22
doc • Summer 2015
Kentucky
Medical Marijuana Debate
PROS
By Lowell Quenemoen
M.D., Neurology(ret)
Growing up in the “Age of
Aquarius”, the culture of
sandals, beads and “grass”,
many Americans have
continued their interest in “weed” as a recreational product and more recently as a
medicinal product. A Gallop poll in 2013
reveals that 38% of Americans have tried
marijuana at some point in their
lives and 7% continue to do so. The highest
use is in the 56- 65yo group at 32% of the
‐
total users and the second highest is in the
under 25yo group at 25%.
Increasingly there has been pressure to legalize recreational marijuana (currently legal in
Colorado, Washington, Oregon and Alaska
as well as the District of Columbia but commercial sales are banned there.) Medical
marijuana is legalized in 20 states and Guam.
The US federal government continues to list
it as a Schedule 1 substance and is therefore
outlawed. In Kentucky, a non legalized state,
the possession and/or sale of less than 8 oz
is a misdemeanor as is the cultivation of less
than 5 plants but more than that is a class
D felony. Medical marijuana is licensed in
Israel, Canada and the Netherlands.
The use of marijuana for medical purposes
has largely been anecdotal since it was
made illegal in 1970 with the passage of the
Controlled Substances Act and research has
been restricted. Negative side effects including addiction potential, impact on neurocognitive performance, mood disorders,
psychosis, cardiovascular, pulmonary and
the potential for accidental overdose have
continued to temper trials and acceptance.
The medicinal use of cannabis dates back
to 2700 BC in China and it was used as an
analgesic in the West in the late 1800s. Of
note, it was sold as an OTC until 1937 when
the Marijuana Tax Act was enacted.
Cannabis includes two species, C. sativa
which is psychotropic and stimulating and
C .indica, the more sedating. Although more
than 100 compounds are found in cannabis
the two most studied are THC (Delta- 9-
‐ ‐
tetrahydrocannabinol) which is psychoactive and CBD (Cannabidiol) which is not.
In recreational use, product with higher
THC levels have been promoted with an
average concentration in 1996 0f 2.2% and
in 2008 was 9.9%. CBD has been selectively
reduced from .24% down to .08%. Efforts
have been made to synthesize cannabis
derivatives and two are currently available in
the US, Dronabinal (Marinol), a synthetic
THC, and Nabilone (Cesamet). In the
UK Nambiximols (Sativa) is available and
contains a THC:CBD ratio of 1:1. Recently
Epidolex, a 98% CBD compound has been
developed in the UK. Pharmacologically,
cannabinoids work through the endocannabinoid system which is spread through the
brain and the spinal cord. CB- 1 receptors
‐
are located in central terminals (hippocampus, basal ganglia and cortex) and peripheral
nerves and CB- 2 receptors in immune
‐
cells and lymph tissue. The CB- ! receptors
‐
inhibit neurotransmitter release while the
CB- 2 receptors influence cytokine release
‐
and cell migration.
In 2014 Koppel et al reviewed multiple
articles (1948- 2013) looking at the use of
‐
cannabis in multiple neurologic diseases
ie.MS, movement disorders and epilepsy.
Thirty four studies were looked
at and the effectiveness of oral cannabis
extract(OCE), Nambiximol and THC
evaluated.
In MS, spasticity and central pain were effectively treated with OCE with the other two
compounds being probably effective.
Bladder dysfunction had a positive benefit
with Nambiximol. but no benefit with the
others. No clear benefit was seen in L- Dopa
‐
induced dyskinesias, Touretts tics,
cervical dystonia or epilepsy.
In 2015 Knezevich et al did a meta- analysis
‐
of 7 published articles using cannabis in the
treatment of refractory epilepsy. The controlled trials were randomized but small,
averaging 9 patients. Standard doses of 200
mg of CBD were used in aerosol. Statistical
benefit was not demonstrated. More recent
studies published by Devinsky et al report
success using Epidolex with reduction of
more than 60% refractory seizures in Dravet
and Lennox- Gastaut syndromes.
‐
Application of cannabis to headache was
studied by Napchan et al in the journal
Headache in 2011. They reviewed the
pathophysiology of migraine and cluster
headache and speculated on a deficiency
in the endocannabinoid system since
anadamide, an endogenous CB receptor
active compound was present in reduced
levels in the CSF. This in turn activated
the trigemino- vascular nucleus triggering
‐
headache. A number of case reports and
anecdotal studies have claimed success with
cannabis for the refractory headache.
Cannabinoids have been used to treat glaucoma since it has been shown to reduce
intraocular pressure. The benefit of one
cigarette lasts about 4 hours and therefore
requires multiple doses leading to cognitive
changes. In addition arterial hypotension
may be induced putting the optic nerve at
risk.
Cannabinoid’s effects on the CB- 2 recep‐
tors are thought to have an anti- inflam‐
matory effect leading to trials in ulcerative
colitis and other inflammatory GI disease.
Positive results have been claimed for fibromyalgia but no benefits in rheumatological
diseases proven.
Recent studies suggest relief of chronic neuropathic pain and, for patients on chronic
opiates, the possibility of reducing doses
with the addition of cannabis. The AMA has
supported the use of cannabinoids in spasticity reduction in MS, in appetite stimulation, in reduction of nausea and vomiting
and for pain relief.
In psychiatry, a recent Cochran review suggests that CBD has some antipsychotic value
and may be helpful in chronic anxiety states
and possibly PTSD.
All things considered, the future role of
medical marijuana depends on more Class
1 studies using rigorous methodology
with adequate numbers of study patients.
Cannabinoids will need to be more refined
to facilitate standardized dosing and placebo
effects related to psychotropic elements
minimized. Physician willingness to prescribe is only going to follow if clear benefit
is shown and the agents are no longer outlawed at the federal as well as the state level.
A recent case in Colorado, a marijuana legal
state, involving a quadriplegic Dish employee using medical marijuana for sev \