Skip to main content
SpringerLink
Log in

Cannabis Drug Interactions

  • Chapter
  • First Online:
Cannabinoids and Pain

Abstract

Cannabis and its various derivatives continue to have a growing presence for both recreational and medicinal purposes. Due to such widespread use, health-care providers will need to develop a general, clinical understanding of cannabis and cannabinoids. Despite the general dearth of research within this field, this chapter will provide an overview of the routes of administration as well as highlight potential drug interactions that cannabis products may have with particular classes of pharmaceuticals.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Haroutounian D, Ratz Y, Ginosar Y, Furmanov K, Saifi F, Meidan R, Davidson E. The effect of medicinal cannabis on pain and quality-of-life outcomes in chronic pain. Clin J Pain. 2016;32(12):1036–43.

    Article  PubMed  Google Scholar 

  2. Castleman M. The new healing herbs: the classic guide to nature’s best medicines; 2001. p. IX; ISBN 1-57954-304-9.

    Google Scholar 

  3. Lucas CJ, Galettis P, Schneider J. The pharmacokinetics and pharmacodynamics of cannabinoids. Br J Clin Pharmacol. 2018;84:2477–82.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Toghi H, Konno S, Tamura K, Kimura B, Kawano K. Effects of low-to-high doses of aspirin on platelet aggregability and metabolites of thromboxane A2 and prostacyclin. Stroke. 1992;23(10):1400–3.

    Article  Google Scholar 

  5. McGilveray I. Pharmacokinetics of cannabinoids. Pain Res Manag. 2005;10(Suppl A):15A–22A.

    Article  PubMed  Google Scholar 

  6. Millar S, Stone N, Yates A, O’Sullivan S. A systematic review on the pharmacokinetics of cannabidiol in humans. Front Pharmacol. 2018;9(1365):1–13.

    Google Scholar 

  7. Ghasemiesfe M, Barrow B, Leonard S. Association between marijuana use and risk of cancer: a systematic review and meta-analysis. Subst Use Addict. 2019;2(11):e1916318. https://doi.org/10.1001/jamanetworkopen.

    Article  Google Scholar 

  8. Huestis MA. Human cannabinoid pharmacokinetics-review. Chem Biodivers. 2007;4:1770–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. MacCallum C, Russo E. Practical consideration in medicinal cannabis administration and dosing. Eur J Intern Med. 2018;49:12–9.

    Article  CAS  PubMed  Google Scholar 

  10. Russo E. Current therapeutic cannabis controversies and clinical trial design issues. Front Pharmacol. 2016;7(309):1–19.

    Google Scholar 

  11. Nagarkatti P, Pandey R, Rieder S, Hegde V, Nagarkatti M. Cannabinoids as novel anti-inflammatory drugs. Future Med Chem. 2009;1(7):1333–49.

    Article  CAS  PubMed  Google Scholar 

  12. Stott C, Guy G, Wright S, Whittle B. The effects of cannabis extracts Tetranabinex and Nabidiolex on human cytochrome P450-mediated metabolism. In: Symposium on the cannabinoids; 2005. p. 163.

    Google Scholar 

  13. Russo E. Cannabinoids in the management of difficult to treat pain. Ther Clin Risk Manag. 2008;4(10):245–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Anderson B. Paracetamol (acetaminophen): mechanisms of action. Pediatr Anesth. 2008;18(10):915–21.

    Article  Google Scholar 

  15. Ewing L, McGill M, Yee E, Quick C, Skinner C, Kennon-McGill S, Clemens M, Vazquez J, McCullough S, Williams D, Kutanzi K, Walker L, ElSholy M, James L, Gurley B, Koturbash I. Paradoxical patterns of sinusoidal obstruction syndrome-like liver injury in aged female CD-1 mice triggered by cannabidiol-rich cannabis extract and acetaminophen co-administration. Molecules. 2019;24(2256):1–12.

    Google Scholar 

  16. Sills G. The mechanism of action of gabapentin and pregabalin. Curr Opin Pharmacol. 2006;6(1):108–13.

    Article  CAS  PubMed  Google Scholar 

  17. Howlett A, Blume L, Dalton G. CB(1) cannabinoid receptors and their associated proteins. Curr Med Chem. 2010;17:1382–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lozovaya N, Min R, Tsintsadze V, Burnashev N. Dual modulation of CNS voltage-gated calcium channels by cannabinoids: focus on CB1 receptor-independent effects. Cell Calcium. 2009;46:154–62.

    Article  CAS  PubMed  Google Scholar 

  19. Atwal N, Case S, Mitchell V, Vaughan C. THC and gabapentin interactions in mouse neuropathic pain model. Neuropharmacology. 2019;144:115–21.

    Article  CAS  PubMed  Google Scholar 

  20. Lile J, Wesley M, Kelly T, Hays L. Separate and combined effects of gabapentin and delta-THC in humans discriminating delta THC. Behav Pharmacol. 2017;27(2–3):215–24.

    Google Scholar 

  21. Aracil-Fernández A, Almela P, Manzanares J. Pregabalin and topiramate regulate behavioural and brain gene transcription changes induced by spontaneous cannabinoid withdrawal in mice. Addict Biol. 2013;18:252–62.

    Article  PubMed  CAS  Google Scholar 

  22. Benbouzid M, Gaveriaux-Ruff C, Yalcin I, Waltisperger E, Tessier L, Muller A, Kieffer B, Freund-Mercier M, Barrot M. Delta-opioid receptors are critical for tricyclic antidepressant treatment of neuropathic allodynia. Biol Psychiatry. 2008;63(6):633–6.

    Article  CAS  PubMed  Google Scholar 

  23. Wilens T, Bierderman J, Spencer T. Case study: adverse effects of smoking marijuana while receiving tricyclic antidepressants. J Acad Child Adolesc Psychiatry. 1997;36(1):45–8.

    Article  CAS  Google Scholar 

  24. Kizer K. Possible interaction of TCA and marijuana. Ann Emerg Med. 1980;9(8):444.

    Article  CAS  PubMed  Google Scholar 

  25. Mannion V. Case report: adverse effects of taking tricyclic antidepressant and smoking marijuana. Can Fam Physician. 1999;45:2683–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Wilson N, Kariisa M, Seth P, Smith H, Davis N. Drug and opioid-involved overdose deaths – United States 2017–2018. Weekly. 2020;69(11):290–7.

    Google Scholar 

  27. Abrams D, Couey P, Shade S, Kelly M, Benowitz N. Cannabinoid-opioid interaction in chronic pain. Clin Pharmacol Ther. 2011;90(6):844–51.

    Article  CAS  PubMed  Google Scholar 

  28. Manini A, Yiannoulos G, Bergamaschi M, Hernandez S, Olmedo R, Barnes S, Jutras-Aswad D, Huestis M. Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans. J Addict Med. 2015;9(3):204–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Cichewicz D. Synergistic interactions between cannabinoid and opioid analgesics. Life Sci. 2004;74:1317–24.

    Article  CAS  PubMed  Google Scholar 

  30. Vierke C, Marxen B, Boettcher M, Hiemke C, Havemann-Reinecke U. Buprenorphine-cannabis interaction in patients undergoing opioid maintenance therapy. Eur Arch Psychiatry Clin Neurosci. 2020. https://doi.org/10.1007/s00406-019-01091-0.

  31. Johnson J, Lossignol D, Burnell-Nugent M, Fallon M. An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patient with terminal cancer related pain refractory to strong opioid analgesics. J Pain Symptom Manag. 2013;46:207–18.

    Article  CAS  Google Scholar 

  32. Friedman D, Devinsky O. Cannabinoids in the treatment of epilepsy. N Engl J Med. 2015;373:1048–58.

    Article  CAS  PubMed  Google Scholar 

  33. O’Connell B, Gloss D, Devinsky O. Cannabinoids in treatment-resistant epilepsy: a review. Epilepsy Behav. 2017;70:341–8.

    Article  PubMed  Google Scholar 

  34. Chang B. Cannabidiol and serum antiepileptic drug levels: The ABCs of CBD with AEDs. Epilepsy Curr. 2018;18(1):33–4.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Gaston T, Szaflarksi J. Cannabis for the treatment of epilepsy: an update. Curr Neurol Neurosci Rep. 2018;18(73):1–9.

    CAS  Google Scholar 

  36. Gaston T, Bebin E, Cutter G, Liu Y, Szaflarski J. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia. 2017;58(9):1586–92.

    Article  CAS  PubMed  Google Scholar 

  37. Consroe P, Wolkin A. Cannabidiol–antiepileptic drug comparisons and interactions in experimentally induced seizures in rats. J Pharmacol Exp Ther. 1977;201:26–32.

    CAS  PubMed  Google Scholar 

  38. Geffrey A, Pollack S, Bruno P, Thiele E. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia. 2015;56(8):1246–51.

    Article  CAS  PubMed  Google Scholar 

  39. Rao T, Andrade C. Classification of psychotropic drugs: problems, solutions, and more problems. Indian J Psychiatry. 2016;58(2):111–3.

    Article  Google Scholar 

  40. Rong C, Carmona N, Lee Y, Ragguett R, Pan Z, Rosenblat J, Subramaniapillai M, Shekotikhina M, Almatham F, Alageel A, Mansur R, Ho R, McIntyre R. Drug-drug interactions as a result of co-administering delta-THC and CBD and other psychotropic agents. Expert Opin Drug Saf. 2018;17(1):51–4.

    Article  CAS  PubMed  Google Scholar 

  41. Patel R, Wilson R, Jackson R, Ball M, Shetty H, Broadbent M, Stewart R, McGuire P, Bhattacharyya S. Association of cannabis use with hospital admission and antipsychotic treatment failure in first episode psychosis: an observational study. Br Med J. 2016;6(3):1–9.

    Google Scholar 

  42. Brzozowska N, Tonnerre E, Li K, Wang X, Boucher A, Callaghan P, Kuligowski M, Wong A, Arnold J. The differential binding of antipsychotic drugs to the ABC transporter P-glycoproteins predicts cannabinoid-antipsychotic drug interactions. Neuropyschopharmacology. 2017;42:2222–31.

    Article  CAS  Google Scholar 

  43. Brown J. Potential adverse drug events and drug-drug interactions with medical consumer cannabidiol (CBD) use. J Clin Med. 2019;8(989):1–14.

    CAS  Google Scholar 

  44. Flockhart DA. Drug interactions: cytochrome P450 drug interaction table. Indiana University School of Medicine; 2007.

    Google Scholar 

  45. Watanabe K, Yamaori S, Funahashi T, Kimura T, Yamamoto I. Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes. Life Sci. 2007;80(15):1415–9.

    Article  CAS  PubMed  Google Scholar 

  46. Purcell C, Davis A, Moolman N, Taylor S. Reduction of benzodiazepine use in patients prescribed medical cannabis. Cannabis Cannabinoid Res. 2019;4(3):214–8.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Benowitz N, Nguyen T, Jones R, Heming R, Bachman J. Metabolic and psychophysiologic studies of cannabidiol-hexobarbital interaction. Clin Pharmacol Ther. 1980;28(1):115–20.

    Article  CAS  PubMed  Google Scholar 

  48. Coetzee C, Levendal R, Van De Venter M, Frost C. Anticoagulant effects of a Cannabis extract in an obese rat model. Phytomedicine. 2007;14:333–7.

    Article  CAS  PubMed  Google Scholar 

  49. Greger J, Bates V, Mechtler L, Gengo F. A review of cannabis and interactions with anticoagulant and antiplatelet agents. J Clin Pharamcol. 2020;60(4):432–8.

    Article  CAS  Google Scholar 

  50. Yamaori S, Koeda K, Kushihara M, Hada Y, Yamamoto I, Watanabe K. Comparison in the in vitro inhibitory effects of major phytocannabinoids and polycyclic aromatic hydrocarbons contained in marijuana smoke on cytochrome P450 2C9 activity. Drug Metab Pharmacokinet. 2012;27(3):294–300.

    Article  CAS  PubMed  Google Scholar 

  51. Damkier P, Lassen D, Christensen M, Madsen K, Hellfritzsch M, Pottegard A. Interaction between warfarin and cannabis. Basical Clin Pharmacol Toxicol. 2019;124:28–31.

    Article  CAS  Google Scholar 

  52. Grayson L, Vines B, Nichol K, Szaflarski J. An interaction between warfarin and cannabidiol, a case report. Epilepsy Behav Case Rep. 2018;9:10–1.

    Article  PubMed  Google Scholar 

  53. Zhu H, Wang J, Markowitz J, Donovan J, Gibson B, Gefroh H, Devane C. Characterization of P-glycoprotein inhibition by major cannabinoids from marijuana. J Pharmacol Exp Ther. 2006;317(2):850–7.

    Article  CAS  PubMed  Google Scholar 

  54. Ford N. The metabolism of clopidogrel: CYP2C19 is a minor pathway. J Clin Pharmacol. 2016;56(12):1474–83.

    Article  CAS  PubMed  Google Scholar 

  55. Jiang R, Yamaori S, Okamoto Y, Yamamoto I, Watanabe K. Cannabidiol is a potent inhibitor of the catalytic activity of cytochrome P450 2C19. Drug Metab Pharmacokinet. 2013;28(4):332–8.

    Article  CAS  PubMed  Google Scholar 

  56. Stout S, Cimino N. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systemic review. Drug Metab Rev. 2014;46(1):86–95.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

No financial disclosures to report.

Author information

Authors and Affiliations

  1. Department of Pain Medicine, Division of Anesthesiology, Critical Care and Pain Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    George Polson, Matthew Chung, Salman Hirani & Christina Le-Short

  2. Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, TX, USA

    George Polson

Authors
  1. George Polson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Salman Hirani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christina Le-Short
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to George Polson .

Editor information

Editors and Affiliations

  1. Western Reserve Hospital, Center For Pain Medicine, Cuyahoga Falls, OH, USA

    Samer N. Narouze

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Polson, G., Chung, M., Hirani, S., Le-Short, C. (2021). Cannabis Drug Interactions. In: Narouze, S.N. (eds) Cannabinoids and Pain. Springer, Cham. https://doi.org/10.1007/978-3-030-69186-8_13

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-69186-8_13

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-69185-1

  • Online ISBN: 978-3-030-69186-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation