Cytokine antagonists for neurological and neuropsychiatric disorders

• US 20030049256A1
• Filed: 10/09/2002
• Published: 03/13/2003
• Est. Priority Date: 02/24/1999
• Status: Active Grant

• Current Assignee: TACT IP LLC
• Original Assignee: TACT IP LLC
• Inventors: Tobinick, Edward Lewis
• Granted Patent: US 6,982,089 B2
• Time in Patent Office: Days
• US Class Current: 424/145.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 38/1793 for cytokines; for lymphokines; for interferons
• CPC Class Codes: A61K 38/20 Interleukins [IL]
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 47/6811 the drug being a protein or peptide, e.g. transferrin or bleomycin
• CPC Class Codes: A61K 47/6835 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/34 Tobacco-abuse
• CPC Class Codes: C07K 16/241 Tumor Necrosis Factors
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C07K 2319/32 fusions with soluble part of a cell surface receptor, "decoy receptors"

Abstract

Methods for treating neurological or neuropsychiatric diseases or disorders in humans by administering to the human a therapeutically effective dose of specific biologics are presented. The biologics of consideration include antagonists of tumor necrosis factor or of interleukin-1. The administration of these biologics is performed by specific methods, most, but not all of which fall into the category of anatomically localized administration designed for perispinal use. Anatomically localized administration involving perispinal use includes, but is not limited to the subcutaneous, intramuscular, interspinous, epidural, peridural, parenteral or intrathecal routes. Additonally, intranasal administration is discussed as a method to provide therapeutic benefit.

The clinical conditions of consideration include, but are not limited to the following: diseases of the brain, including neurodegenerative diseases such as Alzheimer'"'"'s Disease and Parkinson'"'"'s Disease; migraine headache; spinal radiculopathy associated with intervertebral disc herniation, post-herpetic neuralgia, reflex sympathethic dystrophy, neuropathic pain, vertebral disc disease, low back pain, amyotrophic lateral sclerosis, chronic fatigue syndrome; and neuropsychiatric diseases, including bipolar affective disorder, anorexia nervosa, nicotine withdrawal, narcotic addiction, alcohol withdrawl, postpartum depression, and schizoaffective illness.

Claims

1. A method for treating neuropsychiatric diseases or disorders in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP571 (a humanized monoclonal anti-TNF-alpha IgG4 antibody), CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), soluble TNF receptor Type I, pegylated soluble TNF receptor Type I (PEGs TNF-R1) and onercept, a recombinant TNF binding protein (r-TBP-l) (Serono); and

b) administering said dose parenterally by perispinal administration.

2. A method for inhibiting the action of TNF in accordance with claim 1, wherein the step of administering said dosage level is for treating bipolar or unipolar affective disorder.

3. A method for inhibiting the action of TNF in accordance with claim 1, wherein the step of administering said dosage level is for treating schizophrenia.

4. A method for inhibiting the action of TNF in accordance with claim 1, wherein the step of administering said dosage level is for treating anorexia nervosa.

5. A method for inhibiting the action of TNF in accordance with claim 1, wherein the step of administering said dosage level is for treating schizoaffective illness.

6. A method for inhibiting the action of TNF in accordance with claim 1, wherein the step of administering said dosage level is for treating autism.

7. A method for inhibiting the action of TNF in accordance with claim 1, wherein the step of administering said dosage level is for treating clinical depression.

8. A method for inhibiting the action of TNF in accordance with claim 1, wherein the step of administering said dosage level is for treating post-partum depression.

9. A method for inhibiting the action of TNF in accordance with claim 1, wherein the step of administering said dosage level is for treating obsessive-compulsive disorder.

10. A method for inhibiting the action of TNF in accordance with claim 1, wherein the step of administering said dosage level is for treating chronic fatigue syndrome.

11. A method for treating neurological diseases or disorders in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP571 (a humanized monoclonal anti-TNF-alpha IgG4 antibody), CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), soluble TNF receptor Type I, pegylated soluble TNF receptor Type I (PEGs TNF-R1) and onercept, a recombinant TNF binding protein (r-TBP-1) (Serono); and

b) administering said dose parenterally by perispinal administration.

12. A method for inhibiting the action of TNF in accordance with claim 11, wherein the step of administering said dosage level is for treating neurodegenerative disorders, including idiopathic dementia.

13. A method for inhibiting the action of TNF in accordance with claim 11, wherein the step of administering said dosage level is for treating Alzheimer'"'"'s Disease.

14. A method for inhibiting the action of TNF in accordance with claim 11, wherein the step of administering said dosage level is for treating Parkinson'"'"'s Disease.

15. A method for inhibiting the action of TNF in accordance with claim 11, wherein the step of administering said dosage level is for treating spinal cord injury.

16. A method for inhibiting the action of TNF in accordance with claim 11, wherein the step of administering said dosage level is for treating fibromyalgia.

17. A method for inhibiting the action of TNF in accordance with claim 11, wherein the step of administering said dosage level is for treating amyotrophic lateral sclerosis

18. A method for inhibiting the action of TNF in accordance with claim 11, wherein the step of administering said dosage level is for treating post-herpetic neuralgia.

19. A method for inhibiting the action of TNF in accordance with claim 11, wherein the step of administering said dosage level is for treating neuropathic pain.

20. A method for inhibiting the action of TNF in accordance with claim 11, wherein the step of administering said dosage level is for treating reflex sympathetic dystrophy.

21. A method for inhibiting the action of TNF in accordance with claim 11, wherein the step of administering said dosage level is for treating lumbar or cervical radiculopathy.

22. A method for inhibiting the action of TNF in accordance with claim 11, wherein the step of administering said dosage level is for treating nerve root inflammation.

23. A method for inhibiting the action of TNF in accordance with claim 11, wherein the step of administering said dosage level is for treating vertebral disc disease.

24. A method for inhibiting the action of TNF in accordance with claim 11, wherein the step of administering said TNF antagonist is performed through any of the following routes:

subcutaneous, intramuscular, interspinous, intrathecal, peridural, parenteral, or epidural.

25. A method for treating neurological diseases or disorders in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP571 (a humanized monoclonal anti-TNF-alpha IgG4 antibody), CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), soluble TNF receptor Type I, pegylated soluble TNF receptor Type I (PEGs TNF-R1) and onercept, a recombinant TNF binding protein (r-TBP-1) (Serono); and

b) administering said dose parenterally by perispinal administration using the interspinous route.

26. A method for treating nerve root inflammation in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP571 (a humanized monoclonal anti-TNF-alpha IgG4 antibody), CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), soluble TNF receptor Type I, pegylated soluble TNF receptor Type I (PEGs TNF-R1) and onercept, a recombinant TNF binding protein (r-TBP-1) (Serono); and

b) administering said dose parenterally by perispinal administration using the interspinous route.

27. A method for treating Alzheimer'"'"'s Disease in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP571 (a humanized monoclonal anti-TNF-alpha IgG4 antibody), CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), soluble TNF receptor Type I, pegylated soluble TNF receptor Type I (PEGs TNF-R

     1) and onercept, a recombinant TNF binding protein (r-TBP-1) (Serono); and

b) administering said dose parenterally by perispinal administration using the interspinous route.

28. A method for treating Parkinson'"'"'s Disease in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP571 (a humanized monoclonal anti-TNF-alpha IgG4 antibody), CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), soluble TNF receptor Type I, pegylated soluble TNF receptor Type I (PEGs TNF-R1) and onercept, a recombinant TNF binding protein (r-TBP-1) (Serono); and

b) administering said dose parenterally by perispinal administration using the interspinous route.

29. A method for treating neuropsychiatric diseases or disorders in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP571 (a humanized monoclonal anti-TNF-alpha IgG4 antibody), CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), soluble TNF receptor Type I, pegylated soluble TNF receptor Type I (PEGs TNF-R1) and onercept, a recombinant TNF binding protein (r-TBP-1) (Serono); and

b) administering said dose parenterally by perispinal administration using the interspinous route.

30. A method for treating neuropsychiatric diseases or disorders in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP571 (a humanized monoclonal anti-TNF-alpha IgG4 antibody), CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), soluble TNF receptor Type I, pegylated soluble TNF receptor Type I (PEGs TNF-R1) and onercept, a recombinant TNF binding protein (r-TBP-1) (Serono); and

b) administering said dose by intranasal administration.

40. A method for inhibiting the action of TNF in accordance with claim 30, wherein the step of administering said TNF antagonist in the form of a TNF antagonist is performed by administering a therapeutic dosage level in said human wherein said dosage level is in the range of 5 mg to 350 mg per dose.

31. A method for treating anorexia nervosa in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the step of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP571 (a humanized monoclonal anti-TNF-alpha IgG4 antibody), CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), soluble TNF receptor Type I, pegylated soluble TNF receptor Type I (PEGs TNF-R

     1) and onercept, a recombinant TNF binding protein (r-TBP-1) (Serono).

32. A method for treating anorexia nervosa in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP571 (a humanized monoclonal anti-TNF-alpha IgG4 antibody), CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), soluble TNF receptor Type I, pegylated soluble TNF receptor Type I (PEGs TNF-R

     1) and onercept, a recombinant TNF binding protein (r-TBP-1) (Serono); and

b) administering said dose by intranasal administration.

33. A method for treating anorexia nervosa in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP571 (a humanized monoclonal anti-TNF-alpha IgG4 antibody), CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), soluble TNF receptor Type I, pegylated soluble TNF receptor Type I (PEGs TNF-R1) and onercept, a recombinant TNF binding protein (r-TBP-1) (Serono); and

b) administering said dose by perispinal administration.

34. A method for treating neurological or neuropsychiatric diseases in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of infliximab comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said infliximab; and

b) administering said dose parenterally by perispinal administration.

35. A method for treating neurological or neuropsychiatric diseases in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of onercept comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said onercept; and

b) administering said dose parenterally by perispinal administration.

36. A method for treating neurological or neuropsychiatric diseases in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of etanercept comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said etanercept; and

b) administering said dose parenterally by perispinal administration.

37. A method for treating neurological or neuropsychiatric diseases in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of D2E7 comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said D2E7; and

b) administering said dose parenterally by perispinal administration.

38. A method for treating neurological or neuropsychiatric diseases in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of CDP 870 comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said CDP 870; and

b) administering said dose parenterally by perispinal administration.

39. A method for treating neurological or neuropsychiatric diseases or disorders in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist; and

,

b) administering said dose parenterally by perispinal administration.

41. A method for treating low back pain in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP571 (a humanized monoclonal anti-TNF-alpha IgG4 antibody), CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), soluble TNF receptor Type I, pegylated soluble TNF receptor Type I (PEGs TNF-R1) and onercept, a recombinant TNF binding protein (r-TBP-1) (Serono); and

b) administering said dose parenterally by perispinal administration using the interspinous route.

42. A method for treating fibromyalgia in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP571 (a humanized monoclonal anti-TNF-alpha IgG4 antibody), CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), soluble TNF receptor Type I, pegylated soluble TNF receptor Type I (PEGs TNF-R1) and onercept, a recombinant TNF binding protein (r-TBP-1) (Serono); and

b) administering said dose parenterally by perispinal administration using the interspinous route.

43. A method for treating vertebral disc disease in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP571 (a humanized monoclonal anti-TNF-alpha IgG4 antibody), CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), soluble TNF receptor Type I, pegylated soluble TNF receptor Type I (PEGs TNF-R

     1) and onercept, a recombinant TNF binding protein (r-TBP-1) (Serono); and

b) administering said dose parenterally by perispinal administration using the interspinous route.

44. A method for treating vertebral disc disease in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), and onercept, a recombinant TNF binding protein (r-TBP-1) (Serono); and

b) administering said dose parenterally by perispinal administration.

45. A method for treating low back pain in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), and onercept, a recombinant TNF binding protein (r-TBP-1) (Serono); and

b) administering said dose parenterally by perispinal administration.

46. A method for treating neurological diseases or disorders in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of onercept, a recombinant TNF binding protein (r-TBP-1) (Serono) comprising the step of:

a) administering a therapeutically effective dosage level to said human of said onercept.

47. A method for treating nicotine withdrawal in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP571 (a humanized monoclonal anti-TNF-alpha IgG4 antibody), CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), soluble TNF receptor Type I, pegylated soluble TNF receptor Type I (PEGs TNF-R

     1) and onercept, a recombinant TNF binding protein (r-TBP-1) (Serono); and

b) administering said dose parenterally by perispinal administration.

48. A method for treating nicotine withdrawal in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP571 (a humanized monoclonal anti-TNF-alpha IgG4 antibody), CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), soluble TNF receptor Type I, pegylated soluble TNF receptor Type I (PEGs TNF-R

     1) and onercept, a recombinant TNF binding protein (r-TBP-1) (Serono); and

b) administering said dose by intranasal administration.

49. A method for treating narcotic addiction in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP571 (a humanized monoclonal anti-TNF-alpha IgG4 antibody), CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), soluble TNF receptor Type I, pegylated soluble TNF receptor Type I (PEGs TNF-R1) and onercept, a recombinant TNF binding protein (r-TBP-1) (Serono); and

b) administering said dose parenterally by perispinal administration.

50. A method for treating migraine headache in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP571 (a humanized monoclonal anti-TNF-alpha IgG4 antibody), CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), soluble TNF receptor Type I, pegylated soluble TNF receptor Type I (PEGs TNF-R1) and onercept, a recombinant TNF binding protein (r-TBP-1) (Serono); and

b) administering said dose parenterally by perispinal administration.

51. A method for treating neurological diseases or disorders in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist; and

b) administering said dose by perispinal administration.

52. A method for treating neuropsychiatric diseases or disorders in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist; and

b) administering said dose by perispinal administration.

53. A method for treating neurological diseases or disorders in a human by inhibiting the action of interleukin-1 (IL-1) through the administration of a IL-1 antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said IL-1 antagonist; and

b) administering said dose by perispinal administration.

54. A method for treating neuropsychiatric diseases or disorders in a human by inhibiting the action of interleukin-1 (IL-1) through the administration of a IL-1 antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said IL-1 antagonist; and

b) administering said dose by perispinal administration.

55. A method for treating neurological diseases or disorders in a human by inhibiting the action of interleukin-1 (IL-1) through the administration of a IL-1 antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said IL-1 antagonist selected from the group consisting of IL-1 receptor antagonist;

Kineret (Amgen);

IL-1 Receptor type 2 (Amgen);

AMG719 (Amgen) and IL-1 Trap (Regeneron); and

b) administering said dose parenterally by perispinal administration.

56. A method for treating neuropsychiatric diseases or disorders in a human by inhibiting the action of interleukin-1 (IL-1) through the administration of a IL-1 antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said IL-1 antagonist selected from the group consisting of IL-1 receptor antagonist;

Kineret (Amgen);

IL-1 Receptor type 2 (Amgen);

AMG719 (Amgen) and IL-1 Trap (Regeneron); and

b) administering said dose parenterally by perispinal administration.

57. A method for treating alcohol withdrawal in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP571 (a humanized monoclonal anti-TNF-alpha IgG4 antibody), CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), soluble TNF receptor Type I, pegylated soluble TNF receptor Type I (PEGs TNF-R1) and onercept, a recombinant TNF binding protein (r-TBP-1) (Serono); and

b). administering said dose by intranasal administration.

58. A method for treating narcotic addiction in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP571 (a humanized monoclonal anti-TNF-alpha IgG4 antibody), CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), soluble TNF receptor Type I, pegylated soluble TNF receptor Type I (PEGs TNF-R1) and onercept, a recombinant TNF binding protein (r-TBP-1) (Serono); and

b). administering said dose by intranasal administration.

59. A method for treating alcohol withdrawal in a human by inhibiting the action of tumor necrosis factor (TNF) through the administration of a TNF antagonist comprising the steps of:

a) administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, CDP571 (a humanized monoclonal anti-TNF-alpha IgG4 antibody), CDP 870 (a humanized monoclonal anti-TNF-alpha antibody fragment), D2E7 (a human anti-TNF mAb), soluble TNF receptor Type I, pegylated soluble TNF receptor Type I (PEGs TNF-R

     1) and onercept, a recombinant TNF binding protein (r-TBP-1) (Serono); and

b). administering said dose parenterally by perispinal administration.