Most research on phytocannabinoids, both chemical and biological, has primarily focused on the “big three” —Delta-9-Tetrahydrocannabinol (Δ9-THC), Cannabidiol (CBD), and Cannabigerol (CBG)— due to their high extraction yields from plant sources. However, cannabis plants are also capable of producing over 150 other compounds, known as “minor cannabinoids”, which have distinct structural differences and unique biological properties. Among these, one compound that stands out is cannabinol (CBN) (Figure 1).
While CBN is produced as a natural oxidative degradation product of THC, it is non-intoxicating or only mildly psychoactive compared to THC, making it of interest for its potential therapeutic benefits. But how is CBN made, and how does its production compare to common household goods and typical drugs? Moreover, what makes CBN production safe? Let’s explore these questions to gain a deeper understanding of this fascinating compound.
Why is CBN Production Considered Safe?
Production
The production of CBN from Δ9-THC is considered safe for several reasons, primarily rooted in the chemical stability and known degradation pathways of cannabinoids, as well as established production and quality control practices
- Chemical Stability and Safety
- Natural Degradation Pathway: CBN is a naturally occurring cannabinoid that is formed when D9THC undergoes oxidation and degradation over time. This process can happen naturally when cannabis is exposed to light, heat, and air. Since this is a known and predictable chemical reaction, it can be replicated and controlled in a laboratory setting, ensuring safety.
- No Harmful By-products: The conversion of Δ9-THC to CBN does not produce harmful by-products when properly conducted, making it a safe process.
- Controlled Conversion Process
- Optimized Conditions: In a controlled environment, the conversion of Δ9-THC to CBN is optimized to minimize any unwanted reactions. This includes careful control of temperature, oxygen exposure, and time, ensuring that the reaction proceeds smoothly and predictably.
- Quality Control of the CBN Finished Product
- Purity Testing: The finished CBN product undergoes rigorous testing to ensure it meets purity standards. Techniques like High-Performance Liquid Chromatography (HPLC) combined with Gas Chromatography–Mass Spectrometry (GC/MS) are commonly used to measure the cannabinoid content and confirm that the CBN is free from residual Δ9-THC or other cannabinoids, impurities, or by-products.
- Contaminant Screening: The product is also tested for contaminants, including heavy metals, pesticides, solvents, and microbial contamination. This ensures that the CBN is ok for consumption.
- Consistency and Potency: Batch-to-batch consistency is critical in CBN production. Producers will test each batch for potency to ensure that the concentration of CBN meets the labeled claims. This is important for both safety and efficacy.
- Stability Testing: Stability testing is conducted to ensure that the CBN remains stable over time, maintaining its potency and safety throughout its shelf life. This involves storing the product under various conditions and testing it periodically. It has been confirmed that CBN is a stable cannabinoid at both 25°C and 30°C.
How is CBN made?
CBN is naturally produced in the cannabis plant as a result of the degradation of THC. As Δ9-THC oxidizes, it gradually converts into CBN1. This natural process can occur slowly as cannabis ages, or it can be accelerated by deliberate exposure to heat, light and air. Therefore, CBN is often found in higher concentrations in older cannabis plants or improperly stored cannabis products where THC has had time to degrade2.
This transformation can be accelerated in a chemical laboratory setting, where THC is treated with specific oxidizing agents to produce CBN more efficiently through controlled oxidative aromatization reaction. Oxidation is a common chemical process used in organic chemistry to transform organic compounds by adding oxygen or removing hydrogen. This process has significant implications in various fields, including pharmaceuticals, nutraceuticals, and agrochemicals.
In the synthesis of food supplements like CoQ10, Vitamin E, curcumin, and flavonoids, oxidative aromatization is a key reaction for creating the aromatic structures that give these compounds their biological activity. This chemical transformation is essential for producing supplements that are effective and ok for consumption.
Reaction Conditions:
The oxidation reaction is usually carried out under controlled conditions, including:
- Solvent: Suitable solvents like heptane or ethyl acetate are used to dissolve Δ9-THC.
- Oxidizing agents: Common oxidizing agents for this transformation are chloranil (tetrachloro-1,4-benzoquinone)3, DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone)4 and selenium dioxide5. These oxidizing agents specifically target and oxidize Δ9-THC, leaving other isomeric tetrahydrocannabinols unchanged.
- Temperature: The reaction is often performed at room temperature or slightly elevated temperatures (40-60oC) to ensure the reaction proceeds smoothly.
- Time: The reaction time can vary depending on the oxidizing agent used, but it typically ranges from several hours to a day.
- Purification: Typically, the purification process involves two steps. Short Path Distillation (SPD) and Crystallization
- SPD: it allows the separation of CBN from other components based on differences in their boiling points
- Outcome: This initial step is employed to remove low boiling point impurities, unreacted oxidizing agents (high boiling point) and the reducing species obtained as a by-product during the reaction.
- Crystallization: It is crucial in the pharmaceutical industry for purifying drugs and it is also employed in the purification of food additives and ingredients to ensure efficacy and safety.
- Process: The distillate from the SPD is dissolved under heating in an appropriate solvent like heptane. Upon cooling, CBN crystallizes out of the solution, leaving behind impurities in the solvent. The crystals are then collected, washed, and dried.
- Outcome: The crystallization process results in CBN as a white powder with over 99% purity, as the crystallization selectively isolates the pure compound.
Reaction mechanism starting with Δ9-THC
Δ9-THC contains a partially unsaturated ring, specifically a cyclohexene ring (a six-membered ring with one double bond). The conversion to CBN requires the oxidation of this ring to form an aromatic benzene ring. This transformation is typically carried out using an oxidizing agent that facilitates the loss of hydrogen atoms and the formation of new double bonds, resulting in an aromatic ring. Scheme 1 shows the general mechanism for this reaction.
Step 1: Formation of a Radical
The oxidant abstracts a hydrogen atom (H10a) from the cyclohexene ring of THC, forming a radical intermediate (1a). This step involves the formation of a new double bond, converting the cyclohexene into a diene structure.
Step 2: Further Oxidation
The radical intermediate undergoes further oxidation, leading to the formation of another double bond. This step can occur via the loss of another hydrogen atom (H6a) by interaction with the oxidizing agent. The formation of the second double bond results in a fully conjugated triene system (1b), which stabilizes by forming an aromatic benzene ring.
Step 3: Aromaticity
The newly formed double bonds rearrange to create a stable aromatic ring structure, characteristic of the benzene ring found in CBN.
The acidic isomerization of Δ9-THC produces the thermodynamically more stable Delta-8-Tetrahydrocannabinol (Δ8-THC) isomer, which resists oxidative aromatization, due to the minor resonance stabilization of a C-10a radical (1a) which, in this form, is benzylic rather than benzallylic7.
Other ways to obtain CBN
Δ8-THC or Cannabichromene (CBC) can be used as starting materials for the synthesis of CBN using iodine or iodine salts like potassium iodide (KI) combined with acids such as sulfuric acid as the oxidizing agent.8,9,10 The reaction is typically conducted under reflux in heptane or toluene as the solvent. Alternatively, iodine can be replaced with sulfur, in which case the reaction is solvent-free and carried out at 250°C.
Reaction mechanism starting with Δ8-THC or CBC
When treating Δ8-THC with iodine, CBN is directly formed through a series of iodination and dehydroiodination steps (Scheme 2A)11. In contrast, with CBC, iodine addition to the chromene bond triggers the electrocyclic opening of the heterocyclic ring, followed by a hetero Diels–Alder reaction. This reaction produces tetrahydrocannabinol derivatives, which are then aromatized through iodine addition and hydroiodic acid elimination (Scheme 2B)11. The byproduct in this reaction is hydroiodic acid (HI) and the excess of iodine which is eliminated during the water washes.
What Household Goods are Made Similarly?
The process of creating CBN through oxidation or chemical transformation is not unique to the cannabis industry. Here are a few examples of how similar processes are used in the creation of household goods and other common items:
- Vinegar Production: Vinegar is made by the oxidation of ethanol (alcohol) into acetic acid. This process is comparable to how THC oxidizes into CBN over time.
- Aging Wine: Just as THC degrades into CBN, wine undergoes oxidative changes during aging, which alters its flavor and aroma.
- Vitamin C: In the industrial synthesis of Vitamin C, a key step involves the oxidative aromatization of sorbitol or sorbose to form L-ascorbic acid.
- Vanillin Production: Vanillin, the primary component of vanilla flavoring, can be synthesized from guaiacol through oxidative aromatization.
These examples illustrate that the principles behind CBN production are rooted in common chemical processes that are widely accepted and utilized in everyday products. From vitamins to food supplements, and pharmaceuticals, oxidative aromatization is a versatile and essential transformation in industrial chemistry and the production of household goods.
Conclusion
CBN is emerging as a cannabinoid with significant therapeutic potential and a favorable safety profile. While it shares some similarities with THC in terms of interaction with the endocannabinoid system, its effects are much milder, making it an attractive option for individuals seeking the benefits of cannabinoids without the psychoactive effects. Understanding how CBN is made and the science behind it helps demystify this increasingly popular compound. As with many products, the key to safety and efficacy lies in stringent quality control and a deep understanding of the underlying chemistry. By applying these principles, the cannabis industry can continue to offer safe, effective, and innovative products to consumers.
More Questions About CBN?
Check out our in depth break down on CBN here
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