IP Library Granted Patent US 7,915,285
Granted Patent B2
US 7,915,285 · App. 11/527,757 · Granted Mar 29, 2011

Method for treating drug and behavioral addictions

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Quick Facts
Patent No.
US 7,915,285
App. No.
11/527,757
Granted
Mar 29, 2011
Kind
B2
Abstract

The present invention is directed to the use of ibudilast for treating addictions, including drug and behavioral addictions. In particular, ibudilast is used to diminish the dopamine-mediated reward associated with addictions and to treat withdrawal syndromes after discontinuance of addictive drug use or behavior.

Claims (53)

1. A method for suppressing the release of dopamine in the nucleus accumbens of a subject suffering from a drug addiction or drug dependence comprising administering to the subject an effective amount of ibudilast.

2. The method of claim 1 , wherein the drug addiction or dependence is an opioid addiction or dependence to one or more opioids selected from the group consisting of morphine, methadone, buprenorphine, levomethadyl acetate, L-α-acetylmethadol, fentanyl, alfentanyl, alphaprodine, anileridine, bezitramide, codeine, dihydrocodeine, diphenoxylate, ethylmorphine, heroin, hydrocodone, hydromorphone, isomethadone, levomethorphan, levorphanol, metazocine, metopon, opium extracts, opium fluid extracts, powdered opium, granulated opium, raw opium, tincture of opium, oxycodone, oxymorphone, pethidine, phenazocine, piminodine, racemethorphan, racemorphan and thebaine.

3. The method of claim 1 , wherein the subject is human.

4. The method of claim 1 , wherein the ibudilast is administered systemically.

5. The method of claim 4 , wherein the ibudilast is administered intravenously, subcutaneously, orally, intranasally, or sublingually.

6. The method of claim 1 , wherein the ibudilast is administered centrally.

7. The method of claim 6 , wherein the ibudilast is administered intrathecally.

8. The method of claim 1 , wherein multiple therapeutically effective doses of ibudilast are administered to the subject.

9. The method of claim 8 , wherein ibudilast is administered according to a daily dosing regimen.

10. The method of claim 9 , wherein ibudilast is administered twice a day.

11. The method of claim 8 , wherein ibudilast is administered intermittently.

12. A method for treating a drug addiction or drug dependence comprising administering to a subject in need thereof a therapeutically effective amount of ibudilast.

13. The method of claim 12 , wherein the drug addiction or dependence is an opioid addiction or dependence to one or more opioids selected from the group consisting of morphine, methadone, fentanyl, alfentanyl, alphaprodine, anileridine, bezitramide, codeine, dihydrocodeine, diphenoxylate, ethylmorphine, heroin, hydrocodone, hydromorphone, isomethadone, levomethorphan, levorphanol, metazocine, metopon, opium extracts, opium fluid extracts, powdered opium, granulated opium, raw opium, tincture of opium, oxycodone oxymorphone, pethidine, phenazocine, piminodine, racemethorphan, racemorphan and thebaine.

14. The method of claim 12 , wherein ibudilast diminishes or eliminates addiction-related or dependence-related behavior of the subject.

15. The method of claim 12 , wherein ibudilast diminishes or eliminates cravings associated with addiction to one or more drugs in the subject.

16. The method of claim 12 , wherein ibudilast diminishes or eliminates incentive salience of drug- or addictive behavior-associated cues in the subject.

17. The method of claim 12 , wherein ibudilast diminishes or eliminates symptoms of withdrawal syndrome in the subject.

18. The method of claim 12 , wherein ibudilast diminishes or eliminates weight loss related to withdrawal syndrome in the subject.

19. The method of claim 12 , wherein ibudilast diminishes or eliminates glial cell activation in the subject.

20. The method of claim 19 , wherein ibudilast diminishes or eliminates astrocyte or microglia activation in the subject.

21. The method of claim 12 , wherein ibudilast diminishes or eliminates drug-induced increases in interleukin-1 expression in the subject.

22. The method of claim 12 , wherein the subject is human.

23. The method of claim 12 , wherein the ibudilast is administered systemically.

24. The method of claim 23 , wherein the ibudilast is administered intravenously, subcutaneously, orally, intranasally, or sublingually.

25. The method of claim 12 , wherein the ibudilast is administered centrally.

26. The method of claim 25 , wherein the ibudilast is administered intrathecally.

27. The method of claim 12 , wherein multiple therapeutically effective doses of ibudilast are administered to the subject.

28. The method of claim 27 , wherein ibudilast is administered according to a daily dosing regimen.

29. The method of claim 28 , wherein ibudilast is administered twice a day.

30. The method of claim 27 , wherein ibudilast is administered intermittently.

31. The method of claim 12 , further comprising administering one or more agents other than ibudilast for treating an addiction or dependence.

32. The method of claim 31 , wherein one or more agents are selected from the group consisting of analgesics, NSAIDs, antiemetics, antidiarrheals, alpha -2-antagonists, benzodiazepines, anticonvulsants, antidepressants and insomnia therapeutics.

33. The method of claim 32 , wherein one or more agents are selected from the group consisting of buprenorphine, naloxone, methadone, levomethadyl acetate, L-alpha acetylmethadol (LAAM), hydroxyzine, diphenoxylate, atropine, chlordiazepoxide, carbamazepine, mianserin, benzodiazepine, phenoziazine, disulfiram, acamprosate, topiramate, ondansetron, sertraline, bupropion, amantadine, amiloride, isradipine, tiagabine, baclofen, propranolol, desipramine, carbamazepine, valproate, lamotrigine, doxepin, fluoxetine, imipramine, moclobemide, nortriptyline, paroxetine, sertraline, tryptophan, venlafaxine, trazodone, quetiapine, zolpidem, zopiclone, zaleplon, gabapentin, naltrexone, paracetamol, metoclopramide, loperamide, clonidine, lofexidine and diazepam.

34. A method of treating an opioid withdrawal syndrome in a mammalian subject comprising administering one or more doses of ibudilast.

35. The method of claim 34 , wherein the subject is human.

36. The method of claim 34 , wherein the opioid withdrawal syndrome is caused by reduction or cessation of administration of an opioid in the subject.

37. The method of claim 36 , wherein the opioid is selected from the group consisting of morphine, methadone and fentanyl.

38. The method of claim 37 , wherein the opioid is morphine.

39. The method of claim 34 , wherein the ibudilast is administered systemically.

40. The method of claim 39 , wherein the ibudilast is administered intravenously, subcutaneously, orally, intranasally, or sublingually.

41. The method of claim 34 , wherein the ibudilast is administered centrally.

42. The method of claim 41 , wherein the ibudilast is administered intrathecally.

43. The method of claim 34 , wherein multiple therapeutically effective doses of ibudilast are administered to the subject.

44. The method of claim 43 , wherein ibudilast is administered according to a daily dosing regimen.

45. The method of claim 44 , wherein ibudilast is administered twice a day.

46. The method of claim 34 , wherein ibudilast is administered intermittently.

47. The method of claim 34 , further comprising administering one or more agents other than ibudilast for treatment of opioid withdrawal.

48. The method of claim 47 , wherein one or more agents are selected from the group consisting of analgesics, NSAIDs, antiemetics, antidiarrheals, alpha -2-antagonists and benzodiazepines.

49. The method of claim 48 , wherein one or more agents are selected from the group consisting of naltrexone, paracetamol, metoclopramide, loperamide, clonidine, lofexidine and diazepam.

50. The method of claim 34 , wherein ibudilast diminishes or eliminates weight loss related to withdrawal syndrome in the subject.

51. The method of claim 34 , wherein ibudilast diminishes or eliminates glial cell activation in the subject.

52. The method of claim 34 , wherein ibudilast diminishes or eliminates astrocyte or microglia activation in the subject.

53. The method of claim 34 , wherein ibudilast diminishes or eliminates drug-induced increases in interleukin-1 expression in the subject.

Assignments (5)
CORRECTIVE ASSIGNMENT TO CORRECT THE ADDRESS OF THE ASSIGNEE NAMED "THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE" PREVIOUSLY RECORDED ON REEL 018583 FRAME 0194. ASSIGNOR(S) HEREBY CONFIRMS THE THE CORRECT ADDRESS IS: 1800 GRANT STREET 8TH FLOOR, DENVER, CO 80203. Recorded Feb 14, 2011
From: WATKINS, LINDA MAY ROTHBLUM
To: THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE
Reel/Frame 025790/0087 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 20, 2010
From: AVIGEN, INC.
To: MEDICINOVA, INC.
Reel/Frame 024416/0786 →
EXECUTIVE ORDER 9424, CONFIRMATORY LICENSE Recorded May 15, 2008
From: UNIVERSITY OF COLORADO
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 020948/0039 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 30, 2006
From: JOHNSON, KIRK W.
To: AVIGEN, INC.
Reel/Frame 018577/0215 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 30, 2006
From: WATKINS, LINDA MAY ROTHBLUM
To: REGENTS OF THE UNIVERSITY OF COLORADO, THE, A BODY CORPORATE
Reel/Frame 018583/0194 →