more_vert
MEDICINAL cannabis has been the hottest of hot-button issues in medicine for some years now. It’s one the few medications where media hype and patient demand seem to have moulded – some would say muddied – the regulatory framework in a way that has troubled many clinicians.
In Australia, there are now three different pathways to legally accessing medicinal cannabis. The Category A Special Access Scheme (SAS) allows the importation of unregistered products on compassionate grounds, but requires import licences and customs clearance, while Category B SAS gives access to locally stored medicinal cannabis, but requires TGA and state review and approval. Specialists can also obtain an Authorised Prescriber status to prescribe cannabis – these will usually be either oncologists for cancer-related pain, or paediatric neurologists for the control of severe epilepsy in children.
But what is the evidence for medicinal cannabis, and is it sufficient for clinicians to feel comfortable prescribing it? These issues are explored in two articles published in the MJA, one a Perspective from the Royal Australasian College of Physicians (RACP) and the other a Narrative Review on the challenges of prescribing cannabis for paediatric epilepsy, authored by researchers from the Sydney Children’s Hospital.
The RACP comes down on the side of caution. It notes that Australia, along with the rest of the world, is “navigating unchartered waters with pharmaceutical grade cannabinoids”, and that more research is needed before we can say whether or not cannabis has a place in contemporary medical practice.
In paediatric epilepsy, some of that research seems to be coming into focus. Last May, a randomised, double-blind trial of cannabidiol, a cannabis derivative that does not contain the psychoactive ingredient tetrahydrocannabinol, provided hard data for the first time that the treatment may work in children with Dravet syndrome – a severe form of childhood epilepsy with often drug-resistant seizures. This was followed by another trial, published last month in the Lancet, that showed similar efficacy of cannabidiol in Lennox–Gastaut syndrome, another form of paediatric epilepsy characterised by multiple seizure types.
Laureate Professor Ingrid Scheffer, who is Chair of Paediatric Neurology Research at The University of Melbourne and co-author of the trial of cannabadiol in Dravet syndrome, says that although her study does provide solid evidence for the drug’s efficacy, it should in no way be considered a miracle cure.
“It’s been sold as a magic bullet by the media. And you have families who are on a terrible rollercoaster, they’re vulnerable and medicinal cannabis is being cast as this drug that may save their child. And the answer is that it often does not. It may help, and in our study cannabidiol had a 43% responder rate, defined as at least a 50% reduction in the seizure frequency. But that’s exactly the same as some of the other drugs we use.”
But she says that doesn’t mean it shouldn’t be prescribed.
“Dravet syndrome is usually drug-resistant and you don’t know which drugs will work, so it could be worth trying if others have failed. But the families should be aware of its chances of success and the fact that it can have side effects.”
She says the key is more research.
“What people are accessing is very variable. They’re importing it from all over the place, they may even be getting friends to grow it in their backyard, so we do not know what they’re giving their child. What we need to do is go forward with more trials in different populations and with different formulations. If we’re going to invest in this, we need to know it works and we’re not wasting our health dollar on it.”
Professor Scheffer says that another drug currently being trialled, fenfluramine, may end up the more successful treatment. Trial results have yet to be published, but interim findings suggest that fenfluramine may have a dramatically higher responder rate of up to 70%.
Dr John Lawson, a Sydney-based paediatric neurologist and co-author of the Narrative Review on cannabis and childhood epilepsy, agrees that cannabidiol, though worth trying in some children, is no wonder drug.
“I’m not hanging my hopes on cannabidiol,” he says in an exclusive podcast for MJA Insight.
“I came in as quite a sceptic, but my attitude has changed. I now believe that it is an antiepileptic, but I’m not sure what place it has. It’s the early stages of development, and there are other compounds that haven’t been looked at.”
Dr Lawson says that he wouldn’t suggest it to a family until many other antiepileptics had already failed, and the chances of the next drug working were already low.
“I’ve come around to bringing it up in conversation because everyone knows about it, and families know I’ve prescribed it. But the biggest reason to not prescribe is cost. For a small child, it will cost over $1000 every couple of weeks to give a Therapeutics Goods Administration-approved product. Almost the only people I have prescribed it for are those who have an absolute ‘bucketload’ of money. Or I form a contract with them, and I say look, this will cost you $3000, but all the trials say you will know very quickly if it’s working or not.”
He says that in the patients who are helped by cannabidiol, the effect is still relatively modest.
“Patients are very rarely seizure-free. It may have a role in the future, once the hype has died down, but it will be a very low [on a list of preferred antiepileptics].”
To find a doctor, or a job, to use GP Desktop and Doctors Health, book and track your CPD, and buy textbooks and guidelines, visit doctorportal.
Loading ...
Thanks to Dr John Lawson, a Sydney-based paediatric neurologist and co-author of the Narrative Review on cannabis and childhood epilepsy, because he agrees that cannabidiol, though worth trying in some children. It is no wonder drug. Great post!
Note when folks are talking pharma Cannabis, remember it is not Cannabis. In 2016 Australia legalised medical Cannabis but also redefined it to include synthetics, GMO, and pharma. The end result is medical cannabis need not include Cannabis any more and in the case of synthetics need not even come from a plant. Absorb that in for a moment, then it starts to explain why the laws are so messed up in the last 2 years. Also the global standard for dosing REAL medical Cannabis is the RSOP used in Austrlaia legislature it is the Rick Simpson Oil Protocol. It states using FECO (full extract Cannabis Oil), 1 gm a day of THC (30gm a month) is good for cancer and extreme pain, while 1/2 doses are good for epilepsy and less serious conditions, and the tincture was invented for skin cancer also. THe pharma products dosing is all different as they are NEVER FECO. Quite simply anyone that accessed legal CBD, Cannabis, or THC in Australia, ZERO came from Cannabis. We now have a bill in the upper house in Australia trying to fix this.
It has been demonstrably dangerous to extrapolate from the experience in Palliative Care to general medical use, including for persistent pain.
This has proven to be an international disaster with respect to opioid medications, after being recommended for use in persistent pain on the basis of palliative care experience, with many many thousands dying from use as prescribed, and extensive morbidity as well, without demonstrated sustained benefit. These deaths are in addition to those from suicide and accidental death from recreational use, often by diversion of prescribed medication.
While a focus on symptomatic relief is good in palliative care, especially for those not likely to survive long, it is not appropriate for management of persistent pain as the only focus of therapy. A balanced, sensitive focus on function is important, with many medications, including opioid and cannabis, putting this at unacceptable risk while chasing symptom relief, often only by use of medication despite many other approaches also being available.
While those with persistent pain may ‘feel better’, this should not be used as the only outcome assessment, particularly in view of the disadvantage and risk of inactivity enhanced by these substances.
The studies of cannabis use in persistent pain have not yet demonstrated sufficient benefit to recommend its use in this context.
Hi, Becky. The term “entourage effect” is used to argue that whole plant cannabis is better than purified active constituents. That makes little sense. We know that modern pharmacology developed from herbal medicine because plant material contains a complexity of useful and less useful chemicals, in a fibrous stroma, with plant-to-plant variability, depending on plant genetics, season, growing conditions etc.
We also know that THC and CBD have different pharmacological profiles and activity.
This article from Scientific American calls into question the validity of this purported effect:
https://www.scientificamerican.com/article/some-of-the-parts-is-marijuana-rsquo-s-ldquo-entourage-effect-rdquo-scientifically-valid/
In your palliative care practice, would you advise people in pain to grow their own opium poppies and smoke tincture of opium? That is the equivalent of using “herbal” cannabis.
I an highly dubious about Joe Kosterich’s comment that “up to 70% of palliative care patients use cannabis (often illegaly) and pay from their own pocket”. Would you say it ws that high in your practice?
From the perspective for a Pall Med Physician, I find Joe Kosterich’s comments to be the most helpful so far.
I don’t believe that the issue of ‘medicinal cannabis’ is clouded by the lobby for legalisation of recreational use. They are & can be kept completely separate. In any case, the recreational users are not likely to want the ratios of THC:CBD that we are likely to need in medicine.
It is not at all as simple as extracting compounds from cannabis, as demonstrated by the lack of success with such compounds available thus far. We need, at least a component of the ‘Entourage effect’ & the amount of evidence in the community worldwide is overwhelming, so we need to get on & get a system that provides safe product.
I am still very grumpy that the patient for whom I submitted my first application(SAS-A) died before I could get all the paperwork the requirements. She was one who would never have gone to the black market for fear of getting someone into trouble.
Well said Joe.
With respect to “evidence” there’s few – if any – drugs with the depth of Real World Evidence that cannabis does. Decades and decades of recreational and therapeutic experience by a not insignificant cohort of the population who typically have high rates of contact with the health system.
Talk of “harm”, “safety”, and other motherhood statements totally ignore this experience and signals an overly cautious approach to a medication with well understood safety profile and for which there is a clear therapeutic role. The current regulatory approach is deeply unethical at best – not to mention the Ponzi-like behaviour of some of the local startups.
Richard Horton writes in The Lancet that “…public health science needed to pay more attention to the lived experiences of people in societies”. Patients who have used medicinal cannabis here and internationally have reported benefit. Yet public health is quite happy to ignore this. Medicinal Cannabis like all other medications is not for everyone nor for everything. It has specific uses. Yet it is far safer in pain management than opioids being associated with no deaths from overdose. Up to 70% of palliative care patients use cannabis (often illegaly) and pay from their own pocket- why? because they get benefit. The type that come from relief of symptoms not a research paper. Ultimately we need a level playing field where those who might benefit can gain access like they can with any other medical product that may benefit them. And as time passes we will get more local research to complement that done overseas. To again quote Horton ” Public health today is crudely reductionist, often ignoring or denying the lives of those it purports to defend”. Time for public health to do more listening and less hectoring. http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(18)30304-0.pdf Declaration – The commenter is an advisor to a Medicinal Cannabis start up company.
Readers are recommended to review the article in the latest MJA: “Compassion and evidence in prescribing cannabinoids: a perspective from the Royal Australasian COllege of Physicians.” This rational article notes that compassionate access schemes, which bypass the usual research evidence standards for medications, should not be used to short-circuit good regulatory processes for more widespread use.
The article points out that “the regulatory processes designed to protect patients from serious harms are incomplete for medicinal cannabinoids” and also that “evidence for their effectiveness for many medical conditions is at present limited.”
“Recent systematic reviews and meta-analyses of the evidence for the effectiveness of cannabinoids for analgesia show no benefit over placebo in pain reduction and that significantly more patients experience adverse events” (three references are cited). The analgesia reference is in JAMA 2015: Cannabinoids for Medical Use
A Systematic Review and Meta-analysis – (the entire paper is accessible at https://jamanetwork.com/journals/jama/fullarticle/2338251?alert=1). The review found “moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs.”
So, it’s too early to just start prescribing on the basis of copy-pasted guidelines from the commercial manufacturer “MedReleaf”, as the poster above has done.
A very well reasoned comment from Sue Ieraci.
A very strange, difficult to read, with odd grammar and capatalisation from Dr Mark Jeffrey. I can see why your application for a patient would be rejected. Statements such as “EBM shows benfit for neuropathic pain just like lyric a without the horrible side effects of lyrica .” are complete nonsense. Any objective reviewer would realise there are potential benefits that come at the cost of side effects just like any medication. There will be some place for CBD but it’s role will likely be a lot more limited than people like Dr Jeffrey assert.
I have PAH (pulmonary artery hypertension) . For years I have been unable to walk more than a few metres without severe dyspnoea.
I also have problems with tingling feet and hands, the result of two lumbar and one cervical laminectomy. I refuse to take opiates or etc.
because of their side-effects but wonder if medical cannabis could help. I am 90 yrs old and confined to my home most of the time
because I need a helper to push my wheelchair. I know it has not been approved for any of this but wonder if it could help me put up with
these symptoms.
Is there any way I can give this a try?.
The dose equivalent of medicinal marijauana is small 10-25 mg cbd for treatment of pain as is the dose of THC/CBD COMBINATIONS.
cbd is schedule 4 like panadiene forte .One dose of oxycontin(schedule 8) 60 mg laced with a benzodiazepine is enough to kill someone who is opiate naiive .Lyrica (SCHEDULE 5)is known as the next valium /budweiser on the streets,tHERE HAVE been deaths in the UK from lyrica Prescription opiates cause 50 percent of all overdoses in emergency departments .The lethal dose of marijuana is 600 kg =600 x 10 to power 6MG smoked in 15 minutes -this is impossible .In queensland we have 30 registrations a day for opiates .There is no formal assessment by a pain specialist unlike the ridiculous process required to prescribe cbd .Given the crisis with opiates why dont the same processes that exist through the medicinal cannibis unit apply to opiates .I hasHAVE SPENT 6 months trying to get an approval for a patient -2 submissions.Imagine if this was applied to opiates and it should be the public would at least be protected from diversion of opiaTES..Whilst these application processes are onerous no GP will bother prescribing for this-WE dont get paid for 6 hours of time with applications gathering ridiculous amounts of information .EBM shows benfit for neuropathic pain just like lyric a without the horrible side effects of lyrica .It is the regulators that are creating this false perception of medicinal marijuana.The public hear medicinal marijuana and have no idea of dose equivalents but rather have the perception of using bongs which are used recreationallyeg 1 gram in bongs =1000mg -cbd =10-25 mg
it is useful in palliative care ,neuropathies,neuropathic pain ,agitated alzheimers .Far more safe than using benzoodiazepines uin elderly which increase risk of falls
CaNNABIS OIL EQUIVALENCY FACTOR
Health Canada requires Licensed Producers to share the product’s “Equivalency Factor” – which will help patients calculate the number of grams of dried cannabis has been converted into the oil.
All of the CanniMed® Oils have a very simple equivalency factor of:
1 gram dried cannabis = 6 mL cannabis oil.
For ordering purposes, each 60 mL bottle of CanniMed® Oil is equivalent to 10 grams listed on a patient’s 30 day order limit.
The equivalency factor, however, should not be used as a guide for dosing.
CANNABIS OIL PRECAUTIONS
When ingested, cannabis oil is processed through the liver. Compared to when cannabis is inhaled through vapor or smoke into the lungs and takes effect almost immediately, CanniMed® Oil will have a much slower onset time and the effects will last longer.
It can take anywhere from 1-1.5 hours before you will begin to notice the effects and can take 2-4 hours to reach its peak effect.
To avoid overconsumption, wait 4 hours after the first dose before taking a second.
Start low and go slow.
Edible Oils
Patients who are new to edible cannabis oil should begin their therapy with a dose less than 0.5 ml
It is important to remember that cannabis taken orally has a slower onset time than when it is vaporized because it is absorbed through the digestive system. Wait at least four hours after the first dose before taking a second of cannabis oils.
Patients should follow extreme caution when dosing cannabis oils for the first time.
How do I dose dried medical cannabis?
Unlike conventional pharmaceutical products, cannabis is available in multiple varieties that differ in potency and composition. Determining a therapeutic dose and THC level for each patient is highly individualized.
MedReleaf, along with Health Canada, suggests starting “low and slow”
A typical starting dose falls between 1-3 grams per day
THC levels range by product; like with other medications, individual response rates to THC will vary
Depending on one’s previous experience with cannabis, general guidelines for vaporizing are: inhale 1-2 times (each inhalation should be brief and followed by a deep breath in and out of the lungs). Wait 10-15 minutes for the cannabis to take effect. If the effect is sufficient, this is your dose. If the effect is insufficient, inhale 1-2 additional times and wait another 10-15 minutes. Repeat as necessary until reaching the desired effect.
How do I dose cannabis extracts?
Oil:
When first trying MedReleaf THC rich cannabis oil we highly recommend starting with a dose no greater than 0.2 ml. This 0.2 ml will deliver approximately 10 mg of THC. Be sure to increase dose amounts in small increments.
A good starting dose for AvidekelMR CBD rich oil is 1 ml, which will deliver approximately 25 mg of CBD.
A good starting dose for MidnightMR THC + CBD balanced oil is 0.5 ml, which will deliver approximately 5mg of THC and 6 mg of CBD.
Capsules:
A good starting dose for cannabis oil capsules is one capsule. Be sure to wait at least 2-3 hours after ingesting the capsule before assessing the effects of the medication.
It will likely take 45 – 90 minutes before you begin to feel the effects*
The peak effects of ingested cannabis are often not achieved for up to 2 hours
Effects can last for up to 6 – 8 hours
It is recommended that extract users keep a Dosing Journal to record the amounts and effects of each dose. Sample Journal pages are found at the back of this manual.
Click here to Reply, Reply to all, or Forward
Question – Have the older style medications been used in varying doses or only the newer compounds?
The debate about the “medicinal” use of cannabis is clouded by the lobby for legalisation of recreational use. While there are arguments for and against this issue, recreational or “herbal” (raw plant) use of cannabis is not essential to the rational use of the purified active compounds. There is already a precedent in the opiates – while recreational use of some narcotics remains illegal, symptomatic use is essential to medicine – with morphine being one of the most commonly used drugs in acute medicine.
Like the opiates, the active compounds within cannabis – including THC and cannabidiol – are not miracle cures for any disease – they assist in symptomatic relief. Cannabidiol does appear to be useful for the particular type of treatment-resistant childhood epilepsy known as Dravet’s syndrome, but no better than newer alternatives such as Topiramate.
The argument for the use of the “raw plant” or “herbal” cannabis can also be compared to the opiates. Raw cannabis extract is analagous to tincture of poppy – raw plant extracts are complex mixtures that are highly variable in their content of active ingredients. Raw plant material is highly varied in its phytochemistry, dependent on factors such as plant genetics, season, location and many other factors. That is why herbal medicine developed into modern pharmaceutical science, with active compounds isolated, purified and dose-standardised. We then can predict, and provide, the ideal dose that maximises effect and minimises toxicity.
So, cannabis is no more “medicinal” than opium poppy. It contains active compounds with potentially useful effects for nausea, pain, anxiety, muscle spasticity and certain types of seizures, but also has potential side-effects and toxicity. Like morphine, cannabis extracts can be potentially useful for symptom control, and for some rare types of epilepsy, but are no miracle cure for anything. Let’s research and make the best therapeutic use of the purified active compounds without confusing the argument with recreational use, which also needs discussion – but it is a different discussion.