If a person would like to try CBD to treat a medical condition, what dose would you recommend?

Dose is extremely important and because the CBD market is unregulated, there are no established doses. People might be underdosing and therefore seeing no effect and giving up on potential benefits, or might be taking too much, which can have potential adverse effects. There needs to be some type of understanding, but we are a long way from knowing what a minimal or excessive dose might be.

There is an old adage, “Start low, go slow.” If CBD is ineffective, I recommend that people increase the dose in small increments so long as they do not feel adverse effects, and that they continue increasing until the drug is effective. This is what we do with prescription products—titrate the dose upwards, assess vital signs, assess pain, and raise the dose again if necessary. The caveat is that higher doses may cause adverse effects at any time during use, not necessarily immediately. It is always best to do this under supervision of a physician or pharmacist.

Do you think that CBD is a viable alternative to opioids for pain management?


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Some research has shown that people can discontinue opioid therapy and use CBD instead or use CBD or cannabis as adjunct therapy to minimize opioid dose increases.7,8 Unlike opioids, CBD does not have any clear dependency issues when used without THC and, comparatively speaking, has a relatively good side effect profile. If I had chronic pain myself I would consider almost anything before opioids, including CBD. And it is definitely safer than the way we use opioids as a society, where we are seeing rampant opioid use disorder and overdose epidemics. But again, we do not know enough about CBD to offer strong recommendations.

References

1.    Peters J, Chien J. Contemporary Routes of Cannabis Consumption: A Primer for Clinicians. J Am Osteopath Assoc. 2018 Feb 1;118(2):67-70.

2.    Brown JD, Winterstein AG. Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. J Clin Med. 2019;8(7):989.

3.      Corroon J, Phillips JA. A Cross-Sectional Study of Cannabidiol Users. Cannabis Cannabinoid Res. 2018;3(1):152–161. 

4.    Rong C, Lee Y, Carmona NE, et al. Cannabidiol in medical marijuana: Research vistas and potential opportunities. Pharmacol Res. 2017 Jul;121:213-218.

5.    National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington (DC): National Academies Press (US):  Jan 12. Available at: https://www.ncbi.nlm.nih.gov/books/NBK425757/. Accessed: September 2, 2019.

6.    Zanger, U.M.; Schwab, M. Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol. Ther. 2013;138:103–141.

7.    Boehnke KF, Scott JR, Litinas E, et al. Pills to Pot: Observational Analyses of Cannabis Substitution Among Medical Cannabis Users With Chronic Pain. J Pain. 2019 Jul;20(7):830-841.5.    Romero-Sandoval EA, Fincham JE, Kolano AL, et al. Cannabis for Chronic Pain: Challenges and Considerations. Pharmacotherapy. 2018 Jun;38(6):651-662.

Table 1

Metabolic Drug-Drug Interactions between CBD and Enzyme Substrates, Inhibitors, and Inducers

EnzymeMedication ExamplesEffectRecommendation
CYP3A4
substrates
  • Immunosuppressants
  • Chemotherapeutics
  • Antidepressants
  • Antipsychotics
  • Opioids
  • Benzodiazepines
  • Z-hypnotics
  • Statins
  • Calcium channel blockers
  • Increased risk of side effects related to substrate
  • Avoid co-administration
  • Reduce substrate dose
  • Monitor for adverse effects
  • Monitor for toxicity
  • Avoid prescribing cascade with new treatment for side effects
CYP3A4
inhibitors
  • Protease inhibitors
  • Ketoconazole
  • Loperamide
  • Nefazodone
  • Amiodarone
  • Verapamil
  • Cimetidine
  • Aprepitant
  • Imatinib
  • Increased CBD bioavailability
  • Possible increase in adverse effects
  • Reduce CBD dose
  • CYP3A4 inducers
    • Enzalutamide
    • Phenytoin
    • Carbamazepine
    • Topiramate
    • Phenobarbital
    • Rifampicin
    • Efavirenz
    • Pioglitazone
  • Decreased CBD bioavailability
  • Possible decrease in CBD effectiveness
  • Increase CBD dose
  • CYP2C19
    substrates
    • Antidepressants
    • Antiepileptics
    • Proton pump inhibitors
    • Clopidogrel
    • Propranolol
    • Carisoprodol
    • Cyclophosphamide
    • Warfarin
    • Increased risk of side effects related substrate
    • Avoide co-administration
    • Reduce substrate dose
    • Monitor for adverse events
    • Monitor for toxicity
    • Avoid prescribing cascade with new treatment for side effects
    CYP2C19 inhibitors
    • Fluvoxamine
    • Fluoxetine
    • Proton pump inibitors
    • Cimetidine
    • Ketoconazole
    • Clopidogrel
    • Fluconazole
    • Efavirenz
    • Increased CBD bioavailability

    • Possible increase in risk of adverse effects
    • Reduced CBD dose
    CYP2C19
    inducers
    • Rifampin
    • Carbamazepine
    • Phenobarbital
    • Phenytoin
    • St. John’s Wort
    • Decreased CBD bioavailability

    • Possible decrease in CBD effectiveness
    • Increase CBD dose
    CYP2C8/9 substrates
    • Rosiglitazone
    • Buprenorphine
    • Montelukast
    • Celecoxib
    • Sulfonylureas
    • Losartan
    • Naproxen
    • Phenobarbital
    • Phenytoin
    • Rosuvastatin
    • Valsartan
    • Warfarin
    • Increased risk of side effects related to substrate
    • Avoid co-administration
    • Reduce substrate dose
    • Monitor for toxicity
    • Avoid prescribing cascade with new treatment for side effects

    Brown JD, Winterstein AG. J Clin Med. 2019;8(7):989

    Table 2

    Drug-Drug Interactions between CBD and Secondary Metabolism or Transport Proteins

    EnzymeMedication ExamplesEffect/Recommendation
    UGT1A9
    • Regorafenib
    • Acetaminophen
    • Canagliflozin
    • Sorafenib
    • Irinotecan
    • Propofol
    • Mycophenolate
    • Valproic acid
    • Haloperidol
    • Ibuprofen
    • Dabigatran
    • Dapagliflozin




















    • Increased risk of side effects
    • Avoid co-administration
    • Reduce substrate dose
    • Monitor for adverse effects
    • Monitor toxicity
    UGT2B7
    • Hydromorphone
    • Losartan
    • Ibuprofen
    • Naproxen
    • Ezetimibe
    • Lovastatin
    • Simvastatin
    • Carbamazepine
    • Valproate
    BCRP
    • Glyburide
    • Imatinib
    • Methotrexate
    • Mitoxantrone
    • Nitrofurantoin
    • Prazosin
    • Statins
    • Dipyridamole
    BSEP
    • Paclitaxel
    • Digoxin
    • Statins
    • Telmisartan
    • Glyburide
    • Ketoconazole
    • Rosiglitazone
    • Celecoxib

    UGT = uridine 50-diphospho-glucoronosyltransferase; BCRP = breast cancer resistance protein; BSEP = bile salt export pump

    Brown JD, Winterstein AG. J Clin Med. 2019;8(7):989.