Use of medicinal cannabis products

Position

The Royal Australian College of General Practitioners (RACGP) highlights the need for further high-quality research into the safety and effectiveness of medicinal cannabis products, as the current evidence is limited and inconclusive.

The current available evidence does, however, suggest a possible role for medicinal cannabis products in a number of areas. Therefore, if after conventional, evidence-based treatments have failed, and the specialist general practitioner (GP) feels that medicinal cannabis products are a viable treatment option for their patients, they should, as other specialists can, be able to prescribe appropriate medicinal cannabis products in accordance with the current regulatory framework.

Background

The February 2016 amendments¹ to the Narcotic Drugs Act 1967 ² allowed the supply of medicinal cannabis products for the management of patients with certain medical conditions. The amendments allow the supply of pharmaceutical, nonsmokeable, medicinal-grade products. They do not include the provision of medicinal-grade herbal cannabis products and do not relate to the decriminalisation of cannabis for general cultivation or recreational use.

However, only one such product is currently registered in Australia. Therefore, most pharmaceutical grade medicinal cannabis products that are available overseas are not registered medicines in Australia, and approval from federal and/or state and territory authorities is required through the Therapeutic Goods Administration’s (TGA’s) Special Access Scheme or Authorised Prescriber Scheme. The RACGP has further developed a position statement on The regulatory framework for medicinal use of cannabis products.

GPs are faced with the pressing need to help patients who are unable to manage chronic and debilitating conditions using conventional, evidence-based treatments. Given the significant media and political coverage on medicinal cannabis products, GPs may experience greater patient demand to prescribe these products. However, as with all clinical decisions, GPs need to balance patient initiated demands for treatment and the clinician’s therapeutic responsibility, while considering federal and state or territory legislative requirements before considering the prescription of medicinal cannabis products. Refer to Appendix 1. Medicinal cannabis products checklist for more information.

This position statement does not recommend nor encourage the use of medicinal cannabis products; however, it recognises that as specialists, GPs may offer to prescribe medicinal cannabis products to a very limited number of patients with specific conditions in consultation with them and their care team. Importantly, medicinal cannabis products should only be considered when all first-line, conventional, evidence-based treatment options have been exhausted, and after detailed discussions of the potential benefits and harms of medicinal cannabis products with the patient.

The RACGP has always been a strong advocate for evidence-based medicine, and as the evidence around the efficacy and effectiveness of medicinal cannabis products evolve, this position statement will be reviewed to reflect the emerging evidence.

Types of medicinal cannabis products

Cannabis is a complex plant comprising more than 500 constituents, including approximately 100 cannabinoids.³ The main active ingredients used for medical purposes are tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the psychoactive part of cannabis that produces a ‘high’, and has been used to treat symptoms such as nausea, pain and muscle spasticity. CBD has no psychoactive properties, and has been used to treat several inflammatory disorders and epilepsy.

Only pharmaceutical, non-smokeable, medicinal-grade products (listed in point one below) can now be supplied lawfully in Australia but medicinal cannabis products can come in three main forms:

1. Pharmaceutical: Natural and synthetic medical-grade products with standardised content. The three main products are:
   • Dronabinol: Synthetic form of THC
   • Nabilone: Synthetic form of THC
   • Nabiximols: Chemically pure 50:50 mixture of TCH and CBD.
2. Medicinal-grade herbal cannabis: Produced and processed in controlled standard conditions to a medical grade, free of adulterants, higher levels of CBD and other cannabinoids, and contains lower levels of THC. This is provided in herbal form, or processed as an oil, balm, capsule or pill.
3. Herbal cannabis on the illegal market: Potentially unstable THC and CBD, and may contain adulterants.

Currently, the only medicinal cannabis product registered for use in Australia is Nabiximols for the management of spasticity in patients with multiple sclerosis; however, this is not listed on the Pharmaceutical Benefits Scheme (PBS).

The cost of accessing medicinal cannabis products varies depending on the type and dose required, and the patient is responsible for all costs associated with this access. In several states and territories, patients may be eligible for medicinal cannabis products compassionate use schemes.

Evidence base for medicinal cannabis

At present, the evidence base for the use of medicinal cannabis products is limited. The current evidence base for the use of medicinal cannabis products is heterogeneous, comprising a small number of randomised clinical trials when stratified by condition, symptom or intervention type. These studies are of variable quality, including those with high risk of bias (eg incomplete outcome data), low statistical power, and short follow-up time.

Recent reviews and analyses indicate there may be some therapeutic benefits of medicinal cannabis products in certain conditions;^4,5,6 however, further research on the treatment efficacy and longer term side effects are warranted.

Currently, most research and evidence on medicinal cannabis products have come from five clinical conditions – multiple sclerosis, palliative care, epilepsy, nausea and vomiting, and chronic non-cancer pain (refer to Table 1. Summary of evidence on medicinal cannabis products for more information). Numbers needed to treat and numbers needed to harm are included where possible.

Multiple sclerosis

Around half the studies in a recent systematic reviews found that medicinal cannabis products may be effective for pain, spasticity, sleep and bladder function; the others were inconclusive.⁷

Epilepsy

A number of studies have found low evidence for the use of medicinal cannabis products for the treatment of paediatric epilepsy, and for patients up to aged 25 years, especially when first-line treatments (ie anti-epileptic drugs) have been found to be ineffective.⁸ The numbers needed to treat are as follows:

• 50% or greater reduction in seizure frequency: 8
• Complete seizure freedom: 171
• Improvement in parental-reported quality of life: 5

The numbers needed to harm for any adverse event was 3, and serious adverse event was 23.

Palliative care

The use of medicinal cannabis products in palliative care is currently unclear.⁹

Nausea and vomiting

A small number of studies have found relief of nausea and vomiting in patients with cancer who are undergoing chemotherapy; however, the evidence is lacking and some were compared with now out-of-date practices.

Chronic non-cancer pain

There is some evidence available for the treatment of neuropathic pain using medicinal cannabis products; however, the magnitude of effect is small.¹⁰ One systematic review found that the numbers needed to treat was 22 for a 30% reduction and 26 for a 50% reduction in self-reported pain intensity.⁵

Table 1. Summary of evidence on medicinal cannabis products¹¹

Adverse effects and drug interactions

A 2015 systematic review did not find any studies that evaluated the long-term side effects of using medicinal cannabis products.⁵ However, medicinal cannabis products were found to increase the risk of short-term adverse effects such as disorientation, dizziness, euphoria, confusion, among others (refer to Table 2. Adverse effects of medicinal cannabis products for a full list). Side effects from medicinal cannabis products generally depend on the amount of THC in the product.

Recommendations from the Therapeutic Goods Administration (TGA) also highlight that THC is not appropriate for:¹³

• patients with a previous history of psychosis, or concurrent active mood or anxiety disorder¹⁴
• expectant mothers, female patients planning a pregnancy or those breastfeeding
• patients with an unstable cardiovascular disease.

Medicinal cannabis products are generally believed to have low acute toxicity; however, its concurrent use with other drugs may mask adverse effects such as cardiovascular effects, and mortality may be under-recognised.¹⁵

Table 2. Adverse effects of medicinal cannabis products⁵

Future developments

The RACGP recognises that while there are significant community and political interests in the medicinal use of cannabis products for therapy, the safety and effectiveness profiles of medicinal cannabis products are currently incomplete. The RACGP therefore highlights the need for further high-quality research into the safety and effectiveness on the use of medicinal cannabis products in Australia.

There is also a need to ensure that education for the general public and medical practitioners is available. This education should reflect the current state of knowledge and contextualise the use of medical cannabis products as a last-resort medication for specific categories of illness that should only be prescribed in rare circumstances after stringent legislative criteria are satisfied.