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Home > Articles > Science & Health > Content Piece

The Degradation Pathways of Cannabinoids and How to Manage Them – Part 2

By Paul Barr

, Paul Hardman

Published: Feb 02, 2023   
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In the second of two articles, Broughton, a regulatory consultancy currently focused on EU and UK cannabis regulation, discusses the susceptibility of cannabinoids to degrade and summarizes the main degradation pathways of the primary cannabinoid products on the market: THC and CBD.

You can read part one here.

Degradation of cannabinoid products in the UK market

Some of the major degradation pathways and their catalyst or environmental condition that triggers breakdown have been described in this two-part series. But when considering the degradation of these products, it is critical to consider, too, the dosage form and delivery format. The mode of delivery, sample matrix, excipients, packaging, and storage conditions may all contribute to these products’ degradation and the extent of that degradation.

Inhalable products

Inhalation can be an effective way to administer cannabinoids. Rapid absorption to the bloodstream via the lungs is possible due to the high surface area of the alveoli. Yet this mode of delivery is more suitable for low therapeutic doses. Examples of inhalation products include nebulizers, pressurized metered dose inhalers (pMDIs), dry powder inhalers (DPIs), and vaping products.

Inhalation by vaping represents a challenging dose form for controlling the degradation of cannabinoid products.

Initially, the cannabinoids may be stored for a period in liquid formulations, where degradation may occur by oxidation and light exposure. Studies have shown that light is the greatest single factor in the loss of cannabinoids, especially in solution.

Subsequently, these liquids are heated, a known catalyst for cannabinoid degradation. In this instance, manufacturing processes and controls, mode of delivery, sample matrix, excipients, and storage conditions may all contribute to degradation. As heating is a known catalyst for degradation, it is essential that the content and degradation profile within the e-liquid and the aerosol are characterized over the product shelf life. Other mechanisms of inhalable delivery without heat, such as pMDIs or DPIs, may overcome this specific challenge but may come with new challenges. pMDIs or DPIs come in different container closure systems and will require a different sample matrix for delivery, these may also impact the degradation pathways.

Oral products

A variety of oral CBD products are available in the UK market, ranging from oils, tinctures, drops, beverages, capsules, gummies, pouches, and other foodstuffs. These products are adsorbed sublingually, buccally, or absorbed in the gastrointestinal fluid and enter the bloodstream through the digestive system. The potential degradation of these products should be monitored over the shelf life where the manufacturing processes and controls sample matrix, excipients, packaging, and storage conditions may all have an impact on the product stability prior to consumption.

Topical products

Cannabinoid products may also be administered topically. Topical products are applied to the skin; the medicine treats the area of application or is absorbed into the bloodstream through the dermis. These products may include but are not restricted to creams, ointments, oils, lotions, gels, sprays, and patches. In line with inhalable and oral products, the degradation profile of these products should be monitored over the product’s shelf life through stability studies. The manufacturing processes and controls, sample matrix, excipients, packaging, and storage conditions may all impact product stability. However, with these products, an important consideration may also be in use stability and potential exposure of the product to heat and light on the skin surface before it is absorbed.

Impact of degradation of cannabinoid products

The degradation of cannabinoids in consumer and medicinal products can have various impacts, from regulatory to legal implications. Although it is difficult to comprehensively cover all expected forms of degradation and its consequences, this section of the series aims to provide a summary of some of these issues and highlight why it is pivotal that manufacturers formulate and monitor their products over the shelf life to mitigate these.

The immediate impact of degradation of these products is a decreased efficacy for medicinal products due to the breakdown of the primary active compound responsible for the therapeutic response, this also may result in a lower-than-advertised label claim for medicinal and consumer products. This may impact the consumer’s well-being and health but also may affect the brand reputation and erode consumer trust due to poor product performance and potentially misleading label claims. Inaccurate label claim is a common issue with these products.

A study of over-the-counter cannabinoid products in the UK found that out of 29 tested products, only 38% of the products were within 10% of the advertised CBD content. Although this study did not investigate the root cause of the low CBD content, it highlights the extent of the issue. Furthermore, controlling the degradation of cannabinoid products and their stated label claim is important for regulatory compliance.

In addition to the label claim, another impact of not understanding the degradation pathways of these products is the potential toxicological effects and patient safety. It is critical that new compounds generated from degradation pathways are quantified and toxicologically risk assessed.

The legal considerations for manufacturers to characterize and understand cannabinoid products and their degradation pathways over the product shelf life are paramount. The liability of these products and their known route of degradation from known noncontrolled to controlled substances has been discussed in detail within this series. Independent laboratory analysis of over-the-counter CBD products concluded that 55% of the products had measurable levels of the controlled substances THC and CBN. Manufacturers must control and monitor these controlled substances in their products with analytical methodology of suitable sensitivity to ensure they comply with the law and avoid potential enforcement action.

Finally, regulators will want evidence that product manufacturers have control of their manufacturing processes and produce a consistent quality product. As discussed in the degradation pathway review, changes in the product appearance and batch-to-batch variability risk denting consumer confidence in the product and the brand.

Mitigation of degradation pathways

With the degradation potential of cannabinoid products, it seems prudent that manufacturers would take a cautious approach in their formulation and packaging of these products. Although it may be impossible to prevent degradation pathways entirely, formulation of these products with long-term stability and control monitoring of the products in mind could potentially mitigate some of these effects.

With that in mind, many manufacturers take a proactive approach in including appropriate chemical stabilizers and preservatives in their formulations. Knowing that acidic and basic environments can be a catalyst for degradation, controlling pH within the sample matrix may help mitigate these effects. Additionally, the effects of light exposure, oxidation, and heat concerning cannabinoid degradation have been described in detail within this series.

Appropriate storage of the product while under the manufacturer's control will help, although temperature control is not something that can be guaranteed throughout the product shelf life, especially for consumer non-medical products, where control around temperature may not be as tightly controlled. The selection of appropriate packaging material that blocks light in combination with a low oxygen vapor transmission rate (OVTR) should provide a substantial barrier to the external environment and potentially reduce degradation stimulants such as light and oxygen.

In addition to introducing these controls, it is crucial that suitable stability indicating analytical methodology is available to monitor the product from the point of manufacture and over the shelf life. These analytical methods should be specific to identify and quantify the main active cannabinoid ingredient and any new cannabinoid degradants that may be formed. The analytical techniques used should be a highly sensitive method of detection (mass spectrometry, for instance) to determine the low level of cannabinoid degradation.


In conclusion, cannabinoid products with a particular focus on THC and CBD as the two most marketed consumer and medical products are highly labile. Manufacturers have a duty of care to consumers to characterize their products thoroughly and not only understand what is present at the point of manufacture but also to understand the potential degradation pathways of these products and how they will perform and change over the shelf-life of the product.

Any shelf-life claims added to products should be substantiated through stability studies with analytical methods of appropriate sensitivity. Any new products formed throughout stability should be toxicologically assessed for potential impact on patient or consumer safety. By having a thorough understanding of these degradation pathways, manufacturers may reduce the degradation levels through innovative formulation and appropriate packaging materials.

A thorough understanding of how these products behave over their lifecycle is vital from a regulatory viewpoint and in keeping within UK legislation. There is potential for these substances, such as CBD, to degrade into controlled substances, such as THC, which may result in legal consequences.

Regardless of the regulatory pathway a manufacturer pursues for their cannabinoid product, fully characterizing products and having a thorough understanding will help navigate the regulatory process. For medical cannabinoid products, the regulatory standards are well defined, and the expectation is a complete product characterization and toxicological understanding of the cannabinoid product and its potential breakdown products.

For manufacturers pursuing the novel food regulations for CBD products, this regulatory process is in its infancy. There is guidance available. However, the status of products currently under review via this regulation is still unclear. For manufacturers, it would be prudent to fully understand the degradation pathways of their products so that they can provide as much information as required to the regulator to help approve these products.

With this in mind, Broughton has developed and validated highly sensitive stability indicating methods that can identify and quantify a range of cannabinoids in combination with regulatory, chemistry, and toxicological support from our range of consultants as part of our cannabis and consulting services offer.

Paul Barr

Principle Scientist at Broughton

As a principal scientist at Broughton, Paul works as a consultant specializing in designing studies for understanding product chemistry across pharmaceuticals and consumer products. Paul studied a BSc in Analytical Science from Dublin City University. He started his career in Almac overseeing the method development, method validation, clinical release, and stability testing of clinical supplies from phase I through to phase III/PRE-commercial solid oral dose products. Following seven years at Almac, Paul led the analytical method development team at Pharmaserve for three years overseeing the development of methods for pressurized metered dose inhalers. Prior to joining Broughton, Paul worked in the characterization team at Nerudia and Imperial Brands. As a characterization scientist, Paul worked on next generation nicotine products spanning e-vapour and heated tobacco areas at all stages in the products' lifecycle. Paul is an active member of the CEN standard group to raise standards of e-vapour products across the industry and assist in compliance to regulations.

Paul Hardman

Head of Scientific Affairs at Broughton

As head of scientific affairs at Broughton, Paul manages a team of consultants specializing in understanding product chemistry across pharmaceuticals and consumer products. Paul studied a BSc in Pharmacology from the University of Sheffield and commenced his career at Vectura, where experience was gained in developing dry powder inhaled medicines. He was the co-inventor of a novel powder dispersion engine design for a passive dry powder inhaler, with potential for use across a range of API and with a range of inhalers. Following ten years at Vectura, Paul led the quality control laboratory at one of Perrigo’s manufacturing sites. Prior to joining Broughton, Paul led product characterization at Nerudia and Imperial Brands. This included assessment of next generation nicotine products spanning e-vapour, oral, and heated tobacco areas at all stages in the products' lifecycle. In this role, Paul has met with the FDA to discuss e-vapour product chemistry approaches to meet premarket tobacco product application requirements and written regulatory packages to support the marketing of products in the UK, US, Japan, New Zealand, and the Middle East.


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