Methods for restoration of histamine balance

1. A method for restoring histamine balance in a subject to treat histadelia or histapenia by normalizing activity of histamine receptors through multiple doses of a histamine composition administered in successive therapy segments, comprising:

administering to said subject an escalating dosing regimen comprising:

a first dosing segment comprising two or more sequential doses of a histamine receptor activator said composition separated by a first time interval,

wherein the histamine receptor activator said composition comprises a histamine salt selected from the group consisting of histamine diphosphate, histamine phosphate, and histamine dihydrochloride,

wherein the doses increase in histamine receptor activator said composition concentration from dose to dose while the administered volume of each dose stays constant; and

a second dosing segment comprising two or more sequential doses of a histamine receptor activator said composition separated by a second time interval, wherein the doses increase in histamine receptor activator concentration from dose to dose while the administered volume of each dose stays constant;

wherein the volume of each histamine receptor activator said composition dose in the second dosing segment is greater than the volume of each histamine receptor activator said composition dose in the first dosing segment, and the second time interval is longer than the first time interval.

2. The method of claim 1 , wherein the first dosing segment comprises a first, a second, a third, and a fourth dose,

wherein said first dose of the histamine receptor activator composition is administered subcutaneously at a concentration of 1.1 ng/mL+/−30% and activates a histamine H3 receptor,

wherein said second dose of the histamine receptor activator composition is administered subcutaneously at a concentration of 3 ng/mL+1-50% and activates a histamine H4 receptor,

wherein said third dose of the histamine receptor activator composition is administered subcutaneously at a concentration of 1.1 μg/mL+/−30% and activates a histamine H1 receptor,

wherein said fourth dose of the histamine receptor activator composition is administered subcutaneously at a concentration of 3.33 μg/mL+/−30% and activates a histamine H2 receptor.

3. The method of claim 1 , wherein the administration of the histamine receptor activator composition comprises administration via a route selected from the group consisting of subcutaneous injection, intravenous injection, intraarterial injection, intramuscular injection, oral delivery, transdermal delivery, sublingual delivery, infusion, suppository, and inhalation delivery.

4. The method of claim 1 , wherein said subject is susceptible to migraine headaches as a result of histamine imbalance and said restored histamine balance leads to a reduction in frequency and/or intensity of migraine headaches.

5. The method of claim 1 , wherein the successive therapy segments comprise at least the first dosing segment, the second dosing segment, a third dosing segment comprising two or more sequential doses of a histamine receptor activator composition separated by a third time interval, wherein the doses increase in histamine receptor activator composition concentration from dose to dose while the administered volume of each dose stays constant, and a fourth dosing segment comprising two or more sequential doses of a histamine receptor activator composition separated by a fourth time interval, wherein the doses increase in histamine receptor activator composition concentration from dose to dose while the administered volume of each dose stays constant.

6. The method of claim 5 , wherein the volume of each histamine receptor activator composition dose in the third dosing segment is greater than the volume of each histamine receptor activator composition dose in the second dosing segment, and the third time interval is longer than the second time interval.

7. The method of claim 5 , wherein the volume of each histamine receptor activator composition dose in the fourth dosing segment is greater than the volume of each histamine receptor activator composition dose in the third dosing segment, and the fourth time interval is longer than the third time interval.

8. The method of claim 5 ,

wherein the first dosing segment occurs over 10-16 days,

wherein the second dosing segment occurs over 20-35 days, and

wherein the third dosing segment occurs over 38-50 days.

9. The method of claim 5 ,

wherein the administration of the histamine receptor activator composition comprises subcutaneous injection of a histamine salt,

wherein the total dose of the first dosing segment is 200 ng to 600 ng,

wherein the total dose of the second dosing segment is 650 ng to 1000 ng,

wherein the total dose of the third dosing segment is 1050 ng to 1500 ng,

wherein the second dosing segment is longer than the first dosing segment, and

wherein the third dosing segment is longer than the dosing therapy segment.

10. The method of claim 1 , wherein the first sequential dose of said histamine receptor composition activator in the first dosing segment has a histamine receptor activator said composition concentration ranging from between 0.1 pg/mL to 10 pg/mL, wherein the second dose of the histamine receptor activator composition in the first dosing segment has a concentration ranging from between 0.1 ng/mL to 10 ng/mL.

11. The method of claim 1 , wherein the first dosing segment comprises at a least a third and a fourth sequential dose,

wherein the third dose of the histamine receptor activator composition in the first dosing segment has a concentration ranging from between 0.1 μg/mL to 2.999 μg/mL, and

wherein the fourth dose of the histamine receptor activator composition in the first dosing segment has a concentration ranging from between 3.0 pg/mL to 10 pg/mL.

12. The method of claim 1 , wherein the histamine receptor activator composition is administered with a frequency of between one and three times per week during the first dosing segment.

13. The method of claim 1 , further comprising administering an additional agonist of any of the histamine H1, H2, H3, or H4 receptors.

14. The method of claim 1 , wherein the two or more sequential doses of the histamine receptor activator composition in each dosing segment is administered within a total time frame of less than about 5 minutes.

15. The method of claim 1 , wherein the restoration of histamine balance is further suitable for a reduction in duration, frequency or intensity of migraine headaches or reduction of the symptoms of one or more of Parkinson's Disease, Alzheimer's Disease, coronary disease, leukemia, amyotrophic lateral sclerosis, and epilepsy.

16. A method for reducing the duration, frequency, or intensity of migraine headaches by restoring histamine balance in a subject through normalization of histamine receptor activity through multiple doses administered in successive therapy segments, comprising:

administering to said subject an escalating dosing regimen comprising:

a first dosing segment comprising two or more sequential doses of a physiologically acceptable histamine salt separated by a first time interval, wherein the physiologically acceptable histamine salt is a histamine salt selected from the group consisting of histamine diphosphate, histamine phosphate, and histamine dihydrochloride,

wherein the histamine salt activates one or more of a histamine H1, H2, H3, or H4 receptor,

wherein the doses increase in histamine salt concentration from dose to dose while the administered volume of each dose stays constant; and

a second dosing segment comprising two or more sequential doses of a histamine salt separated by a second time interval, wherein the doses increase in histamine salt concentration from dose to dose while the administered volume of each dose stays constant;

wherein the volume of each histamine salt dose in the second dosing segment is greater than the volume of each histamine salt dose in the first dosing segment, and the second time interval is longer than the first time interval.