The U.S. Food and Drug Administration (FDA) has been at the forefront of evaluating cannabis and cannabis-derived products (CCDPs) for human clinical trials since the early 1970s. With an impressive tally of over 800 investigational new drug applications (INDs) and pre-INDs submitted, the research landscape surrounding cannabis has seen a surge in both academic and commercial interest. The focus has primarily honed in on four major clinical areas: addiction and pain medicine, neurology, immunology and inflammation, and psychiatry. However, the journey through these applications has not been without its complexities, with the FDA grappling with the unique challenges posed by the complex nature of botanical products like cannabis.
Historical Landscape and Application Proliferation
Over the past half-century, cannabis drug development in the United States has undergone a profound evolution. The early 1970s marked the initial wave of applications, predominantly exploring smokable forms of cannabis or single-molecule synthetic active pharmaceutical ingredients encapsulated in capsules or tablets. Notably, the last decade has witnessed a remarkable proliferation of new product types proposed for use in human clinical trials, indicative of the burgeoning interest and advancements in cannabis research. During this period, researchers have submitted over 800 INDs evaluating CCDPs, encompassing both naturally occurring compounds and synthetics, to the FDA.
Exploring Clinical Areas and Product Types
Applications for CCDP research have consistently demonstrated a focus on addiction and pain medicine (53%), neurology (19%), immunology and inflammation (14%), and psychiatry (9%). This distribution underscores the diverse therapeutic avenues researchers are exploring within the cannabis domain. The product types studied have expanded exponentially, ranging from smokable forms to topical, inhalable, injectable, and oral products. The FDA's Botanical Review Team (BRT) plays a pivotal role in evaluating the chemically complex nature of these products, ensuring compliance with regulatory requirements.
Challenges and Recommendations
Amid the surge in applications, the FDA faces the intricate task of reviewing CCDP submissions to ascertain their compliance with regulatory standards. Botanical products, such as cannabis, present a unique challenge due to their complex mixtures and multiple active constituents. The authors of this article, intimately acquainted with the challenges of reviewing these applications, share their experiences and provide recommendations for researchers venturing into cannabis research. The journey involves navigating essential IND criteria, leveraging the pre-IND consultation program, understanding drug master files (DMFs), and utilizing various guidance documents and resources.
Looking Ahead: The Future of Cannabis Drug Development
Despite the growing interest and substantial progress, the FDA has yet to approve a marketing drug application for cannabis to treat any disease or condition. However, the authors highlight historical instances where clinical investigations of botanicals led to the isolation of naturally occurring compounds or derivatives that evolved into well-known pharmaceuticals. Examples include Marinol (1985), Cesamet (1985), Syndros (2016), and Epidiolex (2018). These milestones underscore the potential trajectory of cannabis drug development.
As the landscape continues to evolve, the authors provide their perspective on the future of cannabis drug development. They emphasize the need for meticulous adherence to FDA requirements, regardless of the source of cannabis or any other botanical product under study. The article concludes by offering insights into the potential future trajectory of cannabis drug development, providing a comprehensive perspective on the dynamic and evolving nature of this field.