Canopy Growth and its medical division, Spectrum Therapeutics, have completed and published a new study on the long-term effects of cannabidiol (CBD), which has crucially indicated a lack of long-term toxicity at physiologically relevant concentrations.
The study was conducted in partnership with NemaLife Inc., and is published in Cannabis and Cannabinoid Research journal and available online.
Currently, a major hurdle in the acceptance of CBD as treatment for chronic conditions relates to the general lack of long-term safety data. Indeed, the U.S. Food and Drug Administration (FDA) has publicly stated that data gaps on long-term safety risks hinder the establishment of guidelines for the safe and legal use of CBD in foods and supplements.
Given that data on the long-term CBD use in humans and mammalian surrogate models may not be available for some time, a well-established preclinical model of long-term toxicity has been needed to immediately inform evidence-based understanding of the effects of CBD.
This study was commissioned to evaluate the solubility, stability, acute toxicity, thermotolerance, and effects on lifespan of CBD in C. elegans as part of Canopy Growth’s ongoing commitment to provide the data required to support and influence public policy through research. The Company has suggested that this study represents the first long-term toxicity and lifespan research regarding the effects of chronic exposure to cannabidiol (CBD) – one of the cannabinoids found in cannabis.
Acute and long-term exposure studies of CBD at physiologically relevant concentrations were studied in a worm model Caenorhabditis elegans (C. elegans) on the basis that 60-80% of their genes are shared with humans, and their comparatively short lifespan of 2-3 weeks makes such studies feasible.
In the C. elegans model, which is recognised as a valid model for this kind of research, CBD did not demonstrate any degree of acute or life-long toxicity or related liabilities at physiological concentrations. Instead, CBD extended mean lifespan up to 18% and increased late-stage life activity by up to 206% compared to the untreated controls within the study.
The study authors highlight that CBD did not demonstrate any degree of acute or lifelong toxicity or related liabilities at physiologically relevant concentrations. Indeed, CBD extended mean lifespan up to 18.3% and increased late-stage life activity by up to 206.4% compared to controls. At low (10 μM) and medium (40 μM) concentrations, CBD attenuated age-related declines in motility on days 12 and 15. Moreover, treatment with 40 μM CBD significantly increased thermotolerance compared to the untreated controls.
Acute toxicity assays with CBD did not have a significant impact on C. elegans survival or motility, with the exception of 4000 μM CBD, which significantly reduced motility; however, this concentration is at least 10 times outside of physiologically relevant concentrations.
“Despite widespread use of CBD, no life-long toxicity studies had been conducted to date to determine the impact – or potential impact – of long-term exposure to CBD,” shared Hunter Land, Senior Director of Translational and Discovery Science at Canopy Growth. “These results serve as the only CBD life-long exposure data in an in vivo model to date, and the absence of long-term toxicity gives us the evidence we need as an industry to continue researching the potential health benefits for the broader application of CBD.”
The regulatory implications of the findings demonstrated by this study are of paramount importance.
Governments around the world are increasingly aware of the need to implement scientifically led regulations on the CBD industry, particularly in relation to food and beverage products. However, the lack of robust evidence to support the safe use of the compound continues to hinder these regulatory processes.
In the U.S. following the passage of the Agriculture Improvement Act of 2018,13 also known as the “Farm Bill,” hemp-derived CBD was removed from the Controlled Substance Act. Under this regulatory framework, management of CBD product manufacturing and sale falls under the FDA and Federal Trade Commission, yet no formal regulations of manufacturing or sale have been implemented.
Widespread use of CBD products continues to proliferate, despite lack of regulation. The FDA has publicly stated that two significant concerns that are both difficult to address and have little available data remain a barrier to formalized regulations: safe levels of CBD for daily consumption and the effects of lifelong use. The results of this study directly address these two needs, and fill some of the data gaps needed to establish evidence-based safety-oriented regulations.
Data from studies like this is increasingly needed to ensure that the CBD industry can continue to grow.
The research is an extremely positive first-step in building a body of evidence that underscores the safe and effective use of CBD as an ingredient.
The researchers suggest that further investigations into the life-long use of CBD should be carried out in mammalian models. Canopy Growth and its medical division Spectrum Therapeutics are already undertaking a range of research initiatives aimed at furthering the understanding of – and unleashing – the full potential of cannabidiol.