Navigating tomorrow: 5 lessons from the FDA’s 50 years of experience with cannabis research and product development

Summary

• Over the last 50 years, the US Food and Drug Administration (FDA) has built up a bank of knowledge in the evolving landscape of cannabis and cannabis-derived products (CCDPs) –reviewing over 800 research applications.  
• In a recent article, the FDA summarized its experiences and challenges in this space to assist researchers looking to embark on their own CCDP drug development journey, covering quality safeguarding, therapeutic potential, medical misconceptions, routes of administration and new CCDPs emerging on the market.
• Read on to discover five valuable lessons learned and new opportunities for pharmaceutical companies to enter the medicinal cannabis market with high-quality, high-purity CCDPs that hold huge potential for global patient health. 

Cannabis (such as marijuana and hemp) and cannabis-derived products, or CCDPs, (such as cannabidiol or CBD), have become an intense area of research across the pharmaceutical industry, driven by their potential therapeutic benefits for human health. In the early 1970s, the US Food and Drug Administration (FDA) started receiving applications to study CCDPs in humans, and since then, the organization has received over 800 investigational new drug applications (INDs) and pre-investigational new drug applications (pre-INDs).  

The FDA is committed to supporting these submissions, providing guidance, advice and recommendations at every turn – recently releasing an article on its thoughts, experiences and challenges associated with cannabis research and drug development in the last 50 years. It reveals the evolution of the market, considerations for success and predictions for the future. But one thing is clear. As high-quality active pharmaceutical ingredients (APIs) develop and robust scientific evidence dispels medical misconceptions and outdated stigmas, the CCDP market is witnessing an exciting era for pharmaceutical companies to tap into. Read on to find out five valuable lessons learned from the agency’s involvement in cannabis-based research and development, as well as future opportunities to innovate in the market with APIs that are setting a new standard in quality and purity.

CCDP quality is paramount for clinical trial success

The FDA has stringent quality and safety requirements for CCDPs in clinical research. However, quality controls and therapeutic consistency are known challenges associated with CCDP drug development. As such, the FDA has provided clear guidance and quality considerations for CCDP investigators – helping to increase the chances of successful clinical research outcomes. Based on the agency’s recommendations, CCDP innovators should conduct stability tests to ensure cannabis-based drug products remain stable over time. In addition, it is important to use scientifically validated methods to characterize these molecules for future clinical research. This includes testing for the identity, purity, strength and quality of the compounds. For example, using: 

• High-performance liquid chromatography (HPLC) to test for the identity and purity of cannabinoids 
• Gas chromatography-mass spectrometry (GC-MS) to test for residual solvents 
• Validated microbiological methods to test for microbial contamination. 

These recent advancements in CCDP safety and quality promise significant benefits for pharmaceutical companies pioneering in this market, bolstering long-term success, providing a competitive edge and ensuring safety for patients. At dsm-firmenich, we also believe that quality is the key to clinical trial success. That’s why we offer, together with Brains Bioceutical, a cannabinoid API portfolio that is of the highest and purest quality and supported by the relevant Drug Master File (DMF). Our APIs are manufactured under pharmaceutical Good Manufacturing Practice (GMP) in certified manufacturing facilities, which guarantees consistent production to reliably meet compendial-defined product specifications, ensuring that patient safety is not compromised by the manufacturing process.

The potential therapeutic benefits of CCDPs are expanding

In the past 10 years, the FDA has witnessed a proliferation of CCDP applications and new product types proposed for exploration in human clinical trials. The agency has revealed that most of these trials have focused on the following therapeutic areas:  

• Addiction and pain medicine - 53% 
• Neurology - 19%  
• Immunology and inflammation - 14%  
• Psychiatry - 9% 
• Other – 5% 

To date though, the FDA has only approved one naturally occurring cannabis-based drug – Epidiolex (approved in 2018), which is a natural form of cannabidiol (CBD) used to treat epilepsy. However, the promising therapeutic potential of CCDPs is undeniable and pharmaceutical companies should be excited about the evolving opportunities to help more patients with high-quality CCDPs.

For CBD alone, there are currently over 200 active clinical trials (Q3 2023) and 25 indications for which this molecule may have therapeutic benefits.1 As such, the future could bring a new wave of approved CCDP drugs with potentially life-changing benefits for patients suffering with pain, neurological disorders, mental health and much more. CCDPs are also being investigated in difficult-to-treat conditions, such as addiction. Although still in the early stages of study, scientific evidence suggests that CCDPs could play a vital role in mitigating the impact of opioid use disorder for instance.2 This underlines the potential of cannabinoid-based interventions in addressing pressing public health issues, such as the opioid crisis in North America. 

As research on the therapeutic benefits of CCDPs continues to grow, there has never been a more opportune time for pharmaceutical companies to enter the market with novel CCDP-based drugs. Together, Brains Bioceutical and dsm-firmenich have developed a cannabinoid innovation platform that is designed to help drug developers along the entire drug development journey to unlock customized cannabinoid-based therapeutics. We are at the forefront of CCDP research, with a spotlight set on exploring the science behind these molecules in promising indications like pain management, stress and anxiety. 

Clearing the fog: The evidence behind CCDPs is emerging

Despite increasing interest in CCDPs over the last 50 years, medicinal cannabis is no new phenomenon, with evidence indicating that it was used by the Romans and in Chinese medicine almost 5,000 years ago.3,4 However, despite its origins as a natural medicinal substance, cannabis and its derivatives have grappled with a negative stigma, often portrayed as an unsafe and addictive drug. This – combined with a lack of research and quality standards – has led to many medical misconceptions surrounding the benefits of CCDP’s for human health. Nevertheless, the significant increase in robust scientific evidence supporting their therapeutic potential is unravelling the truth behind these unique molecules. 

The fading stigma surrounding CCDP’s has several positive implications for pharmaceutical companies looking to innovate in the cannabis medical industry, including increased patient acceptance, expanded research opportunities, enhanced regulatory support and diversification of treatment options.  

We are committed to advancing science in the CCDP space to help realize the full potential of these ingredients for human health. Our scientific expertise in early-stage drug development combined with our innovation platform can help customers facilitate novel scientific discoveries in the rapidly evolving CCDP market.  

Patient-centric routes of administration are evolving

During the early years of CCDP research, much of the cannabis used in clinical trials was inhaled, with few oral product types on the market. Since then, different routes of administration were used, but it was not until 2010 that the variety of product types dramatically expanded. For instance, the FDA revealed that capsules and tablets, oils, purified extracts, sweets, baked goods, tinctures (herbal extracts) and vaporized products have all been proposed for use in clinical trials. Since 2020 especially, administration routes have continued to expand rapidly and now include products for inhalation, oral ingestion, topical application and injection.  

While the routes of administration for CCDPs have developed significantly since the 1970s, there is still an opportunity to spearhead innovation in this space and pioneer the creation of appealing solid oral dosage formats supporting optimal bioavailability and patient experience. We believe that solid oral formats represent the future of cannabinoid innovation – because they can help to achieve enhanced efficacy while simultaneously increasing patient convenience and therapy adherence. However, developing solid oral dosage systems with cannabinoid APIs comes with its own unique set of challenges due to the low and variable oral bioavailability of these molecules. That is why we are exploring several different drug delivery technologies to identify the best approach for enhanced CBD bioavailability. So far, our in-vivo research has already delivered promising results as we have identified drug delivery technologies that are superior to current leading liquid formulations.

Innovative CCDP’s are on the rise

The FDA anticipates an increase in INDs for innovative CCDPs, such as newly identified or minor cannabinoids. These lesser-known molecules are present in much smaller concentrations in the cannabis plant compared to CBD. However, despite their reduced concentrations, early research demonstrates that they too hold potentially favorable therapeutic benefits in multiple treatment areas.⁵ The FDA also foresees increasing interest in additional components from the cannabis plant, such as terpenes. These naturally occurring chemicals are responsible for the aroma of the cannabis plant and while more research is needed, they could offer interesting health benefits thanks to their possible anti-depressant and anti-cancer properties.^6,7

This is just the beginning for CCDP innovators worldwide. Together with Brains Bioceutical, we are tapping into this rapidly evolving market with a rich pipeline of minor cannabinoids. In the future, we hope to tailor the technologies we have developed in the CBD space – such as the creation of solid oral dosage formats with enhanced bioavailability – to benefit companies exploring and developing pharmaceuticals inspired by minor cannabinoids. 

The insights gained from the FDA underscore the remarkable evolution of the medicinal cannabis landscape, underscoring that the success of introducing new CCDP drugs to market hinges on the quality of these molecules. The recent strides in this area, encompassing emerging scientific evidence, a promising regulatory landscape and the refinement of high-quality, natural APIs, have firmly established the foundations for success in this space.