18-MC FOR TREATMENT OF SUBSTANCE USE DISORDERS

1 . A composition for treating substance use disorders comprising an effective amount of 18-Methoxycoronaridine salt (18-MC) in a pharmaceutical carrier.

2 . The composition of claim 1 , wherein said composition is formulated in an oral dose.

3 . The composition of claim 1 , wherein said composition is a hydrochloride salt.

4 . A method of treating substance use disorders, including the steps of:

administering an effective amount of 18-Methoxycoronaridine salt (18-MC) in a pharmaceutical carrier to an individual; and

preventing substance abuse in the individual.

5 . The method of claim 4 , wherein the substance is chosen from the group consisting of cocaine, nicotine, opiates, alcohol, morphine, and methamphetamine.

6 . The method of claim 4 , wherein the individual is a human.

7 . The method of claim 4 , wherein said preventing step is further defined as reducing reinforcing and rewarding effects of the substance.

8 . The method of claim 4 , wherein said administering step is performed orally.

9 . The method of claim 4 , wherein the salt is a hydrochloride salt.

10 . The method of claim 4 , wherein said administering step is further defined as administering 0.01-10 mg/kg of 18-MC.

11 . The method of claim 10 , wherein said administering step is further defined as administering 20 mg or less per day of 18-MC.

12 . The method of claim 4 , wherein 18-MC administered follows a multiple-compartment model and a half-life is about 48 hours.

13 . The method of claim 4 , further including the step of blocking α3β4 nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala.

14 . The method of claim 4 , further including the step of inhibiting enzymes CYP2C9, CYP2C19, CYP2C8, CYP2E1, and CYP3A4.

15 . A method of preventing addictive behavior in an individual, including the steps of:

administering an effective amount of 18-Methoxycoronaridine salt (18-MC) in a pharmaceutical carrier to an individual; and

preventing addictive behavior in the individual.

16 . The method of claim 15 , wherein the salt is a hydrochloride salt.

17 . The method of claim 15 , wherein the substance is chosen from the group consisting of cocaine, nicotine, opiates, alcohol, morphine, and methamphetamine.

18 . The method of claim 15 , wherein the individual is a human.

19 . The method of claim 15 , wherein said preventing step is further defined as reducing reinforcing and rewarding effects of the substance.

20 . The method of claim 15 , wherein said administering step is performed orally.

21 . The method of claim 15 , wherein said administering step is further defined as administering 0.01-10 mg/kg of 18-MC.

22 . The method of claim 21 , wherein said administering step is further defined as administering 20 mg or less per day of 18-MC.

23 . The method of claim 15 , wherein 18-MC administered follows a multiple-compartment model and a half-life is about 48 hours.

24 . The method of claim 15 , further including the step of blocking α3β4 nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala.

25 . The method of claim 15 , further including the step of inhibiting enzymes CYP2C9, CYP2C19, CYP2C8, CYP2E1, and CYP3A4.

26 . A method of preventing craving in an individual, including the steps of:

administering an effective amount of 18-Methoxycoronaridine salt (18-MC) in a pharmaceutical carrier to an individual; and

preventing craving in the individual.

27 . The method of claim 26 , wherein the salt is a hydrochloride salt.

28 . The method of claim 26 , wherein the substance is chosen from the group consisting of cocaine, nicotine, opiates, alcohol, morphine, and methamphetamine.

29 . The method of claim 26 , wherein the individual is a human.

30 . The method of claim 26 , wherein said preventing step is further defined as reducing reinforcing and rewarding effects of the substance.

31 . The method of claim 26 , wherein said administering step is performed orally.

32 . The method of claim 26 , wherein said administering step is further defined as administering 0.01-10 mg/kg of 18-MC.

33 . The method of claim 32 , wherein said administering step is further defined as administering 20 mg or less per day of 18-MC.

34 . The method of claim 26 , wherein 18-MC administered follows a multiple-compartment model and a half-life is about 48 hours.

35 . The method of claim 26 , further including the step of blocking α3β4 nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala.

36 . The method of claim 26 , further including the step of inhibiting enzymes CYP2C9, CYP2C19, CYP2C8, CYP2E1, and CYP3A4.

37 . A composition comprising a metabolite of 18-MC salt.

38 . The composition of claim 37 , wherein said metabolite is chosen from the group consisting of M1, M2, M3, M4, M5, M6, M7, M8, M9, P1, P2, P3, and P10 and wherein the salt is a hydrochloride salt.

39 . The composition of claim 37 , wherein said metabolite is M4 or M5.

40 . A method of treating substance use disorders including the steps of:

administering an effective amount of a metabolite of 18-MC salt in a pharmaceutical carrier to an individual; and

preventing substance abuse in the individual.

41 . The method of claim 40 , wherein the metabolite is chosen from the group consisting of M1, M2, M3, M4, M5, M6, M7, M8, M9, P1, P2, P3, and P10 and wherein the salt is a hydrochloride salt.

42 . The method of claim 40 , wherein the metabolite is M4 or M5.

43 . The method of claim 40 , wherein the substance is chosen from the group consisting of cocaine, nicotine, opiates, alcohol, morphine, and methamphetamine.

44 . The method of claim 40 , wherein the individual is a human.

45 . The method of claim 40 , wherein said preventing step is further defined as reducing reinforcing and rewarding effects of the substance.

46 . The method of claim 40 , wherein said administering step is performed orally.

47 . The method of claim 40 , wherein said administering step is further defined as administering 0.01-10 mg/kg of a metabolite of 18-MC.

48 . The method of claim 47 , wherein said administering step is further defined as administering 20 mg or less per day of a metabolite of 18-MC.

49 . The method of claim 40 , wherein a metabolite of 18-MC administered has a half-life of about 48 hours.

50 . The method of claim 40 , further including the step of blocking α3β4 nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala.

51 . The method of claim 40 , further including the step of inhibiting enzymes CYP2C9, CYP2C19, CYP2C8, CYP2E1, and CYP3A4.

52 . A composition having the binding profile shown in FIG. 2 .

53 . A composition having an action potential duration in rabbit cardiac Purkinje fibers shown in FIG. 13 .

54 . A composition having a pharmacokinetic profiles of parent and a metabolite in human plasma shown in FIG. 17 .

55 . A composition having an IC 50 profiles of parent and one or more metabolites as shown in FIG. 18 E .

56 . A composition having an alpha3-beta4 nicotinic cholinergic receptor patch clamp assay profile as shown in FIGS. 19 A and 19 B .

57 . A composition having a human metabolite alpha3-beta4 nicotinic cholinergic receptor patch clamp assay profile as shown in any of FIGS. 20 A, 20 B, 20 C and 20 D .

58 . A composition having an ICSS study profile in rats as shown in any of FIG. 22 , 23 , or 24 .