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

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Abstract

Introduction

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.

Methods

We reviewed four clinical trial registries (International Clinical Trials Registry Program [ICTRP], ClinicalTrials.gov, 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.

Results

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.

Conclusion

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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Acknowledgments

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

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Authors and Affiliations

  1. Concinto Inc., 7398 Yonge St, Thornhill, Toronto, ON, L4J 8J2, Canada

    Farhang Modaresi MD., MBE & Kaivan Talachian PharmD

Authors
  1. Farhang Modaresi MD., MBE
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  2. Kaivan Talachian PharmD
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Correspondence to Farhang Modaresi MD., MBE.

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Funding

No grant or financial contribution was received from a third party.

Conflict of Interest

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.

Data Access Statement

Data supporting this study are openly available from the website of respective clinical trial registries: https://clinicaltrials.gov/, https://www.clinicaltrialsregister.eu/, https://www.anzctr.org.au/Default.aspx, https://www.who.int/clinical-trials-registry-platform/the-ictrp-search-portal.

Ethical Approval

There is no human subject or identifiable personal information in this article, and informed consent is not applicable.

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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). https://doi.org/10.1007/s40290-022-00447-7

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