Methods of treating tuberous sclerosis complex with cannabidiol and everolimus

1. A method of initiating everolimus treatment in a human who is suffering from tuberous sclerosis complex and has partial onset seizures who is currently being treated with a therapeutically effective amount of cannabidiol, the method comprising:

(a) co-administering a reduced starting dose of everolimus and the therapeutically effective amount of cannabidiol to the human;

(b) monitoring the human's blood plasma concentration of everolimus;

(c) increasing the reduced starting dose of everolimus administered in step (a) by at least 10% to a dose that achieves a blood plasma trough concentration of everolimus ranging from 5-15 ng/mL, Cmax of everolimus that is less than or equal to 50 ng/mL, or AUC 0-24 of everolimus that is less than or equal to 500 h*ng/mL;

wherein said monitoring in step (b) occurs one to two weeks after the human begins receiving everolimus;

wherein cannabidiol is synthetic or purified; and

wherein the starting dose of everolimus for treating tuberous sclerosis complex in the human is 5 mg/m 2 once daily.

2. The method of claim 1 , wherein the therapeutically effective amount of cannabidiol ranges from about 5 mg/kg/day to about 25 mg/kg/day.

3. The method of claim 1 , wherein the therapeutically effective amount of cannabidiol is 25 mg/kg/day.

4. The method of claim 1 , wherein the human has normal hepatic status or mild hepatic impairment, and the therapeutically effective amount of cannabidiol administered in step (a) is about 25 mg/kg/day.

5. The method of claim 1 , wherein the human has moderate hepatic impairment, and the therapeutically effective amount of cannabidiol administered in step (a) is about 12.5 mg/kg/day.

6. The method of claim 1 , wherein the human has severe hepatic impairment, and the therapeutically effective amount of cannabidiol administered in step (a) is about 5 mg/kg/day.

7. The method of claim 1 , wherein the cannabidiol is purified.

8. The method of claim 7 , wherein the cannabidiol has a purity of at least 95% (w/w) cannabidiol.

9. The method of claim 8 , wherein the cannabidiol has a purity of at least 98% (w/w) cannabidiol.

10. The method of claim 1 , wherein the reduced starting dose of everolimus administered in step (a) is less than 4.5 mg/m 2 of everolimus once daily.

11. The method of claim 1 , wherein the reduced starting dose of everolimus administered in step (a) ranges from about 2.5 mg/m 2 to about 4.5 mg/m 2 of everolimus.

12. The method of claim 1 , wherein the reduced starting dose of everolimus administered in step (a) is about 2.5 mg/m 2 .

13. The method of claim 1 , wherein the reduced starting dose of everolimus administered in step (a) ranges from about 2.25 mg/m 2 to about 4.1 mg/m 2 of everolimus.

14. The method of claim 1 , wherein the reduced starting dose of everolimus administered in step (a) is about 2.25 mg/m 2 .

15. The method of claim 1 , further comprising treating generalized seizures in the human.

16. The method of claim 15 , wherein the generalized seizures are tonic-clonic, tonic, clonic or atonic seizures.

17. The method of claim 1 , further comprising treating focal seizures in the human.

18. The method of claim 17 , wherein the focal seizures are focal motor seizures without impairment of consciousness or awareness; focal seizures with impairment of consciousness or awareness; or focal seizures evolving to bilateral generalized convulsive seizures and generalized seizures.

19. The method of claim 1 , which reduces the total number of seizures compared to the number of seizures experienced during a baseline period before cannabidiol was administered in the human.

20. The method of claim 19 , wherein the number seizures is reduced by at least 50% compared to the number of seizures experienced during a baseline period before cannabidiol was administered in the human.

21. The method of claim 1 , wherein step (c) comprises increasing the reduced starting dose of everolimus administered in step (a) to a dose that achieves a blood plasma trough concentration of everolimus ranging from 5-15 ng/mL.

22. The method of claim 1 , wherein the reduced starting dose of everolimus administered in step (a) comprises administering 5 mg/m 2 or 4.5 mg/m 2 of everolimus every other day.

23. The method of claim 21 , wherein the reduced starting dose of everolimus administered in step (a) ranges from about 2.5 mg/m 2 to about 4.5 mg/m 2 of everolimus.

24. The method of claim 21 , wherein the reduced starting dose of everolimus administered in step (a) is about 2.5 mg/m 2 .

25. The method of claim 21 , wherein the reduced starting dose of everolimus administered in step (a) comprises administering 5 mg/m 2 or 4.5 mg/m 2 of everolimus every other day.