1. 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

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.
– 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 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.