ECHO Discussion

June 2015

Joseph Bubalo PharmD, BCOP, BCPS

OHSU Hospital and Clinics

Marijuana Use Topics

• Medical marijuana

• Recreational marijuana

• What does it mean for medical practitioners

• Listed in U.S Pharmacopeia 1850-1941

– marijuana & hashish extracts were the 1st, 2nd, or 3rd most prescribed meds in the US from 1842-1890s

Marijuana

• Cannabis sativa – herbal plant containing >

80 different cannabinoid compounds

• Primary cannabinoids are delta-9-

tetrahydrocannibinol (THC), cannabidiol

(CBD), and cannbinol.

DeVane CL Pharmacotherapy 2013;33(10):1009-1011

Cannabinoid Receptors

• Cannabinoid -1 (CB1) – primarily located

throughout the brain and nervous system

• Cannabinoid -2 (CB2) – peripheral tissues

and immune system

• Body produces endocannabinoids ,

anandamide and 2-arachidonoylglycerol,

which natural stimulants of the CB

receptors

DeVane CL Pharmacotherapy 2013;33(10):1009-1011 Collins S Pharmacy Today 2014;Apeil:HSE6-7

This is actually how it works

Product Issues

• Purity – (herbicides, pesticides)

• Potency (THC content)

– Recent Oregonian project showed just 2 of 15

products within 10% of stated amount

• Dose per condition?

• All medical research marijuana grown on a

single plot in Mississippi –supplied via FDA

• >700 strains currently cultivated outside this

plot

– Dosing is dependent on strain and route

Collins S Pharmacy Today 2014;Apeil:HSE6-7 Crombie N Oregonian March 8, 2015 A1, A12-14

Smoking

Other methods of ingestion: include

tinctures, oils, etc.

• Tinctures, made with 90% alcohol and marijuana, crosses transdermally, or orally.

• Rapid high - won the award at the Cannabis Cup.

• Matched with peppermint, sage, or cinnamon as well.

Endless video

available on

YouTube.

Rarely discuss the

medical effects, vs the quality of the high

Butane Honey oil (BHO) is different

than “essential oils”

• Extracted using butane

– Between 75% and 99% THC.

• Designer refiners using vodka to enhance

cache’.

– “Dabs”

– “Wax”

– Smoked much more like crack or meth. Gas

fumes are inhaled.

– May be sprinkled on or combined with other

forms of deliver e.g. oral consumables

Available Routes of Administration

• Inhaled – onset 2-30 minutes with 2-3 hr.

duration (smoked or vaporized)

• Oral – 2-3 hour onset with 5-8 hr. duration

– Often in the forms of cookies, brownies, or

candy

• Topical – oils or tinctures (also used orally)

• Not the same as hemp lotions

Bioavailability • Proposed potency categories (oral) based on THC

content (2-3 mg smoked for average “high”)

– Low - < 7 mg/dose

– Medium 7-18 mg/dose

– High >18 mg/dose

– Note: THC may not be the most prevalent cannabinoid in each

strain or the desired one

• Need 3-5 x the dose orally vs. inhaled dose due to

stomach acid effects on THC and hepatic first pass

effect

• Oral bioavailability - 4-12% THC, 13-19% CBD vs.

inhaled ~35% for both

Ashton CH et al J Psychopharmacology 2005;19(3):293-300 Hall W Addiction 2014;110:19-35

Cannabinoid Metabolism

• Distribute into fatty tissues and released

slowly (tissue half-life 5-7 days)

• Hepatic metabolism

• Many different metabolites eliminated over

days to weeks via urine and feces

Drug-Drug Interactions

• THC inhibits effects of cannabidiol

• Various cannabinoids inhibit P-glycoprotein

• Additive or opposing effects with sedating

agents, antidepressants, sympathomimetics,

alpha-adrenergic agonists, and lithium.

• Inhibit and induce CYP 450 enzymes

DeVane CL Pharmacotherapy 2013;33(10):1009-1011 Collins S Pharmacy Today 2014;Apeil:HSE6-7

Ashton CH et al J Psychopharmacology 2005;19(3):293-300

Oral Product Examples

• Colorado: standard dose 10 mg THC

– Most products have multiple servings

• Recent survey or Oregon based products - rated dose (actual)

– Coma treats pizza 350 mg (52)

– Infinite Flower Cookie 197 mg (50 mg)

– Steve’s Root Beer 70 mg (62)

– Lunchbox Alchemy Squib Candy 106 mg(59)

– Happy Snaps Cookie 100 mg (58)

– BhombChellys Jelly Candy 79 mg (76)

– Cheeba Chews 77 mg (78)

– Leif Medicinals Chocolate truffle 75 mg (98)

– Sour Bhotz candy 75 mg (33)

– Drip ice cream 46 mg (70)

Crombie N Oregonian April 12, 2015 A1,A8-9 Crombie N Oregonian March 8, 2015 A1, A12-14

Medical Marijuana

• 22 states and the District of Columbia have

medical marijuana laws

• Changing trend from illegal drug the

therapeutic botanical

• As it becomes increasingly legal and

prevalent

• …. public infers safe and effective

Wilkinson ST JAMA 2014;311:2377-2378

Limited Scientific Studies • As the legal landscape evolves, the

medical one remains confusing – fewer than 20 randomized, controlled

clinical trials of smoked marijuana for all possible uses

• these involved relatively small numbers of people in all—well short of the evidence typically required for a pharmaceutical to be marketed in the U.S.

Potential Medical Effects

• Sedative

• Hypnotic

• Anxiolytic

• Antidepressant

• Antipsychotic

• Anticonvulsant

• Antimania/Bipolar

• Appetite stimulant

THC vs Cannabidiol (CBD)

Effect THC CBD

Agonist at CB1 + -

Anxiolytic +/- +

Psychotropic + -

Antipsychotic - +

Anticonvulsant - +

Antidepressant + -

Sedative/hypnotic + +

Antinociceptive + +

Neuroprotectant + +

Antiemetic + -

Appetite stimulant + No data

Cardiovascular effects + +

Ashton CH et al J Psychopharmacology 2005;19(3):293-300 THC = Delta 9 tetrahydrocannabinol

Potential Medical Benefits for

Individuals • Analgesia

• Anorexia

• Nausea

• Glaucoma

• Multiple sclerosis

• Seizures, spasticity,

• Others – HIV/AIDs

California Medical Association White Paper 2011

Cannabis Effects on Youth

• Neuropsychological decline over functional

domains

– Impaired concentration

– IQ loss

• Poorer educational outcomes

• Decreased employment/job attainment

California Medical Association White Paper 2011

Meier MH et al. PNAS early edition 2012; 1-8

Oregon Impact of Marijuana

Legalization • Medical marijuana approved 1998

• Can be used in non-public places

• Use requires authorization by an MD to get

a card allowing use

• Patient can grow enough for themselves (7

plants, 3 mature, 4 immature and 1 oz..) or

can have a designated grower

• As of 6/2014 Oregon had > 60,500 card

holders

CD Summary June 17, 2014 cd.summary@state.or.us

Oregon Impact of Marijuana

Legalization • 2005

– Increased marijuana possession to 24 oz. and grow limits to 6

mature, 18 immature plants.

– Created a grow registry

– Growers could be reimbursed for cost of supplies and utilities

but not labor

• 2012

– Dispensary system approved, reduced offenses for possession

of < 4 oz.

• 2013

– Moratorium on dispensaries to draw up rules around labeling

and packaging

Crombie N Oregonian 11/9/14 pp A2, A18, A19

Oregon Impact of Marijuana

Legalization • 2014

• Voters approve measure 91

– State will create a taxed and regulated system for retail sales

– Can be smoked in non-public places

• As of 6/1/15

– Individuals > 21 years old can possess 1 oz. in public, 8 oz. at

home, 4 plants per household

– Edibles – 1 lb. solid, 72 oz. of infused liquids, and 1 oz. of extract

• As of 1/1/16

– Liquor commission will have rules for production, processing, and

sale of marijuana

– Licensing or outlets begins 1/4/16 with expectation that stores will

open in the first half of 2016

Crombie N Oregonian 11/9/14 pp A2, A18, A19

Workplace Related Impairing Effects of Marijuana Include

• Inability to accurately gauge lengths of time and distance as well as impairment of hearing and vision and short term memory

• Inability to cope with sudden changes in surrounding and/or emergency situations

• Loss of balance

• Visual and/or auditory hallucinations

• Non-caring, uncommitted, unconcerned attitude

•Decreased cognitive

reasoning

•Decreased motor

coordination

•Inability to concentrate or

remain focused on a single

thought or idea

•Increased drowsiness,

fatigue and lethargy

How Does This Affect

Employment and Work on the Job

• Employers may mandate drug testing

• Medical professionals often required to

report “impaired” individuals

• Expect clarification of job descriptions

• What roles in a healthcare facility or

institution are not “safety sensitive”?

Summary

• Medical cannabinoids are here to stay

– Non-THC cannabinoids appear to be where medical

progress is likely

• Medical information is unclear but likely to

improve considerably in the next 5-10 years

• Current commercial products are not regulated in

a meaningful manner, production is non-

standardized, and dosage unknown

• Children appear to be at he most significant risk

for harm, currently 10% of Oregonian 8th graders

and 20% of 11th graders report current use

CD Summary June 17, 2014 cd.summary@state.or.us