III. Indications: Purified Cannabidiol (CBD, Epidiolex)

IV. Indications: Combined THC and CBD

  1. Chronic Neuropathic pain
    1. Oral Mucosal spray and oral agents may offer small pain relief (NNT 10)
    2. May also demonstrate small improvement in sleep quality and physical functioning
    3. High THC to CBD ratios offer greatest relief, but also are with the greatest adverse effects
    4. Busse (2021) BMJ 374: n2040 [PubMed]
    5. Seehusen (2022) Am Fam Physician 106(2): 202-4 [PubMed]

V. Mechanism: Two product types derived from Marijuana and hemp

  1. Synthetic Tetrahydrocannabinol (THC)
    1. Will generate a positive Urine Drug Screen
  2. Purified Cannabidiol (CBD)
    1. Does not cause the "high" seen with THC
    2. Typically will not generate a positive Urine Drug Screen (but may if trace THC in product)

VI. Preparations: Cannabidiol (CBD)

  1. Preparations
    1. Cannabidiol (Epidiolex) oral solution
      1. FDA approved in U.S. as of 2018, with a cost of $32,000/year
      2. DEA Schedule 5
    2. OTC products (various forms)
      1. Legal status depends on U.S. State
      2. Not regulated or studied for efficacy and safety
  2. Indications: Used to treat rare forms of childhood Epilepsy
    1. Dravet Syndrome
    2. Lennox-Gastaut Syndrome
    3. Tuberous Sclerosis
  3. Dosing
    1. Dosed 2.5 mg/kg twice daily (max: 20 mg/kg/day)

VII. Preparations: Synthetic Tetrahydrocannabinol (THC)

  1. Nabilone (Cesamet)
    1. THC analogue used to treat intractable Nausea, Vomiting (e.g. Chemotherapy)
    2. Dosed 1 mg orally twice daily (max: 6 mg/day in divided doses)
    3. DEA Schedule 2
  2. Dronabinol (Marinol)
    1. THC formulation Indicated for intractable Nausea, Vomiting (e.g. Chemotherapy, AIDS-related Anorexia)
    2. Dosed 2.5 mg orally (or SL, PR) twice daily, increased to 5-10 mg orally twice daily (max: 20 mg/day)
    3. DEA Schedule 3 (misuse is less likely due to formulation)

VIII. Drug Interactions: Cannabidiol (CBD)

  1. Cannabidiol inhibits CYP2C19, CYP2C8, CYP2C9
    1. Increases levels of Citalopram, Phenytoin, Amitriptyline, Valproic Acid, Warfarin
  2. Cannabidiol levels may be lowered
    1. Strong CYP3A4 Inducers lower CBD levels (e.g. St. John's Wort, Carbamazepine, Phenytoin, Rifampin)
    2. Strong CYP3A4 inhibitors raise CBD levels (e.g. Clarithromycin)

IX. Protocol: Chronic Neuropathic Pain

  1. Start with Cannabidiol (CBD) spray, tablet or sublingual oil drops
    1. Initial: 5 mg orally twice daily
    2. Next: Increase total daily dose by 10 mg up to every 2 to 3 days to a maximum of 40 mg/day
  2. Add Tetrahydrocannabinol (THC)
    1. Initial: 1 to 2.5 mg/day
    2. Next: Increase by 1 to 2.5 mg/day every 2 to 7 days to a maximum of 40 mg/day
  3. References
    1. (2022) Am Fam Physician 106(2): 208-9
    2. Busse (2021) BMJ 374:n2040 +PMID: 34497062 [PubMed]

X. Adverse Effects: CBD

  1. Drowsiness or sedation (esp. in combination with other CNS Depressants)
  2. Diarrhea
  3. Liver Function Test abnormalities

XI. Safety

  1. Avoid THC and CBD in pregnancy, Lactation and those taking multiple medications
  2. Check CBD product for a certificate of analysis that reports CBD levels, THC levels and contaminants

XII. Resources

  1. Simplified Guideline for prescribing Medical Cannabinoids in Primary Care
    1. http://www.cfp.ca/content/cfp/64/2/111.full.pdf
    2. Allan (2018) Can Fam Physician 64(2): 111-20 [PubMed]

XIII. References

  1. (2019) Presc Lett 26(6)
  2. (2018) Presc Lett 25(4)
  3. (2018) Presc Lett 25(9):51

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Cost: Medications

dronabinol (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
DRONABINOL 10 MG CAPSULE Generic $3.22 each
DRONABINOL 2.5 MG CAPSULE Generic $1.20 each
DRONABINOL 5 MG CAPSULE Generic $2.45 each