Skip to main content

Advertisement

SpringerLink
Log in

Comparative Pharmacokinetics of Commercially Available Cannabidiol Isolate, Broad-Spectrum, and Full-Spectrum Products

  • Original Research Article
  • Published:
European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

Abstract

Background and Objectives

A wide variety of products containing cannabidiol (CBD) are available on the commercial market. One of the most common products, CBD oil, is administered to self-treat a variety of conditions. These oils are available as CBD isolate, broad-spectrum [all terpenes and minor cannabinoids except Δ-9-tetrahydrocannabinol (THC)], or full-spectrum (all terpenes and minor cannabinoids with THC < 0.3% dried weight) products. A systematic pharmacokinetic study was performed to determine whether there are differences in the pharmacokinetic parameters and systemic exposure of CBD after oral dosing as an isolate, broad-spectrum, or full-spectrum product.

Methods

Male and female Sprague Dawley rats were treated with a single, equivalent oral dose of CBD delivered as isolate, broad-spectrum, or full-spectrum product. An additional study using an in-house preparation of CBD isolate plus 0.2% THC was performed. A permeability assay was also conducted to investigate whether the presence of THC alters the intestinal permeability of CBD.

Results

There was an increase in the oral bioavailability of CBD (12% and 21% in male and female rats, respectively) when administered as a full-spectrum product compared with the isolate and broad-spectrum products. There was no difference in the bioavailability of CBD between the commercially available full-spectrum formulation (3.1% CBD; containing 0.2% THC plus terpenes and other minor cannabinoids) versus the in-house preparation of CBD full-spectrum (CBD isolate 3.2% plus 0.2% THC isolate). In vitro permeability assays demonstrated that the presence of THC increases permeability of CBD while also decreasing efflux through the gut wall.

Conclusions

The presence of 0.2% THC increased the oral bioavailability of CBD in male and female rats, indicating that full-spectrum products may produce increased effectiveness of CBD due to a greater exposure available systemically.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Brenan M. 14% of Americans Say They Use CBD Products. 2019. https://news.gallup.com/poll/263147/americans-say-cbd-products.aspx. Accessed 07 Mar 2023.

  2. Dorbian I. CBD Market Could Reach $20 Billion by 2024, Says New Study 2019. https://www.forbes.com/sites/irisdorbian/2019/05/20/cbd-market-could-reach-20-billion-by-2024-says-new-study/?sh=7832ab1049d0. Accessed 07 Mar 2023.

  3. Corroon J, Phillips JA. A cross-sectional study of cannabidiol users. Cannabis Cannabinoid Res. 2018;3(1):152–61. https://doi.org/10.1089/can.2018.0006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Veltri C, Grundmann O. Current perspectives on the impact of Kratom use. Subst Abuse Rehabil. 2019;10:23–31. https://doi.org/10.2147/SAR.S164261.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Schoedel KA, Szeto I, Setnik B, Sellers EM, Levy-Cooperman N, Mills C, et al. Abuse potential assessment of cannabidiol (CBD) in recreational polydrug users: a randomized, double-blind, controlled trial. Epilepsy Behav. 2018;88:162–71. https://doi.org/10.1016/j.yebeh.2018.07.027.

    Article  PubMed  Google Scholar 

  6. Nelson KM, Bisson J, Singh G, Graham JG, Chen S-N, Friesen JB, et al. The essential medicinal chemistry of cannabidiol (CBD). J Med Chem. 2020;63(21):12137–55. https://doi.org/10.1021/acs.jmedchem.0c00724.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. U.S. Food and Drug Administration. FDA Approves First Drug Comprised of an Active Ingredient Derived from Marijuana to Treat Rare, Severe Forms of Epilepsy. Silver Spring, MD; 2018. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-comprised-active-ingredient-derived-marijuana-treat-rare-severe-forms. Accessed 07 Mar 2023.

  8. Wagner H, Ulrich-Merzenich G. Synergy research: approaching a new generation of phytopharmaceuticals. Phytomedicine. 2009;16(2–3):97–110. https://doi.org/10.1016/j.phymed.2008.12.018.

    Article  CAS  PubMed  Google Scholar 

  9. Ben-Shabat S, Fride E, Sheskin T, Tamiri T, Rhee MH, Vogel Z, et al. An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. Eur J Pharmacol. 1998;353(1):23–31. https://doi.org/10.1016/s0014-2999(98)00392-6.

    Article  CAS  PubMed  Google Scholar 

  10. Mechoulam R, Ben-Shabat S. From gan-zi-gun-nu to anandamide and 2-arachidonoylglycerol: the ongoing story of cannabis. Nat Prod Rep. 1999;16(2):131–43. https://doi.org/10.1039/a703973e.

    Article  CAS  PubMed  Google Scholar 

  11. 115th Congress of the United States. Agriculture Improvement Act of 2018. 2018. Available from: https://uscode.house.gov/statutes/pl/115/334.pdf. Accessed 07 March 2023.

  12. Cox-Georgian D, Ramadoss N, Dona C, Basu C. Therapeutic and medicinal uses of terpenes. Med Plants. 2019;1:333–59. https://doi.org/10.1007/978-3-030-31269-5_15.

    Article  Google Scholar 

  13. LaVigne JE, Hecksel R, Keresztes A, Streicher JM. Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity. Sci Rep. 2021;11(1):8232. https://doi.org/10.1038/s41598-021-87740-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Liktor-Busa E, Keresztes A, LaVigne J, Streicher JM, Largent-Milnes TM. Analgesic potential of terpenes derived from Cannabis sativa. Pharmacol Rev. 2021;73(4):1269–97. https://doi.org/10.1124/pharmrev.120.000046.

    Article  CAS  Google Scholar 

  15. Cogan PS. The “entourage effect” or “hodge-podge hashish”: the questionable rebranding, marketing, and expectations of cannabis polypharmacy. Expert Rev Clin Pharmacol. 2020;13(8):835–45. https://doi.org/10.1080/17512433.2020.1721281.

    Article  CAS  PubMed  Google Scholar 

  16. Ferber SG, Namdar D, Hen-Shoval D, Eger G, Koltai H, Shoval G, et al. The “Entourage Effect”: terpenes coupled with cannabinoids for the treatment of mood disorders and anxiety disorders. Curr Neuropharmacol. 2020;18(2):87–96. https://doi.org/10.2174/1570159X17666190903103923.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Gallily R, Yekhtin Z, Hanua L. Overcoming the bell-shaped dose-response of cannabidiol by using cannabis extract enriched in cannabidiol. J Pharm Pharmacol. 2015;6:75–85. https://doi.org/10.4236/pp.2015.62010

    Article  Google Scholar 

  18. Johnson JR, Burnell-Nugent M, Lossignol D, Ganae-Motan ED, Potts R, Fallon MT. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. J Pain Symptom Manage. 2010;39(2):167–79. https://doi.org/10.1016/j.jpainsymman.2009.06.008.

    Article  PubMed  Google Scholar 

  19. Pamplona FA, da Silva LR, Coan AC. Potential clinical benefits of CBD-rich cannabis extracts over purified CBD in treatment-resistant epilepsy: observational data meta-analysis. Front Neurol. 2018;9:759. https://doi.org/10.3389/fneur.2018.00759.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Russo EB. The case for the entourage effect and conventional breeding of clinical cannabis: no “Strain”, No Gain. Front Plant Sci. 2018;9:1969. https://doi.org/10.3389/fpls.2018.01969.

    Article  PubMed  Google Scholar 

  21. Wilkinson JD, Whalley BJ, Baker D, Pryce G, Constanti A, Gibbons S, et al. Medicinal cannabis: is delta9-tetrahydrocannabinol necessary for all its effects? J Pharm Pharmacol. 2003;55(12):1687–94. https://doi.org/10.1211/0022357022304.

    Article  CAS  PubMed  Google Scholar 

  22. Boggs DL, Nguyen JD, Morgenson D, Taffe MA, Ranganathan M. Clinical and preclinical evidence for functional interactions of cannabidiol and δ9-tetrahydrocannabinol. Neuropsychopharmacology. 2018;43(1):142–54. https://doi.org/10.1038/npp.2017.209.

    Article  CAS  PubMed  Google Scholar 

  23. Finlay DB, Sircombe KJ, Nimick M, Jones C, Glass M. Terpenoids from cannabis do not mediate an entourage effect by acting at cannabinoid receptors. Front Pharmacol. 2020;11:359. https://doi.org/10.3389/fphar.2020.00359.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Harris HM, Rousseau MA, Wanas AS, Radwan MM, Caldwell S, Sufka KJ, et al. Role of cannabinoids and terpenes in cannabis-mediated analgesia in rats. Cannabis Cannabinoid Res. 2019;4(3):177–82. https://doi.org/10.1089/can.2018.0054.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Varvel SA, Bridgen DT, Tao Q, Thomas BF, Martin BR, Lichtman AH. Delta9-tetrahydrocannbinol accounts for the antinociceptive, hypothermic, and cataleptic effects of marijuana in mice. J Pharmacol Exp Ther. 2005;314(1):329–37. https://doi.org/10.1124/jpet.104.080739.

    Article  CAS  PubMed  Google Scholar 

  26. Berthold EC, Yang R, Sharma A, Kamble SH, Kanumuri SR, King TI, et al. Regulatory sampling of industrial hemp plant samples (Cannabis sativa L.) using UPLC-MS/MS method for detection and quantification of twelve cannabinoids. J Cannabis Res. 2020;2(1):42. https://doi.org/10.1186/s42238-020-00050-0.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Krishna G, Chen K, Lin C, Nomeir AA. Permeability of lipophilic compounds in drug discovery using in-vitro human absorption model, Caco-2. Int J Pharm. 2001;222(1):77–89. https://doi.org/10.1016/s0378-5173(01)00698-6.

    Article  CAS  PubMed  Google Scholar 

  28. Mehran M, Levy E, Bendayan M, Seidman E. Lipid, apolipoprotein, and lipoprotein synthesis and secretion during cellular differentiation in caco-2 cells. In Vitro Cell Dev Biol Anim. 1997;33(2):118–28. https://doi.org/10.1007/s11626-997-0032-3.

    Article  CAS  PubMed  Google Scholar 

  29. U.S. Food and Drug Administration, Bioanalytical Method Validation Guidance for Industry. Silver Spring, MD; 2018. https://www.fda.gov/files/drugs/published/Bioanalytical-Method-Validation-Guidance-for-Industry.pdf. Accessed 07 Mar 2023.

  30. Cocetta V, Governa P, Borgonetti V, Tinazzi M, Peron G, Catanzaro D, et al. Cannabidiol isolated from Cannabis sativa L. protects intestinal barrier from in vitro inflammation and oxidative stress. Front Pharmacol. 2021;12:911. https://doi.org/10.3389/fphar.2021.641210.

    Article  CAS  Google Scholar 

  31. Zgair A, Lee JB, Wong JCM, Taha DA, Aram J, Di Virgilio D, et al. Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation. Sci Rep. 2017;7(1):14542. https://doi.org/10.1038/s41598-017-15026-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Nauli AM, Whittimore JD. Using Caco-2 cells to study lipid transport by the intestine. J Visual Exp. 2015;102:53086-e. https://doi.org/10.3791/53086.

    Article  CAS  Google Scholar 

  33. Luchoomun J, Hussain MM. Assembly and secretion of chylomicrons by differentiated Caco-2 cells: nascent triglycerides and preformed phospholipids are preferentially used for lipoprotein assembly. J Biol Chem. 1999;274(28):19565–72. https://doi.org/10.1074/jbc.274.28.19565.

    Article  CAS  PubMed  Google Scholar 

  34. Megias MMP, Pombal MA: Atlas of Plant and Animal Histology; 2019. http://mmegias.webs.uvigo.es/index.html. Accessed 07 Mar 2023.

Download references

Acknowledgements

The author(s) would like to acknowledge Dr. Bonnie A. Avery for her contributions to the success of this work group.

Author information

Author notes

  1. Lance R. McMahon

    Present address: Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center at Amarillo, Amarillo, TX, USA

Authors and Affiliations

  1. Department of Pharmaceutics, University of Florida College of Pharmacy, Gainesville, FL, USA

    Erin C. Berthold, Shyam H. Kamble, Siva Rama Raju Kanumuri, Michelle A. Kuntz, Alexandria S. Senetra, Yi-Hua Chiang, Christopher R. McCurdy & Abhisheak Sharma

  2. Translational Drug Development Core, University of Florida Clinical and Translational Science Institute, Gainesville, FL, USA

    Shyam H. Kamble, Siva Rama Raju Kanumuri, Christopher R. McCurdy & Abhisheak Sharma

  3. Department of Pharmacodynamics, University of Florida College of Pharmacy, Gainesville, FL, USA

    Lance R. McMahon

  4. Department of Medicinal Chemistry, University of Florida College of Pharmacy, Gainesville, FL, USA

    Christopher R. McCurdy

Authors
  1. Erin C. Berthold
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shyam H. Kamble
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Siva Rama Raju Kanumuri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michelle A. Kuntz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alexandria S. Senetra
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yi-Hua Chiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lance R. McMahon
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Christopher R. McCurdy
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Abhisheak Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Abhisheak Sharma.

Ethics declarations

Authors contributions

ECB: conceptualization, methodology, investigation, data curation, writing—original draft, preparation. SHK, SRRK, and MAK: methodology, investigation, writing—review and editing. ASS and YHC: investigation, writing—review and editing. LRM and CRM: supervision, material supply, review and editing, AS: conceptualization, funding acquisition, methodology, investigation, supervision, review and editing.

Conflict of interest

The authors declare no conflict of interest.

Ethics approval

All the animal studies were performed after approval from the University of Florida Institutional Animal Care and Use Committee.

Availability of data and material

The data that support the findings of this study are available upon reasonable request to the corresponding author.

Code availability

Not applicable.

Consent for publication

Not applicable.

Consent to participate

Not applicable.

Funding

This project is part of the University of Florida’s “Creating the Healthiest Generation” Moonshot Initiative, which is supported by the UF Office of the Provost, UF Office of Research, UF Health, UF College of Medicine, and the UF Clinical and Translational Science Institute.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Berthold, E.C., Kamble, S.H., Kanumuri, S.R.R. et al. Comparative Pharmacokinetics of Commercially Available Cannabidiol Isolate, Broad-Spectrum, and Full-Spectrum Products. Eur J Drug Metab Pharmacokinet 48, 427–435 (2023). https://doi.org/10.1007/s13318-023-00839-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13318-023-00839-3

Search

Navigation