The legislative moves here, which spurred the creation of the New Zealand Medicinal Cannabis Agency, were in response to an accumulation of evidence that cannabis is safe and effective for certain medical uses.

But it is still early days and the scientific picture is a complicated one, obscured somewhat by a lack of evidence, in the form of large and well-designed clinical trials, for some potential uses. After all, medicinal cannabis generally wasn’t on the table as a legal option in most countries just a decade ago. The scientific community and pharmaceutical companies alike didn’t invest as heavily in this promising area of medicine as much as in other areas of research.

Medical cannabis - what’s on offer

A relatively small number of medicinal cannabis products, which require a doctor’s prescription, are currently available in New Zealand. They include the Sativex oral spray, other oral liquids and dried cannabis flower for use in tea and for oral consumption.

Technically, these products have been assessed by the Medicinal Cannabis Agency as meeting the “minimum quality standard”. It means they haven’t been officially tested locally for safety and efficacy. As local producers develop their own products, the range of options will grow, subject to them getting the prerequisite approvals allowing their use.

But what do we currently know about the efficacy and safety of cannabis-based medicines? A decent snapshot of the evidence base is given by the Royal Society of New Zealand in its report Health impacts of cannabis – benefits, harms and many unknowns, released in December, 2019.

The evidence base - a snapshot

That report looked at both the medical and recreational uses of cannabis. When it came to medicinal cannabis, the report authors concluded:

“There is evidence that cannabis-based medicines may have some effect as an additional treatment option for controlling chronic pain in adults, reducing nausea and vomiting from chemotherapy, easing pain from muscle spasms in people with multiple sclerosis and treating two rare forms of severe epilepsy in children.”

The Royal Society report, which sought to lay out the evidence base for the public as New Zealand looked to introduce a scheme for controlling the use of medicinal cannabis, is itself based on a major summary of the evidence produced by the US National Academies of Sciences, Engineering and Medicine in 2017.

That report assessed whether there was a conclusive, substantial or moderate evidence base for the use of cannabis to treat different conditions. 

It found conclusive or substantial evidence that cannabis or cannabinoids are effective for:

- Treatment for chronic pain in adults (cannabis).

- As an antiemetic ( a drug for reducing nausea and vomiting) in patients receiving chemotherapy (oral cannabinoids).

- For improving patient-reported multiple sclerosis spasticity symptoms (oral cannabinoids) 

It found moderate evidence that cannabis or cannabinoids are effective for:

- Improving short-term sleep outcomes in individuals with sleep disturbance associated with sleep apnea syndrome, fibromyalgia, chronic pain, and multiple sclerosis (cannabinoids, primarily nabiximols - a type of cannabis extract).

It found limited evidence that cannabis or cannabinoids are effective for:

 - Increasing appetite and decreasing weight loss associated with HIV/AIDS (cannabis and oral cannabinoids) 

- Improving clinician-measured multiple sclerosis spasticity symptoms (oral cannabinoids) 

- Improving symptoms of Tourette syndrome (THC capsules) 

- Improving anxiety symptoms, as assessed by a public speaking test, in individuals with social anxiety disorders (cannabidiol)

- Improving symptoms of posttraumatic stress disorder (nabilone; one single, small fair-quality trial) 

- A statistical association between cannabinoids and: better outcomes (mortality, disability) after a traumatic brain injury or intracranial haemorrhage. 

There is limited evidence that cannabis or cannabinoids are ineffective for:

- Improving symptoms associated with dementia (cannabinoids) 

- Improving intraocular pressure associated with glaucoma (cannabinoids) 

- Reducing depressive symptoms in individuals with chronic pain or multiple sclerosis (nabiximols, dronabinol, and nabilone)

Then we start to encounter the really large gaps in knowledge that exist when it comes to the use of cannabis-based medicines to treat a plethora of other illnesses and conditions.

There is no or insufficient evidence to support or refute the conclusion that cannabis or cannabinoids are an effective treatment for:

- Cancers, including glioma (cannabinoids). 

- Cancer-associated anorexia cachexia syndrome and anorexia nervosa (cannabinoids). 

- Symptoms of irritable bowel syndrome (dronabinol). 

- Epilepsy (cannabinoids).

- Spasticity in patients with paralysis due to spinal cord injury (cannabinoids). 

- Symptoms associated with amyotrophic lateral sclerosis (cannabinoids). 

- Chorea and certain neuropsychiatric symptoms associated with Huntington’s disease (oral cannabinoids).

- Motor system symptoms associated with Parkinson’s disease or the levodopa-induced dyskinesia (cannabinoids). 

- Dystonia (nabilone and dronabinol).

- Achieving abstinence in the use of addictive substances (cannabinoids).

- Mental health outcomes in individuals with schizophrenia or schizophreniform psychosis (cannabidiol). 

Gaps in our knowledge

Such literature reviews and meta-analyses reveal just how much work is still to be done investigating the efficacy of cannabis-based medicines. As Dr Irene Braithwaite, a reviewer of the Royal Society report points out, many cannabis-based medicines haven’t been tested to the same standards as existing medicines.

“The levels and types of cannabinoids in these plant-based preparations can vary greatly due to different growing, harvest and storage conditions. This makes it difficult to draw conclusions by comparing or pooling the results from the limited number of studies that do exist,” she says.

If the evidence base for efficacy is mixed, what do we know about the safety of cannabis-based medicines?

Part of it comes down to how cannabis is taken. While cannabis is commonly smoked as a recreational drug, its use in medicinal cannabis products more commonly comes in the form of sprays, oils or capsules.

Mild side effects

That’s because, as the Royal Society points out, “smoking cannabis exposes users to toxic compounds created at high temperatures and it can lead to a chronic cough and phlegm production.”

Even using a vaporiser, like an e-cigarette device can expose a user to toxic compounds from “additives, solvents and flavouring”.

The side effects of ingesting or smoking cannabis are generally reported in the literature as being mild but can include nausea, increased weakness, behavioural or mood changes, suicidal ideation or hallucinations and fatigue.

Studies have captured an association between higher concentrations of THC (delta-9-tetrahydrocannabinol) and reported psychosis, dysphoria (general dissatisfaction, restlessness, low mood) and anxiety.

An absence of evidence for the efficacy of cannabis-based medicines for some diseases and conditions doesn’t mean cannabis can’t be a useful treatment for them. They just haven’t been widely tested in clinical trials. The literature base is incredibly thin in areas.

Much work is also still to be done to compare the efficacy of cannabis-based medicines to existing drugs and treatments that are already on the market. Could cannabis-based medicines have fewer side effects and offer a viable, natural alternative to synthetic drugs? Again, the evidence base needs more depth. Only well-constructed trials, studies and literature reviews can answer that question.

New Zealand’s fledgling medicinal cannabis industry is quite rightly focusing on the areas of greatest need where the evidence base for efficacy is strongest, including chronic pain, sleep disorders and the side effects of chemotherapy.

But there is so much more potential for medicinal cannabis that ultimately can only be unlocked through innovation, rigorous scientific testing and clinical trials. 

Sources:

NIH: The Health Effects of Cannabis and Cannabinoids

Royal Society Te Apārangi: Health impacts of cannabis – benefits, harms and many unknowns

United Kingdom All Party Parliamentary Group for Drug Policy Reform: Cannabis - The Evidence for Medical Use