Safety Considerations in Cannabinoid-Based Medicine

Abstract

Cannabinoids are a diverse class of chemical compounds that are increasingly recognized as potential therapeutic options for a range of conditions. While many studies and reviews of cannabinoids focus on efficacy, safety is much less well reported. Overall assessment of the safety of cannabinoid-based medicines is confounded by confusion with recreational cannabis use as well as different study designs, indications, dosing, and administration methods. However, clinical studies in registered products are increasingly available, and this article aims to discuss and clarify what is known regarding the safety profiles of cannabinoid-based medicines, focusing on the medical and clinical safety evidence and identifying areas for future research. The two most well-studied cannabinoids are Δ⁹-tetrahydrocannabinol (THC), or its synthetic variants (dronabinol, nabilone), and cannabidiol (CBD). Across diverse indications, dizziness and fatigue are generally the most common adverse events experienced by patients receiving THC or combined THC and CBD. Patients receiving THC may experience adverse cognitive effects and impairment in psychomotor skills, with implications for driving and some occupations, while CBD may help to lower the psychotropic effects of THC when used in combination. Studies on dependency and addiction in a medical context are limited, but have shown inconsistent findings regarding misuse potential. Generally, the recommended route of administration is oral ingestion, as smoking medicinal cannabinoid products potentially releases mutagenic and carcinogenic by-products. There are several potential drug–drug interactions and contraindications for cannabinoid-based medicines, which physicians should account for when making prescribing decisions. The available evidence shows that, as with any other class of pharmaceuticals, cannabinoid-based medicines are associated with safety risks which should be assessed in the context of potential therapeutic benefits. Each patient should be assessed on an individual basis and physicians must rely on informed, evidence-based decision-making when determining whether a cannabinoid-based medicine could be an appropriate treatment option.

Keywords:

• cannabis
• cannabinoid
• safety
• cannabidiol
• Δ⁹-tetrahydrocannabinol

Acknowledgments

Medical writing assistance was provided to the authors by Helena Cant, MChemPhys, of Complete HealthVizion, McCann Health Medical Communications, and funded by Spectrum Therapeutics, Ontario, Canada. The first draft was prepared based on detailed discussion and input from the authors and revised in accordance with their critical feedback.

Abbreviations

AE, adverse event; CBD, cannabidiol; THC, Δ⁹-tetrahydrocannabinol.

Author Contributions

The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. All authors contributed to the conception and design of the manuscript and data interpretation, and critically revised the manuscript for important intellectual content. The authors take full responsibility for the scope, direction, and content of the manuscript, and have approved the submitted manuscript. They received no compensation related to the development of the manuscript.

Disclosure

Sven Gottschling has received consultancy fees from Bioevents, Bionorica, Biotest, Boehringer Ingelheim, Cogitando, Experten-Futrue, Grünenthal, Hexal, IQQ Institut, Kyowa Kirin, MedConcept, Novartis, Roche, Sandoz, Spectrum Therapeutics, and Tilray.

Oyedeji Ayonrinde has no disclosures to declare.

Arun Bhaskar has received consultancy fees from Spectrum Therapeutics.

Marc Blockman has received consultancy fees from Spectrum Therapeutics.

Oscar D’Agnone has received consultancy fees from Spectrum Therapeutics.

Danial Schecter is a former employee of Spectrum Therapeutics, a former employee of Canopy Growth Corp from February 2019 to March 2020 and has provided consulting services both prior and after this, was previously Chief Medical Advisor of AusCann, and received honoraria from and provided consulting services for the following: Aleafia Health Inc, Shoppers Drug Mart, Khiron, Tilray, and Organigram, outside the submitted work.

Luis David Suárez Rodríguez has received consultancy fees from Spectrum Therapeutics and funding from the Asociacion Mexicana de Medicina Cannabinoide AC, and reports personal fees and non-financial support from Asociación Mexicana de Medicina Cannabinoide AC, outside the submitted work; and is the current President of the Asociación Mexicana de Medicina Cannabinoide AC.

Sherry Yafai has received consultancy fees from Canopy Growth.

Claude Cyr has received consultancy fees from Aurora, Shoppers/Inventiv, Spectrum Therapeutics, and Tilray.

The authors report no other potential conflicts of interest for this work.

Additional information

Funding

This review was sponsored and funded by Spectrum Therapeutics, Ontario, Canada. The sponsor was involved in the conception and design of the article. Medical writing assistance was funded by Spectrum Therapeutics, Ontario, Canada. Neither honoraria nor payments were made for authorship.