Cannabis Use in Palliative Care: History, Legality, and Implications for Practice

1. National Hospice and Palliative Care Organization’sPalliative Care Resource SeriesCannabis Use in Palliative Care: History, Legality and Implications for PracticeWritten by: Peter A. Radice, MD, FACP, FAAHPM

2. Objectives • Discuss the history, background, state and federal laws and regulations around the use of marijuana • Understand the Endocannabinoid System (ECS) • Identify the physiological and cognitive effects of cannabis • Describe the routes of administration and dosing of cannabis • List the side effects and contraindications for its use

3. History of Marijuana • 2737 BC – first recorded medicinal use in Chinese Pharmacopoeia • 1400 BC to AD – trade moves product through India, Mediterranean countries, Europe – numerous medicinal uses reported • Major crop in colonial North America, hemp was grown as a fiber

4. History of Marijuana • Introduced to North America in 1600’s by Puritans – Hemp for ropes, sails, clothing. Cannabis a common ingredient in medicines, sold openly in pharmacies. • 1937 – Marijuana Tax Act – transfer of cannabis illegal throughout US except for medicinal and industrial use, expensive excise tax and detailed logs required. • The “gateway theory” of marijuana use still prevails.

5. History of Marijuana • 1970’s – The Controlled Substance Act of 1970 classified marijuana as a Schedule I drug. • 1981-1993 – Zero tolerance climate of Reagan and Bush Administrations; war on drugs. • 1990’s – Marijuana smoking on upward trend. • 1996 –California becomes first state to legalize marijuana for medicinal purposes.

6. Cannabis • Complex alkaloid mixture of more than 400 compounds derived from the Cannabis sativa plant. • 60 different compounds described with activity on the cannabinergic system. • Most abundant cannabinoids are: • Delta-9 tetrahydrocannabinol (THC) (most psychoactive) • Cannabidiol (CBD) • Cannabinol (CBN)

7. Endocannabinoid System • Endogenous agents • CB1-present throughout CNS • Hippocampus • Cortex • Olfactory areas • Basal ganglia • Cerebellum • Spinal cord • CB2 – located peripherally, linked with autoimmune system • Spleen • Macrophages

8. Cannabis-Based Pharmaceutical Drugs • Sativex– THC/CBD –Nasal Spray – Neuropathy/Spasticity • Marinol – Synthetic THC – Capsule – Cancer/AIDS • Nabilone – Synthetic – Capsule – Cancer/AIDS • Dexanabinol – Synthetic – Capsule – Traumatic Brain Injury • Ajulemic– Synthetic – Capsule – Pain in MS • Cannabino – Synthetic – Solution – HTN/Inflammation • HU 331 – Synthetic – Solution – Antineoplastic, weight loss, neurodegenerative • RED – Not yet approved

9. Physiological and Cognitive Side Effects Dependent on many factors: • Dose • Ratio of various cannabinoids used • Route of administration • Timing • Health status of patient • Age of the patient • Co-administration of other drugs • Prior recreational use

10. Physiological and Cognitive Side Effects • Acute cognitive and psychomotor changes • Impaired and non-cohesive reasoning • Decreased concentration on tasks requiring motor skills • Appetite stimulant • Anti-emetic properties

11. Physiological and Cognitive Side Effects • 20%-100% increase in heart rate immediately after smoking • THC/CBD alter hypothalamic/pituitary function • Lowers intraocular pressure

12. Physiological and Cognitive Side Effects • Studies suggest cannabis intoxication can increase the odds ratio of motor vehicle accidents. • Meta-analysis of long term users consistent with negative neuro-cognitive testing. • Inconclusive about permanent changes in the brain.

13. Administration and Dosing of Cannabis Products • Smoking or vaporization • Liquid or oil for vaporization, oromucosal, sublingual, tube administration • Patch • Capsules for oral use • Edible products • Rectal suppositories • Ointments, creams, lotions

14. Administration and Dosing of Cannabis • Route of administration determines pharmacokinetics and effects of the cannabinoids. • Smoking or vaporizing reaches lung alveoli and bloodstream. Psychoactive effects occur in 90 seconds, max at 15-30 minutes and taper off 2-3 hours. • Water pipe removes gas toxins.

15. Administration and Dosing of Cannabis • Vaporization causes more rapid delivery, higher concentrations, less risk of byproducts inhaled. • Oral – psychoactive effects at 90 minutes, max of 2-3 hours, lasting 4-12 hours. • Drawbacks – delayed onset of action, variable gut availability, first pass metabolism, difficulty with vomiting and anorexic patients, regulating difficulty.

16. Administration and Dosing of Cannabis • Significant variation of cannabis types • Limited pharmacological data and lack of uniformity of studies in humans • Tolerance and adverse effects are variable • Personal variation in metabolism

17. Administration and Dosing of Cannabis • Physiological changes in ECS • Different physiological responses in differing medical conditions • Drug-drug interactions

18. Contraindications • Absolute • Any patient with psychotic illness • THC is associated with aggravating or precipitating psychotic episodes • THC is a vasodilator, increasing cardiac demand

19. Contraindications • Relative • Primary liver, renal and pulmonary diseases or a past history of seizures or drug abuse • Close monitoring of symptoms • Patients with COPD and asthma, avoid smoking • Special precautions in pediatric and elderly patients • Minimize drug interactions • Cannabis reinforces sedative effects of other sedative-hypnotics, benzodiazepines and alcohol

20. Summary • Recent trend in state legislatures is to pass rules and regulations to allow medicinal marijuana - trend continues. • Use in PC is evident in patients with cancer, neurodegenerative diseases, inflammatory diseases, end-of-life angst, uncontrolled seizures and HIV cachexia. • Further study is needed.