Skip to main content

Therapeutic Efficacy of Cannabidiol (CBD): a Review of the Evidence From Clinical Trials and Human Laboratory Studies

Abstract

Purpose of Review

Global policy changes have increased access to products containing cannabidiol (CBD), a primary constituent of hemp and cannabis. The CBD product industry has experienced tremendous growth, in part, because CBD is widely touted as an effective therapeutic for myriad health conditions. However, only 1 CBD product (Epidiolex®) has been approved by the US Food and Drug Administration (FDA) to date. There is substantial interest among consumers and the medical and scientific communities regarding the therapeutic potential of CBD, including for indications that are not recognized by the FDA. The purpose of this review was to synthesize available evidence from clinical research regarding the efficacy of CBD as a therapeutic.

Recent Findings

Human laboratory studies and clinical trials (e.g., randomized controlled trials and single-arm, open-label trials) evaluating the efficacy of CBD as a therapeutic were identified for various medical conditions, including epilepsy, anxiety, pain/inflammation, schizophrenia, various substance use disorders, post-traumatic stress disorder, and others. There is clear evidence supporting the utility of CBD to treat epilepsy. For other health conditions reviewed, evidence was often mixed and/or there was a general lack of well-powered randomized, placebo-controlled studies to draw definitive conclusions.

Summary

Rigorous, controlled evidence for the therapeutic efficacy of CBD is lacking for many health conditions. Possible concerns with the use of CBD as a therapeutic include the potential for adverse effects (e.g., liver toxicity), drug-drug interactions, and lack of sufficient regulatory oversight of retail CBD products.

This is a preview of subscription content, access via your institution.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. • Bonn-Miller MO, Loflin MJE, Thomas BF, Marcu JP, Hyke T, Vandrey R. Labeling accuracy of cannabidiol extracts sold online. Jama. 2017;318(17):1708–9. https://doi.org/10.1001/jama.2017.11909This study analyzed commercially-available CBD extracts. 69% were labeled inaccurately (43% underlabeled, 26% overlabeled for CBD concentrations) and 21% contained THC (up to 6.4 mg/mL).

    PubMed  PubMed Central  Article  Google Scholar 

  2. Gurley BJ, Murphy TP, Gul W, Walker LA, ElSohly M. Content versus label claims in cannabidiol (CBD)-containing products obtained from commercial outlets in the state of Mississippi. J Diet Suppl. 2020:1–9. https://doi.org/10.1080/19390211.2020.1766634.

  3. Poklis JL, Mulder HA, Peace MR. The unexpected identification of the cannabimimetic, 5F-ADB, and dextromethorphan in commercially available cannabidiol e-liquids. Forensic Sci Int. 2019;294:e25–e7. https://doi.org/10.1016/j.forsciint.2018.10.019.

    CAS  PubMed  Article  Google Scholar 

  4. Stockings E, Zagic D, Campbell G, Weier M, Hall WD, Nielsen S, et al. Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence. J Neurol Neurosurg Psychiatry. 2018;89(7):741–53. https://doi.org/10.1136/jnnp-2017-317,168.

    PubMed  Article  Google Scholar 

  5. • Devinsky O, Marsh E, Friedman D, Thiele E, Laux L, Sullivan J, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016;15(3):270–8. https://doi.org/10.1016/s1474-4422(15)00379-8In a 12-week open-label trial, oral CBD (2-5 mg/kg/day, increased to maximum dose of 25-50 mg/kg/day) reduced monthly motor seizures by 36.5% (median) among patients (ages 1-30 years) with severe, intractable, childhood-onset, treatment-resistant epilepsy. This study supported the FDA approval of CBD (i.e., Epidiolex®) to treat seizures associated with Lennox-Gastaut and Dravet syndromes.

    CAS  PubMed  Article  Google Scholar 

  6. Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med. 2017;376(21):2011–20. https://doi.org/10.1056/NEJMoa1611618.

    CAS  PubMed  Article  Google Scholar 

  7. Devinsky O, Patel AD, Cross JH, Villanueva V, Wirrell EC, Privitera M, et al. Effect of cannabidiol on drop seizures in the Lennox-Gastaut syndrome. N Engl J Med. 2018;378(20):1888–97. https://doi.org/10.1056/NEJMoa1714631.

    CAS  PubMed  Article  Google Scholar 

  8. GW Pharmaceuticals and Greenwich Biosciences Announce FDA Acceptance of sNDA Filing with Priority Review for EPIDIOLEX® (cannabidiol) in the Treatment of Seizures Associated with Tuberous Sclerosis Complex. http://ir.gwpharm.com/node/11346/pdf: GW Pharmaceuticals; 2020. p. 1–2.

  9. Hess EJ, Moody KA, Geffrey AL, Pollack SF, Skirvin LA, Bruno PL, et al. Cannabidiol as a new treatment for drug-resistant epilepsy in tuberous sclerosis complex. Epilepsia. 2016;57(10):1617–24. https://doi.org/10.1111/epi.13499.

    CAS  PubMed  Article  Google Scholar 

  10. Wheeler M, Merten JW, Gordon BT, Hamadi H. CBD (cannabidiol) product attitudes, knowledge, and use among young adults. Subst Use Misuse. 2020;55(7):1138–45. https://doi.org/10.1080/10826084.2020.1729201.

    PubMed  Article  Google Scholar 

  11. Graeff FG, Parente A, Del-Ben CM, Guimarães FS. Pharmacology of human experimental anxiety. Braz J Med Biol Res. 2003;36(4):421–32. https://doi.org/10.1590/s0100-879x2003000400003.

    CAS  PubMed  Article  Google Scholar 

  12. Zuardi AW, Cosme RA, Graeff FG, Guimaraes FS. Effects of ipsapirone and cannabidiol on human experimental anxiety. J Psychopharmacol. 1993;7(1 Suppl):82–8. https://doi.org/10.1177/026988119300700112.

    CAS  PubMed  Article  Google Scholar 

  13. Linares IM, Zuardi AW, Pereira LC, Queiroz RH, Mechoulam R, Guimaraes FS, et al. Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test. Braz J Psychiatry. 2019;41(1):9–14. https://doi.org/10.1590/1516-4446-2017-0015.

    PubMed  Article  Google Scholar 

  14. Zuardi AW, Rodrigues NP, Silva AL, Bernardo SA, Hallak JEC, Guimarães FS, et al. Inverted U-shaped dose-response curve of the anxiolytic effect of cannabidiol during public speaking in real life. Front Pharmacol. 2017;8:259. https://doi.org/10.3389/fphar.2017.00259.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  15. • Bergamaschi MM, Queiroz RH, Chagas MH, de Oliveira DC, De Martinis BS, Kapczinski F, et al. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients. Neuropsychopharmacology. 2011;36(6):1219–26. https://doi.org/10.1038/npp.2011.6The efficacy of CBD (600 mg) to reduce anxiety in a simulated public speaking test was evaluated in patients with generalized social anxiety disorder. Pretreatment with CBD decreased anxiety, cognitive impairment, and discomfort in speech performance relative to placebo.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. Crippa JA, Derenusson GN, Ferrari TB, Wichert-Ana L, Duran FL, Martin-Santos R, et al. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. J Psychopharmacol. 2011;25(1):121–30. https://doi.org/10.1177/0269881110379283.

    CAS  PubMed  Article  Google Scholar 

  17. Arndt DL, de Wit H. Cannabidiol does not dampen responses to emotional stimuli in healthy adults. Cannabis Cannabinoid Res. 2017;2(1):105–13. https://doi.org/10.1089/can.2017.0014.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  18. Das RK, Kamboj SK, Ramadas M, Yogan K, Gupta V, Redman E, et al. Cannabidiol enhances consolidation of explicit fear extinction in humans. Psychopharmacology. 2013;226(4):781–92. https://doi.org/10.1007/s00213-012-2955-y.

    CAS  PubMed  Article  Google Scholar 

  19. Hindocha C, Freeman TP, Schafer G, Gardener C, Das RK, Morgan CJ, et al. Acute effects of delta-9-tetrahydrocannabinol, cannabidiol and their combination on facial emotion recognition: a randomised, double-blind, placebo-controlled study in cannabis users. Eur Neuropsychopharmacol. 2015;25(3):325–34. https://doi.org/10.1016/j.euroneuro.2014.11.014.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. Hundal H, Lister R, Evans N, Antley A, Englund A, Murray RM, et al. The effects of cannabidiol on persecutory ideation and anxiety in a high trait paranoid group. J Psychopharmacol. 2018;32(3):276–82. https://doi.org/10.1177/0269881117737400.

    CAS  PubMed  Article  Google Scholar 

  21. • 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.2018.0006A self-selected convenience sample was recruited via an online survey designed to characterize whom, how, and why individuals are currently using CBD. Roughly 62% of respondents reported using CBD to treat a medical condition. The top three medical conditions were chronic pain, arthritis/joint pain, and anxiety.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. Hunter D, Oldfield G, Tich N, Messenheimer J, Sebree T. Synthetic transdermal cannabidiol for the treatment of knee pain due to osteoarthritis. Osteoarthr Cartil. 2018;26:S26. https://doi.org/10.1016/j.joca.2018.02.067.

    Article  Google Scholar 

  23. Wade DT, Robson P, House H, Makela P, Aram J. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clin Rehabil. 2003;17(1):21–9. https://doi.org/10.1191/0269215503cr581oa.

    PubMed  Article  Google Scholar 

  24. Cuñetti L, Manzo L, Peyraube R, Arnaiz J, Curi L, Orihuela S. Chronic pain treatment with cannabidiol in kidney transplant patients in Uruguay. Transplant Proc. 2018;50(2):461–4. https://doi.org/10.1016/j.transproceed.2017.12.042.

    PubMed  Article  Google Scholar 

  25. Palmieri B, Laurino C, Vadalà M. Short-term efficacy of CBD-enriched hemp oil in girls with dysautonomic syndrome after human papillomavirus vaccination. Isr Med Assoc J. 2017;19(2):79–84.

    PubMed  Google Scholar 

  26. Brown JD, Costales B, van Boemmel-Wegmann S, Goodin AJ, Segal R, Winterstein AG. Characteristics of older adults who were early adopters of medical cannabis in the Florida Medical Marijuana Use Registry. J Clin Med. 2020;9(4). https://doi.org/10.3390/jcm9041166.

  27. Boggs DL, Surti T, Gupta A, Gupta S, Niciu M, Pittman B, et al. The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial. Psychopharmacology. 2018;235(7):1923–32. https://doi.org/10.1007/s00213-018-4885-9.

    CAS  PubMed  Article  Google Scholar 

  28. Leweke FM, Piomelli D, Pahlisch F, Muhl D, Gerth CW, Hoyer C, et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2012;2:e94. https://doi.org/10.1038/tp.2012.15.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  29. McGuire P, Robson P, Cubala WJ, Vasile D, Morrison PD, Barron R, et al. Cannabidiol (CBD) as an adjunctive therapy in schizophrenia: a multicenter randomized controlled trial. Am J Psychiatry. 2018;175(3):225–31. https://doi.org/10.1176/appi.ajp.2017.17030325.

    PubMed  Article  Google Scholar 

  30. Hurd YL, Spriggs S, Alishayev J, Winkel G, Gurgov K, Kudrich C, et al. Cannabidiol for the reduction of cue-induced craving and anxiety in drug-abstinent individuals with heroin use disorder: a double-blind randomized placebo-controlled trial. Am J Psychiatry. 2019;176(11):911–22. https://doi.org/10.1176/appi.ajp.2019.18101191.

    PubMed  Article  Google Scholar 

  31. Hurd YL, Yoon M, Manini AF, Hernandez S, Olmedo R, Ostman M, et al. Early phase in the development of cannabidiol as a treatment for addiction: opioid relapse takes initial center stage. Neurotherapeutics. 2015;12(4):807–15. https://doi.org/10.1007/s13311-015-0373-7.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  32. Morgan CJ, Das RK, Joye A, Curran HV, Kamboj SK. Cannabidiol reduces cigarette consumption in tobacco smokers: preliminary findings. Addict Behav. 2013;38(9):2433–6. https://doi.org/10.1016/j.addbeh.2013.03.011.

    PubMed  Article  Google Scholar 

  33. Hindocha C, Freeman TP, Grabski M, Stroud JB, Crudgington H, Davies AC, et al. Cannabidiol reverses attentional bias to cigarette cues in a human experimental model of tobacco withdrawal. Addiction. 2018. https://doi.org/10.1111/add.14243.

  34. Pokorski I, Clement N, Phung N, Weltman M, Fu S, Copeland J. Cannabidiol in the management of in-patient cannabis withdrawal: clinical case series. Future Neurol. 2017;12(3):133–40. https://doi.org/10.2217/fnl-2016-0035.

    CAS  Article  Google Scholar 

  35. Solowij N, Broyd SJ, Beale C, Prick JA, Greenwood LM, van Hell H, et al. Therapeutic effects of prolonged cannabidiol treatment on psychological symptoms and cognitive function in regular cannabis users: a pragmatic open-label clinical trial. Cannabis Cannabinoid Res. 2018;3(1):21–34. https://doi.org/10.1089/can.2017.0043.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  36. • Haney M, Malcolm RJ, Babalonis S, Nuzzo PA, Cooper ZD, Bedi G, et al. Oral cannabidiol does not alter the subjective, reinforcing or cardiovascular effects of smoked cannabis. Neuropsychopharmacology. 2016;41(8):1974–82. https://doi.org/10.1038/npp.2015.367Healthy adults received placebo or oral CBD (200, 400, or 800 mg) prior to administration of high-THC smoked cannabis. CBD pretreatment did not alter self-reported subjective drug effects including reinforcing effects or cardiovascular outcomes relative to placebo.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  37. Chagas MH, Zuardi AW, Tumas V, Pena-Pereira MA, Sobreira ET, Bergamaschi MM, et al. Effects of cannabidiol in the treatment of patients with Parkinson’s disease: an exploratory double-blind trial. J Psychopharmacol. 2014;28(11):1088–98. https://doi.org/10.1177/0269881114550355.

    PubMed  Article  CAS  Google Scholar 

  38. Leehey MA, Liu Y, Hart F, Epstein C, Cook M, Sillau S, et al. Safety and tolerability of cannabidiol in Parkinson disease: an open label, dose-escalation study. Cannabis Cannabinoid Research. 2020. https://doi.org/10.1089/can.2019.0068.

  39. Consroe P, Laguna J, Allender J, Snider S, Stern L, Sandyk R, et al. Controlled clinical trial of cannabidiol in Huntington’s disease. Pharmacol Biochem Behav. 1991;40(3):701–8. https://doi.org/10.1016/0091-3057(91)90386-g.

    CAS  PubMed  Article  Google Scholar 

  40. Elms L, Shannon S, Hughes S, Lewis N. Cannabidiol in the treatment of post-traumatic stress disorder: a case series. J Altern Complement Med. 2019;25(4):392–7. https://doi.org/10.1089/acm.2018.0437.

    PubMed  PubMed Central  Article  Google Scholar 

  41. Loflin MJ, Babson KA, Bonn-Miller MO. Cannabinoids as therapeutic for PTSD. Curr Opin Psychol. 2017;14:78–83. https://doi.org/10.1016/j.copsyc.2016.12.001.

    PubMed  Article  Google Scholar 

  42. Carlini EA, Cunha JM. Hypnotic and antiepileptic effects of cannabidiol. J Clin Pharmacol. 1981;21(S1):417 s–27 s. https://doi.org/10.1002/j.1552-4604.1981.tb02622.x.

    CAS  Article  Google Scholar 

  43. Shannon S, Opila-Lehman J. Effectiveness of cannabidiol oil for pediatric anxiety and insomnia as part of posttraumatic stress disorder: a case report. Perm J. 2016;20(4):16–005. https://doi.org/10.7812/tpp/16-005.

    PubMed  PubMed Central  Article  Google Scholar 

  44. Chagas MH, Eckeli AL, Zuardi AW, Pena-Pereira MA, Sobreira-Neto MA, Sobreira ET, et al. Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson’s disease patients: a case series. J Clin Pharm Ther. 2014;39(5):564–6. https://doi.org/10.1111/jcpt.12179.

    CAS  PubMed  Article  Google Scholar 

  45. Naftali T, Mechulam R, Marii A, Gabay G, Stein A, Bronshtain M, et al. Low-dose cannabidiol is safe but not effective in the treatment for Crohn’s disease, a randomized controlled trial. Dig Dis Sci. 2017;62(6):1615–20. https://doi.org/10.1007/s10620-017-4540-z.

    CAS  PubMed  Article  Google Scholar 

  46. Jadoon KA, Ratcliffe SH, Barrett DA, Thomas EL, Stott C, Bell JD, et al. Efficacy and safety of cannabidiol and tetrahydrocannabivarin on glycemic and lipid parameters in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel group pilot study. Diabetes Care. 2016;39(10):1777–86. https://doi.org/10.2337/dc16-0650.

    CAS  PubMed  Article  Google Scholar 

  47. Tomida I, Azuara-Blanco A, House H, Flint M, Pertwee RG, Robson PJ. Effect of sublingual application of cannabinoids on intraocular pressure: a pilot study. J Glaucoma. 2006;15(5):349–53. https://doi.org/10.1097/01.ijg.0000212260.04488.60.

    PubMed  Article  Google Scholar 

  48. Iffland K, Grotenhermen F. An update on safety and side effects of cannabidiol: a review of clinical data and relevant animal studies. Cannabis Cannabinoid Res. 2017;2(1):139–54. https://doi.org/10.1089/can.2016.0034.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  49. White CM. A review of human studies assessing cannabidiol’s (CBD) therapeutic actions and potential. J Clin Pharmacol. 2019;59(7):923–34. https://doi.org/10.1002/jcph.1387.

    CAS  PubMed  Article  Google Scholar 

  50. Epidiolex (Cannabidiol) prescribing information. In: Greenwich Biosciences I, editor. Carlsbad, CA; 2018.

  51. Stout SM, Cimino NM. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. Drug Metab Rev. 2014;46(1):86–95. https://doi.org/10.3109/03602532.2013.849268.

    CAS  PubMed  Article  Google Scholar 

  52. 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). https://doi.org/10.3390/jcm8070989.

  53. Anderson GD, Chan LN. Pharmacokinetic drug interactions with tobacco, cannabinoids and smoking cessation products. Clin Pharmacokinet. 2016;55(11):1353–68. https://doi.org/10.1007/s40262-016-0400-9.

    CAS  PubMed  Article  Google Scholar 

  54. Madden K, Tanco K, Bruera E. Clinically significant drug-drug interaction between methadone and cannabidiol. Pediatrics. 2020;145(6). https://doi.org/10.1542/peds.2019-3256.

  55. Geffrey AL, Pollack SF, Bruno PL, Thiele EA. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia. 2015;56(8):1246–51. https://doi.org/10.1111/epi.13060.

    CAS  PubMed  Article  Google Scholar 

  56. Corroon J, Kight R. Regulatory status of cannabidiol in the United States: a perspective. Cannabis Cannabinoid Res. 2018;3(1):190–4. https://doi.org/10.1089/can.2018.0030.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

Download references

Funding

This work was supported by the National Institute on Drug Abuse (NIDA) Training Grant T32DA07209.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tory R. Spindle.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Cannabis

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sholler, D.J., Schoene, L. & Spindle, T.R. Therapeutic Efficacy of Cannabidiol (CBD): a Review of the Evidence From Clinical Trials and Human Laboratory Studies. Curr Addict Rep 7, 405–412 (2020). https://doi.org/10.1007/s40429-020-00326-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40429-020-00326-8

Keywords

  • Cannabidiol
  • Cannabis
  • Clinical trials
  • Cannabinoids