Therapeutic Compositions and Methods

Abstract

This invention relates the use of cortisol blockers (glucocorticoid receptor [GR] antagonists) for the prevention or addiction induced anxiety and withdrawal side effects as a therapeutic and in concert with a diagnostic. Such addictions could be, but are not limited to, alcohol, drugs, caffeine, sugar, food, nicotine, etc. The present invention further relates to the use of cortisol blockers (GR antagonists) for wound healing and transplants, the prevention or treatment of stress induced osteoporosis and the rapid healing of bone related injuries, and regenerative therapy.

What is claimed is: 
     
         1 . A method for treating and/or preventing addiction to, and physiological dependence upon, addictive substances wherein said method comprises:
 selecting a patient in need of treating and/or preventing addiction to, and physiological dependence upon, addictive substances;   administering to the patient in need of treating and/or preventing addiction to, and physiological dependence upon, addictive substances at least ORG 34517 in a therapeutically effective amount, thereby treating and/or preventing addiction to, and physiological dependence upon, addictive substances.   
     
     
         2 . The method of  claim 1 , wherein the addictive substance is selected from the group consisting of Opiates, opiate analogues, heroine, oxycodone, hydrocodone, hydromorphone, methadone, dextromethorphan, benzodiazepines, MDMA, GHB, barbiturates, khat, kratom, PCP, LSD, ketamine, peyote, mescaline, psilocybin, rohypnol,  Salvia divinorum , antidepressants, anti-anxiety medications, sleep aids, allergy medications, and combinations thereof. 
     
     
         3 . The method, according to  claim 1 , wherein the at least ORG 34517 is in a pharmaceutical preparation. 
     
     
         4 . A method of treating and/or preventing addiction to, and physiological dependence upon, addictive substances in a patient in need thereof, comprising:
 selecting a patient in need of treating and/or preventing addiction to, and physiological dependence upon, addictive substances;   administering a composition comprising:   i) ORG 34517, or pharmaceutically acceptable salts thereof;   ii) at least one additional therapeutic agent(s) selected from the group consisting of anxiolytics, antidepressants, neuroleptics, or other psychotropic medications and combinations thereof; and   iii) at least one pharmaceutically acceptable carrier, wherein the ORG 34517 and at least one additional therapeutic agents are each present in an amount which, in combination, is a therapeutically effective amount for treating or preventing the condition.   
     
     
         5 . The method of  claim 4  wherein the addictive substance is selected from the group consisting of opiates, opiate analogues, heroine, oxycodone, hydrocodone, hydromorphone, methadone, dextromethorphan, benzodiazepines, MDMA, GHB, barbiturates, khat, kratom, PCP, LSD, ketamine, peyote, mescaline, psilocybin, rohypnol,  Salvia divinorum , antidepressants, anti-anxiety medications, sleep aids, allergy medications, and combinations thereof. 
     
     
         6 . The method of  claim 4  wherein the additional therapeutic agent is selected from the group consisting of at least one anti-anxiety drug, at least one anti-depressant drug, and at least one neuroleptic medication and combinations thereof, wherein the at least one anti-anxiety drug is selected from the group consisting of alprazolam, bromazepam, diazepam, lorazepam, clonazepam, temazepam, oxazepam, flunitrazepam, triazolam, chlordiazepoxide, flurazepam, estazolam, nitrazepam, and pharmaceutically acceptable salts, isomers, and mixtures thereof; and/or at least one anti-depressant drug selected from the group consisting of citalopram, escitalopram oxalate, fluoxetine, fluvoxamine, paroxetine, sertraline, dapoxetine; venlafaxine and duloxetine; harmaline, iproniazid, isocarboxazid, nialamide, pargyline, phenelzine, selegiline, toloxatone, tranylcypromine, brofaromine, moclobemide; amitriptyline, amoxapine, butriptyline, clomipramine, desipramine, dibenzepin, dothiepin, doxepin, imipramine, iprindole, lofepramine, melitracen, nortriptyline, opipramol, protriptyline, trimipramine; maprotiline, mianserin, nefazodone, trazodone, and pharmaceutically acceptable salts, isomers, and combinations thereof and/or at least one neuroleptic drug selected from the group consisting of Haloperidol, Droperidol, Benperidol, Triperidol, Melperone, Lenperone, azaperone, Domperidone, risperidone, Chlorpromazine, Fluphenazine, Perphenazine, Prochlorperazine, Thioridazine, Trifluoperazine, Mesoridazine, Periciazine, Promazine, Triflupromazine, Levomepromazine, Promethazine, Pimozide, Cyamemazine, Chlorprothixene, Clopenthixol, Flupenthixol, Thiothixene, Zuclopenthixol, Clozapine, Olanzapine, Risperidone, Quetiapine, Ziprasidone, Amisulpride, Asenapine, Paliperidone, Iloperidone, Zotepine, Sertindole, Lurasidone, Aripiprazole, and pharmaceutically acceptable salts, isomers, and combinations thereof. 
     
     
         7 . A method of treating and/or preventing addiction to, and physiological dependence upon, addictive substances in a patient, comprising the steps of:
 a) obtaining a test sample from the patient using a test sample collection unit;   b) combining said test sample with a buffering system to form a mixture in a reaction unit;   c) measuring a parameter of the mixture to determine a blank measurement;   d) combining said test sample and buffer mixture with a labeled ligand which binds cortisol in the reaction unit to produce an assay solution; or combining said test sample and buffer mixture and delivering it to a carrier containing a labeled ligand which binds cortisol in the reaction unit to produce an assay immobilized complex;   e) measuring a parameter of said assay solution or complex;   f) comparing the measurement of the assay solution relative to the blank measurement;   g) determining the patient's circulating cortisol levels based on the change of the measurement;   h) comparing the measured cortisol levels to a predetermined reference range cortisol levels, wherein when the level of cortisol is elevated relative to the predetermined reference range, then the patient has elevated cortisol, and thus is suitable for GCR (glucocorticoid receptor) antagonist therapy; and   i) when the patient is suitable for GCR antagonist therapy, administering at least ORG 34517, thereby treating and/or preventing addiction to, and physiological dependence upon, addictive substances in the patient.   
     
     
         8 . The method of  claim 7 , wherein the patient's test sample is selected from the group consisting of saliva, blood, plasma, serum, urine, other bodily fluids, and combinations thereof. 
     
     
         9 . The method of  claim 7 , wherein the sample is obtained from the patient one time, selected from the group consisting of morning, noon, and evening. 
     
     
         10 . The method of  claim 7 , wherein the sample is obtained from the patient over more than one time, and the predetermined time is selected to determine the nature of the cortisol circadian rhythm (including its possible disruption or elimination) from the group consisting of morning, noon, and evening. 
     
     
         11 . The method of  claim 7 , wherein the sample is obtained from the patient over consecutive days. 
     
     
         12 . The method of  claim 7 , wherein the method is to determine the circadian cycle of the cortisol levels in the patient, and the predetermined time is selected from the group consisting of hourly, every 4 hours, every 6 hours, every 8 hours, and every 12 hours. 
     
     
         13 . The method of  claim 7 , wherein the predetermined reference range is a medically standard reference range. 
     
     
         14 . The method of  claim 7 , wherein the predetermined reference range is the patient's previously measured level. 
     
     
         15 . The method of  claim 7 , wherein the ligand is detectably labeled with a moiety selected from the group consisting of a radioisotope, a fluorophore, a quencher of fluorescence, an enzyme, an affinity tag, and an epitope tag. 
     
     
         16 . The method of  claim 7 , wherein said measuring of said parameter of said mixture and said assay solution is performed using a method selected from spectroscopic, photochemical, radiochemical, biochemical, enzymatic, immunochemical, chemical label displacement, surface plasmon resonance, fluorescence resonance energy transfer, fluorescence quenching, lateral flow, and fluorescence polarization means. 
     
     
         17 . The method of  claim 7 , wherein the addictive substance is selected from the group consisting of opiates, opiate analogues, heroine, oxycodone, hydrocodone, hydromorphone, methadone, dextromethorphan, benzodiazepines, MDMA, GHB, barbiturates, khat, kratom, PCP, LSD, ketamine, peyote, mescaline, psilocybin, rohypnol,  Salvia divinorum , antidepressants, anti-anxiety medications, sleep aids, allergy medications, and combinations thereof.