Learn More About: Medical Marijuana

Medical Marijuana

Kate Juba, PharmD
Angela Nagel, PharmD
Jennifer Mathews, PhD

Learning Objectives:

  1. Differentiate between endogenous and exogenous cannabinoids
  2. Identify the locations of CB1 and CB2 receptors and the primary functions they affect
  3. Describe the pharmacology of the endogenous cannabinoid system


  • 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


Cannabis and Cannabinoid Research 2017;2.1:197-201.

University of Rochester logo
University of Rochester