Cannabinoid research and development: FAQs

Cannabinoids for therapeutic use treat conditions and are therefore subject to specific pharmaceutical quality and regulatory standards, whereas cannabinoids used in food supplements (also known as dietary supplements for consumer health) are not subject to pharmaceutical regulations. The strength and recommended dose for cannabinoids in pharmaceutical preparations are also higher, and they are more rigorously researched in clinical trials to prove their therapeutic effect in preventing and fighting specific diseases. Meanwhile, food supplements are meant to complement a balanced lifestyle, and support wellness more generally.

Synthetic CBD is a chemical-based formula that is manufactured to replicate the structure of natural CBD, whereas natural CBD is a compound found in hemp. Key differences between synthetic CBD vs natural CBD include its origin, purity and even preference.

• Origin: Natural CBD is extracted from Cannabis sativa, with precise stereochemistry. Synthetic CBD is created chemically, often producing isomers (molecules with the same formula but different properties), requiring extra processing.

• Purity: Synthetic CBD may contain impurities and potentially THC from synthesis, whereas natural CBD isolate for pharmaceutical uses must contain >98% CBD.  

• Preference: Regulators and patients often favor natural CBD vs synthetic CBD. For instance, Mexico, Brazil and Australia permit only natural cannabinoids, current approved medicines use plant-derived CBD, and the European pharmacopeia monograph excludes synthetic forms

CBD and other cannabinoid molecules can be isolated, purified, and used as APIs for therapeutic use. However, like any API, they must demonstrate safety, efficacy, and quality through rigorous clinical trials, and adhere to GMP and pharmacopeial standards. As with any drug compound, marketing claims for CBD-based products are also heavily regulated and must be supported by clinical data to gain approval from agencies such as the FDA or EMA.

Regulations surrounding cannabinoid-based pharmaceuticals are evolving and vary across countries too. Currently, there are only four FDA-approved cannabinoid-based medicines on the market* and access is still limited to prescription use or specific medical settings. Many countries also enforce stringent rules on the international movement of cannabinoid APIs. It is therefore important to check and comply with the specific regulatory requirements of the country where research is planned as specific permits or certifications may be required.

*Cannabidiol (Epidiolex®); Dronabinol (Marinol® and Syndros®); Nabilone (Cesamet®).

CBD is poorly absorbed in the body and undergoes pre-systemic elimination in the liver, resulting in low oral bioavailability in humans (6%).¹ This limits the therapeutic potential of CBD-based medicines, because bioavailability directly impacts API efficacy and dosage needed to achieve a benefit.

The low bioavailability of CBD is partly why most formulations are in oil-based delivery systems. However, patients must ingest large volumes because the active concentration of CBD in oil is low. Further challenges exist in liquid forms; at high doses the amount of ethanol ingested may exceed the guidance threshold for ethanol containing medicines for children aged < 6 years and limit shelf-life.

CBtru®, a premium formulated drug product intermediate, optimizes CBD bioavailability in oral solid dosage forms with higher drug loading, potentially enabling more patient-friendly medicines.  

1. Perucca and Bialer. Critical aspects affecting cannabidiol oral bioavailability and metabolic elimination, and related clinical implications. Cannabinoids in Neurology and Psychiatry, 2020.