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

Images: Related links to external sites (from Bing)

Related Studies

Cost: Medications

dronabinol (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
DRONABINOL 10 MG CAPSULE Generic $7.86 each
DRONABINOL 2.5 MG CAPSULE Generic $2.86 each
DRONABINOL 5 MG CAPSULE Generic $4.85 each

Ontology: Tetrahydrocannabinol (C0039663)

Definition (CHV) an organic chemical extracted from Marihuana
Definition (CHV) an organic chemical extracted from Marihuana
Definition (CHV) an organic chemical extracted from Marihuana
Definition (CHV) an organic chemical extracted from Marihuana
Definition (CHV) an organic chemical extracted from Marihuana
Definition (MSH) A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound.
Definition (NCI_NCI-GLOSS) A synthetic pill form of delta-9-tetrahydrocannabinol (THC), an active ingredient in marijuana that is used to treat nausea and vomiting associated with cancer chemotherapy.
Definition (NCI) A synthetic form of delta-9-tetrahydrocannabinol, a psychoactive substance found in Cannabis sativa. Dronabinol acts directly on the appetite and vomiting control centers in the brain to stimulate appetite and prevent emesis. (NCI04)
Definition (PDQ) A synthetic form of delta-9-tetrahydrocannabinol, a psychoactive substance found in Cannabis sativa. Dronabinol acts directly on the appetite and vomiting control centers in the brain to stimulate appetite and prevent emesis. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39707&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39707&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C867" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D013759
SnomedCT 386846008, 72024007, 108415005, 96225007
LNC LP16059-5, MTHU003348
English delta(1)-Tetrahydrocannabinol, delta(1)-THC, delta(9)-Tetrahydrocannabinol, delta(9)-THC, THC, 6H-Dibenzo(b,d)pyran-1-ol, 6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-, (6aR-trans)-, 9 ene Tetrahydrocannabinol, 9-ene-Tetrahydrocannabinol, Delta 9-Tetrahydrocannabinol, Tetrahydrocannabinol, Synthetic delta-9-Tetrahydrocannabinol, delta-9-tetrahydrocannabinol, DELTA THC 09, dronabinol (medication), DRONABINOL, tetrahydrocannabinol (THC), Dronabinol, dronabinol, Dronabinol [Chemical/Ingredient], (-)-.DELTA.9-Tetrahydrocannabinol, tetrahydrocannabinol, delta-9-Tetrahydrocannabinol, Dronabinol (product), Dronabinol (substance), Tetrahydrocannabinol (substance), delta-9-Tetrahydrocannabinol (substance), delta 9-tetrahydrocannabinol
Swedish Tetrahydrocannabinol
Spanish delta-9-tetrahidrocannabinol (sustancia), delta-9-tetrahidrocanabinol sintético, delta-9-tetrahidrocanabinol, delta-9-tetrahidrocannabinol, delta-9-tetrahidrocanabinol (sustancia), Dronabinol, Tetrahidrocannabinol, Not Translated[Dronabinol], dronabinol (producto), dronabinol (sustancia), dronabinol, tetrahidrocanabinol (sustancia), tetrahidrocanabinol, THC, delta(9)-THC
Czech tetrahydrokanabinol
Finnish Tetrahydrokannabinoli
Italian THC, Delta(1)-THC, Delta(1)-tetraidrocannabinolo, Delta(9)-THC, Delta(9)-tetraidrocannabinolo, 9-ene-tetraidrocannabinolo, Dronabinolo, Tetraidrocannabinolo
Russian TETRAGIDROKANNABINOL, DRONABINOL, ТЕТРАГИДРОКАННАБИНОЛ, ДРОНАБИНОЛ, DELTA (9)-THC, THC
Japanese テトラヒドロカンナビノール, デルタ9THC, ドロナビノール, Δ1-3,4-trans-テトラヒドロカンナビノール
German DELTA THC 09, Delta(9)-THC, Dronabinol, THC, Tetrahydrocannabinol
Polish Tetrahydrokannabinol
French D9-THC, THC (TétraHydroCannabinol), Dronabinol, Tétrahydrocannabinol
Portuguese Not Translated[Dronabinol], Tetra-Hidrocanabinol, Dronabinol, THC, delta (9)-THC

Ontology: nabilone (C0068333)

Definition (NCI) A synthetic cannabinoid and dibenzopyrane derivative with anti-emetic activity. Although the mechanism of action has not been fully elucidated yet, it has been suggested that nabilone is a highly selective and strong agonist for the cannabinoid receptors CB1 and CB2, both of which are coupled to Gi/o proteins. The CB1 receptors are expressed predominantly in central and peripheral neurons and receptor stimulation has been implicated in the reduction of chemotherapy-induced nausea.
Definition (PDQ) A synthetic cannabinoid and dibenzopyrane derivative with anti-emetic activity. Although the mechanism of action has not been fully elucidated yet, it has been suggested that nabilone is a highly selective and strong agonist for the cannabinoid receptors CB1 and CB2, both of which are coupled to Gi/o proteins. The CB1 receptors are expressed predominantly in central and peripheral neurons and receptor stimulation has been implicated in the reduction of chemotherapy-induced nausea. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39760&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39760&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1171" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C011941
SnomedCT 322124005, 395806009
English 3-(1,1-dimethylheptyl)-6,6a,7,8,10,10a- hexahydro-1-hydroxy-6,6-dimethyl-9H-dibenzo(b,d)pyran-9-one, nabilone, NABILONE, nabilone [Chemical/Ingredient], Nabilone, Nabilone (product), Nabilone (substance)
Spanish nabilona (producto), nabilona (sustancia), nabilona

Ontology: Marinol (C0728767)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D013759
Italian Marinolo, Tetraidrocannabinolo, Solvay
English marinol, Marinol, Solvay Brand of Tetrahydrocannabinol

Ontology: Cesamet (C1263104)

Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
MSH C011941
English cesamet, Lilly Brand of Nabilone, Cesamet

Ontology: Synthetic cannabinoid receptor agonist (C1720260)

Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
SnomedCT 421537003, 422207008
English Synthetic cannabinoid receptor agonist (product), Synthetic cannabinoid receptor agonist (substance), Synthetic cannabinoid receptor agonist
Spanish agonista sintético del receptor canabinoide (producto), agonista sintético del receptor canabinoide, agonista sintético del receptor canabinoide (sustancia)