Prescription Cannabinoid

See Cachexia in Cancer
See Geriatric Failure to Thrive
See Nausea in Terminally Ill Patients
Synthetic Tetrahydrocannabinol (THC)
1. Anorexia in Chronic Renal Failure
2. Chemotherapy induced Nausea or Vomiting
3. Cachexia in AIDS
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]
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]

Although THC and CBD are the best studied extracts, Cannabis contains more than 60 active substances
Synthetic Tetrahydrocannabinol (THC)
1. THC is the most psychoactive substance in Cannabis
2. Will generate a positive Urine Drug Screen
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)

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
Indications: Used to treat rare forms of childhood Epilepsy (age over 2 years)
1. Dravet Syndrome
2. Lennox-Gastaut Syndrome
3. Tuberous Sclerosis
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
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

Cannabidiol inhibits CYP2C19, CYP2C8, CYP2C9
1. Increases levels of Citalopram, Phenytoin, Amitriptyline, Valproic Acid, Warfarin
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)

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
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
References
1. (2022) Am Fam Physician 106(2): 208-9
2. Busse (2021) BMJ 374:n2040 +PMID: 34497062 [PubMed]

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

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