Download Marijuana as Medicine: Current Understanding and Trends

MARIJUANA AS MEDICINE:
CURRENT UNDERSTANDING
AND TRENDS
Penelope P. Ziegler, M.D.
Medical Director
Professionals Resource
Network (PRN)
Primary Psychoactive IngredientTetrahydrocannabinol
THC Mimics Neurotransmitter Anandamide
in the Brain’s Endocannabinoid System
Cannabis Is a Plant
• 484 known biological compounds
• Flowers, seeds, leaves and stems are consumed
• Smoking
• Vaporization
• Concentrated oils
• Infused “teas”
• Edibles, plant usually cooked into foods
• At least 84 brain-active cannabinoids
• THC
• Cannabidiol (CBD)
• Cannabinol (CBN)
• Many others with unclear or unknown effects
Marijuana Has Been Used As Medicine
Throughout History
• Ancient History
• Used in Chinese medicine dating back 10,000 years; still a basic herbal
in Traditional Chinese Medicine
• Ancient Egypt- hemorrhoids and other inflammatory conditions
• India- used for insomnia, pain, digestive problems
• Ancient Greece- extensive veterinary uses, also in humans (nosebleeds,
tapeworms, etc.)
• Middle East- used as antiemetic, diuretic, antiepileptic, anti-inflammatory
• Western Medicine
• Europe- used for muscle spasms, stomach cramps
• America- widespread use in “patent medicines”
• Modern times- Advocates Support Use for Many Conditions
• Insomnia
• Pain
• Nausea and vomiting
• Decreased appetite with weight loss
• Muscle spasms
• Epilepsy
• Glaucoma
What Is the Evidence for Cannabis as
a Medication?
• Nausea and vomiting in cancer chemotherapy (CINV)
• 2010 Cochran review- “probably effective” in children but with high
incidence of side effects; inadequate evidence for effectiveness in adults
• European meta-analysis of synthetic cannabinoids showed superior antiemetic effects but higher side effects
• Additional concern- cannabis induced hyperemesis
• Glaucoma- probably not effective in reasonable doses
• Wasting syndrome in AIDS- inadequate evidence, studies flawed
• Muscle spasms, spasticity- variable results with MS, small studies
• Insomnia- small study showed improvement in sleep patterns in
fibromyalgia patients
• Pain- reviews show some benefits but studies are hard to compare
Recent Review of Medical Marijuana
in Neurological Disorders
Koppel BS, Brust JCM, Fife T et al. 2014 Neurology. 82:1556-1563
• Spasticity
•
Oral cannabis extract (OCE) effective, nabiximols and THC probably effective for reducing
patient-centered measures
• OCE and THC possibly effective for both patient-centered and objective measures at 1 year
• Central pain, painful spasms
•
•
OCE effective
THC and nabiximols probably effective
• Urinary dysfunction
•
•
Nabiximols probably effective for reducing voids/day
THC and OCE probably ineffective for reducing all bladder complaints
• Tremor
•
•
THC and OCE probably ineffective
Nabiximols possibly ineffective
• Other conditions
•
•
Unknown efficacy in Huntington’s disease, Tourette syndrome, cervical dystonia, epilepsy
Probably ineffective in Parkinson disease
• High incidence of serious adverse reactions (almost 1%) and side effects
What Are Risks, Adverse Effects
• Side effects
• Addiction
• Impaired motor skills
• Cognitive impairment
• Motivational impairment
• Risks associated with method of consumption
• Special risks for adolescents
• Impact on brain development
• Psychotic syndromes
• Cyclic vomiting syndrome
FDA- Approved Cannabinoids Are Already
Available in U.S.
• Dronabinol (Marinol®)- Schedule III, approved for
CINV, wasting syndrome in AIDS
• Nabilone (Cesamet®)- Schedule II, approved for
CINV
• Nabiximols (Sativex®)- oral mucosal spray, not
approved in U.S., used in Canada and Europe.
Currently in Phase III trials in US for MS, cancer
pain, CINV
What Is “Charlotte’s Web”
• “Charlotte’s Web” or “Realm Oil” is extracted from a strain of
marijuana bred by crossing Cannabis sativa (marijuana) and
Cannabis indica (hemp) that has low levels of THC and high levels of
CBD (cannabidiol)
• Developed by the Stanley brothers, major marijuana growers in Colorado
• Named after Charlotte Figi, a seven year old diagnosed with Dravet Syndrome
or SMEI, who had intractable seizures until tried on Realm Oil
• This strain of cannabis is not associated with a “high” because of its
low THC level and, if imported, would be classified as hemp.
• Originally called “Hippie’s Disappointment”
• The Stanleys plan to move their Realm Oil operations to Uruguay and import
the oil to the U.S. as hemp oil
• Hemp oil is legal in all 50 states but most lacks the high levels of CBD
Recent References
• Degenhardt L, Lintzeris N, Campbell G, et al. Experience of adjunctive cannabis
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use for chronic non-cancer pain: Findings from the Pain and Opioids IN Treatment
(POINT) study. Drug Alcohol Depend. 2015;147:144-150.
Koppel BS, Brust JC, Fife T, et al. Systematic review: efficacy and safety of
medical marijuana in selected neurologic disorders: report of the Guideline
Development Subcommittee of the American Academy of Neurology Neurology.
2014;82:1556-1563.
Kahan M, Srivastava A, Spithoff S, Bromley L. Prescribing smoked cannabis for
chronic noncancer pain: Preliminary recommendations. Can Fam Physician.
2014;60:1083-1090.
Borgelt LM1, Franson KL, Nussbaum AM, Wang GS. The pharmacologic and
clinical effects of medical cannabis. Pharmacotherapy. 2013;33:195-209.
Cooper ZD, Comer SD, Haney M. Comparison of the analgesic effects of
dronabinol and smoked marijuana in daily marijuana smokers.
Neuropsychopharmacology 2013 38:1984-92.
Bostwick M. Blurred boundaries: the therapeutics and politics of medical
marijuana. Mayo Clin Proc. February 2012 87(2):172-186.
Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, et al.
Cannabinoids for medical use: A systematic review and meta-analysis. JAMA
2015 313(24): 2456-2473.