (derived from the selected Cannabis varieties) subjected to an ethanol extraction process as known in the art, or a modified process thereof (see an exemplified ethanol extraction protocol in Pasquali et al., Preliminary data on the antimicrobial effect of Cannabis sativa L. variety Futura 75 against food-borne pathogens in vitro as well as against naturally occurring microbial populations on minced meat during storage. Italian Journal of Food Safety 2020; volume 9:8581, p. 80-87, incorporated herein by reference). The extracts may be diluted, for example by an oil such as olive and/or soybean oil. [00321] The extracts/cannabinoids were subjected to de-carboxylation steps during preparations. This procedure results in achieving mainly the non-acid forms of the cannabinoids. Thus the acid forms of the cannabinoids in the extracts are present at very low levels. Analyses of the extracts were performed using a high-performance liquid chromatography (HPLC) system coupled with UV detector.

[00322] Reference is now made to Table 1, presenting THC and CBD content in each of the tested Cannabis extracts.

[00323] Table 1: THC and CBD content in tested Cannabis extracts

[00324] Table 1 shows that the extracts demonstrating anti-inflammatory and/or pain relieving or analgesic effects, are characterized by THC content of about 40 to 65 % (w/w), and CBD content of less than 0.2 % (w/w). Alternatively, the extracts are characterized by a THC to CBD ratio of about 1:1 % (w/w), for example, THC content of about 15 to 35 % (w/w), preferably 28-31 % (w/w).

[00325] In addition, analysis of the profile of various active compounds/ingredients including various cannabinoids and terpenes was performed using high-performance liquid chromatography (HPLC) system coupled with UV detector and/or Liquid chromatography-mass spectrometry (LCMS) and/or Gas chromatography-mass spectrometry (GCMS).

[00326] Table 2: Content of extracts from strains Precise- A, Precise-B,

Precise-C and Precise-D, with pain management activity

[00327] Table 2 presents the chemical analysis of various phytochemicals that differed in the extracts showing pain management activity, from the non-active strains. The extracts were analyzed according to relevant/acceptable methods (LCMS, GCMS and UPLC).

[00328] Table 3: Comparison between the active and inactive extracts

[00329] Table 3 shows the difference in chemical composition between the active and inactive extracts (used as a control).

[00330] Table 4: Content of extracts from strains Precise- A, Precise-B,

Precise-C and Precise-D, with anti-inflammatory activity

[00331] Table 4 presents the chemical analysis of selected phytochemicals that differed in the extracts showing anti-inflammatory activity, from the non-active strains. The extracts were analyzed according to relev ant/acceptable methods (LCMS, GCMS and UPLC).

[00332] Table 5: Comparison between the active and inactive extracts

[00333] Table 5 shows the difference in chemical composition between the active and inactive extracts (used as a control in the experiment).

[00334] EXAMPLE 2

[00335] Effect of different Cannabis extracts on inflammation

[00336] This example provides a pre- clinical study presenting evaluation of anti-inflammatory effect of extracts derived from five Cannabis varieties on immune system cells including macrophages (RAW cells) and lymphocyte cells.

[00337] 1. Macrophage immune assay

[00338] Study design:

[00339] Macrophage (RAW) cells were subjected to activation by lipopolysaccharide (LPS) or other conventionally used stimulant, in the presence of extracts of the Cannabis varieties tested. Nitric oxide (NO) secretion into the culture medium of the cells was examined. The secreted NO levels are an indication of the level of activity of the cells and therefore of the level of activity of the immune system. Extracts conferring high inhibition of NO secretion (compared to non-treated cells control) have the potential of delaying the inflammatory process.

[00340] The Cannabis extracts were prepared from inflorescences that had undergone an ethanolic extraction process as detailed in Example 1 above. [00341] Each extract has been tested in at least two independent biological experiments (biological experiment means cultivation of the varieties in the greenhouse, extract production and examination in a selected assay/system/setup). Each biological experiment included 2-3 independent technical experimental repeats. The extract samples were optionally tested at predefined dilutions.

[00342] Each experiment also included samples used for the following controls:

[00343] 1. Baseline control- inactivated (non-treated) cells

[00344] 2. Negative control -Technical assessment or test of the inflammation process. In this assessment, activated cells with a control culture medium (without Cannabis extracts) were used. In Figs 1 and 2, such a control, recited as "activated cells" (referred in the experiment as 100%) is used for comparing the effects of the various Cannabis extracts on inflammation of activated cell.

[00345] 3. Positive control- synthetic CBD at a concentration of 5pg / ml. It is noted that CBD was reported as having anti-inflammatory activity in a variety of preclinical models (see for example, the review of S. Burstein, Cannabidiol (CBD) and its analogs: a review of their effects on inflammation. Bioorganic & Medicinal Chemistry 23 (2015) 1377-1385, incorporated herein in its entirety).

[00346] Results:

[00347] Reference is now made to Figs. 1A - 1C, graphically presenting the effect of extracts of various Cannabis varieties (varieties 'Precise-A', 'Precise-B', 'Precise-C, 'Precise-D' and 'Precise-E') on inhibition of activated macrophage (RAW) cells. The inhibition was measured by NO secretion, as compared to the above indicated negative and positive controls. As can be seen, all Cannabis extracts tested showed an inhibitory effect of about 40% or more, specifically 35%-60%, more specifically 50%- 60%, as compared to the activated control cells not exposed to any Cannabis extract. The inhibitory effect on stimulated macrophage-like cells (RAW cells) was similar to the effect observed by the synthetic CBD positive control, or even higher than the positive control (see Figs 1A, IB and 1C, varieties 'Precise-A', 'Precise-B' and 'Precise- C', respectively). Thus the alcohol based Cannabis extracts of the tested varieties demonstrate a significant inhibitory effect on stimulated macrophage immune system cells. This means that the present invention provides Cannabis extracts with a significant anti-inflammatory effect on macrophage stimulated immune cells. [00348] Reference is now made to Fig. 2 showing toxicity test results of varieties 'Precise-A', 'Precise-B', 'Precise-C, 'Precise-D' and 'Precise-E'. In order to verify that the anti-inflammatory effect of the various Cannabis extracts did not result from their toxicity to the cells, an experiment was conducted that examined the viability of the cells (MTT assay).

[00349] The MTT assay is used to measure cellular metabolic activity as an indicator of cell viability, proliferation and cytotoxicity. This colorimetric assay is based on the reduction of a yellow tetrazolium salt (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide or MTT) to purple formazan crystals by metabolically active cells. The viable cells contain NAD(P)H-dependent oxidoreductase enzymes which reduce the MTT to formazan. The insoluble formazan crystals are dissolved using a solubilization solution and the resulting colored solution is quantified by measuring absorbance at 500-600 nanometers using a multi-well spectrophotometer. The darker the solution, the greater the number of viable, metabolically active cells.

[00350] Fig. 2, graphically illustrate viability (%) of RAW cells treated with the different Cannabis extracts (derived from Cannabis varieties 'Precise-A', 'Precise-B', 'Precise-C, 'Precise-D' and 'Precise-E') as compared to non-treated activated cells (negative control) and activated cells treated with synthetic CBD (positive control). As shown in Fig. 2, the viability of the stimulated macrophage (RAW) cells was similar (up to 10% reduction in cell viability) in cells treated with Cannabis extract or synthetic CBD, and non-treated cells. Thus it can be concluded that the anti-inflammatory effect on immune system cells was not due to the toxicity of the Cannabis extract to the cells (or any other effect on cell viability), but resulted from an anti-inflammatory effect on the activity of macrophage immune system cells.

[00351] 2. Lymphocyte immune -assay

[00352] Study design:

[00353] Lymphocytes (spleen cells isolated from mice) were labeled and activated by antibody against T cells- receptor, to activate the inflammatory process in the presence of the Cannabis varieties tested. Cell division (cell proliferation) was examined using Flow Cytometry. The lymphocyte activation method used, is as published in Khuja I. et al., Cannabinoids Reduce Inflammation but Inhibit Lymphocyte Recovery in Murine Models of Bone Marrow Transplantation. Int. J. Mol. Sci. 2019, 20, 668; doi:10.3390/ijms20030668, incorporated in its entirety, herein by reference, with some modifications. [00354] The Cannabis extracts were prepared from inflorescences using ethanolic extraction process as detailed above (extracts prepared from Cannabis varieties 'Precise-A', 'Precise-C and 'Precise-E').

[00355] Each extract was tested in triplicate * 3 independent experiments (in each experiment spleen cells were isolated from a mouse and activated).

[00356] Each experiment also included the following controls:

[00357] 1. Baseline control- inactivated cells

[00358] 2. Negative control -Technical control for the inflammation process

(cells are activated with a cell culture medium solution, without the Cannabis extracts). The effect of the extract on the activated cell culture is compared to (or normalized according to) the effect of the activated cells without the extracts (referred to as 100% in the experiment, see Fig. 3 "activated cells" column).

[00359] 3. Positive control (synthetic CBD) at a concentration of 5pg / ml.

[00360] Results:

[00361] Reference is now made to Fig.3 graphically illustrating the antiinflammatory effect of extracts from different Cannabis varieties on activated lymphocyte immune system cells. This figure shows the inhibitory effect of extracts from tested Cannabis varieties on proliferation of lymphocyte immune system cells as compared to positive and negative controls (detailed above).

[00362] As can be seen, all Cannabis extracts tested (derived from varieties 'Precise-A', 'Precise-C and 'Precise-E') inhibited lymphocyte cell proliferation as compared to activated lymphocyte cells not treated with Cannabis extract (technical negative control). The Cannabis extract inhibition was dramatic, in the range of about 60% to about 90%. The extracts derived from variety 'Precise-A' and variety 'Precise- E' showed a higher cell-proliferation inhibitory effect on activated lymphocyte cells (about 90%-95% proliferation inhibition) than the effect observed by exposing the cells to synthetic CBD (about 70% proliferation inhibition).

[00363] The experiments described herein clearly show the anti- inflammatory effect of the Cannabis extracts provided by the current invention, conferring inhibition of macrophage and lymphocyte activated immune system cells. [00364] EXAMPLE 3

[00365] Effect of Cannabis extract on pain symptoms

[00366] This example provides a pre- clinical study presenting evaluation of the effect of extracts derived from five Cannabis varieties (varieties 'Precise- A', 'Precise- B', 'Precise-C, 'Precise-D' and 'Precise-E' as detailed above) on pain related symptoms.

[00367] Study design: Zebrafish larvae model system

[00368] This test is based on the fact that the larvae of zebrafish respond to nociceptive stimuli, for example, heat stimuli, or a decrease in pH stimuli. As a result of swimming at temperatures higher than the optimum temperature (about 28°C), the zebrafish larvae respond with a significant increase in movement which is expressed by an increase in swimming distance. In this test the zebrafish larvae were exposed to a predetermined high temperature of 50°C. Such a high temperature causes a significant response of the larvae, but does not cause death. It is noted that usage of compounds or drugs with analgesic activity are supposed to prevent the increase in the swimming distance of the larvae, maintained at high-temperature water.

[00369] In the first stage, the larvae were inserted (1 larvae per well) into a 96- well plate containing an insert of 96 wells. In this plate the larvae were exposed to the various treatments including analgesic substance - Optalgin (Dipyrone), or various Cannabis extracts at a concentration of Ipg / ml, for 30 minutes, in water at a temperature of 28°C. The plate with the larvae was then exposed to either standard temperature of 28°C (control), or water with a high temperature of 50°C in the treatment wells. The plate was inserted into a vision system to monitor the movement of each larvae separately.

[00370] The Cannabis extracts were prepared from inflorescences subjected to an ethanol extraction process as detailed above (the same extracts tested in the above described assays).

[00371] Each extract has been tested in at least two independent biological experiments (biological experiment herein means cultivation of the varieties in the greenhouse, extract production and examination in the preselected assay system). Each biological experiment included 12-36 larvae per extract (or predefined dilutions of the extract were used).

[00372] Each experiment included the following controls: [00373] 1. Technical negative control of the pain process or induction- larvae exposed to heat treatment (pain induction), without extracts. This control was used for comparison (or to 'normalize') of the effects of the extracts on pain relief (referred to as 100% in the experiment, see Fig. 4 "pain induction (control)").

[00374] 2. Positive control - Optalgin

[00375] 4. Positive control- synthetic THC at a concentration of 1.5pg / ml

[00376] It is noted that high doses of THC were correlated with increased pain relief in some studies (see for example, W. Notcutt et al., Initial experiences with medicinal extracts of Cannabis for chronic pain: Results from 34 ‘N of 1’ studies. Anaesthesia, 2004, 59, pages 440-452; and A. Blake. A selective review of medical Cannabis in cancer pain management. Ann Palliat Med 2017;6(Suppl 2):S215-S222, incorporated herein in its entirety, by reference.

[00377] Results:

[00378] Reference is now made to Figs 4A and 4B, which graphically illustrate movement reduction of zebrafish larvae exposed to Cannabis extract (Fig. 4A-varieties 'Precise-C and 'Precise-E' extracts, Fig. 4B -varieties 'Precise- A', 'Precise-B' and 'Precise-D' extracts) as compared to positive and negative controls (detailed above). As can be seen, all Cannabis extracts tested showed significant reduced movement (about 20% to about 65%) relative to the negative control of the non-treated induced pain zebrafish larvae. The movement reduction for the larvae exposed to the different Cannabis extracts was similar or greater than the reduction observed with the THC positive control (about 20%-30%). The extracts derived from Cannabis varieties 'Precise-A', 'Precise-B' and 'Precise-D' conferred the most significant reduction in larvae movement (about 55-65%).

[00379] The results of this experiment clearly show that the present invention provides Cannabis extracts effective in relief or alleviation of pain symptoms such as neuropathic pain symptoms.

[00380] EXAMPLE 4

[00381] Phenotypic and chemotypic characterization of Cannabis varieties used for preparation of extracts tested for anti-inflammatory and pain relief effects [00382] Each of the above tested Cannabis varieties, from which extracts showing anti- inflammatory and pain relief effects were produced, were subjected to chemotypic and phenotypic characterization. Reference is now made to Table 6 presenting chemotype and phenotype properties of the Cannabis varieties 'Precise-A', 5 'Precise-B', 'Precise-C and 'Precise-D' tested.

[00383] Table 6: Phenotypic and chemotypic characterization of selected

Cannabis varieties

[00384] THC and CDB are represented as %w/w, normalized to water content.

[00385] As can be seen from Table 6, the Cannabis varieties demonstrated to 10 provide an anti-inflammatory and pain relieving effects, are THC rich, having THC content of about 5 to 20 % (w/w), preferably 8 to 20 % (w/w), and CBD content of up to 5 % (w/w), preferably less than 1 % (w/w), more preferably less than 0.1 % (w/w).

[00386] Table 7: Chemotypic characterization of the selected Cannabis 15 varieties (non CBD or THC cannabinoids)

<LOQ - below the detection limit of the system (below Limit of quantification) [00387] Table 8: Chemo typic characterization of the selected Cannabis varieties (CBD and THC)

[00388] Reference is now made to Figs 5-9 presenting some representative photographs of varieties 'Precise- A', 'Precise-B', 'Precise-C, 'Precise-D' and 'Precise-E', respectively, at different developmental growth stages, under controlled greenhouse conditions.

[00389] The positive results achieved in the above described studies support the identification of Cannabis varieties with heightened anti-inflammatory and pain relief properties for the production of precise medical Cannabis products for therapy of pain and inflammation related conditions.

[00390] Unless otherwise defined, all technical and scientific terms used herein have the same meanings as are commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods are described herein.

[00391] All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the patent specification, including definitions, will prevail. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.

[00392] It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove. Rather the scope of the present invention is defined by the appended claims and includes both combinations and sub-combinations of the various features described hereinabove as well as variations and modifications thereof, which would occur to persons skilled in the art upon reading the foregoing description. References:

Alexia Blake 1, Bo Angela Wan, Leila Malek, Carlo DeAngelis, Patrick Diaz, Nicholas Lao, Edward Chow, Shannon O’Hearn. A selective review of medical Cannabis in cancer pain management, Vol 6, Supplement 2 (December 2017): Annals of Palliative Medicine :S215-S222.

William Notcutt, Mario Price, Roy Miller, Samantha Newport, Cheryl Phillips, Susan Simmons and Cathy Sansom, Anaesthesia. Initial experiences with medicinal extracts of Cannabis for chronic pain: Results from 34 ‘N of L studies, 2004, 59, pages 440- 452.

Sumner Burstein. Cannabidiol (CBD) and its analogs: A review of their effects on inflammation., Bioorganic & Medicinal Chemistry, Volume 23, Issue 7, 1 April 2015, Pages 1377-1385.

JM Jamontt, A Molleman, RG Pertwee and ME Parsons. The effects of D9- tetrahydrocannabinol and cannabidiol alone and in combination on damage, inflammation and in vitro motility disturbances in rat colitis, British Journal of Pharmacology (2010), 160, 712-723.

Frederique Pasquali, Marco Schinzari, Alex Lucchi, Mara Mandrioli, Tullia Gallina Toschi, Alessandra De Cesare, and Gerardo Manfreda. Preliminary data on the antimicrobial effect of Cannabis sativa L. variety Futura 75 against food-bome pathogens in vitro as well as against naturally occurring microbial populations on minced meat during storage, Italian Journal of Food Safety 2020; volume 9:8581, p. 80-87.

Iman Khuja, Zhanna Yekhtin, Reuven Or and Osnat Almogi-Hazan. Cannabinoids Reduce Inflammation but Inhibit Lymphocyte Recovery in Murine Models of Bone Marrow Transplantation. Int. J. Mol. Sci. 2019, 20, 668; doi:10.3390/ijms20030668.

Paula Berman, Kate Futoran, Gil M. Lewitus, Dzmitry Mukha, Maya Benami, Tomer Shlomi & David Meiri. A new ESLLC/MS approach for comprehensive metabolic profiling of phytocannabinoids in Cannabis, Scientific Reports (2018) 8:14280.

Supporting Information for Publication A new ESI-LC/MS approach for comprehensive metabolic profiling of phytocannabinoids in Cannabis.

Claims

1. A composition comprising a Cannabis derived extract for use in the treatment of inflammation and/or pain related disorders, said extract comprising: a. Tetrahydrocannabinol (THC) or a derivative thereof in an amount of about 35% to about 70% by weight, and Cannabidiol (CBD) in an amount of less than 1% by weight; or b. THC or a derivative thereof in an amount of about 15% to about 35% by weight, and CBD in an amount of 25% to 35% by weight.

2. The composition according to claim 1, wherein said Cannabis derived extract comprises THC or a derivative thereof in an amount of about 40% to about 65% by weight, and CBD in an amount of less than 0.5%, such as less than 0.2 %, by weight.

3. The composition according to claim 1, wherein said Cannabis derived extract comprises THC to CBD ratio, by weight, of 1: 1.66 to 1.4: 1.

4. The composition according to claim 1 , wherein said composition comprises one or more cannabinoids selected from: THCVA, THCV THCOA, THCO, THC-C7 (THCP), THC-C6, THC-C4 (THCB), THCA-OAc, THCA-C7 (THCPA), THCA-C6, THCA-C4 (THCBA), Sesqui-CBGA, Sesqui-CBG, OH-CBNA, OH-CBN, d9-THCMA, d9-THCM, d9-THCA, d9-THC, d8-THC, CNF-B, CNF-A, CBTV-3, CBTV-1, CBTA-3, CBTA-1, CBT-3, CBT- 2, CBT-1, CBNVA, CBNV, CBNOA, CBNO, CBNM, CBNDVA, CBNDA, CBND, CBN- C6, CBN-C4 (CBNB), CBNA-C4 (CBNBA), CBNA-8-OH, CBNA, CBN-8-OH, CBN, CBL, CBGVA, CBGV, CBG-OAc, CBGOA, CBGO, CBGMA, CBGM, CBG-C7 (CBGP), CBG-C6, CBG-C4 (CBGB), CBGA-OAc, CBGA-C7 (CBGPA), CBGA-C6, CBGA-C4 (CBGAB), CBGA, CBG, CBEVA, CBEV, CBEA, CBE, CBDVM, CBDVA, CBDV, CBD- OAc, CBDOA, CBDO, CBDMA, CBDM, CBD-C7 (CBDP), CBD-C6, CBD-C4 (CBDB), CBDA-Oac, CBDA-C7 (CBDPA), CBDA-C6, CBDA-C4 (CBDAB), CBDA, CBD, CBCVA, CBCV, CBCOA, CBCO, CBC-C4 (CBCB), CBCA-C4 (CBCBA), CBCA, CBC, Cannabicitran, CA-5992 , 417-15a , 375-19c , 375-19b , 375-19a , 373-15c, 373-15b, 373- 12d, 373-12c, 373-12b, 373-12a, 371-14b, 371-14a, 361-17b, 361-17a, 357-16a, 331-18d,

65 331-18c, 331-18b, 331-18a, 329-l le, 329-l ld, 329-l lc, 329-l lb, 329-l la, 327-13c, 327- 13b, 327-13a, 313- 16b and any mixtures or combination thereof. The composition according to claim 1, wherein said composition comprises one or more non-cannabinoid components selected from terpenes, terpenoids, phenylpropanoids, amino acids, polyamines, hydrocarbons, sugars and related compounds, nitrogenous compounds, non-cannabinoid phenols, fatty acids, flavonoids, sterols, triglycerides, alkanes, squalene, tocopherol, carotenoids, chlorophyll, glycosides, alkaloids, anthocyanins, vitamins, minerals, macronutrients and any combination thereof. The composition according to claim 5, wherein said non-cannabinoid components are further selected from flavonols such as catechin, epicatechin, flavanone, naringenin, lignanamides, cannabisin a, cannabisin b and cannabisin c; phenolic amides such as n- transcaffeoyltyramine, rutin, quercetin-3-glucoside, kaempferol-3-oglucoside, quercetin and kaempferol; flavones such as cannflavin a, cannflavin b, luteolin-7-oglucoside, apigenin-7-oglucoside, luteolin and apigenin; phenolic acids such as hydroxycinnamic acids, chlorogenic acid, caffeic acid, p-coumaric acid, ferulic acid, and isoflavonoid. The composition according to claim 5, wherein the terpene and/or flavonoids include for example, 1,8-cineole, P-myrcene, P-caryophyllene, cannflavin A, apigenin, quercetin, pulegone, a-Pinene, Camphene, b-Pinene, Sabinene, -(-)b-Myrcene, 3d-Carene, a- Terpinene, D/L-Limonene, p-Cymene, cis-Ocimene, Eucalyptol, trans-Ocimene, D/L- Fenchone, Terpinolene, Linalool, Fenchol, -(-)Camphor, -(-)Isopulegol, D/L-Borneol, Isoborneol, D/L-Menthol, a-Terpineol, Geraniol, Nerol, a-Pulegone, b-Caryophyllene, trans-b-Farnesene, a-Humulene, -(+)Ledene, Valencene, trans-Nerolidol, Caryophyllene oxide, -(+)Cedrol, -(-)Guaiol, (-)a-Bisabolol, cis-Nerolidol, a-Phellandrene, m-Cymene, g- Terpinene, cis-Linalool oxide, trans-Linalool oxide, -(-/+)Terpinen-4-ol, -(-)Bornyl acetate, -(+)Longipinene, a-Curcumene, b-Citronellol, trans-2-pinanol, a-Bulnesol, Selina 4 diene or Selina 3,7 diene and any mixtures or combination thereof. The composition according to any one of claims 5 and 7, wherein said extract comprises Sesqui-CBG 82-637 ppm, CBCOA 0-4 ppm, (-)a-Bisabolol 514-968 ppm, (+)-Ledene 307- 1175, Linalool 121-2317 ppm, trans-Nerolidol 179-483 and CBG-OAc 10-13 ppm.

66 The composition according to claim 8, wherein said composition is useful in pain management. The composition according to any one of claims 5 and 7, wherein said extract comprises (- )a-Bisabolol 18-968 ppm, (+)-Ledene 307-1175 ppm, Linalool 121-1538, trans-Nerolidol 179-483 ppm, trans-b-Farnesene 96-214 ppm and CBG-OAc 10-13 ppm. The composition according to claim 10, wherein said composition is useful in conferring anti-inflammatory effect pain. The composition according to claim 1, wherein said extract is derived from one or more Cannabis species or variety or strain. The composition according to claim 12, wherein said Cannabis species or variety or strain belongs to at least one of Cannabis sativa, Cannabis indica, Cannabis ruderalis and any hybrid or cultivated variety of the genus Cannabis. The composition according to claim 13, wherein the inflorescence of said Cannabis species or variety or strain is characterized as comprising 0.11-0.33% CBCA, <0.1% CBDA, <0.1% CBDVA, 0.03-0.41% CBG, 0.09-0.4% CBGA, <0.1%CBN, <0.1% CBNA, 0.4-0.6% THC, 9.29-15.93% THCA and <0.1% CBD by weight. The composition according to claim 1, wherein said composition is in a dosage form selected from a tablet, a capsule, an inhalant, a parenteral, a transdermal, a sublingual, a rectal, a vaginal, a suppository, a liquid, an aerosol spray, a pastille, a gel, a capsule, a powder or a vaporizer. The composition according to claim 1, wherein said composition is a liquid solution, a Cannabis-based oil preparation, or a liquid suspension. The composition according to claim 1, wherein said composition is used for treating inflammation and/or pain related disorder symptoms. The composition according to claim 1, wherein said composition is useful for treating symptoms associated with diseases or disorders selected from acute inflammation, chronic

67 inflammation, pain associated with inflammation, acute pain, chronic pain, nociceptive pain, referred pain, cancer pain, neuropathic pain, psychogenic pain and visceral pain. The composition according to claim 18, wherein said diseases or disorders are selected from autoimmune diseases and disorders, motor neuron diseases and disorders, neurodegenerative diseases and disorders, diabetes, cardiovascular disease (CVD), arthritis and other joint diseases, allergies, chronic obstructive pulmonary disease (COPD), psoriasis, rheumatoid arthritis, Cancer, Chemotherapy-induced peripheral neuropathy (CIPN), Opioid Use Disorder/Addiction, Carpal Tunnel Syndrome, Osteoarthritis, CRPS/RSD, Osteoporosis, Diabetic Neuropathy, Plantar Fasciitis, Ehlers-Danlos Syndrome (EDS), Postherpetic Neuralgia, Fibromyalgia, Insomnia, Gout, Pelvic Pain, hATTR Amyloidosis, Psoriatic Arthritis, Low Back Pain, Rheumatoid Arthritis, Lupus, Sickle Cell Disease, Lyme Disease, Thigh Pain, Migraine and Headaches, Traumatic Brain Injuries, Neck Pain and TMJ Disorders, Crohn's Disease, inflammatory bowel disorders (IBS and IBD). The composition according to claim 1 , for use as a medicament. The composition according to claim 1, for use as anti-inflammatory therapy. The composition according to claim 1, wherein said composition comprises at least one pharmacologically inactive substance. The composition according to claim 22, wherein said pharmacologically inactive substance is selected from pharmaceutically acceptable carriers, diluents, adjuvants, excipients or any combination thereof. The composition according to claim 1, wherein said composition provides a therapeutic effect selected from an anti-inflammatory effect and a pain relief effect. The composition according to claim 1, wherein said anti-inflammatory effect confers inhibition of immune system cells such as macrophage and lymphocyte cells. The composition according to claim 25, wherein said anti-inflammatory effect confers inhibition of activated immune system cells such as macrophage activated cells by at least 30%.

68 The composition according to claim 24, wherein said anti-inflammatory effect confers reduced proliferation of activated immune system cells such as lymphocyte activated cells by at least 40%. The composition according to claim 1, wherein said pain relief effect confers inhibition, reduction or prevention of nociceptive pain symptoms by at least 20%. The composition according to any one of claims 1 to 28, wherein said effect is additive or synergistic relative to the effect conferred by THC or CBD, administered separately in a similar concentration. The composition according to any one of claim 1-29, wherein the THC ,CBD or any other cannabinoid compound or non- cannabinoid compound or a derivative thereof, is one or more of: (i) natural cannabinoids or non- cannabinoids; (ii) synthetically derived cannabinoids or non- cannabinoids; (iii) semi-synthetic cannabinoids or non- cannabinoids; (iv) active metabolites of any of the foregoing, (vi) pro-drugs of any of the foregoing; and (vii) mixtures thereof. The composition according to claim 1, wherein the composition contains a synthetic analogue of one or more of the cannabinoids or non-cannabinoids compounds. A medicament comprising an effective amount of a composition according to any one of claims 1 to 31. Use of a Cannabis extract in the preparation of a medicament for treating an inflammation or pain disorder, wherein the Cannabis extract is as defined in any one of claims 1-31. A Cannabis based preparation for inhalation, for use in the treatment of inflammation and/or pain related disorders, comprising the composition according to any one of claims 1-31. The Cannabis based preparation according to claim 34, wherein said preparation is in a dosage form selected from a tablet, a capsule, an inhalant, a parenteral, a transdermal, a sublingual, a rectal, a vaginal, a suppository, a liquid, an aerosol spray, a pastille, a gel, a capsule, a powder or a vaporizer.

69

. A method for treating pain and/or inflammation related disorders, the method comprising administering to a patient in need thereof an effective amount of the composition according to any one of claims 1 to 31, or a medicament according to claim 32 or a Cannabis based preparation according to any one of claims 34 and 35. . The method according to claim 36, wherein the composition is administered to the patient in combination with one or more other medicinal substances used in the treatment of pain and inflammation related disorders. . A composition comprising a Cannabis derived extract for use in the treatment of inflammation and/or pain related disorders, produced according to a method comprising steps of: a. obtaining at least one part of a Cannabis plant variety selected from 'Precise-A', 'Precise-B', 'Precise-C, 'Precise-D' or 'Precise-E'; b. generating an extract from said Cannabis plant part; wherein said composition comprises: i. tetrahydrocannabinol (THC) or a derivative thereof in an amount of 40% to 65% by weight, and Cannabidiol (CBD) in an amount of less than 1%; or ii. THC or a derivative thereof in an amount of 15% to 35% by weight, and CBD in an amount of 25% to 35% by weight. . The composition of claim 38, wherein said Cannabis plant part is characterized as inflorescences. . The composition of claim 39, wherein said inflorescence is characterized as comprising 0.11-0.33% CBCA, <0.1% CBDA, <0.1% CBDVA, 0.03-0.41% CBG, 0.09-0.4% CBGA, <0.1%CBN, <0.1% CBNA, 0.4-0.6% THC, 9.29-15.93% THCA and <0.1% CBD.

70 The composition of claim 38, wherein said step of generating an extract comprises at least one step of suspending said part of said Cannabis plant in a solvent, gas or any combination thereof. The composition according to claim 41, wherein said gas is carbon dioxide, or other gases in isolation or combination. The composition according to claim 42, wherein said carbon dioxide is characterized as being supercritical. The composition according to claim 41, wherein said solvent is selected from the group consisting of ethanol, propanol, butanol, hexane, chloroform, dichloromethane, acetone, water and any mixture thereof. The composition of claim 41, wherein said step of extraction compromises steps of proving said solvent and said plant at a ratio of 1 part Cannabis to 5-10 parts of solvent, by weight. The composition of claim 38, wherein said step of generating an extract comprises at least one step, selected from the group consisting of Soxhlet extraction, solvent-extraction, solvent-free-extraction, super-critical fluid extraction, the application of pressure and/or heat, or combinations thereof. The composition of claim 38, wherein said method additionally comprising a step of preparing a plant sample, comprising at least one step selected from the group consisting of tearing, crushing, cutting, shredding, milling and pulverizing. The composition of claim 38, wherein said method additionally comprising at least one step of separating liquid and solid phases. The composition of claim 48, wherein said step of separating said liquid and solid phases is conducted by at least one method selected from the group consisting of decanting, centrifugation, rotary evaporation, benchtop evaporation via the application of heat, evaporation under a stream of inert gas, evaporation under reduced pressure, filtration. The composition of claim 38, wherein said method additionally comprising a step of decarboxylation. The composition according to claim 38, comprising THC to CBD at a ratio of 1: 1.66 to 1.4: 1, by weight. The composition according to claim 38, additionally comprising at least one other cannabinoids selected from the group consisting of THCVA, THCV THCOA, THCO, THC-C7 (THCP), THC-C6, THC-C4 (THCB), THCA-OAc, THCA-C7 (THCPA), THCA- C6, THCA-C4 (THCBA), Sesqui-CBGA, Sesqui-CBG, OH-CBNA, OH-CBN, d9- THCMA, d9-THCM, d9-THCA, d9-THC, d8-THC, CNF-B, CNF-A, CBTV-3, CBTV-1, CBTA-3, CBTA-1, CBT-3, CBT-2, CBT-1, CBNVA, CBNV, CBNOA, CBNO, CBNM, CBNDVA, CBNDA, CBND, CBN-C6, CBN-C4 (CBNB), CBNA-C4 (CBNBA), CBNA- 8-OH, CBNA, CBN-8-OH, CBN, CBL, CBGVA, CBGV, CBG-OAc, CBGOA, CBGO, CBGMA, CBGM, CBG-C7 (CBGP), CBG-C6, CBG-C4 (CBGB), CBGA-OAc, CBGA-C7 (CBGPA), CBGA-C6, CBGA-C4 (CBGAB), CBGA, CBG, CBEVA, CBEV, CBEA, CBE, CBDVM, CBDVA, CBDV, CBD-OAc, CBDOA, CBDO, CBDMA, CBDM, CBD-C7 (CBDP), CBD-C6, CBD-C4 (CBDB), CBDA-Oac, CBDA-C7 (CBDPA), CBDA-C6, CBDA-C4 (CBDAB), CBDA, CBD, CBCVA, CBCV, CBCOA, CBCO, CBC-C4 (CBCB), CBCA-C4 (CBCBA), CBCA, CBC, Cannabicitran, CA-5992 , 417-15a , 375-19c , 375-19b

, 375-19a , 373-15c, 373-15b, 373-12d, 373-12c, 373-12b, 373-12a, 371-14b, 371-14a, 361- 17b, 361-17a, 357-16a, 331-18d, 331-18c, 331-18b, 331-18a, 329-l le, 329-l ld, 329-l lc, 329-l lb, 329-l la, 327-13c, 327-13b, 327-13a, 313-16b and any mixtures or combination thereof. The composition according to claim 38, additionally comprising at least one other noncannabinoid components selected from terpenes, terpenoids, phenylpropanoids, amino acids, polyamines, hydrocarbons, sugars and related compounds, nitrogenous compounds, non-cannabinoid phenols, fatty acids, flavonoids, sterols, triglycerides, alkanes, squalene, tocopherol, carotenoids, chlorophyll, glycosides, alkaloids, anthocyanins, vitamins, minerals, macronutrients, flavonols, phenolic amides, flavones, phenolic acids and any combination thereof. The composition according to claim 53, wherein said flavonol is selected from the group consisting of catechin, epicatechin, flavanone, naringenin, lignanamides, cannabisin a, cannabisin b and cannabisin c; The composition according to claim 53, wherein said phenolic amide is selected from the group consisting of n-transcaffeoyltyramine, rutin, quercetin-3-glucoside, kaempferol-3- oglucoside, quercetin and kaempferol; The composition according to claim 53, wherein said flavone is selected from the group consisting of cannflavin a, cannflavin b, luteolin-7-oglucoside, apigenin-7-oglucoside, luteolin and apigenin; The composition according to claim 53, wherein said phenolic acid is selected from the group consisting of hydroxycinnamic acids, chlorogenic acid, caffeic acid, p-coumaric acid, ferulic acid, and isoflavonoid. The composition according to claim 53, wherein the terpene and/or flavonoids are selected from the groups consisting of 1,8-cineole, P-myrcene, P-caryophyllene, cannflavin A, apigenin, quercetin, pulegone, a-Pinene, Camphene, b-Pinene, Sabinene, -(-)b-Myrcene, 3d-Carene, a-Terpinene, D/L-Limonene, p-Cymene, cis-Ocimene, Eucalyptol, trans- Ocimene, D/L-Fenchone, Terpinolene, Linalool, Fenchol, -(-)Camphor, -(-)Isopulegol, D/L-Borneol, Isoborneol, D/L-Menthol, a-Terpineol, Geraniol, Nerol, a-Pulegone, b- Caryophyllene, trans-b-Farnesene, a-Humulene, -(+)Ledene, Valencene, trans-Nerolidol, Caryophyllene oxide, -(+)Cedrol, -(-)Guaiol, (-)a-Bisabolol, cis-Nerolidol, a-Phellandrene, m-Cymene, g-Terpinene, cis-Linalool oxide, trans-Linalool oxide, -(-/+)Terpinen-4-ol, -(-) Bornyl acetate, -(+)Longipinene, a-Curcumene, b-Citronellol, trans-2-pinanol, a-Bulnesol, Selina 4 diene or Selina 3,7 diene. The composition according to any one of claims 52 and 58, wherein said extraction comprises Sesqui-CBG 82-637 ppm, CBCOA 0-4 ppm, (-)a-Bisabolol 514-968 ppm, (+)- Ledene 307-1175, Linalool 121-2317 ppm, trans-Nerolidol 179-483 and CBG-OAc 10-13 ppm.

73 The composition according to any one of claims 52 and 58, wherein said extraction comprises (-)a-Bisabolol 18-968 ppm, (+)-Ledene 307-1175 ppm, Linalool 121-1538, trans- Nerolidol 179-483 ppm, trans-b-Farnesene 96-214 ppm and CBG-OAc 10-13 ppm. The composition according to claim 38, for use as a medicament. The composition according to claim 38, for use as anti-inflammatory therapy and/or for pain management. The composition according to claim 38, wherein said composition is used for treating symptoms associated with diseases or disorders selected from acute inflammation, chronic inflammation, pain associated with inflammation, acute pain, chronic pain, nociceptive pain, referred pain, cancer pain, neuropathic pain, psychogenic pain and visceral pain. The composition according to claim 63, wherein said diseases or disorders are selected from autoimmune diseases and disorders, motor neuron diseases and disorders, neurodegenerative diseases and disorders, diabetes, cardiovascular disease (CVD), arthritis and other joint diseases, allergies, chronic obstructive pulmonary disease (COPD), psoriasis, rheumatoid arthritis, Cancer, Chemotherapy-induced peripheral neuropathy (CIPN), Opioid Use Disorder/Addiction, Carpal Tunnel Syndrome, Osteoarthritis, CRPS/RSD, Osteoporosis, Diabetic Neuropathy, Plantar Fasciitis, Ehlers-Danlos Syndrome (EDS), Postherpetic Neuralgia, Fibromyalgia, Insomnia, Gout, Pelvic Pain, hATTR Amyloidosis, Psoriatic Arthritis, Low Back Pain, Rheumatoid Arthritis, Lupus, Sickle Cell Disease, Lyme Disease, Thigh Pain, Migraine and Headaches, Traumatic Brain Injuries, Neck Pain and TMJ Disorders, Crohn's Disease, inflammatory bowel disorders (IBS and IBD). The composition according to claim 38, wherein said method additionally comprises a step of adding at least one pharmacologically inactive substance. The composition according to claim 65, wherein said pharmacologically inactive substance is selected from pharmaceutically acceptable carriers, diluents, adjuvants, excipients or any combination thereof.

74 The composition according to claim 38, wherein said composition provides a therapeutic effect selected from an anti-inflammatory effect and a pain relief effect. The composition according to claim 67, wherein said anti-inflammatory effect confers inhibition of immune system cells such as macrophage and lymphocyte cells. The composition according to claim 67, wherein said anti-inflammatory effect confers inhibition of activated immune system cells such as macrophage activated cells by at least 30%. The composition according to claim 67, wherein said anti-inflammatory effect confers reduced proliferation of activated immune system cells such as lymphocyte activated cells by at least 40%. The composition according to claim 67, wherein said pain relief effect confers inhibition, reduction or prevention of nociceptive pain symptoms by at least 20%. A method of producing a composition for the management of pain and inflammation, comprising steps of: a. obtaining at least one Cannabis plant variety selected from 'Precise-A', 'Precise-B', 'Precise-C, 'Precise-D' or 'Precise-E', or from any part of the Cannabis plant thereof; and b. generating an extract from said Cannabis plant; wherein said composition comprises: i. tetrahydrocannabinol (THC) or a derivative thereof in an amount of 40% to 65% by weight, and Cannabidio (CBD) in an amount of less than 1%; or ii. THC or a derivative thereof in an amount of 15% to 35% by weight, and CBD in an amount of 25% to 35% by weight. The method of claim 72, wherein said Cannabis plant part is characterized as inflorescences.

75 The method of claim 73, wherein said inflorescences comprises 0.11-0.33% CBCA, <0.1% CBDA, <0.1% CBDVA, 0.03-0.41% CBG, 0.09-0.4% CBGA, <0.1%CBN, <0.1% CBNA, 0.4-0.6% THC, 9.29-15.93% THCA and <0.1% CBD. The method of claim 72, wherein said step of generating an extract comprises at least one step of suspending said part of said Cannabis plant in a solvent, gas or any combination thereof. The method of claim 75, wherein said gas is carbon dioxide. The method of claim 76, wherein said carbon dioxide is characterized as being supercritical. The method of claim 75, wherein said solvent is selected from the group consisting of ethanol, propanol, butanol, hexane, chloroform, dichloromethane, acetone, water and any mixture thereof. The method of claim 72, wherein said step of extraction comprising steps of providing said solvent and said plant at a ratio of 1 part Cannabis to 5-10 parts of solvent, by weight. The method of claim 72, wherein said step of generating an extract comprises at least one step, selected from the group consisting of Soxhlet extraction, solvent-extraction, solvent- free-extraction, super-critical fluid extraction, the application of pressure and/or heat, or combinations thereof. The method of claim 72, additionally comprising a step of preparing a plant sample, comprising at least one step selected from the group consisting of tearing, crushing, cutting, shredding, milling and pulverizing. The method of claim 72, additionally comprising at least one step of separating liquid and solid phases. The method of claim 82, wherein said step of separating said liquid and solid phases is conducted by at least one method selected from the group consisting of decanting, centrifugation, rotary evaporation, benchtop evaporation via the application of heat, evaporation under a stream of inert gas, evaporation under reduced pressure, filtration.

76 The method of claim 72, additionally comprising a step of de-carboxylation. The method according to claim 72, wherein said composition comprises THC to CBD at a ratio of 1: 1.66 to 1.4: 1, by weight. The method according to claim 72, wherein said composition additionally comprising at least one other cannabinoids selected from the group consisting of THCVA, THCV THCOA, THCO, THC-C7 (THCP), THC-C6, THC-C4 (THCB), THCA-OAc, THCA-C7 (THCPA), THCA-C6, THCA-C4 (THCBA), Sesqui-CBGA, Sesqui-CBG, OH-CBNA, OH-CBN, d9-THCMA, d9-THCM, d9-THCA, d9-THC, d8-THC, CNF-B, CNF-A, CBTV- 3, CBTV-1, CBTA-3, CBTA-1, CBT-3, CBT-2, CBT-1, CBNVA, CBNV, CBNOA, CBNO, CBNM, CBNDVA, CBNDA, CBND, CBN-C6, CBN-C4 (CBNB), CBNA-C4 (CBNBA), CBNA-8-OH, CBNA, CBN-8-OH, CBN, CBL, CBGVA, CBGV, CBG-OAc, CBGOA, CBGO, CBGMA, CBGM, CBG-C7 (CBGP), CBG-C6, CBG-C4 (CBGB), CBGA-OAc, CBGA-C7 (CBGPA), CBGA-C6, CBGA-C4 (CBGAB), CBGA, CBG, CBEVA, CBEV, CBEA, CBE, CBDVM, CBDVA, CBDV, CBD-OAc, CBDOA, CBDO, CBDMA, CBDM, CBD-C7 (CBDP), CBD-C6, CBD-C4 (CBDB), CBDA-Oac, CBDA-C7 (CBDPA), CBDA-C6, CBDA-C4 (CBDAB), CBDA, CBD, CBCVA, CBCV, CBCOA, CBCO, CBC-C4 (CBCB), CBCA-C4 (CBCBA), CBCA, CBC, Cannabicitran, CA-5992 , 417-15a , 375-19c , 375-19b , 375-19a , 373-15c, 373-15b, 373-12d, 373-12c, 373-12b, 373- 12a, 371-14b, 371-14a, 361-17b, 361-17a, 357-16a, 331-18d, 331-18c, 331-18b, 331-18a, 329-1 le, 329-1 Id, 329-11c, 329-1 lb, 329-1 la, 327-13c, 327-13b, 327-13a, 313-16b and any mixtures or combination thereof. The method according to claim 72, wherein said composition additionally comprising at least one other non-cannabinoid components selected from terpenes, terpenoids, phenylpropanoids, amino acids, polyamines, hydrocarbons, sugars and related compounds, nitrogenous compounds, non-cannabinoid phenols, fatty acids, flavonoids, sterols, triglycerides, alkanes, squalene, tocopherol, carotenoids, chlorophyll, glycosides, alkaloids, anthocyanins, vitamins, minerals, macronutrients, flavonols, phenolic amides, flavones and phenolic acids any combination thereof.

77 The method according to claim 87, wherein said flavonol is selected from the group consisting of catechin, epicatechin, flavanone, naringenin, lignanamides, cannabisin a, cannabisin b and cannabisin c. The method according to claim 87, wherein said phenolic amide is selected from the group consisting of n-transcaffeoyltyramine, rutin, quercetin-3-glucoside, kaempferol-3- oglucoside, quercetin and kaempferol. The method according to claim 87, wherein said flavone is selected from the group consisting of cannflavin a, cannflavin b, luteolin-7-oglucoside, apigenin-7-oglucoside, luteolin and apigenin; The method according to claim 87, wherein said phenolic acid is selected from the group consisting of hydroxycinnamic acids, chlorogenic acid, caffeic acid, p-coumaric acid, ferulic acid, and isoflavonoid. The method according to claim 87, wherein the terpene and/or flavonoids are selected from the groups consisting of 1,8-cineole, P-myrcene, P-caryophyllene, cannflavin A, apigenin, quercetin, pulegone, a-Pinene, Camphene, b-Pinene, Sabinene, -(-)b-Myrcene, 3d-Carene, a-Terpinene, D/L-Limonene, p-Cymene, cis-Ocimene, Eucalyptol, trans-Ocimene, D/L- Fenchone, Terpinolene, Linalool, Fenchol, -(-)Camphor, -(-)Isopulegol, D/L-Borneol, Isoborneol, D/L-Menthol, a-Terpineol, Geraniol, Nerol, a-Pulegone, b-Caryophyllene, trans-b-Farnesene, a-Humulene, -(+)Ledene, Valencene, trans-Nerolidol, Caryophyllene oxide, -(+)Cedrol, -(-)Guaiol, (-)a-Bisabolol, cis-Nerolidol, a-Phellandrene, m-Cymene, g- Terpinene, cis-Linalool oxide, trans-Linalool oxide, -(-/+)Terpinen-4-ol, -(-)Bornyl acetate, -(+)Longipinene, a-Curcumene, b-Citronellol, trans-2-pinanol, a-Bulnesol, Selina 4 diene or Selina 3,7 diene. The method according to any one of claims 87 and 92, wherein said extract comprises Sesqui-CBG 82-637 ppm, CBCOA 0-4 ppm, (-)a-Bisabolol 514-968 ppm, (+)-Ledene 307- 1175, Linalool 121-2317 ppm, trans-Nerolidol 179-483 and CBG-OAc 10-13 ppm.

78 The method according to any one of claims 87 and 92, wherein said extract comprises (-)a- Bisabolol 18-968 ppm, (+)-Ledene 307-1175 ppm, Linalool 121-1538, trans-Nerolidol 179- 483 ppm, trans-b-Farnesene 96-214 ppm and CBG-OAc 10-13 ppm. A method of treating a disorder associated with inflammation and/or pain, comprising steps of: a. obtaining the composition or preparation of any one of claim 1-31, 34-45 and 38-71; and b. administering a pharmacologically active dose of said composition or preparation to a subject. The method of claim 95, wherein said pain or inflammation is selected from acute inflammation, chronic inflammation, pain associated with inflammation, acute pain, chronic pain, nociceptive pain, referred pain, cancer pain, neuropathic pain, psychogenic pain and visceral pain.

79