US4189491A - Tetrahydrocannabinol in a method of treating glaucoma - Google Patents
Tetrahydrocannabinol in a method of treating glaucoma Download PDFInfo
- Publication number
- US4189491A US4189491A US05/751,079 US75107976A US4189491A US 4189491 A US4189491 A US 4189491A US 75107976 A US75107976 A US 75107976A US 4189491 A US4189491 A US 4189491A
- Authority
- US
- United States
- Prior art keywords
- thc
- glaucoma
- treatment
- tetrahydrocannabinol
- miotic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 208000010412 Glaucoma Diseases 0.000 title claims abstract description 12
- CYQFCXCEBYINGO-UHFFFAOYSA-N THC Natural products C1=C(C)CCC2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3C21 CYQFCXCEBYINGO-UHFFFAOYSA-N 0.000 title claims abstract 10
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 title claims abstract 10
- 229960004242 dronabinol Drugs 0.000 title claims abstract 10
- 238000000034 method Methods 0.000 title claims description 13
- 208000024891 symptom Diseases 0.000 claims abstract description 6
- 230000003547 miosis Effects 0.000 claims description 5
- PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 claims description 3
- 230000037396 body weight Effects 0.000 claims description 3
- 229960001697 physostigmine Drugs 0.000 claims description 3
- PIJVFDBKTWXHHD-HIFRSBDPSA-N physostigmine Chemical compound C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C PIJVFDBKTWXHHD-HIFRSBDPSA-N 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims 4
- 229960002139 pilocarpine hydrochloride Drugs 0.000 claims 2
- RNAICSBVACLLGM-GNAZCLTHSA-N pilocarpine hydrochloride Chemical compound Cl.C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C RNAICSBVACLLGM-GNAZCLTHSA-N 0.000 claims 2
- 244000025254 Cannabis sativa Species 0.000 abstract description 5
- 235000012766 Cannabis sativa ssp. sativa var. sativa Nutrition 0.000 abstract description 5
- 235000012765 Cannabis sativa ssp. sativa var. spontanea Nutrition 0.000 abstract description 5
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 abstract description 4
- 229930091371 Fructose Natural products 0.000 abstract description 4
- 239000005715 Fructose Substances 0.000 abstract description 4
- 238000002560 therapeutic procedure Methods 0.000 abstract description 3
- 239000003085 diluting agent Substances 0.000 abstract description 2
- 239000004480 active ingredient Substances 0.000 abstract 1
- 230000001384 anti-glaucoma Effects 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 7
- 239000000654 additive Substances 0.000 description 6
- 230000000996 additive effect Effects 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- BZKPWHYZMXOIDC-UHFFFAOYSA-N acetazolamide Chemical compound CC(=O)NC1=NN=C(S(N)(=O)=O)S1 BZKPWHYZMXOIDC-UHFFFAOYSA-N 0.000 description 3
- 230000004410 intraocular pressure Effects 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 230000000506 psychotropic effect Effects 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 208000032140 Sleepiness Diseases 0.000 description 2
- 206010041349 Somnolence Diseases 0.000 description 2
- 208000012886 Vertigo Diseases 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229940099238 diamox Drugs 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 230000001077 hypotensive effect Effects 0.000 description 2
- 239000003604 miotic agent Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 231100000889 vertigo Toxicity 0.000 description 2
- QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 206010051625 Conjunctival hyperaemia Diseases 0.000 description 1
- 241001539473 Euphoria Species 0.000 description 1
- 206010015535 Euphoric mood Diseases 0.000 description 1
- 206010016352 Feeling of relaxation Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010029216 Nervousness Diseases 0.000 description 1
- 206010033864 Paranoia Diseases 0.000 description 1
- 208000027099 Paranoid disease Diseases 0.000 description 1
- QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 description 1
- -1 Substituted Chemical class 0.000 description 1
- 229960000571 acetazolamide Drugs 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000000744 blepharospasm Effects 0.000 description 1
- 206010005159 blepharospasm Diseases 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000019365 chlortetracycline Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000004081 narcotic agent Substances 0.000 description 1
- 229960001416 pilocarpine Drugs 0.000 description 1
- 230000003236 psychic effect Effects 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 230000037321 sleepiness Effects 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
Definitions
- the invention relates to the treatment of glaucoma.
- a method for alleviating the symptoms of glaucoma comprising orally administering to a glaucoma sufferer a therapeutically effective but sub-psychotropic dose of THC for at least about 5 days.
- the therapeutic effects can be achieved without the undesirable effects ordinarily manifested by the ingestion of THC, for example, as in smoking marijuana.
- the method can be used as the sole form of treatment of the disease with, however, only marginal success.
- the dosage regimen followed is between 10-20 mg/day for the first few days, after which the dose is increased to 20-40 mg/day.
- the THC In administering the THC, it is diluted with an innocuous diluent such as fructose.
- the 18 subjects were divided into four groups as follows:
- the THC was diluted in capsules with mannitol. It was feared, however, that mannitol itself, which is a known hypotensive agent might have some effect on the intraocular pressure and thus, fructose, which is entirely innocuous was substituted for the mannitol.
- the dosage unit which was finally used comprised gelatin capsules containing 5-10 mg of THC with the balance being fructose.
Abstract
Significant success in alleviating the symptoms of glaucoma is achieved by orally administering to a glaucoma sufferer a therapeutically effective, but sub-psychotropic dose of tetrahydrocannabinol (THC), which is the most active ingredient in marijuana. The most significant results are achieved when this form of treatment is combined with conventional types of anti-glaucoma treatment, although in a limited number of cases, THC therapy alone proved successful. Also disclosed is a dosage unit form for THC comprising a suitable dose of THC in combination with an innocuous diluent such as fructose.
Description
1. Field of the Invention
The invention relates to the treatment of glaucoma.
2. The Prior Art
In an article by one of us (Shapiro) entitled "The Ocular Manifestations of the Cannabinols" in Ophthalmologica 168: 366-369 (1974), the ocular effects, including decreased intraocular pressure, manifested by the long term use of marijuana were noted.
In September, 1974 applicants orally presented the results of certain investigations leading to this invention at a meeting of the Swiss Opthalmological Society in Interlaken, Switzerland. These results were subsequently published in Ophthalmologica 172: 122-127 (1976).
Finally, in the Nov. 8, 1976 issue of Newsweek, at page 53, there appeared an article which states, inter alia, that "Researchers have known for several years that marijuana relieves the main symptom of glaucoma: pressure within the eye due to improper drainage of optic fluid". To the best of our knowledge, researchers have not known this for several years and in fact, it is we who first discovered and reported this fact, in Ophthalmologica 172: 122-127 (1976).
According to the invention, there is provided a method for alleviating the symptoms of glaucoma, said method comprising orally administering to a glaucoma sufferer a therapeutically effective but sub-psychotropic dose of THC for at least about 5 days. Thus, the therapeutic effects can be achieved without the undesirable effects ordinarily manifested by the ingestion of THC, for example, as in smoking marijuana. The method can be used as the sole form of treatment of the disease with, however, only marginal success. In contrast, when the method of the invention is used in conjunction with conventional forms of treatment, such a topical application of miotics and/or systemic administration of known ocular hypotensive agents, especially where surgery is not possible, remarkable success has been observed with doses of THC ranging from 10-40 mg/day for about 6-60 days based on a body weight of about 70 kg. In most cases, it is necessary to continue treatment for at least about 10 days before the therapeutic effect is observed.
In more detail, the dosage regimen followed is between 10-20 mg/day for the first few days, after which the dose is increased to 20-40 mg/day. In administering the THC, it is diluted with an innocuous diluent such as fructose.
A series of experiments using 18 adult humans including 14 glaucoma patients was conducted by us under the auspices of the Federal Public Hygiene Service at Berne, Switzerland using pure THC obtained from the Scientific Service of the Division of Narcotics of the United Nations in Geneva, Switzerland.
The 18 subjects were divided into four groups as follows:
I Control group (normal eyes)--4 patients
II Substituted treatment (glaucoma patients in which the method of the invention was substituted for conventional modes of treatment)--6 patients
III Additive treatment (glaucoma patients in which the method of the invention was used together with conventional treatment)--8 patients
IV Substituted and additive treatment--1 patient.
In the following Table there are given the data for these 18 patients showing the dose, duration of treatment and the results thereof.
TABLE I
__________________________________________________________________________
Duration of
Dose Psychotropic
Ocular Pressure
Treatment
mg/day/70 kg
Effect
Success
Failure
(days)
body weight
absent
present
__________________________________________________________________________
I Normal Eyes
1 X 3 15 X
2 X 18 15-40 X(40 mg)
3 X 8 15-20 X
II Substituted - Treatment
4 X 7 10 X
5 X 15 15-40 X
6 X 15 15-40 X
7 (X) 29 15-50 X(50 mg)
8 X 4 15 X
9 X 2 40 X
III Additive
Treatment
10 X 7 30-20 X
11 (X) 60 20-30 X
12 X 6 20 X
13 X 8 20 X
14 X 62 10-20 X
15 X 16 10-20 X
16 X 32 20 X
17 X 32 20-30 X
IV Substituted
and Additive
Treatment
18 X 32 20-30 X
__________________________________________________________________________
In the first or preliminary tests, the THC was diluted in capsules with mannitol. It was feared, however, that mannitol itself, which is a known hypotensive agent might have some effect on the intraocular pressure and thus, fructose, which is entirely innocuous was substituted for the mannitol. The dosage unit which was finally used comprised gelatin capsules containing 5-10 mg of THC with the balance being fructose.
Administration was by mouth using two or three capsules per day. The initial dose varied between 10 and 20 mg per day for the first 3 to 5 days depending upon the weight and age of the subject. The dose was increased to 20-40 mg per day thereafter. During the course of the test, all of the patients were examined and questioned with regard to any psychotropic effects. None of them presented any of the classic signs of marijuana intoxication, such as euphoria, unmotiviated laughter, a fixed feeling of relaxation or perceptual difficulties in the visual, acoustic and olfactory areas. None of the patients noticed cenestopathy (bizarre sensations of the body) nor of any space-time modifications, nor did we note any acute anxiety.
Only 4 patients (2, 7, 9 and 10) manifested psychic symptoms, and only of a minor nature. Case 2 exhibited reactions of discrete paranoia at a maximal dose of 40 mg of THC. Case 7 complained of nervousness and fatigue in his legs at a maximum dose of 50 mg. Case 9 complained of vertigo, minor headaches and sleepiness with 40 mg. Finally, case 10 complained of vertigo and somnolence. The treatment was, of course, discontinued in these four cases.
In group I (normal eyes) no effect was observed in two cases with a short duration of treatment (3 and 8 days). In one case, however, after ingestion of THC for 18 days one began to observe some effect on intraocular pressure but at the same time, certain secondary general problems occurred, i.e., a psychotropic effect at 40 mg doses.
In group II, that is, substitution by THC for conventional treatment, was found to be successful in 2 cases, i.e., 6 and 9, and unsuccessful in 3 cases (4, 5 and 8). Finally, in one case (case 7), a definite but weak hypotensive effect was observed. These data clearly suggested that if THC was used as an additive rather than a substitutive therapy quite remarkable success could be achieved.
The data for cases 10-17 bear this out. Thus, THC is useful as an additive to conventional medical treatment which in itself is insufficient, particularly in cases where surgical intervention is neither indicated nor possible. In the 8 cases in this group (III) there were achieved 5 successes, one partial success and only 2 failures. Finally, in group IV success was achieved in one patient who was originally being treated systemically with Diamox®; Lederle brand of acetazolamide and topically with a topical miotic drug such as pilocarpine.HCl or eserine, but where the use of Diamox had to be suspended because of intolerance to this product. In this case, the topical treatment was continued together with the THC therapy.
In is to be noted that the hypotensive effect and therefore, the therapeutic effect becomes evident much more slowly than had been predicted. It is not rare to have to wait as much as 10 days before obtaining significant results. Once observed, the therapeutic effect often continues for several weeks after interruption of the treatment. Moreover, other, undesirable ocular effects such as conjunctival hyperemia, blepharospasm and modification of the pupilary diameter were not observed.
Variations and modifications can, of course, be made without departing from the spirit and scope of the invention.
Claims (5)
1. A method for alleviating the symptoms of glaucoma in a glaucoma patient said method comprising simultaneously
(a) topically administering to said patient a therapeutically effective amount of a conventional miotic compound selected from the group consisting of pilocarpine hydrochloride and eserine and
(b) orally administering to said patient a subpsychotropic, but therapeutically effective amount of tetrahydrocannabinol which is about 10-40 mg. of tetrahydrocannabinol per day based on a body weight of about 70 Kg, wherein said therapeutically effective amount of the miotic compound is, when administered along, ineffective to alleviate said symptoms.
2. A method according to claim 1, wherein the miotic compound is pilocarpine hydrochloride.
3. A method according to claim 1, wherein the miotic compound is eserine.
4. A method according to claim 1, wherein the tetrahydrocannabinol is administered for about 6-60 days.
5. A method according to claim 4, wherein the amount of tetrahydrocannabinol is about 10-20 mg. per day for 3 to 5 days and thereafter about 20-40 mg. per day.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/751,079 US4189491A (en) | 1976-12-16 | 1976-12-16 | Tetrahydrocannabinol in a method of treating glaucoma |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/751,079 US4189491A (en) | 1976-12-16 | 1976-12-16 | Tetrahydrocannabinol in a method of treating glaucoma |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US4189491A true US4189491A (en) | 1980-02-19 |
Family
ID=25020381
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US05/751,079 Expired - Lifetime US4189491A (en) | 1976-12-16 | 1976-12-16 | Tetrahydrocannabinol in a method of treating glaucoma |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US4189491A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0257887A2 (en) * | 1986-08-18 | 1988-03-02 | Houston Biotechnology Incorporated | Ophthalmic compositions |
| US6132762A (en) * | 1997-05-05 | 2000-10-17 | Cristobal; Walter | Transcutaneous application of marijuana |
| EP1267903A1 (en) * | 2000-02-08 | 2003-01-02 | Pharmacia Corporation | Methods for treating glaucoma |
| US20100012118A1 (en) * | 2008-07-19 | 2010-01-21 | Markus Storz | Medicament dosage for inhaler |
| EP2640379A2 (en) * | 2010-11-18 | 2013-09-25 | Pier Pharmaceuticals | Low dose cannabinoid medicaments |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3668224A (en) * | 1970-07-02 | 1972-06-06 | Theodor Petrzilka | PROCESS OF PRODUCING 6a, 10a-TRANS-6a,7,8,10a-TETRAHYDRODIBENZO (b,d)-PYRANS |
| US3728360A (en) * | 1971-08-31 | 1973-04-17 | Little Inc A | Ester derivatives of tetrahydrocannabinol |
| US3734930A (en) * | 1971-09-22 | 1973-05-22 | R Razdan | Direct synthesis of ({31 )-trans-{66 {11 tetrahydrocannabinol from olivetol and ({30 )-trans-{66 {11 -carene oxide |
| US3799946A (en) * | 1972-03-13 | 1974-03-26 | Smithkline Corp | Dibenzo(b,d)pyran compounds |
| US3920809A (en) * | 1973-11-05 | 1975-11-18 | Lilly Co Eli | Dibenzo(b,d)pyranone dispersions |
| US4025536A (en) * | 1975-09-05 | 1977-05-24 | Abbott Laboratories | Tri-cyclic compounds derived from thiaphloroglucinol ethers |
-
1976
- 1976-12-16 US US05/751,079 patent/US4189491A/en not_active Expired - Lifetime
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3668224A (en) * | 1970-07-02 | 1972-06-06 | Theodor Petrzilka | PROCESS OF PRODUCING 6a, 10a-TRANS-6a,7,8,10a-TETRAHYDRODIBENZO (b,d)-PYRANS |
| US3728360A (en) * | 1971-08-31 | 1973-04-17 | Little Inc A | Ester derivatives of tetrahydrocannabinol |
| US3734930A (en) * | 1971-09-22 | 1973-05-22 | R Razdan | Direct synthesis of ({31 )-trans-{66 {11 tetrahydrocannabinol from olivetol and ({30 )-trans-{66 {11 -carene oxide |
| US3799946A (en) * | 1972-03-13 | 1974-03-26 | Smithkline Corp | Dibenzo(b,d)pyran compounds |
| US3920809A (en) * | 1973-11-05 | 1975-11-18 | Lilly Co Eli | Dibenzo(b,d)pyranone dispersions |
| US4025536A (en) * | 1975-09-05 | 1977-05-24 | Abbott Laboratories | Tri-cyclic compounds derived from thiaphloroglucinol ethers |
Non-Patent Citations (5)
| Title |
|---|
| Chem. Abst. 83 158,044(r) (1975)--Purnell et al. "A.sup.9 -Tetrahydrocannabinol . . . in Man". * |
| Chem. Abst. 83 158,044(r) (1975)--Purnell et al. "A9 -Tetrahydrocannabinol . . . in Man". |
| Chem. Abst. 84 130,270(h) (1976)--Green et al. Interaction of . . . Tetrahydrocannabinol in the Eye". * |
| Ophthalmologica 168 366-369 (1974)--D. Shapiro--The Ocular Manifestations of the Cannabinols, Newsweek, 11/8/76, Pot and Glaucoma. * |
| The Merck Index, 8th ed. pp. 830, 831 and 833 (1968) Merck & Co. * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0257887A2 (en) * | 1986-08-18 | 1988-03-02 | Houston Biotechnology Incorporated | Ophthalmic compositions |
| EP0257887A3 (en) * | 1986-08-18 | 1990-06-27 | Houston Biotechnology Incorporated | Ophthalmic compositions |
| US6132762A (en) * | 1997-05-05 | 2000-10-17 | Cristobal; Walter | Transcutaneous application of marijuana |
| EP1267903A1 (en) * | 2000-02-08 | 2003-01-02 | Pharmacia Corporation | Methods for treating glaucoma |
| EP1267903A4 (en) * | 2000-02-08 | 2003-08-06 | Pharmacia Corp | Methods for treating glaucoma |
| US20050032691A1 (en) * | 2000-02-08 | 2005-02-10 | Wax Martin B. | Methods for treating glaucoma |
| US20100012118A1 (en) * | 2008-07-19 | 2010-01-21 | Markus Storz | Medicament dosage for inhaler |
| EP2640379A2 (en) * | 2010-11-18 | 2013-09-25 | Pier Pharmaceuticals | Low dose cannabinoid medicaments |
| EP2640379A4 (en) * | 2010-11-18 | 2014-08-13 | Pier Pharmaceuticals | Low dose cannabinoid medicaments |
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