USE OF CANNABINOID COMPOUND IN NEURODERMATITIS TREATMENT

Abstract

The present invention discloses use of a cannabinoid compound or pharmaceutically available salts thereof in preparation of a pharmaceutical composition for treatment of neurodermatitis, wherein the cannabinoid compound may be one selected from the group consisting of tetrahydrocannabinol, cannabidiol, cannabidivarin and tetrahydrocannabinovarin, or selected from the group consisting of: (1) a combination of tetrahydrocannabinol and tetrahydrocannabinovarin; (2) a combination of cannabidiol and cannabidivarin; (3) a combination of tetrahydrocannabinol and cannabidivarin; (4) a combination of cannabidiol and tetrahydrocannabinovarin; (5) a combination of cannabidiol, cannabidivarin, and tetrahydrocannabinovarin; (6) a combination of tetrahydrocannabinol, cannabidivarin, and tetrahydrocannabinovarin.

Claims

1. (canceled)

2. Use of a cannabinoid compound or a pharmaceutically available salt thereof in preparation of a pharmaceutical composition for treatment of neurodermatitis, the cannabinoid compound being selected from the group consisting of: (1) a combination of tetrahydrocannabinol (THC) and tetrahydrocannabinovarin (THCV); (2) a combination of cannabidiol (CBD) and cannabidivarin (CBDV); (3) a combination of tetrahydrocannabinol (THC) and cannabidivarin (CBDV); (4) a combination of cannabidiol (CBD) and tetrahydrocannabinovarin (THCV); (5) a combination of cannabidiol (CBD), cannabidivarin (CBDV), and tetrahydrocannabinovarin (THCV); and (6) a combination of tetrahydrocannabinol (THC), cannabidivarin (CBDV), and tetrahydrocannabinovarin (THCV).

3. The use of the cannabinoid compound or the pharmaceutically available salt thereof in preparation of the pharmaceutical composition for treatment of neurodermatitis according to claim 2, wherein: (1) the combination of tetrahydrocannabinol (THC) and tetrahydrocannabinovarin (THCV) has a ratio of tetrahydrocannabinol (THC) to tetrahydrocannabinovarin (THCV) of 100:5-20 by weight; (2) the combination of cannabidiol (CBD) and cannabidivarin (CBDV) has a ratio of cannabidiol (CBD) to cannabidivarin (CBDV) of 100:20-50 by weight; (3) the combination of tetrahydrocannabinol (THC) and cannabidivarin (CBDV) has a ratio of tetrahydrocannabinol (THC) to cannabidivarin (CBDV) of 100:40-100 by weight; (4) the combination of cannabidiol (CBD) and tetrahydrocannabinovarin (THCV) has a ratio of cannabidiol (CBD) to tetrahydrocannabinovarin (THCV) of 100:2.5-10 by weight; (5) the combination of cannabidiol (CBD), cannabidivarin (CBDV) and tetrahydrocannabinovarin (THCV) has a ratio of cannabidiol (CBD) to cannabidivarin (CBDV) to tetrahydrocannabinovarin (THCV) of 100:20-50: 2.5-10 by weight; and (6) the combination of tetrahydrocannabinol (THC), cannabidivarin (CBDV) and tetrahydrocannabinovarin (THCV) has a ratio of tetrahydrocannabinol (THC) to cannabidivarin (CBDV) to tetrahydrocannabinovarin (THCV) of 100:40-100:5-20 by weight.

4. (canceled)

5. A pharmaceutical composition for treating neurodermatitis, characterized in that the pharmaceutical composition comprises the following components: 1) a cannabinoid compound or a pharmaceutically available salt thereof; and 2) one or more pharmaceutically acceptable carriers or excipients; wherein the cannabinoid compound is selected from the group consisting of: (1) a combination of tetrahydrocannabinol (THC) and tetrahydrocannabinovarin (THCV); (2) a combination of cannabidiol (CBD) and cannabidivarin (CBDV); (3) a combination of tetrahydrocannabinol (THC) and cannabidivarin (CBDV); (4) a combination of cannabidiol (CBD) and tetrahydrocannabinovarin (THCV); (5) a combination of cannabidiol (CBD), cannabidivarin (CBDV), and tetrahydrocannabinovarin (THCV); and (6) a combination of tetrahydrocannabinol (THC), cannabidivarin (CBDV) and tetrahydrocannabinovarin (THCV).

6. The pharmaceutical composition according to claim 5, characterized in that the cannabinoid compound is selected from the group consisting of: (1) the combination of tetrahydrocannabinol (THC) and tetrahydrocannabinovarin (THCV) in a ratio of tetrahydrocannabinol (THC) to tetrahydrocannabinovarin (THCV) of 100:5-20 by weight; (2) the combination of cannabidiol (CBD) and cannabidivarin (CBDV) in a ratio of cannabidiol (CBD) to cannabidivarin (CBDV) of 100:20-50 by weight; (3) the combination of tetrahydrocannabinol (THC) and cannabidivarin (CBDV) in a ratio of tetrahydrocannabinol (THC) to cannabidivarin (CBDV) of 100:40-100 by weight; (4) the combination of cannabidiol (CBD) and tetrahydrocannabinovarin (THCV) in a ratio of cannabidiol (CBD) to tetrahydrocannabinovarin (THCV) of 100:2.5-10 by weight; (5) the combination of cannabidiol (CBD), cannabidivarin (CBDV) and tetrahydrocannabinovarin (THCV) in a ratio of cannabidiol (CBD) to cannabidivarin (CBDV) to tetrahydrocannabinovarin (THCV) of 100:20-50:2.5-10 by weight; and (6) the combination of tetrahydrocannabinol (THC), cannabidivarin (CBDV) and tetrahydrocannabinovarin (THCV) in a ratio of tetrahydrocannabinol (THC) to cannabidivarin (CBDV) to tetrahydrocannabinovarin (THCV) of 100:40-100:5-20 by weight.

7. The composition according to claim 5, characterized in that the pharmaceutical composition is selected from the group consisting of capsules, tablets, pills, lozenges, granules, solutions, emulsions, suspensions, syrups, sterile injections, sterile powders, suppositories, sprays, ointments, creams, gels, inhalants, dermal patches or implants.

8. A method for preparing the composition of claim 5, characterized by comprising the step of: uniformly mixing one or more cannabinoid compounds, or pharmaceutically available salts thereof in proportion to obtain the composition.

Description

DETAILED DESCRIPTION

[0062] It is to be noted that the embodiments and the features in the embodiments of the present application may be combined with each other without conflict. The present invention will be described in detail below in connection with the embodiments.

Embodiment 1. Capsules in a Unit Dosage Form

[0063] Prescription ingredients: Cannabidiol 200 mg [0064] Microcrystalline cellulose 90 mg [0065] Pregelatinized starch 100 mg [0066] Cross-linked carboxymethyl cellulose 7 mg [0067] Magnesium stearate 0.5 mg

[0068] Preparation method: the active ingredient was sieved and mixed with the excipients, and the mixture was packed into hard gelatin capsules.

Embodiment 2. Capsules in a Unit Dosage Form

[0069] Prescription ingredients: Cannabidiol 400 mg [0070] Microcrystalline cellulose 100 mg [0071] Pregelatinized starch 150 mg [0072] Cross-linked carboxymethyl cellulose 10 mg [0073] Magnesium stearate 0.2 mg

[0074] Preparation method was the same as that in Embodiment 1.

Embodiment 3. Tablets in a Unit Dosage Form

[0075] Prescription ingredients: Tetrahydrocannabinol 100 mg [0076] Dextrin 100 mg [0077] Microcrystalline cellulose 25 mg [0078] Polyvinylpyrrolidone 10 mg [0079] Sodium carboxymethyl starch 15 mg [0080] Magnesium stearate 1 mg

[0081] Preparation method: the active ingredient was sieved and mixed with dextrin, microcrystalline cellulose, polyvinylpyrrolidone and sodium carboxymethyl starch until a homogeneous mixture was formed. The homogeneous mixture was sieved and mixed with magnesium stearate. The resulting powder mixture was then pressed into tablets of the desired shape and size.

Embodiment 4. Tablets in a Unit Dosage Form

[0082] Prescription ingredients: Tetrahydrocannabinol 40 mg [0083] Pregelatinized starch 150 mg [0084] Microcrystalline cellulose 25 mg [0085] Sodium carboxymethyl starch 15 mg [0086] Magnesium stearate 1 mg

[0087] Preparation method: the active ingredient was sieved and mixed with pregelatinized starch, microcrystalline cellulose and sodium carboxymethyl starch until a homogeneous mixture was formed. The homogeneous mixture was sieved and mixed with magnesium stearate. The resulting powder mixture was then pressed into tablets of the desired shape and size.

Embodiment 5. Tablets in a Unit Dosage Form

[0088] Prescription ingredients: Cannabidiol 200 mg [0089] Cannabidivarin 40 mg [0090] Dextrin 150 mg [0091] Sodium carboxymethyl starch 15 mg [0092] Magnesium stearate 1 mg

[0093] Preparation method: the active ingredients were sieved and mixed with dextrin and sodium carboxymethyl starch until a homogeneous mixture was formed. The homogeneous mixture was sieved and mixed with magnesium stearate. The resulting powder mixture was then pressed into tablets of the desired shape and size.

Embodiment 6. Tablets in a Unit Dosage Form

[0094] Prescription ingredients: Tetrahydrocannabinol 100 mg [0095] Cannabidivarin 40 mg [0096] Pregelatinized starch 150 mg [0097] Microcrystalline cellulose 25mg [0098] Sodium carboxymethyl starch 15 mg [0099] Magnesium stearate 1 mg

[0100] Preparation method: the active ingredients were sieved and mixed with pregelatinized starch, microcrystalline cellulose and sodium carboxymethyl starch until a homogeneous mixture was formed. The homogeneous mixture was sieved and mixed with magnesium stearate. The resulting powder mixture was then pressed into tablets of the desired shape and size.

Embodiment 7. Tablets in a Unit Dosage Form

[0101] Prescription ingredients: Cannabidiol 200 mg [0102] Tetrahydrocannabinovarin 10 mg [0103] Pregelatinized starch 150 mg [0104] Microcrystalline cellulose 25 mg [0105] Polyvinylpyrrolidone 10 mg [0106] Sodium carboxymethyl starch 15 mg [0107] Magnesium stearate 1 mg

[0108] Preparation method: the active ingredients were sieved and mixed with pregelatinized starch, microcrystalline cellulose, polyvinylpyrrolidone and sodium carboxymethyl starch until a homogeneous mixture was formed. The homogeneous mixture was sieved and mixed with magnesium stearate. The resulting powder mixture was then pressed into tablets of the desired shape and size.

Embodiment 8. Tablets in a Unit Dosage Form

[0109] Prescription ingredients: Tetrahydrocannabinol 100 mg [0110] Tetrahydrocannabinovarin 10 mg [0111] Pregelatinized starch 150 mg [0112] Microcrystalline cellulose 25 mg [0113] Polyvinylpyrrolidone 10 mg [0114] Sodium carboxymethyl starch 15 mg [0115] Magnesium stearate 1 mg

[0116] Preparation method: the active ingredients were sieved and mixed with pregelatinized starch, microcrystalline cellulose, polyvinylpyrrolidone and sodium carboxymethyl starch until a homogeneous mixture was formed. The homogeneous mixture was sieved and mixed with magnesium stearate. The resulting powder mixture was then pressed into tablets of the desired shape and size.

Embodiment 9. Tablets in a Unit Dosage Form

[0117] Prescription ingredients: Tetrahydrocannabinol 100 mg [0118] Cannabidivarin 40 mg [0119] Tetrahydrocannabinovarin 10 mg [0120] Dextrin 150 mg [0121] Sodium carboxymethyl starch 15 mg [0122] Magnesium stearate 1 mg

[0123] Preparation: the active ingredients were sieved and mixed with dextrin and sodium carboxymethyl starch until a homogeneous mixture was formed. The homogeneous mixture was sieved and mixed with magnesium stearate. The resulting powder mixture was then pressed into tablets of the desired shape and size.

Embodiment 10. Tablets in a Unit Dosage Form

[0124] Prescription ingredients: Cannabidiol 200 mg [0125] Cannabidivarin 40 mg [0126] Tetrahydrocannabinovarin 10 mg [0127] Dextrin 150 mg [0128] Sodium carboxymethyl starch 15 mg [0129] Magnesium stearate 1 mg

[0130] Preparation method: the active ingredients were sieved and mixed with dextrin and sodium carboxymethyl starch until a homogeneous mixture was formed. The homogeneous mixture was sieved and mixed with magnesium stearate. The resulting powder mixture was then pressed into tablets of the desired shape and size.

Embodiment 11. Injection in Unit Dosage Form (10 mL of Aqueous Injection)

[0131] Prescription ingredients: Tetrahydrocannabinovarin 500 mg [0132] Hydroxypropyl-β-cyclodextrin q.s. [0133] 0.1 mol/L HCl q.s. [0134] Sodium chloride q.s. [0135] Water for injection to 1000 mL

[0136] Preparation method: about 800 ml of the water for injection was taken, and hydroxypropyl-β-cyclodextrin (q.s.) was added, followed by addition of tetrahydrocannabinovarin component to be dissolved, then the pH was adjusted to 6.2-6.5 with 0.1 mol/L HCl, the water for injection was added to the full amount, uniform stirring was conducted, then sodium chloride was added to blend to be isotonic, filtering was conducted, and the filtered material was sealed into an ampoule, and sterilized by steam at 121° C. for 15 min 10 ml of the sterilized material was filled.

Embodiment 12. Injection in Unit Dosage Form (10 mL of Powder Injection)

[0137] Prescription ingredients: Cannabidivarin 4000 mg [0138] Mannitol 50g [0139] 0.1 mol/L HCl q.s. [0140] Hydroxypropyl-β-cyclodextrin q.s. [0141] Sodium chloride q.s. [0142] Water for injection to 1000 mL

[0143] Preparation method: about 800 ml of the water for injection was taken, mannitol in a prescribed dose and hydroxypropyl-β-cyclodextrin (q.s.) were added, then respective cannabinoid active ingredient was added to be dissolved, the pH was adjusted to 6.2-6.5 with stirring by adding an appropriate amount of 0.1 mol/L HCl, then the water for injection was added to the full amount, sodium chloride was added to blend to be isotonic, filtering was conducted, and the filtered material was freeze-dried according to the process of lyophilized powder injection to prepare the powder injection. 10 ml of the powder injection was filled.

Embodiment 13. Impact of Administration of Cannabinoid Compound Alone on the Itch-Causing Effect of Histamine Phosphate

Experimental Principle

[0144] Itching sensation is modulated by the central nervous system, and the modulation is achieved through the excitatory and inhibitory circuits of neurons located in the spinal cord and the opioid-like system. Therefore, psychological factors can cause neuroimmune changes that dysregulate the excitatory and inhibitory functions of the central nervous system, resulting in the disorder of the modulation mechanism of itching sensation to induce central itching sensation. Cannabinoid compounds are able to modulate the central nervous system through cannabinoid CB1 and/or CB2 receptors to achieve alleviation of itching.

Implementation Method

[0145] 70 guinea pigs were taken and randomly and equally divided into a blank control group (100 mg/day of distilled water), a cannabidiol group (50 mg/day, 100 mg/day, 200 mg/day), a tetrahydrocannabinol group (40 mg/day, 80 mg/day, 100 mg/day), a cannabidivarin group (40 mg/day, 80 mg/day, 100 mg/day), a tetrahydrocannabinovarin group (5 mg/day, 10 mg/day, 20 mg/day), and a control group (10 mg/day of chlorphenamine maleate), 5 guinea pigs in each group. The guinea pigs in each group were shaved 2 cm×2 cm on the dorsal surface of the right hind foot and administered orally for 3 consecutive days according to the above administration dosage, respectively. On day 3 of administration, the shaved area was abraded with coarse sandpaper to the extent that the epidermis was injured with mild bleeding. After 10 minutes, 0.05 ml of 0.01% histamine phosphate solution was added dropwise to the wounded area of each guinea pig, respectively, after that, the histamine phosphate solutions with increased concentration of histamine phosphate (e.g., 0.02%/0.03%/0.04%/0.05%/0.06%, etc.) were sequentially added dropwise every other 3 min until the guinea pigs turned back and licked their feet. The total amount of histamine given to each guinea pig was recorded, which was the itch-causing threshold.

Experimental Results

[0146]

TABLE-US-00001 group administration dosage itch-causing threshold/μL blank control group 100 mg/day of distilled water 44.35 ± 38.12 cannabidiol group 50 mg/day 90.24 ± 45.98 200 mg/day 96.55 ± 42.34 400 mg/day 117.67 ± 44.67  tetrahydrocannabinol 40 mg/day 90.65 ± 32.08 group 80 mg/day 92.10 ± 50.78 100 mg/day 94.98 ± 48.96 cannabidivarin group 40 mg/day 56.23 ± 45.87 80 mg/day 59.55 ± 39.84 100 mg/day 56.89 ± 34.25 tetrahydrocannabinovarin 5 mg/day 50.45 ± 45.67 group 10 mg/day 56.43 ± 34.18 20 mg/day 55.23 ± 40.92 control group 10 mg/day of chlorphenamine 127.03 ± 54.05  maleate

[0147] It can be seen from this experiment that the administration of cannabidiol and tetrahydrocannabinol alone significantly alleviates the itch-causing effect of histamine phosphate.

Embodiment 14. Impact of Administration of Composition of Cannabinoid Compound on the Itch-Causing Effect of Histamine Phosphate

[0148] Although the administration of cannabidiol and tetrahydrocannabinol alone showed a certain relief of the itch-causing effect of histamine phosphate, it would be more desirable to be able to find active ingredients with better effects. Therefore, this experiment compared the impact of different groups of the compositions of cannabinoid compounds on the itch-causing effect of histamine phosphate.

Experimental Method

[0149] 90 guinea pigs were taken and randomly and equally divided into:

[0150] a tetrahydrocannabinol (THC) and tetrahydrocannabinovarin (THCV) combination group;

[0151] a cannabidiol (CBD) and cannabidivarin (CBDV) combination group;

[0152] a tetrahydrocannabinol (THC) and cannabidivarin (CBDV) combination group;

[0153] a cannabidiol (CBD) and tetrahydrocannabinovarin (THCV) combination group;

[0154] a cannabidiol (CBD), cannabidivarin (CBDV) and tetrahydrocannabinovarin (THCV) combination group;

[0155] a tetrahydrocannabinol (THC), cannabidivarin (CBDV) and tetrahydrocannabinovarin (THCV) combination group:

[0156] 5 guinea pigs in each group, experimental steps the same as that in Embodiment 13.

Experimental Results

[0157]

TABLE-US-00002 group administration dosage itch-causing threshold/μL THC + THCV 100 mg/day of THC + 5 mg/day of  98.31 ± 33.23 combination group THCV 100 mg/day of THC + 10 mg/day of 109.78 ± 50.34 THCV 100 mg/day of THC + 20 mg/day of 112.01 ± 52.18 THCV CBD + CBDV 200 mg/day of CBD + 40 mg/day of 103.34 ± 44.14 combination group CBDV 200 mg/day of CBD + 80 mg/day of 122.10 ± 56.32 CBDV 200 mg/day of CBD + 100 mg/day of 128.98 ± 45.68 CBDV THC + CBDV 100 mg/day of THC + 40 mg/day of 102.11 ± 39.78 combination group CBDV 100 mg/day of THC + 80 mg/day of 104.68 ± 44.47 CBDV 100 mg/day of THC + 100 mg/day of 111.76 ± 50.98 CBDV CBD + THCV 200 mg/day of CBD + 5 mg/day of 101.45 ± 46.98 combination group THCV 200 mg/day of CBD + 10 mg/day of 111.45 ± 45.87 THCV 200 mg/day of CBD + 20 mg/day of 119.76 ± 25.98 THCV CBD + CBDV + THCV 200 mg/day of CBD + 40 mg/day of 131.87 ± 46.87 combination group CBDV + 5 mg/day of THCV 200 mg/day of CBD + 80 mg/day of 139.13 ± 54.09 CBDV + 10 mg/day of THCV 200 mg/day of CBD + 100 mg/day of 140.56 ± 42.34 CBDV + 20 mg/day of THCV THC + CBDV + THCV 100 mg/day of THC + 40 mg/day of 112.21 ± 54.97 combination group CBDV + 5 mg/day of THCV 100 mg/day of THC + 80 mg/day of 118.56 ± 35.87 CBDV + 10 mg/day of THCV 100 mg/day of THC + 100 mg/day of 124.77 ± 35.35 CBDV + 20 mg/day of THCV

[0158] From this experiment, it can be seen that the combination of two or more cannabinoid compounds has a superior effect compared with the administration of cannabidiol as well as tetrahydrocannabinol alone, which may be related to the fact that different cannabinoid compounds act on different receptor targets.

Embodiment 15. Clinical Study of Cannabinoid Compound for Neurodermatitis

[0159] Patients with generalized neurodermatitis in dermatology outpatient and inpatient departments were selected.

[0160] Diagnostic criteria: all meet the diagnosis of neurodermatitis in Clinical Dermatology. Its clinical manifestations are mainly characterized by skin lichen-like changes and intense itching. It mostly occurs on the back of the neck or both sides thereof, cubital fossae, popliteal fossae, forearms, thighs, calves and a lumbosacral area. Subjective symptoms are often severe paroxysmal itching, even at night. Most patients have dizziness, insomnia, irritability, anxiety and other symptoms of neurosism.

[0161] Exclusion criteria: (1) patients with skin lesions with bacterial or fungal infections; (2) pregnant or lactating women; (3) patients with local administration of glucocorticoid drugs or antihistamines within 1 week before selection; (4) patients with systemic administration of glucocorticoids within 1 month; (5) patients who are known to be allergic to the drug for study and its matrix components; (6) patients with chronic liver or kidney disease or other serious illness; (7) patients with diabetes mellitus or severe immunocompromise.

[0162] 90 patients with diagnosed neurodermatitis were selected for clinical observation, and the patients were randomly divided into nine groups, including eight cannabinoid compound treatment groups, a total of 80 people, 56 men and 24 women, aged 30 to 61 years, using preparations prepared in Embodiments 1/3/5/6/7/8/9/10, with 10 cases sex randomly selected in each group. 10 people was in a doxepin hydrochloride group as a control group, 5 males and 5 females, aged 30 to 61 years.

[0163] Treatment method: the cannabinoid compound treatment groups took the preparations prepared in Embodiments 1/3/5/6/7/8/9/10 orally, once per day, at bedtime, for 2 consecutive weeks; the control group used 25 mg/d of doxepin hydrochloride, orally, once per day, at bedtime, for 2 consecutive weeks.

[0164] The observation indexes included pruritus degree, inflammation degree, scales hypertrophy degree and target skin lesion surface, and the most serious skin lesion site was selected as the target skin lesion site, and the area of the target skin lesion, clinical symptoms and changes in physical signs were recorded at each follow-up visit without any other drugs during the treatment period. Local observation and evaluation of the skin lesions were performed weekly in 1 week before treatment, 2 weeks during treatment and 1 month after discontinuation of the drug. Skin lesions were scored as follows:

TABLE-US-00003 observation scores item 0 1 2 3 4 Pruritus No extremely mild, mild, aware, moderate, clearly aware, frequent scratching degree mildly aware, disturbed but interferes with daily strongly, obviously easily tolerated, tolerated, activities and sleep, but aware, seriously without sometimes able to get enough sleep affects daily life scratching scratching and sleep, poor sleep, waking up 1-2 times inflammation No slightly red slightly infiltrated infiltrated flushed infiltrated obviously degree more red scales No mildly scales, no scales, with skin significant scales and severe hypertrophy lichenification lesions of mild skin lesions of thicker lichenification degree lichenification lichenification target skin completely 75%-100% 50%-74% 25%-49% reduction in 1%-24% or no lesion area faded reduction in area reduction in area area reduction in area

[0165] Criteria for determining efficacy: the scoring criteria were that each index was scored according to a 4-level scoring method in each evaluation, i.e., 0 for none, 1 for mild, 2 for moderate, and 3 for severe. All patients were required to have an erosion score of <1 at the time of enrollment, and the skin lesion area was always recorded as 3, and the total value of each index score was recorded. Efficacy judgment: the efficacy was judged by the percentage reduction of the score value as the efficacy index, and the formula for calculating the efficacy index was: (total score at the initial consultation−total score at each follow-up visit)/total score at the initial consultation×100%. An efficacy index of >90% was considered cured, an efficacy index of 61-89% was considered excellently effective, an efficacy index of 20-60% was considered effective, and an efficacy index of <20% was considered ineffective.

The Results of the Clinical Trials were as Follows

[0166]

TABLE-US-00004 excellently group n Cured effective effective ineffective 200 mg of cannabidiol 10 1 3 6 0 100 mg of tetrahydrocannabinol 10 1 2 6 1 200 mg of cannabidiol + 40 mg of cannabidivarin 10 3 5 2 0 100 mg of tetrahydrocannabinol + 40 mg of cannabidivarin 10 0 6 3 1 100 mg of tetrahydrocannabinol + 10 mg of 10 1 4 4 1 tetrahydrocannabinovarin 200 mg of cannabidiol + 10 mg of tetrahydrocannabinovarin 10 2 4 3 1 200 mg of cannabidiol + 40 mg of cannabidivarin + 10 mg of 10 4 3 3 0 tetrahydrocannabinovarin group 100 mg of tetrahydrocannabinol + 40 mg of cannabidivarin + 10 mg 10 2 3 4 1 of tetrahydrocannabinovarin group doxepin hydrochloride control group 10 0 6 3 1

[0167] From this experiment, it can be seen that the administration of cannabidiol and tetrahydrocannabinol alone and the combination of two or more cannabinoid compounds have clinical efficacy in neurodermatitis, and the combination of two or more cannabinoid compounds administrated at same time has a superior effect.