METHODS OF PERMEABILIZING THE BLOOD BRAIN BARRIER

1 . A method of administering a therapeutic agent to a central nervous system of a mammal, the method comprising administering a monoterpene before or concurrently with the therapeutic agent.

2 . The method of claim 1 , wherein the central nervous system is the brain.

3 . The method of claim 1 , wherein the monoterpene is perillyl alcohol.

4 . The method of claim 3 , wherein perillyl alcohol is administered intraarterially.

5 . The method of claim 3 , wherein perillyl alcohol is administered at a dose ranging from about 0.050 mg/kg to about 500 mg/kg of body weight.

6 . The method of claim 1 , wherein the mammal is a human.

7 . The method of claim 1 , wherein the monoterpene is administered from about 0.2 minutes to about 60 minutes before the therapeutic agent is administered.

8 . The method of claim 7 , wherein the monoterpene is administered from about 1 minute to about 15 minutes before the therapeutic agent is administered.

9 . The method of claim 1 , wherein the monoterpene and the therapeutic agent are administered separately.

10 . The method of claim 1 , wherein the monoterpene and the therapeutic agent are administered concurrently.

11 . The method of claim 10 , wherein the monoterpene and the therapeutic agent are administered together in a pharmaceutical composition.

12 . The method of claim 1 , wherein the therapeutic agent is a chemotherapeutic agent.

13 . The method of claim 12 , wherein the chemotherapeutic agent is selected from the group consisting of a DNA alkylating agent, a topoisomerase inhibitor, an endoplasmic reticulum stress inducing agent, a platinum compound, an antimetabolite, an enzyme inhibitor, a receptor antagonist, a therapeutic antibody, and combinations thereof.

14 . The method of claim 12 , wherein the chemotherapeutic agent is dimethyl-celecoxib (DMC), irinotecan (CPT-11), temozolomide or rolipram.

15 . The method of claim 1 , wherein the therapeutic agent is an antibody or antibody fragment.

16 . The method of claim 1 , wherein the therapeutic agent is an immune cell expressing a chimeric antigen receptor.

17 . The method of claim 16 , wherein the immune cell is a T cell.

18 . The method of claim 16 , wherein the therapeutic agent is a CAR-T cell.

19 . The method of claim 1 , wherein the monoterpene is administered by inhalation, intranasally, orally, intravenously, subcutaneously or intramuscularly.

20 . The method of claim 1 , wherein the mammal has cancer.

21 . The method of claim 20 , wherein the cancer is a tumor of the nervous system.

22 . The method of claim 21 , wherein the tumor is a glioblastoma.

23 . The method of claim 1 , further comprising treating the mammal with radiation.