Cannabidiol (CBD), a prominent non-intoxicating cannabinoid sourced from marijuana and hemp, has surged in use following the 2018 Farm Bill in the United States, which legalized hemp derivatives with THC levels below 0.3%. This regulatory relaxation extends to markets in Canada, China, the UK and Switzerland, enabling CBD's incorporation in numerous consumer products. Although CBD is touted for benefits such as alleviating insomnia, anxiety, pain, inflammation, and immune disorders, only its purified form, Epidiolex, gained FDA and EU approval for specific pediatric epilepsies. The increasing prevalence of CBD necessitates a deeper investigation into its pharmacological and toxicological profiles to elucidate its therapeutic breadth but also its safety as a consumer product.

Despite the growing interest in CBD, substantial gaps persist in our comprehensive understanding of its safety, mechanistic interactions, and efficacy across various medical indications. The complexity inherent in botanical extracts, which include diverse minor cannabinoids and terpenoids, further compounds the challenges faced by regulators and researchers. Research efforts continue to expand; however, a robust elucidation of dose-response relationships and comprehensive toxicological evaluations remains scant. Addressing these knowledge gaps is crucial for optimizing CBD's therapeutic capacities while upholding safety standards. The pursuit of evidence-based knowledge is paramount in shaping policy and clinical practice.

This Research Topic aims to collate cutting-edge findings and foster a nuanced understanding of CBD through expert insights. It seeks to synthesize existing knowledge, identify research priorities, and chart a pathway for evidence-based CBD application. To gather further insights into toxicology, indications, and efficacy of CBD, we welcome articles addressing, but not limited to, the following themes:

o Toxicological evaluation of complex mixtures containing CBD

o Safety considerations for distinct populations

o Mechanisms of toxicity in CBD applications

o Characterization of therapeutic indications and clinical settings

o Definitions of dose-response relationships with CBD products

o Pharmacodynamics, adverse events, and method of delivery implications

o Evaluation of CBD’s abuse liability

o Nonclinical and clinical safety profiles

o Pharmaco(toxico)dynamics and pharmaco(toxico) kinetics including PBPK modeling

o Cannabidiol and cannabidivarin are 5-HT2B receptor agonists

o Effects of cannabidiol on spontaneous opioid withdrawal

o Risks of cannabinoid exposure on birth outcomes

o Dose variability and manufacturing quality

o The impact of product formulation on the pharmacokinetics and pharmacodynamics of cannabis products, including edibles

o Impact of cannabis exposure on gut barrier function and the microbiome in metabolic health and disease

Offering an authoritative reference for researchers, clinicians, and policymakers, this Research Topics seeks to bridge existing gaps, facilitate evidence-based guidance for clinical practices, inform regulation, and support the responsible innovation of cannabinoid-based medicines.

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Understanding cannabidiol: Toxicology, therapeutic potentials, and clinical implications