Dr Adele Hosseini discusses issues of an unregulated market and what to look for when selecting a medicinal cannabis product.
Medicinal cannabis was legalised in Australia in 2016 to be accessible through special access schemes set by the Therapeutic Goods Administration (TGA). Since then, over 120,000 prescriptions have been approved for numerous indications, but the progress hasn’t been without its challenges and the system isn’t perfect. Dr Adele Hosseini, who is the Chief Scientific Officer at Bod and has extensive experience in the pharmaceutical industry says that “Medicinal cannabis needs to meet the same standards of quality, effectiveness and safety expected of any other prescription medicine”, and explained to us the multiple issues that arise from an unregulated market.
Medicinal cannabis: What is it?
A common misunderstanding of medicinal cannabis is that it is a single medicine. It should in fact be considered more as a class of medicines. “Cannabis does not have a fixed chemical composition. Each plant is different,” said Dr Hosseini. The cannabis plant contains more than 400 plant constituents, with approximately 100 that are specific to the cannabis plant and referred to as cannabinoids. These cannabinoids have different biological activity (pharmacology) and different effects on the body, both independently and in combination.
For any plant, including cannabis, the chemical make-up of that plant that makes it useful for us (e.g. flavour of wine grapes) varies dependent on plant species (e.g. Cannabis Sativa vs Indica), cultivar, individual plant genetics, harvest time and growing conditions (e.g. indoor vs outdoor, climate). Additionally, for medicinal cannabis, the manufacturing of plant material into a medicinal format (e.g. oil vs tincture), formulation and storage processes can also impact the composition of cannabis-based medicines. All these factors can influence the overall safety and therapeutic activity of medicinal cannabis products.
Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the best characterised cannabinoids but many medicinal cannabis products contain other cannabinoids (full-spectrum or broad-spectrum products). As these other cannabinoids and plant constituents can have their biologically active and/or influence the plant’s overall therapeutic activity, you can’t expect the same results for different products, even if the CBD and THC concentrations are the same.
What medicinal cannabis products are available in Australia?
In Australia, there are only two medicines registered on the Australian Register of Therapeutic Goods (ARTG): Epidyolex (CBD) for paediatric epilepsy and Sativex (nabiximols; THC:CBD) for multiple sclerosis-associated spasticity. All other medicinal products are unregistered and are prescribed through the TGA’s special access schemes.
It is the responsibility of the prescriber to specify which product they wish to access through the TGA’s special access schemes and the TGA does not maintain a list of unapproved medicinal cannabis products. There are currently over 200 products available, which vary in compositions and quality, creating an overwhelming and deterring minefield for prescribers.
The main issues of an unregulated market
The main issues that arise from an unregulated medicinal cannabis market are:
- Variation in active constituents (cannabinoids); including instability over time and inconsistency between batches.
- Risk of contamination with pesticides, heavy metals, mycotoxins, microbes, manufacturing process materials.
- Adulteration with other psychoactive and potentially toxic compounds.
Without regulation, there is no assurance of a reliable source of medicine and there is risk of exposure to harmful substances. Variance and impurities in medicinal cannabis products has been identified in Australia [1, 2], UK , Europe  and the US [5-7]. A significant portion of tested products had cannabinoid concentrations that varied considerably from their labelled contents. Additionally, some products were contaminated with unwanted constituents, such as THC in THC-free products, heavy metals, solvents and even potent synthetic cannabinoids, which have reported toxicity.
How to select a medicinal cannabis product: Advice from Dr Adele Hosseini, Chief Scientific Officer at Bod
“When selecting an unregistered medicinal cannabis product, there are a few factors to look for to ensure you are receiving a high quality product.
First, check that it has been manufactured under Good Manufacturing Practice (GMP), to ensure goods are of high quality.
Secondly, I recommend that you request certificates of analysis from the manufacturer each time to (1) verify the cannabinoid content, (2) ensure batch-to-catch consistency and (3) confirm the absence of impurities.
If possible, select products that have been used in clinical studies (for example, phase 1 studies) to verify good safety, tolerability, pharmacokinetic and efficacy profiles. This information can inform on dosing guidance and potential side effects to look out for.”
“With plant-based medicines and natural products, there needs to be reproducible chemical constituent profiles and minimum batch to batch variation. Through extract standardisation, we hope to achieve reproducible chemical profile and batch-to-batch consistency. This will improve safety and dosing, and translate into improved research, doctor and patient confidence, and regulatory advancement.”
Why aren’t there more registered medicinal cannabis options?
Dr Hosseini explains that the reason there aren’t more registered cannabis-based medicines is partly because of the difficulty in conducting quality research on a prohibited drug. Some of the barriers to research include:
- Bureaucratic barriers, delays and high costs to obtain licences and permits.
- The additional processes and costs associated with adequate security measure are prohibitive.
- The plant itself is not patentable, resulting in a lack of industry enthusiasm in conducting research. Financial investment is dependent on adequate intellectual property protection to ensure a return on that investment.
- Challenge of proper placebo control.
- Stigma amongst politicians, clinicians and the public.
Additionally, the indications that most people are seeking medicinal cannabis for differ from those on the ARTG (epilepsy and multiple sclerosis). Based on data from the TGA’s special access approvals (over 120, 000), the top five conditions that unregistered medicinal cannabis products are being prescribed for are chronic pain (65%), anxiety (13%), cancer pain and symptom management (5%), sleep disorders (4%) and epilepsy (3%) .
Even though data shows that people would prefer to obtain medicinal cannabis legally , it appears that people will probably continue to use it regardless of its legality. There is a responsibility towards ensuring there are safe and accessible options available to support those in need. The current system can be improved on to make patient and doctor knowledge and access easier, and to give companies incentive to invest in the research and registration process. In the meantime, turn to Dr Hosseini’s tips when selecting unapproved cannabis-based medicines.
Want to know more?
- Suraev, A., et al., Composition and Use of Cannabis Extracts for Childhood Epilepsy in the Australian Community. Sci Rep, 2018. 8(1): p. 10154.
- (TGA), Testing of medicinal cannabis products being supplied via SAS in Australia. 2020; Available from: https://www.tga.gov.au/testing-medicinal-cannabis-products-being-supplied-sas-australia.
- Liebling, J.P., et al., An Analysis of Over-the-Counter Cannabidiol Products in the United Kingdom. Cannabis and Cannabinoid Research, 2020.
- Pavlovic, R., et al., Quality Traits of “Cannabidiol Oils”: Cannabinoids Content, Terpene Fingerprint and Oxidation Stability of European Commercially Available Preparations. Molecules, 2018. 23(5).
- Bonn-Miller, M.O., et al., Labeling Accuracy of Cannabidiol Extracts Sold Online. JAMA, 2017. 318(17): p. 1708-1709.
- Oldfield, K., et al., A systematic review of the label accuracy of cannabinoid-based products in regulated markets: is what’s on the label what’s in the product? Australas Psychiatry, 2021. 29(1): p. 88-96.
- Gilman, J.M., et al., Variation in Cannabinoid Metabolites Present in the Urine of Adults Using Medical Cannabis Products in Massachusetts. JAMA Network Open, 2021. 4(4): p. e215490-e215490.
- Lintzeris, N., et al., Medical cannabis use in the Australian community following introduction of legal access: the 2018–2019 Online Cross-Sectional Cannabis as Medicine Survey (CAMS-18). Harm Reduction Journal, 2020. 17(1): p. 37.
- (TGA), Freedom of information (FOI) disclosure log. 2021; Available from: https://www.tga.gov.au/foi-disclosure-log.