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An Overview of Medical Marijuana: Promises and Pitfalls

Currently employed as an ANP at Solstice Family Care

No conflicts of

interest to declare.

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Review the historical use of marijuana

Discuss the legal status of medical marijuana in the U.S. and Alaska

Briefly review the pharmacodynamics of marijuana (THC and CBDs)

Discuss current investigational uses

Discuss potential adverse reactions of medical marijuana use/potential negative impact of longterm, chronic use.

Discuss potential problems with legalization of medical marijuana.

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Marijuana: complex and controversial plant with many uses. Industrial Social Medical

Research: Relatively limited

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Earliest medical use: China, 2350 BC.

Introduced to Western Medicine by W. B. O’Shaughnessy, 19th century.

By 1850, marijuana was incorporated into the U.S. Pharmacopoeia.

History: Social/Ritual Use

Evolved in conjunction

with medical use.

First appeared in

Indian religious texts in

2000 BC and still plays

an important role

today.

Social use in Arab

countries around 1000

BC.

Brought to the West by

Marco Polo and

Napoleon.

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Earliest use: hemp used in Taiwanese pottery dated to approximately 10,000 years ago.

Used as a fiber source from ancient Greece to colonial America.

Historically used in foods as far back as the Roman empire.

Today, burgeoning nutraceutical and industrial use.

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Despite the hashish clubs of 19th century Europe, recreational use was not widespread until the cultural revolution of the 1960s.

Red: industrial use Yellow: social use Green: medical use

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First regulated with the passage of the Pure Food and Drug Act of 1906.

First taxation: the Marihuana Tax Act of 1937.

1942: Formally removed from the U. S. Pharmacopoeia.

The Boggs Act of 1951 introduced mandatory sentencing for drug crimes.

The Comprehensive Drug Abuse and Control Act of 1970: marijuana was designated as a schedule I drug.

FDA: no medical value.

Class I drug.

Illegal on a federal level despite changes in individual state laws.

Lorber (2005); US Food and Drug Administration (2006).

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A recent review of NORML (the National Organization for the Reform of Marijuana Laws) shows:

23 states and the District of Columbia have medical use provisions.

16 states have decriminalized marijuana use.

Only two states have legalized recreational and medical use: Colorado and Washington.

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Schedule I: No accepted medical/legal use.

Schedule II: Require written RX. No refills.

Schedule III: New RX after 6 months or 5

refills.

Schedule IV: Same as III except penalties.

Schedule V: Routine RX drugs. May not

require RX.

Wynne, Woo, & Olyaei (2007).

Privileged Medical Use of Marijuana: Affirmative defense

Documented in the medical record

Includes many medical conditions

Allows for expanded definition

Privileged Medical Use of Marijuana A.S. 17.37.0303 (1999).

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Legal Status: Alaska

2014 Ballot Initiative

proposes legalize, tax and

regulate marijuana in the

same manner as alcohol.

A Yes vote is a vote for

legalization.

www.regulatemarijuanaina

laska.org

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Legal Status:

• Conflicted.

• Federal law trumps state law.

• A States rights issue?

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Pharmacology:

21 Carbon molecules

30 Hydrogen molecules

2 Oxygen molecules 20

Two types of cannabinoid receptors in the human body:

CB1: activity at these sites produce the effects most commonly associated with marijuana (the “high”).

Brain, spinal cord, peripheral nervous system

CB2: activity at these receptors does not produce psychotropic effects.

Immune system: leukocytes, spleen and tonsils.

Primary focus of investigational use: analgesic, anti-inflammatory, anti-neoplastic.

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Cannabis

C. sativa

C. indica

65 total cannabinoids

10 subtypes

cannabigerol/CBG

cannabichrome/CBC

cannabidiol/CBD

Delta-THC/THC

cannabinol/CBN 22

Cannabinoid content varies between strains of plants.

One plant typically contains only 3-4 of the clinically significant cannabinoids in relevant concentrations.

THC content: 2-30% concentration depending on the strain.

Effects of THC are modulated by the presence of other cannabinoids (specifically cannibidiol, a.k.a. CBD).

CNN documentary entitled “Weed” hosted by medical correspondent Dr. Sanjay Gupta

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THC

neuroprotective

immune modulator

anti-emetic

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Cannabidiol/CBD

mediates the effects of THC

does so by inhibiting metabolism of THC via inactivation of the CP450 system

inhibits uptake of anandamide (endogenous cannabinoid)—therefore increases the concentration of available anadamide in circulation

endogenous cannabinoids appear to act as neurotransmitters and modulators of other neurotransmitters

may have implications in appetite, pain relief, perceptions of pleasure

area of investigational use 25 26

The cannabinoids vary; each has varying affinities for the two different receptors.

Example: THC has equal affinity for both CB1 and CB2 but has greater activity at CB1, hence the psychotropic effects.

Toxicity:

Rat studies: lethal dose was 800-1900 mg/kg.

Dogs and monkeys: no lethality at maximum doses.

No documented cases of toxicity in humans.

As an example, Mayo Clinic (2014) shows common analgesic dosing for THC, dronabinol (Marinol) and cannibidiol as 2.5 to 20 mg per day.

Noteably, dronabinol—an isomer of THC—is 6 to 100 times more potent than THC.

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According to Grotenhermen (2004), the adverse effects of medical marijuana use are considered to be consistent with the range tolerated in other medication.

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Hepatically and renal excreted (> renal).

Documentation of one case of renal infarct with heavy marijuana use.

Likely due to:

THC mediated vasodilatation

pre-existing anemia

adrenergic effects of cannabis (Crowe, Howse, Bell, & Henry, 2000).

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Tolerance

appears to be caused by decreased impact on the cannabinoid receptors

down-regulation of receptors

decreased sensitivity of receptors

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Withdrawal:

associated with abrupt cessation after chronic use of high doses

overall, mild

s/s include:

anxiety

irritability

insomnia

hot flashes

sweating

rhinorrhea

loose stools

hiccups

anorexia

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Reportedly low risk of psychologic or physiologic dependence

especially as compared to ETOH, opiates, benzodiazepines, and tobacco

Studies of Marinol (dronabinol) show no evidence of abuse.

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Drug-Drug Interactions:

Highly protein bound

Cytochrome P450 interactions:

antiretrovirals

cessation of cannabis after chronic user may induce the CP450 system and increase antipscyhotics (clozapine and olanzapine)

interaction of greatest clinical signficance: increased sedation in conjunction with ETOH and benzodiazepines

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Cardiac effects (hypotension, adrenergic effects, increased cardiac demand)

potential interactions with medications that impact the cardiovascular system

amphetamines

beta-blockers

diuretics

adrenaline

tricyclic antidepressants

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Strongly related to the additive effects of cannabis.

Emphasis on cannabinoids that are devoid of psychotropic effects and those that modulate our endogenous cannabinoids

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Grotenhermen (2004) discusses the hierarchy of evidence supporting specific clinical uses.

“Established”

“Relatively Well-Confirmed”

“Less Confirmed”

“Basic Research Stage”

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Treatment of refractory nausea and vomiting

Appetite stimulant

Cancer

AIDs

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Treatment of spasticity in neurologic injury or disease

ALS, MS, spinal cord injury

added benefit from “dry mouth”

Treatment of chronic pain

especially neuropathic pain

Treatment of movement disorders

Tourette’s, dystonia, levodopa-induced dyskinesia

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Allergies

Reduction of inflammation

Depression

Bipolar disorder (risk v. benefit in psychiatric disorders)

ETOH and opiate dependency (? use in patients with pre-existing drug and alcohol addictions)

Withdrawl symptoms

Disturbed behavior in dementia patients

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Neuroprotection

hypoxemic and ischemic events such as TBI or CVA

Autoimmune Disorders

MS, for example.

overall improvement in neurologic deterioration

decreased microglia activation and decreased infiltration of CD4 T-cells in spinal cord

Downregulation of hypersensitivity reactions

inhibition of pro-inflammatory mediators such as TNF-alpha, interleukin 1-Beta, and interleukin-6

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Allergies

attenuates increase of interleukins

Anti-neoplastic potential

rat study looking at longterm carcinogenic potential of THC

daily dose of THC=better longterm survival rates

decreased reproductive, pituitary and pancreatic cancers

CBDs induce cell proliferation, growth arrest, and apoptosis (dose dependent)

shown to inhibit angiogenesis in glioblastomas

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CVD

rat study

daily treatment with CB1 antagonists after an MI: reduced heart failure, endothelial disruption, and hypotension

maybe negated by overall elevation in LV end-diastolic pressures

PTSD

positive effect of otherwise pathologic feature

disruption of short-term memories

longterm extinction of aversive memories

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Psychiatric

anxiety

paranoia

psychosis, worsening of schizophrenia

Cognition and performance

memory disturbance

fragmented thinking

ataxia

decreased coordination

weakness

Thermal regulation

lowered body temperature

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CV

tachycardia

increased output

increased oxygen demand

hypotension

hypertension

inhibits platelet activity

Vision

conjunctival injection

dry eye

Respiratory

hyposalivation 45

GI

delayed gastric emptying

reduced frequency of BM

Endocrine

global impact on hormone production: reproductive, thyroid, glucose metabolism

reduced sperm count and motility

menstrual irregularities

suppression of ovulation

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Immune system

impairment of cell-mediated and humoral immunity

Genetics

inhibition of DNA, RNA and protein synthesis

Pregnancy/Fetal development

fetal malformation

IUGD

impaired cerebral development

cognitive impairment

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How do we regulate production and sales?

Banking

New Mexico model

Is there in increase in adolescent use when marijuana is legalized?

Overall increase in non-medical use

Decrease in adolescent use from 1996-2008; increase in adolescent use from 2008-2010.

Lynne-Landsman, Livingston and Wagenaar (2013): statistically no significant increase in the first few years after enactment. Longterm information still needed.

What are the longterm health consequences of chronic marijuana use?

Earleywine’s 2009 study about vaporizing marjuana.

Other forms: edibles, Sativex/SL, transdermal/topical.

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Safety

DUI

Work safety

Safe prescribing

Federal law versus state law

Even when legalized at the state level, it continues to be illegal federally.

Quandry for prescribers.

Lack of research.

Variance among plant strains.

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I always tell family, friends, colleagues and patients that marijuana is NOT a panacea.

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“. . . Some things are neither good nor evil. The common human desire to split the world into two categories is understandable. Decisions are easier when everything is black and white. Yet the world remains in frustrating but glorious color. Forcing everything into two categories can be a depressing and futile task. Every year fire warms some people and kills others. Water quenches thirst but also drowns. Aspirin relieves pain or causes overdose. Labeling these as good or evil requires many caveats and may be a pointless task. Perhaps marijuana is the same. . . .”

Earleywine, 2002, p. xii.

Questions and Answers

We made it!

Any questions?

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