Medical Marijuana
Kate Juba, PharmD
Angela Nagel, PharmD
Jennifer Mathews, PhD
Learning Objectives:
- Differentiate between endogenous and exogenous cannabinoids
- Identify the locations of CB1 and CB2 receptors and the primary functions they affect
- Describe the pharmacology of the endogenous cannabinoid system
Definitions
- Cannabis
- Substances derived from the Cannabis sativa plant
- Cannabinoid
- Chemical compounds that act as agonists for cannabinoid receptors
- Phytocannabinoid
- Compounds found in cannabis extracts
- Endocannabinoid
- Endogenously existing neuromodulators
Endogenous Cannabinoid System
- Widespread localization throughout the body
- Regulates:
- appetite, inflammation, pain, thermoregulations, sensation, metabolism, sleep, stress responses, mood, energy, and memory
Cannabinoid Receptors and Localization
CB1 Receptors: Neuromodulation
- Prefrontal cortext
- Hippocampus
- Amygdala
- Substantia nigra
- Basal ganglia
- Cerebellum
- Hypothalamus
- Mesolimbic dopamine pathways
- Periacqueductal gray
CB2 Receptors: Immunomodulation
- B cells
- Macrophages
- Natural killer cells
- *control for migration and cytokine release
Effects of CB1 Receptor Agonists
- Central Effects
- Impairment of short-term memory and simple learning tasks
- Impairment of motor coordination
- Altered sensory and time perception
- Lethargy, sedation and slowed reaction time
- Catalepsy
- Analgesia
- Antiemetic effect
- Increased appetite
- Peripheral Effects
- Tachycardia
- Vasodilation
- Decrease in intraocular pressure
- Bronchodilation
Tetrahydrocannabinol (THC)
- Activates both CB1 and CB2 receptors
- Most widely used psychoactive agent
- Exerts euphoric effects, altered thinking patterns, altered memory, analgesia, appetite stimulation
- Tolerance!
Cannabidiol (CBD)
- Low binding affinity to CB1 and CB2 receptors
- Does not elicit any psychoactive effects
- Non-psychotropic antioxidant and neuroprotectant
- Decreases the psychotropic activity of THC
- Thought to be beneficial in alleviating pain, inflammation, anxiety, psychosis, muscle spasms, and seizures
Potential Physiologic Responses to Cannabinoids
- Improves sleep
- Anti-seizure effects and neuroprotection
- Reduces anxiety and psychotic symptoms/PTSD
- Prevents nausea and stimulates appetite
- Reduces intraocular pressure
- Bronchodilator
- Relaxes muscles and reduces muscle spasms
- Relieves pain (especially neuropathic)
- Anti-inflammatory, anti-proliferative, anti-viral
Pharmacokinetics and Pharmacodynamics
- IV and inhaled forms have fastest onset of action and highest bioavailability
- Vaporization bypasses the negative effects associated with smoking
- Dosing and titration is highly formulation- and patient-specific
- Potential drug interactions
- THC: substrate of CYP2C9, CYP3A4
- CBD: substrate of CYP2C19, substrate and inhibitor of CYP3A4
- Additive effects with ethanol, barbiturates, benzodiazepines, antihistamines, opioids, anticholinergics and sympathomimetics
Cannabis Use In Patients With Sickle Cell Disease
- Retrospective chart review of 72 adults with sickle cell disease (SCD) at the Jefferson University Hospitals Sickle Cell Program
- Received 270 urine drug tests (UDT) between 1994-2009
- Objectives
- Report demographics and clinical features of patients with SCD with a positive UDT for cannabis
- Compare frequency of vaso-occlusive crises (VOCs) requiring emergency department (ED) and hospital admissions in patients with a positive UDT for cannabis versus whose with a negative UDT
- Statistical analysis
- Paired t-test, chi-square, Fisher’s exact tests
- Key Finding
- Increased frequency of vaso-occlusive crises requiring hospitalization in patients with a positive UDT for cannabis versus whose with a negative UDT
- Limitations
- Retrospective study
- Small sample size
- Recommendations
- Cannabis is not recommended for patients with sickle cell disease
- Additional prospective studies are needed
Reference
Cannabis and Cannabinoid Research 2017;2.1:197-201.
