II. Indications

  1. See Cachexia in Cancer
  2. See Geriatric Failure to Thrive
  3. See Nausea in Terminally Ill Patients
  4. Synthetic Tetrahydrocannabinol (THC)
    1. Anorexia in Chronic Renal Failure
    2. Chemotherapy induced Nausea or Vomiting
    3. Cachexia in AIDS
  5. Purified Cannabidiol (CBD, Epidiolex)
    1. Lennox–Gastaut Syndrome (rare Seizure Disorder)
      1. Devinsky (2018) N Engl J Med 378(20):1888-97 [PubMed]
    2. Dravet Syndrome (rare Seizure Disorder)
      1. Devinsky (2017) N Engl J Med 376(21):2011-20 [PubMed]
  6. 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]
    2. Cancer Related Pain
      1. Reduces mean pain intensity scores, but does not reduce overall pain scores, Insomnia, or Opioid use
      2. Hauser (2023) Cochrane Database Syst Rev (6): CD014915 [PubMed]

III. Mechanism: Two product types derived from Marijuana and Hemp

  1. Although THC and CBD are the best studied extracts, Cannabis contains more than 60 active substances
  2. Synthetic Tetrahydrocannabinol (THC)
    1. THC is the most psychoactive substance in Cannabis
    2. Will generate a positive Urine Drug Screen
  3. Purified Cannabidiol (CBD)
    1. Does not cause the "high" seen with THC (does not cause Intoxication or euphoria)
    2. However non-regulated CBD products frequently contain intoxicating THC levels
    3. Typically will not generate a positive Urine Drug Screen (but may if trace THC in product)

IV. Dosing: 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
      3. Contamination with intoxicating levels of THC are not uncommon
      4. Contamination with Pesticides and Heavy Metals has also been reported
  2. Indications: Used to treat rare forms of childhood Epilepsy (age over 2 years)
    1. Dravet Syndrome
    2. Lennox-Gastaut Syndrome
    3. Tuberous Sclerosis
  3. Dosing
    1. Dosed 2.5 mg/kg orally twice daily
      1. Start at 1.25 mg/kg orally twice daily (maintenance 2.5 mg bid) in moderate hepatic dysfunction
      2. Start at 0.5 mg/kg orally twice daily (maintenance 1 mg bid) in severe hepatic dysfunction
    2. May increase in weekly increments of 2.5 mg/kg orally twice daily
    3. Maximum: 20 mg/kg/day divided twice daily (10 mg/kg orally twice daily)
      1. Decrease maximum dose to 5 mg/kg twice daily in moderate hepatic dysfunction
      2. Decrease maximum dose to 2 mg/kg twice daily in severe hepatic dysfunction
  4. Monitoring: Risk of Hepatocellular Injury (esp. in combination with Valproate, Clobazam)
    1. Obtain AST, ALT and Total Bilirubin at baseline, 1 month, 3 months and 6 months and then periodically

V. Dosing: Synthetic Tetrahydrocannabinol (THC)

  1. Nabilone (Cesamet)
    1. THC analogue used to treat intractable Nausea, Vomiting (e.g. Chemotherapy)
    2. DEA Schedule 2
    3. Dosing
      1. Start 1 mg orally twice daily
      2. May increase to 2 mg orally twice daily as needed
      3. Maximum: 6 mg/day in divided doses
  2. Dronabinol (Marinol, Syndros)
    1. THC formulation Indicated for intractable Nausea, Vomiting (e.g. Chemotherapy, AIDS-related Anorexia)
    2. DEA Schedule 3 (misuse is less likely due to formulation)
    3. Chemotherapy-Induced Nausea or Vomiting (based on BSA in all ages)
      1. Dose 5 mg/m2 orally 1 to 3 hours before Chemotherapy
      2. May repeat 5 mg/m2 dose every 2 to 4 hours as needed up to 4 to 6 doses per day
      3. Maximum: 15 mg/m2
    4. Anorexia in AIDS
      1. Start: 2.5 mg orally (or SL, PR) twice daily
      2. May increase to 5 to 10 mg orally twice daily
      3. Maximum: 20 mg/day

VI. 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)

VII. 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]

VIII. Adverse Effects: CBD

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

IX. 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

XI. References

  1. (2019) Presc Lett 26(6)
  2. (2018) Presc Lett 25(4)
  3. (2018) Presc Lett 25(9):51
  4. (2019) Med Lett Drugs Ther 61(1585): 179-82 [PubMed]

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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