Cannabis-based medicinal products hold promise in the treatment of various conditions but, as Dr Karl Gruber (PhD) reports, there is still a way to go.
It is difficult to find any medicine or remedy that elicits more questions and debate among doctors, patients, researchers, policy makers and the public than medicinal cannabis.
Is it safe? Does it work? How does it work? Is it addictive? Should the public be allowed to grow it? These and many more questions constantly orbit around cannabis-based medicinal products, drawing the interest of a wide range of stakeholders, from patients suffering a myriad of different conditions to entrepreneurs wanting to create the next wonder drug.
The interest in medicinal cannabis is growing and more products are becoming available. Three months ago, the Commonwealth Department of Health’s Therapeutic Goods Administration (TGA) announced its decision to allow certain medicinal cannabis products to be sold over the counter.
GPs are facing a growing number of patients with questions about medicinal cannabis and wanting to try it. But clear answers to key questions about cannabis products are not always readily available.
Cannabis: the basics
Cannabis sativa, also known as Indian hemp, is a plant native to Eastern Asia and used since ancient times as a source of textile fibre, food, oil and medicine.
The medicinal properties of cannabis products can be traced to the myriad of chemicals produced by the plant called cannabinoids. These are substances carrying a specific chemical structure capable of binding to cannabinoid receptors found in the brain and other parts of the human body, such as organs, connective tissues, glands, and immune cells.
These receptors are an integral part of the endocannabinoid system, a cellular communication network that affects the function of the immune and nervous systems, as well as the function of all organs in the body, ultimately affecting processes such as mood, memory, sleep and appetite.
Clinical evidence
Studies testing the clinical efficacy of cannabis products are ongoing, and evidence so far has shown variable degrees of benefit for treating symptoms in conditions such as multiple sclerosis, chronic (non-cancer related) pain and certain types of epilepsy. Patients going through palliative care and chemotherapy-induced nausea and vomiting have also benefited from using cannabis-based products.
Currently, the strongest clinical evidence supports the use of cannabidiol for the treatment of drug-resistant epilepsy in children and young adults up to 25 years. In this cohort, the use of a cannabidiol-based product, alongside standard treatments, has been shown to provide significant benefits in the treatment of symptoms in about half of those taking it.
For other conditions, such as multiple sclerosis, chronic (non-cancer related) pain, evidence is sketchier, with studies showing variable outcomes in drug efficacy for treating symptoms. In other words, some patients may experience significant relief of their symptoms, while others may experience only small or no benefit.
Regulations
Cannabis-based drugs were legalised in Australia in 2016 and are regulated by the commonwealth and state governments. Most products fall within Schedule 8 (controlled drugs) or Schedule 4 medicines (prescription only medicines). These are medicines that only contain the non-psychoactive cannabinoid, cannabidiol (CBD).
TGA registration comes with perks: it means that a drug has been assessed for quality, safety and efficacy. But, so far, the only cannabis-based medicine registered with TGA is Sativex, a drug prescribed to improve symptoms related to muscle stiffness (spasticity) in multiple sclerosis.
Other cannabis drugs are currently in the clinical pipeline, some here in WA. Emyria, a Perth-based company, is conducting clinical testing of various cannabis-based drugs, targeting mental health problems and irritable bowel syndrome.
The company is employing an innovative approach, testing their drugs with actual patients and generating clinically relevant data. With the rescheduling of cannabis products on the table, the availability of high-quality products, and a legal pathway to reach patients, Emyria saw an opportunity.
“We asked, ‘Why don’t we provide safe access to patients when other treatments might not be working and collect high quality clinical evidence that can be used to support drug development,” said Dr Michael Winlo, managing director of Emyria.
Another Perth-based company in the medicinal cannabis space is Zelira Therapeutics. The company is currently conducting various clinical trials, testing the efficacy of different cannabis-based drugs for conditions such as autism, some cancers, insomnia, and chronic pain.
Recently, Zelira joined forces with Emyria to conduct an observational clinical trial for patients diagnosed with autism spectrum disorder, testing the drugs HOPE 1 and HOPE 2. The effort builds on the successful launch of these drugs in the US in 2019. While their HOPE formulation is now expanding across the US, in Australia it gained TGA approval late last year and Zelira’s Managing Director, Dr Richard Hopkins, says the time is ripe to break new ground in Australia.
According to Dr Hopkins, the new clinical trial is one of the world’s largest observational studies and one of the world’s first individual trials for autism.
Autism is not the only condition Zelira is targeting in Australia. Last year, the company launched Zenivol, a cannabis-based formulation aimed at patients with chronic insomnia, following TGA’s approval through their Special Access Scheme.
A disrupting force
According to Dr Hopkins, Australia’s current regulatory schemes and the safe nature of cannabis products offer an opportunity to test efficacy while reaching out to patients.
Normally, a pharmaceutical company would spend billions of dollars and it would take 10 years to get a drug perfected and onto the market. Zelira and Emyria are taking an innovative approach.
“What we’ve developed in the country is something we ought to develop and it completely turns the concept of drug discovery on its head,” Dr Hopkins said. Cannabis-based medicines can be tested in the general population before they are approved by regulatory bodies, he says, because while the efficacy of cannabis products may still be in question, their safety is not.
According to Dr Winlo, this strategy may help accelerate the process of testing drugs and reduce the time it takes for them to reach patients.
“Our care model provides patients with safe access to unregistered treatments like medicinal cannabis. At the same time, we are gathering robust and ethically-sourced data with our patients. We then use this evidence to help identify the most promising doses and indications that could lead to formally registered drug treatments,”he said.
“In a way, we are actively filling in the evidence gap that exists for these treatments while also pioneering a new model of evidence-generating care that can help accelerate drug development more broadly.”
Cannabis prescribing
However, a lack of registration has not stopped medicinal cannabis from reaching patients. Today, more than 100 cannabis-related medicinal products are available as prescription medications, though they must go through some regulatory hurdles.
GPs wanting to prescribe cannabis-based products need to seek approval through TGA’s Category B Special Access Scheme, the most common pathway. In essence, it means that GPs need to justify why a specific patient would benefit from a particular cannabis-based product, but this is just the tip of the cannabis iceberg.
“Many of these products appear to be very similar and are largely undifferentiated. Some come from Canada, some are grown in Australia. Many are oils, some are capsules or sprays. It’s a very crowded space,” Dr Winlo said.
“The other complication is that it’s not easy to write a prescription. It’s not as simple as writing a script. You have to explain what else patients have tried. Why is nothing else working? How are you going to monitor this patient?
“So there’s a bit of extra paperwork and it takes a bit more time. If you’re not used to doing special access or navigating all these product choices, it can be daunting and a deterrent, not to mention the lack of high-quality clinical research that usually helps doctors make these decisions.”
What this means for a GP is that a solid understanding of all the available cannabis products is required, as well as clear information about their efficacy, dosage, side effects, among other aspects. With the growing number of cannabis-based product, this is no easy task.
Medical Forum poll
Early results from a recent e-poll of GPs and specialists conducted by Medical Forum shows that a significant majority (82%) of GPs have never prescribed medicinal cannabis. Among these doctors, about 78% claim that they are not convinced of the benefits associated with MC. Among the few doctors who say they have prescribed MC, 70% said that chronic pain was the main condition treated.
Overall, 94% of all respondents agreed that more clinical research was needed on the efficacy or safety of medicinal cannabis.
Is it safe? Does it work?
In the case of Sativex, the active ingredient, nabiximol, contains the cannabinoids delta-9- tetrahydrocannabinol (THC) and cannabidiol. According to the National Prescribing Service (NPS) Medicinewise website, the drug can improve spasticity symptoms in less than half of patients and has two common side effects: dizziness
and fatigue.
In addition, 10% of patients treated with this drug experience depression, disorientation, dissociation and euphoria. Delusions, hallucinations and paranoia were also reported for some patients.
For the vast majority of cannabis-based medications that lack TGA registration, it is hard to assess efficacy or safety. Regarding quality, the TGA has established guidelines that define the quality requirements for all imported medicinal cannabis products, which need to comply to an international code, the Good Manufacturing Practice (GMP).
Despite these efforts, not all cannabis-based products available in Australia follow regulatory guidelines.
Black markets
For every regulated product that is costly or hard to get, there is always a cheaper, shady alternative, and cannabis is no exception. A current problem in the medicinal cannabis space is the widespread black market of products. These products represent a risky alternative to regulated, TGA-approved, products. Without any regulatory control, it is hard to ensure these products meet adequate safety and quality standards.
Despite the risks, some people still buy these unregulated products.
For Dr Hopkins, it is all about the mindset of users. If you are buying a cannabis product for your child or elderly parent, you are serious about it and will look for the best option. But if you are looking for a recreational drug, that’s another story, he said.
Cannabis-based medications stand as a promising approach for the treatment of symptoms from some serious diseases, but it is still early days.
Companies and doctors who have invested in this area argue that allowing legal access to high-quality, TGA-regulated products could significantly improve the lives of many Australian patients who, so far, have not been able to find relief with standard treatments.
But some of those less invested stakeholders want to see more runs in terms of clinical trial data and evidence before jumping on board.