1. Cannabinoid use in Cancer Patients PAS 646 Univ. of Kentucky Ryan Filiatreau

2. Background Cannabis sativa – used for hundreds of years Cannabis sativa – used for hundreds of years U.S. Pharmacopoiea – 1944 U.S. Pharmacopoiea – 1944 Δ9-THC Δ9-THC –1964 discovered –1986 USDA approval

3. Pathophysiology CB1 & CB2: G-protein coupled membrane receptors CB1 & CB2: G-protein coupled membrane receptors Endogenous ligands: Endogenous ligands: Exogenous ligands: Exogenous ligands: Receptor activation – inhibit calcium channels and adenylate cyclase Receptor activation – inhibit calcium channels and adenylate cyclase

4. Patho, con’t. CB1 receptor: highest density in CNS CB1 receptor: highest density in CNS CB2 receptor: immune system CB2 receptor: immune system Enzymes Enzymes – NAPE-PLD yields anandamide, and DAGLs yield 2-AG – FAAH inactivates anandamide, and MG-lipase inactivates 2-AG

5. Pharmacology chemotherapy-induced nausea and vomiting: antiemetic for pts. unresponsive to other medications chemotherapy-induced nausea and vomiting: antiemetic for pts. unresponsive to other medications Anorexia-cachexia syndrome: possible adjunctive medication Anorexia-cachexia syndrome: possible adjunctive medication Glaucoma: lowers intraocular press. Glaucoma: lowers intraocular press. Asthma: bronchial dilation Asthma: bronchial dilation

6. Pharmacology nabilone (Cesamet®) and dronabinol (Marinol®) nabilone (Cesamet®) and dronabinol (Marinol®) Dronabinol 2.5-5mg orally- 4 th line agent for N&V Dronabinol 2.5-5mg orally- 4 th line agent for N&V control of cancer chemotherapy induced N&V, and as appetite stimulants for AIDS-related wasting control of cancer chemotherapy induced N&V, and as appetite stimulants for AIDS-related wasting

7. Side Effects dysphoria, depression, depersonalization, occasional hallucinations, somnolence, dry mouth, and abnormal thinking. dysphoria, depression, depersonalization, occasional hallucinations, somnolence, dry mouth, and abnormal thinking. At higher doses hypotension, ataxia, blurred vision, paranoia, and dizziness At higher doses hypotension, ataxia, blurred vision, paranoia, and dizziness

8. Future Possibilities for CA pt. tx Suppress pain through the CB1 and CB2 receptors by inhibiting nocioceptive neurotransmission Suppress pain through the CB1 and CB2 receptors by inhibiting nocioceptive neurotransmission Progression of cancer-may inhibit cancer growth, angiogensis, and metastasis Progression of cancer-may inhibit cancer growth, angiogensis, and metastasis

9. Future Possibilities Being pursued - loss of appetite, pain, anxiety, vomiting, nausea, and epilepsy Being pursued - loss of appetite, pain, anxiety, vomiting, nausea, and epilepsy Currently implicated - multiple sclerosis, Huntington’s disease, Tourette’s syndrome, Parkinson’s disease, stroke, and dementia Currently implicated - multiple sclerosis, Huntington’s disease, Tourette’s syndrome, Parkinson’s disease, stroke, and dementia

10. Conclusion Recreational use vs. Medical use Recreational use vs. Medical use Stigma prevents research funding Stigma prevents research funding Development of safer meds without adverse psychoactive effects and greater efficacy Development of safer meds without adverse psychoactive effects and greater efficacy System of great therapuetic potential System of great therapuetic potential