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The Characteristics of Clinical Trials on Cannabis and Cannabinoids: A Review of Trials for Therapeutic or Drug Development Purposes



Patients and healthcare practitioners are increasingly interested in using cannabis and cannabinoids to address unmet clinical needs. Although we have clinical evidence on the medical use of cannabinoids, a significant portion of the data is not based on randomized clinical trials, which are considered the gold standard in clinical research. We have reviewed the registered clinical trials on cannabis and cannabinoids for therapeutic or drug development purposes to underline the past and current attempts to generate robust clinical evidence and identify existing knowledge gaps.


We reviewed four clinical trial registries (International Clinical Trials Registry Program [ICTRP],, European Clinical Trial Registry [EUCTR], Australian New Zealand Clinical Trial Registry [ANZCTR]) to identify clinical trials on cannabinoids (phyto- or synthetic) or cannabis-based medications between January 1, 2000, and December 31, 2021. All interventional clinical trials on cannabinoids and other compounds interacting with the endocannabinoid system, regardless of the investigated medical condition, assessed health outcomes, or choice of comparator, were included, provided they had a therapeutic or drug development purpose. Data on the primary sponsor, type of sponsor, date of registration, recruitment status, number of participants, study design, the phase of the study, country, medical conditions, investigated cannabinoids, and the route of administration were extracted. The therapeutic area and class of cannabinoids were identified based on the details of each trial.


We included 834 out of 2966 reviewed clinical trials. The number of registered clinical trials has constantly increased from 30 in 2013 to 103 in 2021. More than 40% of registered clinical trials in 2021 were phase II and phase III clinical trials. The mean number of trial enrollments for completed, ongoing, and terminated studies were 128, 156, and 542, respectively. Clinical research on Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and the oral routes of administration dominate the field. Approximately two-thirds of clinical trials were conducted in five therapeutic areas (i.e., ‘Chronic pain,’ ‘Mental, behavioral or neurodevelopmental disorders,’ ‘Nervous system diseases,’ ‘Endocrine, nutritional or metabolic diseases,’ and ‘Neoplasms’). Pharmaceutical companies sponsored 39% of all clinical trials. However, trial sponsorships vary noticeably in different jurisdictions, likely due to, in part, different regulatory frameworks.


Our review highlights the diversification of clinical trials on cannabinoid-based medications in the past 21 years. This review underlines the increased interest in conducting clinical studies on new cannabinoid administration methods such as topical applications and on the investigation of emerging phyto- and synthetic cannabinoids. Moreover, more clinical trials have been designed to explore the potential therapeutic benefits of cannabinoids in areas such as mental, behavioral, or neurodevelopmental disorders and skin diseases. There is a need for granular analyses of clinical trials on more commonly studied therapeutic areas such as chronic pain, nervous system diseases, and mental and behavioral disorders to generate more actionable information and insight for all stakeholders.

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  1. Bridgeman MB, Abazia DT. Medicinal cannabis: history, pharmacology, and implications for the acute care setting. Pharm Ther. 2017;42(3):180–8.

    PubMed  PubMed Central  Google Scholar 

  2. Ben AM. Cannabinoids in medicine: a review of their therapeutic potential. J Ethnopharmacol. 2006;105(1–2):1–25.

    Article  CAS  Google Scholar 

  3. Montero-Oleas N, Arevalo-Rodriguez I, Nuñez-González S, et al. Therapeutic use of cannabis and cannabinoids: an evidence mapping and appraisal of systematic reviews. BMC Complement Med Ther. 2020.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Government of Canada. Marihuana Medical Access Regulations (SOR/2001-227) [Internet]. Canada Gaz. 2001 p. 1–30.

  5. Schlag AK. An evaluation of regulatory regimes of medical cannabis: what lessons can be learned for the UK? Med Cannabis Cannabinoids. 2020;3(1):25–60.

    Article  Google Scholar 

  6. Ipsos. New global study: most believe that cannabis will be legal in coming years | Ipsos [Internet]. Glob. Views Vices – 2019. 2019.

  7. Gallup. Support for Legal Marijuana Holds at Record High of 68% [Internet]. 2021.

  8. Kaplan L, Klein T, Wilson M, et al. Knowledge, practices, and attitudes of Washington State health care professionals regarding medical cannabis. Cannabis Cannabinoid Res. 2020;5(2):172–82.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Weisman JM, Rodríguez M. A systematic review of medical students’ and professionals’ attitudes and knowledge regarding medical cannabis. J Cannabis Res. 2021;3(1):47.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Rønne ST, Rosenbæk F, Pedersen LB, et al. Physicians’ experiences, attitudes, and beliefs towards medical cannabis: a systematic literature review. BMC Fam Pract. 2021.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Gardiner KM, Singleton JA, Sheridan J, et al. Health professional beliefs, knowledge, and concerns surrounding medicinal cannabis—a systematic review. PLoS ONE. 2019.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Orjuela-Rojas JM, García Orjuela X, Ocampo SS. Medicinal cannabis: knowledge, beliefs, and attitudes of Colombian psychiatrists. J Cannabis Res. 2021.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Crowley D, Collins C, Delargy I, et al. Irish general practitioner attitudes toward decriminalisation and medical use of cannabis: results from a national survey. Harm Reduct J. 2017.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Hordowicz M, Jarosz J, Czaplińska M, et al. Polish physicians’ perspectives on medical cannabis policy and educational needs: results of an online survey. J Clin Med. 2021;10(19):4545.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Allan GM, Finley CR, Ton J, et al. Systematic review of systematic reviews for medical cannabinoids. Can Fam Physician. 2018;64(2):e78-94.

    PubMed  PubMed Central  Google Scholar 

  16. Petzke F, Tölle T, Fitzcharles MA, et al. Cannabis-based medicines and medical cannabis for chronic neuropathic Pain. CNS Drugs Adis. 2022;1:31–44.

    Article  Google Scholar 

  17. Johal H, Devji T, Chang Y, et al. Cannabinoids in chronic non-cancer pain: a systematic review and meta-analysis. Clin Med Insights Arthritis Musculoskelet Disord. 2020.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Wang L, Hong PJ, May C, et al. Medical cannabis or cannabinoids for chronic non-cancer and cancer related pain: a systematic review and meta-analysis of randomised clinical trials. BMJ. 2021.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA J Am Med Assoc. 2015;313(24):2456–73.

    Article  CAS  Google Scholar 

  20. Black N, Stockings E, Campbell G, et al. Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis. Lancet Psychiatry. 2019;6(12):995–1010.

    Article  PubMed  PubMed Central  Google Scholar 

  21. National Academies of Sciences Engineering and Medicine. The health effects of cannabis and cannabinoids [Internet]. Washington, D.C.: National Academies Press; 2017. (10.17226/24625).

    Google Scholar 

  22. Orsolini L, Chiappini S, Volpe U, et al. Use of medicinal cannabis and synthetic cannabinoids in post-traumatic stress disorder (PTSD): a systematic review. Med Medicina (Kaunas). 2019.

    Article  Google Scholar 

  23. Mücke M, Phillips T, Radbruch L, et al. Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2018.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Amato L, Minozzi S, Mitrova Z, et al. Revisione sistematica sull’efficacia terapeutica e la sicurezza della cannabis per i pazienti affetti da sclerosi multipla, dolore neuropatico cronico e pazienti oncologici che assumono chemioterapie. Epidemiol Prev. 2017.

    Article  PubMed  Google Scholar 

  25. Lim K, See YM, Lee J. A systematic review of the effectiveness of medical cannabis for psychiatric, movement and neurodegenerative disorders. Clin Psychopharmacol Neurosci. 2017;15(4):301–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. World Health Organization. International Classification of Diseases, 11th Revision (ICD-11). Geneva [Internet]: World Heal. Organ; 2018.

    Google Scholar 

  27. ANZCTR. ANZCTR Data field definitions [Internet]. 2019. p. 1–26.

  28. Sam AH, Salem V, Ghatei MA. Rimonabant: from RIO to Ban. J Obes. 2011.

    Article  PubMed  PubMed Central  Google Scholar 

  29. European Medicines Agency T. PRESS RELEASE The European Medicines Agency recommends suspension of the marketing authorisation of Acomplia [Internet]. 2008. p. 4–5.

  30. International Association for Cannabis as Medicine. Recommendation of suspension of the marketing authorisation of rimonabant and discontinuation of clinical research into cannabinoid receptor antagonists [Internet]. 2008.

  31. Cooper ZD, Abrams DI, Gust S, et al. Challenges for clinical cannabis and cannabinoid research in the United States. J Natl Cancer Inst Monogr. 2021;2021(58):114–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Walsh KB, McKinney AE, Holmes AE. Minor cannabinoids: biosynthesis, molecular pharmacology and potential therapeutic uses. Front Pharmacol. 2021.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Pellati F, Borgonetti V, Brighenti V, et al. Cannabis sativa L. and nonpsychoactive cannabinoids: their chemistry and role against oxidative stress, inflammation, and cancer. Biomed Res Int. 2018.

    Article  PubMed  PubMed Central  Google Scholar 

  34. National Center for Drug Abuse Statistics. Opioids crisis statistics: prescription opioid abuse. [Internet]. 2022.

  35. Boscarino JA, Rukstalis M, Hoffman SN, et al. Risk factors for drug dependence among out-patients on opioid therapy in a large US healthcare system. Addiction. 2010;105(10):1776–82.

    Article  PubMed  Google Scholar 

  36. National Institutes of Health (NIH). NIH to investigate minor cannabinoids and terpenes for potential pain-relieving properties [Internet]. ENP Newswire. 2019.

  37. Zhong H, Chan G, Hu Y, et al. A comprehensive map of FDA-approved pharmaceutical products. Pharmaceutics. 2018;10(4):263.

  38. Lutz B. Neurobiology of cannabinoid receptor signaling. Dialogues Clin Neurosci. 2020;22(3):207–22.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Drug Enforcement Administration. Drug Scheduling [Internet]. 2006. p. 299–309.

  40. Therapeutic Goods Administration. Medicinal cannabis: Role of the TGA | Therapeutic Goods Administration (TGA) [Internet]. Ther. Goods Adm. 2021.

  41. Goyal S, Kubendran S, Kogan M, et al. High expectations: The landscape of clinical trials of medical marijuana in oncology. Complement Ther Med. 2020;49:102336.

    Article  PubMed  Google Scholar 

  42. Kowal MA, Hazekamp A, Grotenhermen F. Review on clinical studies with cannabis and cannabinoids 2010–2014. Cannabinoids. 2016;11:1–18.

  43. Disclaimer [Internet].

  44. EU Clinical Trials Register. About the Clinical Trials Register-Legal Notice [Internet].

  45. Australian New Zealand Clinical Trials Registry (ANZCTR). Disclaimer [Internet]. Aust. New Zeal. Clin. Trials Regist. 2021.

  46. Zarin DA, Ide NC, Tse T, et al. Issues in the registration of clinical trials. J Am Med Assoc. 2007;297(19):2112–20.

    Article  CAS  Google Scholar 

  47. Wilbert-Lampen U, Leistner D, Greven S, et al. Cardiovascular events during world cup soccer. N Engl J Med. 2008;358(5):475–83.

    Article  CAS  PubMed  Google Scholar 

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We would like to thank Dr. Pooyeh Graili for her comments on the scientific content of this article.

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Correspondence to Farhang Modaresi MD., MBE.

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FM and KT declare that this study was conducted without any commercial or financial relationships that could be considered a potential conflict of interest.

Authors’ Contributions

FM: Conceptualization, methodology, investigation, data curation, writing—original draft, review and editing, visualization. KT: Conceptualization, methodology, investigation, data curation, writing—review and editing, visualization. All authors approved the final version of this manuscript to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Data supporting this study are openly available from the website of respective clinical trial registries:,,,

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Modaresi, F., Talachian, K. The Characteristics of Clinical Trials on Cannabis and Cannabinoids: A Review of Trials for Therapeutic or Drug Development Purposes. Pharm Med 36, 387–400 (2022).

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