Navigating the CBD Research Landscape: Unveiling Best Practices in the Post-MMCREA Era

Joel Latham, President and CEO of Incannex Healthcare Inc.

Cannabinoids have great potential for medical applications, but this potential will only be achieved through investment in high-quality in vivo and in vitro clinical research. That’s why the Medical Marijuana and Cannabidiol Research Expansion Act (MMCREA) was a major game-changer for the US pharmaceutical industry.

Enacted in December 2022, the law allows for research and clinical trials on new drug candidates that include cannabidiol, better known simply as CBD, and perhaps the most well-known chemical found in cannabis.

Although research on cannabinoids is now allowed in a growing number of countries, including the United States and Australia, there are still a number of restrictions and corresponding licenses and permits required to work with these chemicals. As such, it’s still early days as research institutions and companies work through the administrative barriers that slow down research engagement.

CBD is a drug with powerful healing potential and pharmaceutical companies should treat it as such. This article will outline the best practices for initiating scientific and ethical R&D that may lead to quality, synthetic CBD therapeutics that target unmet treatment needs.

Key changes under the MMCREA

Before MMCREA was enacted, marijuana and cannabidiol were simply classified as Schedule I substances, meaning they had no acceptable medical use, limited data on their safety, and significant potential for abuse.

Section 101 of the MMCREA, titled "Marijuana Research Applications," maintains the Schedule I classification but also amends the Controlled Substances Act to allow the US attorney general to grant research access to marijuana and all its derivatives, including CBD. Of course, there's still a catch: Research applications must be approved by a federal agency that funds scientific research, the Drug Enforcement Agency, or the US Secretary of Health and Human Services (HHS). The project also must adhere to regulations governing research involving Schedule I substances.

How the First FDA-approved Cannabinoid Products Set the Stage

Unfortunately, due to the history of CBD and cannabis in the United States, preconceived notions about these molecules based on anecdotal reports and low-quality experiments that lacked appropriate controls persist. However, the FDA hasn’t been entirely opposed to cannabinoid products.

For example, Epidiolex (cannabidiol), approved by the FDA in 2018 for patients aged two years and older with seizures associated with Dravet syndrome or Lennox-Gastaut Syndrome, is a prescription form of CBD developed from a specific strain of CBD with no THC—the substance that contributes to a “high.” Despite being derived from real CBD, Epidiolex is no longer a controlled substance as of 2020 when the DEA updated its classification.

Although Epidiolex is often credited with shining a spotlight on pharmaceuticals containing CBD, the FDA actually approved the first synthetic cannabinoid products decades ago, specifically Cesamet (nabilone) and Marinol (dronabinol) in 1985 to treat nausea and vomiting associated with chemotherapy treatments for cancer. The latter’s indication expanded in 2016 to include anorexia in adults with HIV/AIDS.

However, the 2023 legislation definitively opened the door to designing and executing high-quality, rigorous clinical studies of drug candidates. The only problem is that the broader pharmaceutical industry is still figuring out how to operate within the law while still producing life-altering cannabinoid products that address conditions with significant unmet medical need.

Producing Pharmaceutical-grade CBD Products

Expectations for quality, safety, consistency, and efficacy in cannabinoid products should be the same as those for any other pharmaceutical product, meaning they must be developed and produced in a facility that follows the World Health Organization’s Good Manufacturing Practices and is GMP-certified. GMP-certified products emphasize quality and require significant documentation and inspections at all stages of the process to ensure safety and efficacy for patients. Additionally, treating cannabinoid products just like other pharmaceuticals requires clinical trials conducted according to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) Guideline for Good Clinical Practice (GCP), better known simply as ICH GCP.

There is value in early-stage academic clinical trials or open-label observational studies that are designed to establish proof of concept, however, randomized, controlled, double-blind clinical trials remain the gold standard to generate high-quality evidence on safety and efficacy.

New Strategy to Accelerate Pharmaceutical-grade Cannabinoids

Unfortunately, the time-consuming clinical research process and administrative hurdles keep many companies from exploring the benefits cannabinoids may offer patient populations as well as value to their investors and bottom line. At Incannex, we’ve identified several strategies to bring new cannabinoid drug candidates to market.

Drug Repurposing: By creating combination medicines that incorporate active pharmaceutical ingredients with pre-established safety and efficacy data, such as generic medications, drugmakers can accelerate the development process while still meeting all the regulatory requirements necessary to produce pharmaceutical-grade cannabinoid products.

Incannex develops synthetic cannabinoid drugs with novel delivery systems not seen in the marketplace before using the highest standards for development and manufacturing. One of our drug candidates,IHL-42x, is a novel cannabinoid compound designed to treat obstructive sleep apnea, a condition with no prescription treatment options. The product combines low-dose dronabinol, a synthetic form of THC, and acetazolamide, a carbonic anhydrase inhibitor. Another drug candidate, IHL-675A, combines hydroxychloroquine and cannabidiol for pain associated with inflammatory conditions, such as rheumatoid arthritis.

Gold-standard clinical trials: Our clinical studies are double-blind and multi-armed so that we can analyze the safety and efficacy of each main active ingredient separately and working together. We’ve also initiated early discussions with the FDA to ensure that our Australian-based Phase II clinical studies meet all regulatory requirements to ensure a smooth transition to US sites as we advance to large-scale Phase III trials.

Patent Protection: Despite working with generic medications, our combinations are proprietary. We have attractive market positions generated from patient-protected drug candidates.

Collaboration and Transparency are Key

In addition to tapping into drugs with already-established data, two other critical components of commercializing cannabinoid products are collaboration and transparency. Since the MMCREA was passed, pharmaceutical companies are still learning what is needed to navigate the regulatory, legal, medical, and ethical requirements to successfully develop synthetic cannabinoid compounds. To that point, the FDA has provided guidance for developing products under the MMCREA, given that the law is so new that there are few established precedents for developing products under it.

Of course, as time goes on, we expect more treatments featuring cannabinoids to appear on the market, particularly because patient populations are demanding and deserving of alternative treatment options. We believe that recognition of the life-altering potential of this chemical has only just begun.

About the Author

Joel Latham, President and CEO of Incannex Healthcare Inc., is responsible for the company’s commercial operations, strategic decision-making, and oversight of all clinical development assets. Joel has 20 years commercial management and executive experience, working for a range multi-national publicly traded companies.