Cannabinoids have been found to have antioxidant properties, unrelated to NMDA receptor antagonism. This new found property makes cannabinoids useful in the treatment and prophylaxis of wide variety of oxidation associated diseases, such as ischemic, age-related, inflammatory and autoimmune diseases. The cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage following ischemic insults, such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and HIV dementia. Nonpsychoactive cannabinoids, such as cannabidoil, are particularly advantageous to use because they avoid toxicity that is encountered with psychoactive cannabinoids at high doses useful in the method of the present invention. A particular disclosed class of cannabinoids useful as neuroprotective antioxidants is formula (I) wherein the R group is independently selected from the group consisting...
Inventors: Aidan J. Hampson, Julius Axelrod, Maurizio Grimaldi
Original Assignee: The United States of America as represented by the Department of Health and Human Services
Primary Examiner: Kevin E. Weddington
Attorney: Klarquist Sparkman, LLP
Current U.S. Classification: 514/454
International Classification: A61K/3135
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Referenced by
Citing Patent Filing date Issue date Original Assignee Title
US7179800 Apr 15, 2003 Feb 20, 2007 Virginia Commonwealth University Cannabinoids
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Claims
1. A method of treating diseases caused by oxidative stress, comprising administering a therapeutically effective amount of a cannabinoid that has substantially no binding to the NMDA receptor to a subject who has a disease caused by oxidative stress.
2. The method of claim 1, wherein the cannabinoid is nonpsychoactive.
3. The method of claim 2, wherein the cannabinoid has a volume of distribution of 10 L/kg or more.
4. The method of claim 1, wherein the cannabinoid is not an antagonist at the NMDA receptor.
5. The method of claim 1, wherein the cannabinoid is:
where R is H, substituted or unsubstituted alkyl, carboxyl, alkoxy, aryl, aryloxy, arylalkyl, halo or amino.
6. The method of claim 5, wherein R is H, substituted or unsubstituted alkyl, carboxyl or alkoxy.
7. The method of claim 2, wherein the cannabinoid is:
where
A is cyclohexyl, substituted or unsubstituted aryl, or
but not a pinene;
R1 is H, substituted or unsubstituted alkyl, or substituted or unsubstituted carboxyl;
R2 is H, lower substituted or unsubstituted alkyl, or alkoxy;
R3 is of H, lower substituted or unsubstituted alkyl, or substituted or unsubstituted carboxyl;
R4 is H, hydroxyl, or lower substituted or unsubstituted alkyl; and
R5 is H, hydroxyl, or lower substituted or unsubstituted alkyl.
8. The method of claim 7, wherein
R1 is lower alkyl, COOH or COCH3;
R2 is unsubstituted C1-C5 alkyl, hydroxyl, methoxy or ethoxy;
R3 is H, unsubstituted C1-C3 alkyl, or COCH3;
R4 is hydroxyl, pentyl, heptyl, or diemthylheptyl; and
R5 is hydroxyl or methyl.
9. The method of claim 1, wherein the cannabinoid is:
where R1, R2 and R3 are independently H, CH3, or COCH3.
10. The method of claim 9, wherein the cannabinoid is:
where:
a) R1R2R3H;
b) R1R3H, R2CH3;
c) R1R2CH3, R3H;
d) R1R2COCH3, R3H; or
e) R1H, R2R3COCH3.
11. The method of claim 2, wherein the cannabinoid is:
where R19 is H, lower alkyl, lower alcohol, or carboxyl; R20 is H or OH; and R21-R25 are independently H or OH.
12. The method of claim 11, wherein R19 is H, CH3, CH2OH, or COOH, and R20-R24 are independently H or OH.
13. The method of claim 2, wherein the cannabinoid is:
where R19 and R20 are H, and R26 is alkyl.
14. The method of claim 10, wherein the cannabinoid is cannabidiol.
15. A method of treating an ischemic or neurodegenerative disease in the central nervous system of a subject, comprising administering to the subject a therapeutically effective amount of a cannabinoid, where the cannabinoid is
where R is H, substituted or unsubstituted alkyl, carboxyl, alkoxy, aryl, aryloxy, arylalkyl, halo or amino.
16. The method of claim 15, wherein the cannabinoid is not a psychoactive cannabinoid.
17. The method of claim 15 where the ischemic or neurodegenerative disease is an ischemic infarct, Alzheimer's disease, Parkinson's disease, and human immunodeficiency virus dementia, Down's syndrome, or heart disease.
18. A method of treating a disease with a cannabinoid that has substantially no binding to the NMDA receptor, comprising determining whether the disease is caused by oxidative stress, and if the disease is caused by oxidative stress, administering the cannabinoid in a therapeutically effective antioxidant amount.
19. The method of claim 18, wherein the cannabinoid has a volume of distribution of at least 1.5 L/kg and substantially no activity at the cannabinoid receptor.
20. The method of claim 19, wherein the cannabinoid has a volume of distribution of at least 10 L/kg.
21. The method of claim 1, wherein the cannabinoid selectively inhibits an enzyme activity of 5- and 15-lipoxygenase more than an enzyme activity of 12-lipoxygenase.
22. A method of treating a neurodegenerative or ischemic disease in the central nervous system of a subject, comprising administering to the subject a therapeutically effective amount of a compound selected from any of the compounds of claims 9 through 13.
23. The method of claim 22 where the compound is cannabidiol.
24. The method of claim 22, wherein the ischemic or neurodegenerative disease is an ischemic infarct, Alzheimer's disease, Parkinson's disease, and human immunodeficiency virus dementia, Down's syndrome, or heart disease.
25. The method of claim 24 wherein the disease is an ischemic infarct.
26. The method of claim 1, wherein the cannabinoid is not an antagonist at the AMPA receptor.
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