Tumescent infiltration drug delivery of cannabinoids
A tumescent composition including a cannabinoid dissolved in a tumescent solution, wherein the tumescent solution includes a local anesthetic; a vasoconstrictor; and a pharmaceutically acceptable carrier, wherein a tumescent concentration of the cannabinoid is 1-2000 μg/kg and is simultaneously: below a threshold for local, subcutaneous tissue toxicity, above a threshold for positive local therapeutic effect, and above a concentration safely achievable by intravenous (IV), intramuscular (IM) or oral (PO) delivery. Also disclosed are methods of subcutaneous delivery of a cannabinoid to a subject including administering to the subject the tumescent composition.
1. A tumescent composition comprising a cannabinoid dissolved in a tumescent solution, wherein the tumescent solution comprises:
(i) a vasoconstrictor;
(ii) a pharmaceutically acceptable carrier; and
(iii) optionally a local anesthetic;
wherein a tumescent concentration of the cannabinoid is simultaneously:
1) below a threshold for local, subcutaneous tissue toxicity,
2) above a threshold for positive local therapeutic effect, and
3) above a concentration safely achievable by intravenous (IV), intramuscular (IM) or oral (PO) delivery.
2. The tumescent composition of claim 1 , wherein the cannabinoid is a variant of cannabidiol (CBD) or tetrahydrocannabinol (THC).
3. The tumescent composition of claim 2 , wherein the cannabinoid is a variant of THC, wherein the alkyl side chain of thereof is derivatized.
4. The tumescent composition of claim 2 , wherein the cannabinoid is a variant of THC, wherein the phenolic hydroxyl group thereof is derivatized.
5. The tumescent composition of claim 1 , wherein said local anesthetic is lidocaine.
6. The tumescent composition of claim 5 , wherein the concentration of lidocaine is approximately 100 mg to 1,500 mg per L of solution.
7. The tumescent composition of claim 1 , wherein said vasoconstrictor component is epinephrine.
8. The tumescent composition of claim 7 , wherein the concentration of epinephrine is approximately 0.2 to 1.5 mg/L.
9. A method of subcutaneous delivery of a cannabinoid to a subject comprising administering to said subject the tumescent composition according to claim 1 .
10. The method of claim 9 , wherein infiltration of the tumescent composition achieves both prolonged local drug concentration within a tumescent subcutaneous tissue as well as a prolonged slow constant systemic absorption of drugs from the tumescent tissue into a systemic circulation.
11. The method of claim 9 , wherein a pharmacokinetic profile of the systemic absorption resembles a slow, constant, intravenous (IV) infusion.
12. The method of claim 9 , wherein the subcutaneous concentration of the cannabinoid achieved is from about 1-100 times the maximum subcutaneous interstitial fluid concentration that can be achieved by conventional IV, IM or oral delivery of the cannabinoid.
13. The method of claim 9 , wherein said local anesthetic is lidocaine.
14. The method of claim 13 , wherein the concentration of lidocaine is approximately 100 mg to 1,500 mg per L of solution.
15. The method of claim 9 , wherein said vasoconstrictor component is comprises epinephrine.
16. The method of claim 15 wherein the concentration of epinephrine is approximately 0.2 to 1.5 mg/L.
17. The method of claim 9 , wherein the subject is treated for a condition selected from the group consisting of surgically-induced neuropathic pain, shingles, inflammation, appetite loss, pain, multiple sclerosis, nausea, vomiting, and epilepsy.
18. A method of claim 17 , wherein said surgically-induced neuropathic pain results from breast cancer surgery, limb amputation, thoracotomy or hernia repair.
19. The method of claim 18 , wherein said breast cancer surgery is mastectomy or lumpectomy.
20. The method according to claim 9 , wherein the tumescent composition further comprises:
an antiviral drug, and optionally a local anesthetic.
21. The method according to claim 20 , wherein the antiviral drug is acyclovir.
22. The tumescent composition of claim 1 , wherein the cannabinoid is cannabidiol (CBD).
23. The method of claim 1 , wherein the tumescent concentration of the cannabinoid is 1-2000 μg/kg of body mass of the subject.
24. An emulsion composition comprising:
a hydrophobic cannabinoid:
an oil phase;
a tumescent solution; and
a surfactant,
wherein the oil phase is emulsified in the tumescent solution, and
wherein the tumescent solution comprises:
(i) a vasoconstrictor;
(ii) a pharmaceutically acceptable carrier; and
(iii) optionally a local anesthetic; and
wherein a tumescent concentration of the hydrophobic cannabinoid is simultaneously:
1) below a threshold for local, subcutaneous tissue toxicity,
2) above a threshold for positive local therapeutic effect, and
3) above a concentration safely achievable by intravenous (IV), intramuscular (IM) or oral (PO) delivery.
25. The emulsion composition according to claim 24 , wherein the emulsion composition is a micro-emulsion or a nano-emulsion.