Methods of and Compositions For the Prevention of Anxiety, Substance Abuse, and Dependence

Abstract

Compositions for reducing dependency and addiction to substances of abuse are provided. Chloride channels such as the GABA A receptors are altered under conditions of dependency and withdrawal such that the electrophysiological properties of the GABA A receptor containing neurons are altered thereby providing a pathophysiological condition resulting in symptoms of dependency and withdrawal such as anxiety. Specifically, under conditions of withdrawal the relative ratio of the a1 receptor subunit decreases relative to the a4 receptor subunit. Endogenous neurosteroid production is also associated with the molecular changes underlying the alterations of GABA-gated chloride channels. Compositions of at least two compounds including at least one inhibitor of neurosteroid production are useful for treating the pathophysiology of addiction, dependency and substance abuse withdrawal.

1 - 36 . (canceled) 
     
     
         37 . A composition comprising a pharmaceutical compound in combination with an inhibitor of endogenous neurosteroid production in a pharmaceutically acceptable carrier, wherein the pharmaceutical compound is a stimulant, contraceptive, tranquilizer, sedative, hypnotic, benzodiazepine, analgesic or barbiturate. 
     
     
         38 . The composition of  claim 37 , wherein the stimulant is amphetamine, methylphenidate, dextroamphetamine, or a mixture thereof. 
     
     
         39 . The composition of  claim 38 , wherein the methylphenidate is present in an amount between 5 mg and 20 mg. 
     
     
         40 . The composition of  claim 38 , wherein the dextroamphetamine is present in an amount between 5 mg and 60 mg. 
     
     
         41 . The composition of  claim 38 , wherein the amphetamine and dextroamphetamine are present in a mixture in an amount of between 2.5 mg and 60 mg. 
     
     
         42 . The composition of  claim 37 , wherein the contraceptive is ethinyl estradiol, mestranol, norethynodrel, norethindrone, norethindrone acetate, norgestimate, desogestrel, ethynodiol diacetate, norgestrel, levonorgestrel, medroxyprogesterone acetate, or drospirenone or a combination thereof. 
     
     
         43 . The composition of  claim 42 , wherein the medroxyprogesterone acetate is present in an amount of 150 mg. 
     
     
         44 . The composition of  claim 37 , wherein the tranquilizer, sedative or hypnotic is chloral hydrate, chloral betaine, chlomethiazole, diphenhydramine, ethchlorvynol, promethazine, zaleplon, zolpidem, or zopiclone, or a combination thereof. 
     
     
         45 . The composition of  claim 37 , wherein the inhibitor of neurosteroid production is finasteride 
     
     
         46 . The composition of  claim 45 , wherein the finasteride is present in an amount between about 0.1 and 150 mg. 
     
     
         47 . The composition of  claim 45 , wherein the finasteride is present in an amount of about 5 mg. 
     
     
         48 . A method of reducing substance abuse in a patient of a pharmaceutical compound comprising administering to the patient a composition comprising the pharmaceutical compound in combination with an inhibitor of endogenous neurosteroid production in a pharmaceutically acceptable carrier, wherein composition is effective to reduce abuse of the pharmaceutical compound in the patient, wherein the pharmaceutical compound is a stimulant, contraceptive, tranquilizer, sedative, hypnotic, benzodiazepine, analgesic or barbiturate. 
     
     
         49 . The method of  claim 48 , wherein the stimulant is amphetamine, methylphenidate, or dextroamphetamine, or a mixture thereof. 
     
     
         50 . The method of  claim 49 , wherein the methylphenidate is present in an amount between 5 mg and 20 mg. 
     
     
         51 . The method of  claim 49 , wherein the dextroamphetamine is present in an amount between 5 mg and 60 mg. 
     
     
         52 . The method of  claim 49 , wherein the amphetamine and dextroamphetamine are present in a mixture in an amount of between 2.5 mg and 60 mg. 
     
     
         53 . The method of  claim 48 , wherein the contraceptive is ethinyl estradiol, mestranol, norethynodrel, norethindrone, norethindrone acetate, norgestimate, desogestrel, ethynodiol diacetate, norgestrel, levonorgestrel, medroxyprogesterone acetate, drospirenone or combinations thereof. 
     
     
         54 . The method of  claim 53 , wherein the medroxyprogesterone acetate is present in an amount of 150 mg. 
     
     
         55 . The method of  claim 48 , wherein the tranquilizer, sedative or hypnotic is chloral hydrate, chloral betaine, chlomethiazole, diphenhydramine, ethchlorvynol, promethazine, zaleplon, zolpidem, or zopiclone, or a combination thereof. 
     
     
         56 . The method of  claim 48 , wherein the inhibitor of neurosteroid production is finasteride. 
     
     
         57 . The method of  claim 56 , wherein the finasteride is present in an amount between about 0.1 and 150 mg. 
     
     
         58 . The method of  claim 56 , wherein the finasteride is present in an amount of about 5 mg. 
     
     
         59 . The method of  claim 48 , further comprising administering a composition comprising a compound that modulates expression of GABA A  subunits in a pharmaceutically acceptable carrier. 
     
     
         60 . The method of  claim 59 , wherein the compound that modulates expression of GABA A  subunits is flumazenil.