Reasons to Market a CBG Product… Stat

The FDA has determined that the drug preclusion clause of the Federal Food, Drug, and Cosmetic Act (FD&C Act) makes it unlawful to market cannabidiol (CBD) as a food ingredient or a dietary supplement [DS]. 

Explanation of the Drug Preclusion Clause and CBD

• The Clause’s Purpose: The drug preclusion clause (specifically sections 301(ll) and 201(ff)(3)(B) of the FD&C Act) is designed to protect incentives for pharmaceutical research and development. It generally prevents an article from being marketed as a food or dietary supplement if it has already been approved as a new drug or authorized for substantial clinical investigation as a new drug.
• FDA’s Position on CBD: In June 2018, the FDA approved Epidiolex, a prescription drug containing a highly purified form of CBD, for the treatment of certain rare, severe forms of epilepsy. Because substantial clinical investigations for CBD as a drug were made public before CBD products were marketed as supplements or food, the FDA has concluded that the preclusion clause applies to CBD.
• Current Regulatory Status: As a result, the FDA maintains that most CBD products on the market are not compliant with federal law if they are sold as dietary supplements or added to conventional foods. The FDA has consistently rejected requests to create a legal pathway for CBD under existing food and supplement regulations, citing the preclusion clause and ongoing safety concerns, such as potential liver damage. 

Path Forward

The FDA has stated that a new regulatory pathway is needed to manage the risks associated with CBD products and has requested that Congress create this pathway through new legislation. 

In the meantime, the FDA has focused its enforcement actions on companies that make unsubstantiated health or disease treatment claims for their CBD products or pose a public health threat. 

For official information from the FDA regarding cannabis and cannabis-derived products, you can visit the FDA’s website. 

That statement is generally true, but with nuances: if a substance was lawfully marketed as a food or supplement before being studied as a drug, the drug company doesn’t get exclusive rights to the supplement form, but the FDA can still regulate it as a drug if used for therapeutic claims, creating a dual-track regulatory path (e.g., fish oil/omega-3s). The key is the “grandfather clause” for existing ingredients, but once a company investigates it for specific drug uses, it falls under drug rules, even if the supplement form continues. 

Why it’s generally true (Grandfathering):

• DSHEA (Dietary Supplement Health and Education Act): Ingredients used as supplements before Oct 15, 1994, aren’t considered “New Dietary Ingredients” (NDIs) and don’t need pre-market approval as supplements.
• Fish Oil Example: Omega-3 fatty acids were supplements long before being approved as prescription drugs (ethyl esters), allowing them to remain available as supplements. 

NOTE: there’s also the precedent of red yeast rice, a food, DS, and a drug.

Why it’s complicated (Drug vs. Supplement):

• Dual Use: The same substance can be both a supplement (structure/function claims, no FDA approval needed) and a drug (disease treatment claims, requires FDA approval).
• Exclusion from Supplement Definition: If an ingredient is approved as a drug, it generally can’t be sold as a supplement unless it was already a supplement before drug approval (the grandfather rule).
• Drug Investigation Exclusion: Even if it was a supplement, if substantial clinical investigations have started for a new drug use, it’s excluded from the supplement definition for that specific use. 

In essence: A company can’t claim exclusivity for a supplement if it was already on the market, but if they develop it into an FDA-approved drug, they get drug exclusivity for that specific drug product, not for the general supplement category. 

• What’s a good FDA orphan disease that a pain reliever like CBG would help?

Complex Regional Pain Syndrome (CRPS) and Erythromelalgia (EM) are two FDA-designated orphan diseases where severe, chronic pain is a primary symptom and the development of effective pain relievers is a critical unmet need. 

Complex Regional Pain Syndrome (CRPS)

CRPS is a debilitating, chronic pain condition often triggered by an injury, fracture, or surgery. 

• Symptoms: Patients experience severe pain, along with depression, anxiety, and sleep disorders.
• Unmet Need: There is currently no FDA-approved treatment for CRPS in the United States, highlighting a critical need for new therapeutic approaches.
• Drug Development: The FDA has granted orphan drug status to several investigational formulations for CRPS, including low-dose naltrexone and a novel cannabinoid therapeutic (BRC-002), as well as ketamine. These therapies aim to address the pain and co-morbidities of the condition. 

Erythromelalgia (EM)

EM is a very painful, rare genetic disorder characterized by intense burning pain and severe redness, heat, and sometimes swelling, most often in the extremities (hands and feet). 

• Symptoms: The pain occurs in sudden, debilitating attacks triggered by minimal stressors such as warmth, walking, or wearing warm socks. Patients often use ice baths for temporary relief, which can lead to severe complications like frostbite and infection.
• Unmet Need: There is no established, effective treatment available, and current management often involves avoiding triggers and symptomatic relief with methods like cooling or, in some cases, opioids.
• Drug Development: The FDA has granted orphan drug designation to several candidates for EM, including a Kv7-activating gene therapy and a topical TRPV1 antagonist, demonstrating active research in this area. 

These diseases present significant opportunities for pain reliever development due to their severe pain component, limited treatment options, and the incentives provided by the FDA’s Orphan Drug Act for research into rare conditions. 

Self-certified Generally Recognized as Safe (GRAS) for CBD means a company uses its own scientific data, often with expert panels, to declare its hemp-derived ingredient safe for food use, without mandatory FDA approval, offering faster market entry but carrying the risk of FDA challenge. While this voluntary process allows innovation, the FDA is exploring eliminating this “loophole,” requiring public notification for new ingredients, with some buyers now preferring notified GRAS or FDA-approved ingredients due to regulatory uncertainty surrounding CBD in food. 

What it is:

• Independent Safety Determination: Companies conduct their own safety assessments, gathering data and potentially using independent experts to verify safety for a specific food use.
• No Mandatory FDA Notification: The key is that the company doesn’t have to submit this to the FDA; they just maintain the records internally.
• Benefits: Faster, cheaper, and confidential market entry for new ingredients, notes this YouTube video. 

CBD & Self-Affirmed GRAS: 

• Common for CBD: Due to FDA’s stance on CBD in food, many companies use self-affirmed GRAS as the only pathway to support safety claims, as seen with Balanced Health Botanicals (CBDistillery) and Verdant Oasis.
• FDA’s Stance: The FDA still maintains it’s illegal to add CBD to food, despite GRAS self-affirmations for hemp seed derivatives (not CBD itself), highlighting regulatory tension. 

Current & Future Landscape:

• “Loophole” Under Review: The HHS Secretary announced plans to potentially close the self-affirmed GRAS “loophole” via rulemaking or legislation, making FDA notification mandatory for new ingredients.

Yes, getting drugs for orphan diseases approved is incentivized and often expedited, but it still requires rigorous review; the process is “easier” due to FDA programs like Orphan Drug Designation, tax credits, and accelerated pathways, which encourage development for rare conditions by offering financial perks and faster timelines, though core safety/efficacy standards remain, with newer pathways (like for gene therapy) potentially easing evidence burdens for severe cases. 

Why It’s “Easier” (Incentivized & Faster)

• Orphan Drug Act (ODA) Incentives: Since 1983, the FDA has offered tax credits, fee waivers, and market exclusivity to companies developing treatments for diseases affecting small patient populations (rare diseases).
• Expedited Pathways: Orphan drugs frequently use accelerated programs (Fast Track, Breakthrough Therapy, Priority Review, Accelerated Approval) more often than other drugs, speeding review.
• Plausible Mechanism Pathway: For severe rare diseases, the FDA has a new pathway allowing approval based on limited patient data if a strong scientific rationale (plausible mechanism) exists, a major shift. 

Why It’s Still Rigorous

• No Compromised Standards: The FDA still requires strong evidence of safety and effectiveness; expedited pathways don’t lower the bar but change how evidence is gathered and reviewed (e.g., using surrogate endpoints).
• Designation vs. Approval: Getting “Orphan Drug Designation” is a separate step from final marketing approval; the drug must still go through full scientific review.
• Post-Market Commitments: Drugs approved via accelerated pathways often require later confirmatory trials to prove clinical benefit.