Opinion

There has been a significant increase in the use of medicinal cannabis globally, with Australia more recently following these trends (Hallinan & Bonomo, 2022). Following a series of regulatory changes which have increased patient access, it is estimated that there have been nearly one million approvals for medicinal cannabis in Australia (Australian Government, 2024b; Australian Institute of Health and Welfare, 2024; Graham et al., 2023a). The increase in prescriptions of medicinal cannabis has been dramatic, particularly given the relatively short time frame since these regulatory changes occurred. In the United States, where liberalised medicinal cannabis policies have been in effect for longer, it is estimated that approximately 27% of the adult population has used medicinal cannabis within their lifetime (Leung et al., 2022). Despite the popularity of medicinal cannabis, the evidence for its effectiveness in the treatment of many common medical conditions which it is prescribed for is nascent and research on the adverse health effects of medical use remains inadequate.

Evidence for the use of medicinal cannabis

Most medicinal cannabis products are considered unapproved medicines as they have not demonstrated clinical efficacy, safety, and quality in manufacturing. In Australia, two medicinal products have demonstrated evidence of clinical efficacy but only one is listed on the Pharmaceutical Benefits Scheme (PBS). One product is an oromuscual spray used as a treatment for multiple sclerosis (MS) in patients who have not benefited from typical, first-line medication (Australian Government, 2024c). The other is an oral liquid as an augmentative treatment for seizures associated with Dravet syndrome (DS) or Lennox-Gastaut syndrome (LGS) (Australian Government, 2024a). A third product has been approved only by the Food and Drug Administration (FDA) in the United States, not in Australia, and is a synthetic cannabinoid prescribed for nausea related to chemotherapy, after the failure of first-line treatment (Food and Drug Administration, 2021).

What other conditions is it being prescribed for?

In recent years, the approval system for medicinal cannabis prescribing in Australia has been simplified, resulting in virtually all applications being approved within 48 hours (Graham et al., 2023a). Under this streamlined system, medicinal cannabis can be prescribed as an unauthorised medication for any health condition. The TGA provides a guide to assist clinical decision-making for medicinal cannabis, but there is limited oversight of medical practice (Graham et al., 2023b; Hallinan et al., 2021). Consequently, medicinal cannabis is now being prescribed by clinicians through telehealth appointments for a range of indications with little to no evidence for the effectiveness of medicinal cannabis. Recent data from the National Drug Strategy Household Survey (NDSHS) shows that a substantial proportion of people are prescribed medicinal cannabis to treat chronic, life-long conditions like anxiety and chronic pain (Australian Institute of Health and Welfare, 2024). These two conditions have limited evidence to suggest the effectiveness of medicinal cannabis and some evidence to suggest a risk of adverse effects (Boehnke et al., 2020; Botsford et al., 2020).

What products can be prescribed?

Contrary to common assumptions, medicinal cannabis products are not free from delta-9-tetrahydrocannabinol (THC), the psychoactive cannabinoid that causes impairment (i.e., the “high”) and is typically desirable in recreational use. Recent TGA data indicate that a substantial proportion of patients are consuming medicinal cannabis products which are THC dominant. Many of the medical cannabis products available in Australia have higher levels of THC (%) than the products tested in clinical trials (Abrams et al., 2020; Bonn-Miller et al., 2021). Of these products, cannabis flower (i.e., cannabis plant matter, as often used recreationally) can be obtained through prescription and smoked in a joint, bong or vaporised. Under the current framework, patients may often select the products that they wish to consume if they are prescribed through Authorised Prescribers who are often based at for-profit medicinal cannabis clinics (Graham et al., 2023a; Hallinan et al., 2021).

Industry influence

There has been a substantial increase in the number of private medical cannabis clinics whose clinicians primarily prescribe medical cannabis products. Advertising for these medicinal cannabis clinics has become increasingly prevalent, with the TGA investigating over 100 advertising code non-compliance complaints, resulting in some financial penalties being applied (Australian Government, 2022, 2023a). The TGA has recently updated the advertising guidance for medicinal cannabis businesses to safeguard against unlawful advertising. The new regulations prohibit marketing which includes terms such as ‘plant medicine’ or promote clinics which specifically dispense medicinal cannabis (Australian Government, 2023b). However, despite these regulations, many businesses are still marketing medicinal cannabis products in these ways (Alternaleaf, 2024) with at least one example to date of corporate sponsorship in free to air televised sport (Alston, 2024).

What are the risks of medical cannabis use?

Cannabis is often promoted as a ‘natural’ herb and perceived as less harmful than pharmaceutical drugs or illicit substances like methamphetamines or opiates. However, the risk of addiction is still substantial in people who use cannabis, with 22% of people who have used cannabis recreationally developing a cannabis use disorder (Leung et al., 2020). Cannabis use disorders are substance use disorders in which people may often use larger amounts of cannabis than was intended and have unsuccessful efforts to reduce or control their use (Cooke et al., 2023). People with cannabis use disorder may continue to use medicinal cannabis despite known adverse consequences (e.g., side effects) (Gendy et al., 2023). They may develop tolerance and suffer from withdrawal symptoms if they attempt to stop using the medication. These patterns of uncontrollable medicinal cannabis use can lead to significant problems at work, within the individual's social and family life and can adversely affect their everyday activities (Hasin et al., 2023).

What does the evidence say?

We recently conducted a review on the prevalence of cannabis use disorder in people who used medicinal cannabis. Across ten studies, 25% (95% CI: 18-33%) of people who used cannabis for medicinal reasons were estimated to have a cannabis use disorder, as assessed by DSM-5 criteria across all prevalence periods. These results indicate that approximately one in four people who used medicinal cannabis developed cannabis use disorder, which is tantamount to the rates observed in recreational use (i.e., 22%, see Leung et al., 2020). Those using medical cannabis while experiencing mental health disorders may be at an elevated risk of cannabis use disorders, as are individuals using medical cannabis to treat chronic pain and substance use disorders (Dawson et al., 2024).

A recent study has suggested that patients with chronic pain who use cannabis may be at risk of more severe cannabis use disorders. The relationship may be explained by medicinal cannabis being ineffective in reducing pain and patients futilely increasing their doses to manage pain interference (Cooke et al., 2023). Gradually, patients may develop tolerance to medicinal cannabis and increase their risks of a cannabis use disorder. The development of cannabis use disorders is often overlooked, particularly in Australia where follow-up care is optional, but may further impair patient’s ability to manage their pain and the demands of everyday life (Cooke et al., 2023).

Patients who use medical cannabis and medical practitioners who prescribe cannabis should be better informed about the potential risks of cannabis use disorder, particularly given the high rates of prescribing for anxiety and chronic pain in Australia. We urgently require high quality data for informed decision making by patients, prescribers, and policy makers on medicinal cannabis.

Conclusions

There is an unappreciated risk of cannabis use disorders for patients prescribed medicinal cannabis. As medicinal cannabis popularity grows, there is a need to advise patients and prescribers of the risk of cannabis use disorder when prescribing medicinal cannabis.

Find out more about Danielle’s research here, and watch Danielle’s rapid fire presentation on her systematic review of the adverse health outcomes of medicinal cannabis at the NCYSUR Research Symposium 2024 here.

References

Abrams, D. I., Couey, P., Dixit, N., Sagi, V., Hagar, W., Vichinsky, E., et al. (2020). Effect of inhaled cannabis for pain in adults with sickle cell disease: a randomized clinical trial. JAMA Network Open, 3(7), pp. e2010874. DOI: https://doi.org/10.1001/jamanetworkopen.2020.10874.

Alston, J. (2024, Mar 7). NRL team makes history by bringing a marijuana company on as a sponsor - and it could be the solution to the code's biggest problem. Daily Mail Australia - Online. Retrieved from https://www.dailymail.co.uk/sport/nrl/article-13170987/NRL-Dolphins-cann... (Accessed 2024 Mar 19)

Alternaleaf. (2024). Alternaleaf Plant Medicine Clinic. Retrieved from https://www.consult.alternaleaf.com.au/?utm_source=google&utm_medium=cpc... (Accessed 2024 Mar 12)

Australian Government. (2022). West Australian health practitioner fined $13,320 for alleged unlawful advertising of medicinal cannabis. Retrieved from https://www.tga.gov.au/news/media-releases/west-australian-health-practi... (Accessed 2024 Mar 12)

Australian Government. (2023a). Court proceedings initiated against CDA Clinics QLD Pty Ltd and its former director for alleged unlawful advertising of medicinal cannabis. Retrieved from https://www.tga.gov.au/news/media-releases/court-proceedings-initiated-a...)

Australian Government. (2023b). Updated medicinal cannabis guidance. Retrieved from https://www.tga.gov.au/news/media-releases/updated-medicinal-cannabis-gu... (Accessed 2024 Mar 12)

Australian Government. (2024a). EPIDYOLEX cannabidiol 100 mg/mL oral liquid solution bottle. Retrieved from https://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStor... (Accessed 2024 Mar 5)

Australian Government. (2024b). SAS-B Approvals Portal. Retrieved from https://dashboard-data.health.gov.au/single/?appid=1066afbe-2b37-427d-8c... (Accessed 2024 Jan 15)

Australian Government. (2024c). Sativex Oromucosal Spray, nabiximols 80 mg/mL pump actuated metered dose aerosol. Retrieved from https://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStor... (Accessed 2024 Mar 5)

Australian Institute of Health and Welfare. (2024). Medical marijuana/cannabis in the NDSHS. Retrieved from https://www.aihw.gov.au/reports/medicines/medical-marijuana-cannabis (Accessed 2024 Mar 11)

Boehnke, K. F., Scott, J. R., Litinas, E., Sisley, S., Williams, D. A. and Clauw, D. J. (2020). High-frequency medical cannabis use is associated with worse pain among individuals with chronic pain. Journal of Pain, 21(5-6), pp. 570-581. DOI: https://doi.org/10.1016/j.jpain.2019.09.006.

Bonn-Miller, M. O., Sisley, S., Riggs, P., Yazar-Klosinski, B., Wang, J. B., Loflin, M. J. E., … and Doblin, R. (2021). The short-term impact of 3 smoked cannabis preparations versus placebo on PTSD symptoms: a randomized cross-over clinical trial. PLoS One, 16(3), pp. e0246990. DOI: https://doi.org/10.1371/journal.pone.0246990.

Botsford, S. L., Yang, S. and George, T. P. (2020). Cannabis and cannabinoids in mood and anxiety disorders: impact on illness onset and course, and assessment of therapeutic potential. American Journal on Addictions, 29(1), pp. 9-26. DOI: https://doi.org/10.1111/ajad.12963.

Cooke, M. E., Potter, K. W., Jashinski, J., Pascale, M., Schuster, R. M., Tervo-Clemmens, B., et al. (2023). Development of cannabis use disorder in medical cannabis users: a 9-month follow-up of a randomized clinical trial testing effects of medical cannabis card ownership. Frontiers in Psychiatry, 14, pp. 1083334. DOI: https://doi.org/10.3389/fpsyt.2023.1083334.

Dawson, D., Stjepanovic, D., Lorenzetti, V., Cheung, C., Hall, W. and Leung, J. (2024). The prevalence of cannabis use disorders in people who use medicinal cannabis: a systematic review and meta-analysis. Drug and Alcohol Dependence, 257, pp. 111263. DOI: https://doi.org/10.1016/j.drugalcdep.2024.111263.

Food and Drug Administration. (2021). SYNDROS® (dronabinol) oral solution, CII. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/205525Orig1s00... (Accessed 2024 Mar 11)

Gendy, M. N. S., Taisir, R., Sousa, S., Costello, J., Rush, B., Busse, J. W. and Mackillop, J. (2023). Prevalence of cannabis use disorder among individuals using medical cannabis at admission to inpatient treatment for substance use disorders. Addictive Behaviors, 142, pp. 107667. DOI: https://doi.org/10.1016/j.addbeh.2023.107667.

Graham, M., Chiu, V., Stjepanovic, D. and Hall, W. (2023a). A provisional evaluation of Australia's medical cannabis program. International Journal of Drug Policy, 122, pp. 104210. DOI: https://doi.org/10.1016/j.drugpo.2023.104210.

Graham, M., Renaud, E., Lucas, C. J., Schneider, J. and Martin, J. H. (2023b). Medicinal cannabis guidance and resources for health professionals to inform clinical decision making. Clinical Therapeutics, 45(6), pp. 527-534. DOI: https://doi.org/10.1016/j.clinthera.2023.03.007.

Hallinan, C. M. and Bonomo, Y. A. (2022). The rise and rise of medicinal cannabis, what now? Medicinal cannabis prescribing in Australia 2017-2022. International Journal of Environmental Research and Public Health, 19(16). DOI: https://doi.org/10.3390/ijerph19169853.

Hallinan, C. M., Gunn, J. M. and Bonomo, Y. A. (2021). Implementation of medicinal cannabis in Australia: innovation or upheaval? Perspectives from physicians as key informants, a qualitative analysis. BMJ Open, 11(10), pp. e054044. DOI: https://doi.org/10.1136/bmjopen-2021-054044.

Hasin, D. S., Wall, M. M., Alschuler, D. M., Mannes, Z. L., Malte, C., Olfson, M., et al. (2023). Chronic pain, cannabis legalisation, and cannabis use disorder among patients in the US Veterans Health Administration system, 2005 to 2019: a repeated, cross-sectional study. Lancet Psychiatry, 10(11), pp. 877-886. DOI: https://doi.org/10.1016/S2215-0366(23)00268-7.

Leung, J., Chan, G., Stjepanovic, D., Chung, J. Y. C., Hall, W. and Hammond, D. (2022). Prevalence and self-reported reasons of cannabis use for medical purposes in USA and Canada. Psychopharmacology, 239(5), pp. 1509-1519. DOI: https://doi.org/10.1007/s00213-021-06047-8.

Leung, J., Chan, G. C. K., Hides, L. and Hall, W. D. (2020). What is the prevalence and risk of cannabis use disorders among people who use cannabis? a systematic review and meta-analysis. Addictive Behaviors, 109, pp. 106479. DOI: https://doi.org/10.1016/j.addbeh.2020.106479.