National Hospice and Palliative Care Organizations Palliative Care

National � Hospice and Palliative Care Organization’s Palliative Care Resource Series Cannabis Use in Palliative Care: History, Legality and Implications for Practice Written by: Peter A. Radice, MD, FACP, FAAHPM

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

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

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.

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.

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)

Endocannabinoid System • Endogenous agents • CB 1 -present throughout CNS – – – Hippocampus Cortex Olfactory areas Basal ganglia Cerebellum Spinal cord • CB 2 – located peripherally, linked with autoimmune system – Spleen – Macrophages

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

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

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

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

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.

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

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.

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.

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

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

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

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

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.