2. The use of cannabis for medicinal purposes

Introduction

  1. 2.1 This chapter provides an account of the Commission’s view of what constitutes medicinal cannabis, a discussion of the way cannabis is currently used medicinally in Victoria, and a record of information provided to the Commission about the effects of cannabis used for medicinal purposes. It also reviews the research base for:
  • the efficacy of cannabis in alleviating the symptoms of particular conditions
  • the adverse effects that cannabis may have for patients when provided to them for medicinal purposes.

What is medicinal cannabis?

Scope of review

  1. 2.2 The Commission has been asked to review and report on options for changes to the law to allow people to be treated with ‘medicinal cannabis’ in exceptional circumstances. For the purposes of its review the Commission must therefore adopt a position on what is meant by ‘medicinal cannabis’.
  2. 2.3 ‘Cannabis’ refers to the flowering tops of plants in the genus Cannabis L.1 Generally, the species used for medicinal and recreational purposes are Cannabis sativa and Cannabis indica,2 with ‘hybrid’ plants also available.3 While the whole of the plant contains varying levels of between 80 and 100 cannabinoids, they are found in the highest concentrations in the flowering tops, meaning this part of the plant is most relevant for those wishing to use cannabis for medicinal purposes.4
  3. 2.4 The efficacy of cannabis for particular medical conditions is affected by the types and amounts of cannabinoids in the product. Products can contain high or low levels of delta-9-tetrahydrocannabinol (THC) or cannabidiol (CBD),5 in various combinations with the other cannabinoids. Some forms are psychoactive, principally because of their concentration of THC.6
  4. 2.5 Cannabis is used for recreational purposes for its euphoriant effect, among other things, but also for medicinal purposes to cure or remedy symptoms of medical conditions.
  5. 2.6 ‘Medicinal’ means ‘relating to, having the properties of, a medicine; curative; remedial’.7 Thus, cannabis should be regarded as ‘medicinal cannabis’ when it is used for a medicinal objective—to achieve a curative or remedial effect.8 In this respect, medicinal purposes are to be equated with ‘therapeutic’ purposes.9 This is to be contrasted with its use for recreational purposes.
  6. 2.7 In consideration of the options for changes to the Drugs, Poisons and Controlled Substances Act 1981 (Vic), the Commission comprehends cannabis to be used medicinally when it is both:
  • taken by a person for the medicinal purpose of attempting to cure or remedy a medical condition,10 and
  • taken in a manner that enables the purported curative or remedial effect to be appropriately supervised and verified by a qualified medical professional.
  1. 2.8 Advances in the understanding of cannabis over the past half-century have enabled the development of synthetic pharmaceuticals that mimic the effects of cannabinoids on the body. For the purposes of this report, though, the Commission does not treat these products as falling within the meaning of ‘medicinal cannabis’. On the other hand, products that are extracted from the cannabis plant and used for medicinal purposes are regarded as falling within the meaning of ‘medicinal cannabis’.

Characteristics of medicinal cannabis

  1. 2.9 The Drug Policy Modelling Program at the University of New South Wales observed in its submission that cannabis products used medicinally can be categorised according to how their production is regulated:
  • pharmaceutical-grade cannabis products, approved by conventional regulators such as the Therapeutic Goods Administration (TGA) and including the nabiximols (Sativex) and synthetic cannabinoids
  • controlled and standardised herbal cannabis, such as the products made in the Netherlands by Bedrocan BV, which have standardised levels of cannabinoids and have been tested to be free of harmful adulterants
  • unregulated illegal herbal cannabis, which is anything bought from the black market and generally has unknown concentrations of cannabinoids and potentially harmful contaminants.11

 

  1. 2.10 Cannabis can also be differentiated by the form in which it is supplied. The categories of product made available for medicinal purposes in other jurisdictions include:
  • the dried flowering tops of the cannabis plant, taken through being smoked, vaporised or infused in tea
  • cannabis resin, collected and compressed from the flowering tops
  • infused cannabis products, such as alcohol-based tinctures, edible oils infused with cannabis and products made from these, and suppositories
  • extracts of cannabis, containing concentrated extracts of cannabinoids, taken orally, topically or by vaporisation
  • raw, undried cannabis leaves, consumed as a food.
  1. 2.11 Some submissions provided to the Commission distinguished between the utility of Cannabis sativa and Cannabis indica for different purposes. Both forms contain a number of compounds that have the potential for medical application.
  2. 2.12 Views differ regarding what makes medicinal cannabis effective. Most submissions highlighted the therapeutic use of THC and CBD, and a number of people stressed the significance of the endocannabinoid system and the role of the Type 1 and 2 cannabis receptors.12 CBD is known to moderate the effects of THC and is being researched for its potential to treat epilepsy, schizophrenia and other psychotic disorders, type II diabetes, inflammatory bowel disease, gliomas and drug dependency, among other conditions.13
  3. 2.13 THC and CBD are not the only compounds of interest in the cannabis plant. Besides THC, researchers at the University of Sydney have identified what they refer to as the ‘big 10’ non-psychoactive and non-addictive cannabinoids that show the most promising therapeutic potential. They are:
  • cannabidiol (CBD) and its acid form (CBDA)
  • cannabidivarin (CBDV)
  • the acid form of THC (THCA)
  • tetrahydrocannabivarin (THCV) and its acid form (THCVA)
  • cannabigerol (CBG) and its acid form (CBGA)
  • cannabinol (CBN)
  • cannabichromene (CBC).14
  1. 2.14 Research as to the effects of these cannabinoids remains at an early phase, but the compounds have possible medical application in the treatment of epilepsy, pain, psychosis, cancer, diabetes, inflammation, anxiety and a host of other conditions.15
  2. 2.15 Besides cannabinoids, up to 300 other compounds found in the cannabis plant are asserted to contribute to its overall therapeutic effect. These include terpenes and flavonoids, which are not unique to the cannabis plant but contribute to each strain’s chemical ‘fingerprint’.16 Some with whom the Commission consulted emphasised the ‘entourage effect’, said to arise from the ‘whole’ cannabis plant which results in an overall beneficial effect beyond what could be obtained from each cannabinoid on its own.17

Use of medicinal cannabis

  1. 2.16 It is apparent from the submissions received and consultations conducted by the Commission that cannabis is currently being used illegally by a wide range of Victorians to attempt to alleviate a broad array of health conditions. Others have informed the Commission that they would use it but are deterred by its current unlawful status.
  2. 2.17 As outlined in the issues paper, cannabis has a long history of medicinal use. It was introduced into Western medicine in the 19th century, at which time medicines were much less refined than contemporary pharmaceuticals. By the early 1900s, botanical extracts of cannabis were still in use, but the product was ‘difficult to store, its extracts were variable in potency, and the effects of oral ingestion were not constant’.18 At the same time, its recreational use increased, and by the mid-20th century its medicinal use had all but disappeared.19
  3. 2.18 The Commission heard compelling stories from users of medicinal cannabis regarding the dramatic changes they had experienced after starting treatment with medicinal cannabis. Many spoke of the ways in which cannabis had enabled them to stop using pharmaceutical drugs with serious side effects, or to ‘get their lives back’. Others without experience of medicinal cannabis told the Commission about the desperation they felt in experiencing, or watching a loved one experience, the pain and suffering of a chronic illness, and expressed sincere hope that cannabis might be effective for them.

Personal accounts of conditions where cannabis has provided relief

  1. 2.19 The following paragraphs summarise some of the personal accounts as to the efficacy of medicinal cannabis, as conveyed in submissions and consultations with members of the public.

Multiple sclerosis

  1. 2.20 Pain and muscle spasms associated with multiple sclerosis were reported as having been effectively treated through the use of medicinal cannabis. KF informed the Commission that she was diagnosed with multiple sclerosis in 2011 ‘after many years in limbo’. Her main symptoms were pins and needles, electric shocks, nerve pain in her feet and legs that made it very painful for her to walk, severe throat spasms, loss of sensation in the right side of her face, cognitive issues and extreme fatigue. She also suffered from alopecia areata for 10 years. She told the Commission that she started taking cannabis oil made according to the ‘Rick Simpson protocol’20 in 2012. The result was that:

I no longer lose my hair, I no longer get the pins and needles or the electric shocks, I have recovered some of the feeling in my face but not all. If I take a small amount of cannabis oil every other day, I am able to do activities that include walking, without extreme pain. My MS has also not progressed.21

Epilepsy

  1. 2.21 The Commission heard from a number of people with children suffering from rare and severe forms of epilepsy. Many told of the dramatic reduction in symptoms their children had experienced following treatment with cannabis oil.
  2. 2.22 The parents of Cooper Wallace told the Commission in person and in a written submission about the major symptom relief that he received from administration of cannabis oil. They acknowledged that it was not a cure for him but asserted that ‘it gives a quality of life for him, and our entire family’.22 Prior to using cannabis oil his condition had been deteriorating. After using cannabis oil for some time they have found that Cooper’s previously extensive fitting has become very limited and he is able to eat and drink instead of relying on tube-feeding. His conventional medications have been reduced and in some cases stopped.

We recently ran out of cbd oil, within days he was in hospital. One day alone he had over 900 seizures. On oil he has only 2–3 seizures. A dramatic change!23

  1. 2.23 A similar account was given to the Commission by the parents of Tara O’Connell, who is treated with an ultra-low dose treatment using THC and THC Acid.24 In 2012, Tara was suffering around 200 seizures per day and had been resuscitated eight times. She used a wheelchair, was not toilet-trained and had limited capacity to speak. Her medications had caused drug-induced anorexia. She was not expected to live for more than 24 months.25 The Commission was told that, upon the administration of cannabis to Tara, her seizures stopped and the respite from the seizures has extended for over 24 months.26 She no longer requires the use of a wheelchair and can attend school part-time. She has also ceased using all pharmacy drugs.27
  2. 2.24 Michelle Whitelaw informed the Commission of a similar response obtained by her son, Jai, who was experiencing in the order of 500 seizures a day. She told the Commission that his incidence of seizures had fallen to three over the previous five months:

His pupils are no longer fixed nor dilated. He is eating/drinking without choking, attending school, able to write, speech is improving, walk steady, kick a ball and ride his bike, socialise, dress and toilet himself. All of these are FIRSTS. His personality is bubbly and he is so incredibly alive and well. Jai has not experienced any negative side effects.28

  1. 2.25 The Commission also received submissions on behalf of adults suffering from intractable epilepsy. Lyn Cleaver wrote about her adult son, Jeremy, who suffers from epilepsy. In 2014, he experienced a drug-induced psychosis after one of his medications was increased on the advice of a neurologist. Subsequent adjustments to his dosages were of no effect, and the family decided to try medicinal cannabis. Ms Cleaver described the results as follows:

Almost immediately we saw improvements, his sleep patterns, behaviours and seizures were all much more tolerable! We knew then that we must find a way to source cannabis medicines to give him the best possible chance at a fulfilling life. … Jeremy has been at the end of the line for available treatment for his seizures for years. We have been forced to wait for the next anti convulsant to be available on the market. ALL of the anti convulsants he has trialled have failed to control his seizures, ALL of them have caused unwanted side effects—some of them very serious. Cannabis is the first medicine we have been able to offer him that is both safe and effective.29

 

Relief from the symptoms of cancer

  1. 2.26 The Commission was informed by a number of people about the advantages in terms of pain relief and comfort obtained by patients with terminal cancer when they took one form or another of medicinal cannabis. Some provided powerful accounts of the help that they and their loved ones had received from different forms of cannabis during the later stages of their experience of terminal illnesses, particularly cancer.
  2. 2.27 Robert Wisbey spoke movingly at a public consultation in Geelong30 about the experience of his son, Mason, who passed away from bowel cancer in April 2015. He told the Commission that when Mason received cannabis oil he was ‘able to sleep, he was able to eat’.31 Mason had previously been unable to eat significantly for an extended period of time. In addition, according to his father, while cannabis did not remove Mason’s pain, it rendered it manageable and significantly increased Mason’s quality of life during the later period of his life.
  3. 2.28 In a subsequent written submission, Mr Wisbey described the unrelenting pain and discomfort from which Mason suffered until he began to take cannabis oil:

As a human being Mason deserved BETTER he deserved to have a life without pain without suffering without the constant side effects caused by his medication and treatment, this was finally found in Cannabis Oil as much as I doubted its effect I could NOT refute what I was seeing before my eyes, my son was able to sleep, he was able to eat, an appetite that had left his body many months before returned with a vengeance he was not pain free but it was manageable at a level far far lower than what Doctors were able to give.32

  1. 2.29 This account has many features in common with the experience of Dan Haslam in Tamworth, New South Wales who also experienced significant relief from the symptoms of bowel cancer from administration of cannabis oil.33
  2. 2.30 The Australian Lawful Use of Cannabis Alliance relayed the story of another parent treating his child with cannabis oil:

The recent tragic experience of one of our members, Mr Adam Koessler, is a sad example of this… He is currently facing criminal charges and family court proceedings for administering cannabis oil to his daughter who has terminal cancer and is undergoing a long process of chemotherapy.34

  1. 2.31 A woman who attended the public consultation in Wodonga said that her husband’s palliative care nurse had suggested cannabis for relief of cancer pain before he passed away. She said she was surprised at this, but that it did provide very good pain relief.35
  2. 2.32 Many who communicated with the Commission lamented the effects of opiate medications which had adversely affected the mental state of cancer sufferers and had caused a variety of side effects including chronic and distressing constipation. However, they asserted that cannabis did not have such effects and was either as effective as, or more effective than, prescribed opiate medications.

 

Chronic pain

  1. 2.33 Many accounts were given to the Commission of respite from chronic pain after using medicinal cannabis.36
  2. 2.34 Matthew Corda has an acquired brain injury and many associated problems, and uses cannabis to treat pain and depression. He stated:

I have tried nearly everything to no real solution to pain etc relief, but found cannabis a magic thing, kills the pain for longer, and am functioning adult. … All [treatments] have been trialled and failed, or as in my case the strong pain [medications] gives the feeling of a zombie and difficult to function. … [T]he benefits far outweigh what is wrote or discussed by people with no experience or used cannabis.37

  1. 2.35 Danielle Rose-de Montignie used cannabis to treat her chronic pain caused by cancer from which she suffered 28 years ago. She also suffers from lymphoedema, which causes pain and swelling. She explained that she has successfully treated herself with cannabis, with her general practitioner’s knowledge, and believes that she has avoided becoming an opiate user as a result.
  2. 2.36 Matthew Pallett described using cannabis medicinally for many years, referring to it as ‘the only substance I have ever found to give relief from debilitating, neuropathic pain caused by spinal injury that occurred at 12 years of age’.38
  3. 2.37 A large number of the people who attended the public consultations had used medicinal cannabis for chronic pain. At the Mildura public consultation, the Commission heard from a woman who suffered chronic pain from prolapsed discs and arthritis. Having taken morphine for 16 years to deal with the pain, she was unable to function and slept for up to 22 hours per day. She was unable to work a full-time job and could not attend university. She had contemplated suicide. After taking cannabis, she found that she can remain awake during the day.39
  4. 2.38 Another person at the Mildura consultation described herself as suffering chronic pain due to car accidents that was so bad that she would ‘vomit’ from nausea. Her weight had dropped to 38kg and she was told she was at risk of death from organ failure. She had been prescribed morphine for over 15 years for the pain. After using cannabis, she found that her nausea disappeared and she was able to eat and eventually return to work.40

Failure or harms of other treatments

  1. 2.39 As is apparent from the accounts described above, many of those who have resorted to medicinal cannabis have done so after the available treatments have failed or had unacceptable consequences.
  2. 2.40 Lindsay Milton started using cannabis after a spinal injury 25 years ago and subsequent surgery which left him in intense pain. He said that the medication he had been prescribed was ineffective, and he was taking extra medication to counteract the side effects of the pain killers:

2 days into using Cannabis I knew things could only get better if what was happening with pain relief continued and it did. I started sleeping better, was getting 5 times the pain relief pharmaceuticals were giving me and I got my appetite back all with no side effects whatsoever.41

  1. 2.41 After another bad accident, which led to several operations and months in hospital being treated with pethidine for pain, he suffered withdrawal symptoms when he returned home. He was then given morphine, in increasing amounts as the pain continued to affect him:

When the family saw me [dying] on the bed taking 700mg a day of morphine and [diazepam] thrown in to help the morphine with pain family and friends had saw enough. I went from a fit 6’ 4” 100 kilo man to a 160 kilo blob and I was slowly [dying], nothing surer, I was waiting on it. I had absolutely no recollection of anything that was going on around me and never spoke about anything anyone could understand. Then family and friends teamed up to firstly get me off the morphine which they did by reintroducing Cannabis back into my life for pain and slowly they kept lowering the morphine dose. It took 12 months to be free of it but my use in Cannabis was now part of my pain control and it works perfectly. 42

  1. 2.42 The Australian Lawful Use of Cannabis Alliance told the Commission about one woman who had turned to cannabis after exhausting conventional treatments:

The story of one of our members, Ms. Debra Lynch, perfectly encapsulates this tragic saga being played out in our communities. Debra suffers from an incurable illness called Raynaud’s Phenomenon with Limited Scleroderma and Gastrointestinal Involvement. She is allergic to every available conventional pharmaceutical treatment option. The only therapeutic treatment she can tolerate is a course of medical-grade cannabis oil. Like many of our members, and the members of the Medical Cannabis Users Association of Australia, she is daily faced with the unconscionable choice of unlawfully accessing the only available treatment for her condition and its symptoms.43

  1. 2.43 Some people informed the Commission that they take cannabis in addition to pharmaceutical preparations. Natalie Vassallo, for instance, said that she has a variety of conditions and is taking a range of medicines to treat them, but finds cannabis more helpful to her than most of her prescription medications:

When I cannot get hold of any Cannabis, my symptoms get worse. I suffer with pain in my neck, shoulders, arms, hands, lower back & knees. I suffer panic attacks that prevent me from leaving the house most of the time. It is debilitating to feel like this.44

Access

Pathways to access

  1. 2.44 The Commission heard from many individuals who obtain cannabis from people who specialise in cultivating and refining cannabis for medicinal purposes. Indeed, several producers attended the Commission’s consultations and made written submissions.45 They showed a detailed knowledge of the cannabis plant, its varieties and refined versions, and expressed strong views about its potential medicinal applications.
  2. 2.45 People who presently access cannabis for medicinal purpose apparently receive significant advice and guidance from the suppliers of cannabis products, including instructions on strains, dosage and indications. The cost of obtaining medicinal cannabis through these illegal channels varies but was described as significant by some who spoke to the Commission.
  3. 2.46 Clearly, for a sufficiently interested person, it is easy to find information regarding medicinal cannabis and its potential uses, particularly on the Internet. Many submissions referred the Commission to resources on the Internet.Some people described how they learnt online about the possible benefits of cannabis for their condition or that of a loved one.Several of them went on to seek out cannabis products through online stores and social media. Despite the illegal nature of all cannabis products in Australia, patients in Australia do not need to rely solely on local networks. They are able to access information or even the product itself from other jurisdictions where cannabis has been legalised for medicinal and/or recreational purposes.

Interest in medicinal cannabis

  1. 2.47 In addition to the accounts received on behalf of people already obtaining relief from cannabis, the Commission heard from a number who are interested in using it to treat a variety of conditions, having been unsuccessful with or disillusioned by conventional treatments.
  2. 2.48 Aaron Johnson and Kelli Russell told the Commission about their two-year-old daughter, Harper, who has Dravet Syndrome and suffers life-threatening seizures as a result. After reading on the Internet about the use of medicinal cannabis for seizures, they started investigating cannabis oil as a treatment for epilepsy. They read about the benefits and concluded that ‘we need to give Australians numerous avenues to access cannabis based medicine legally’.46
  3. 2.49 This account reflects a common theme among submissions: that the patient or their carers do not wish to try cannabis until it is made legal. A mother who attended the Shepparton public consultation, for example, stated that her son suffers from a rare form of epilepsy. She and her partner are desperate for relief, but they need to be able to act legally because they cannot afford to lose their jobs.47
  4. 2.50 Joylene Donovan told the Commission about her 11-year-old daughter, Ava, who also suffers from Dravet Syndrome. She described severe side effects of anticonvulsant medications, and how attempts to wean her daughter off them have only led to increasing seizures and hospital admissions:

I would give anything to be able to have the opportunity to trial Medical Cannabis for Ava given the success we are seeing world wide for many children with the same condition as Ava. I see it as another option, another treatment and potentially a life changer for her. For some it will work, for others it won’t and like any medication therapy it is definitely a trial and error thing due to the many combinations available. I understand the concern of long term effects but the reality is that what we are currently using to treat our children we don’t even know if there is a long term, as we have already seen our beautiful children disappear in front of our eyes using pharmaceutical drugs, which are all addictive or toxic with long term use… Our pharmaceutical treatments may stop seizures but doses are often so high that our children become zombies and cause side effects that no parent should ever have to witness their child going through.48

  1. 2.51 Other examples of carers interested in being able to legally access medicinal cannabis for their loved ones were Diane and Max Lock who spoke of the plight of their granddaughter, Madison, who has epilepsy:

Madison has been on many epilepsy drugs in the past few years, all of which have very nasty side effects, including aggression, pains in her head, psychotic episodes. This is devastating to see, and does not stop the seizures, nothing seems to work. Everything we have researched on medicinal cannabis seems favourable and not destructive like the prescribed medications the neurologist puts our Grand Daughter on. I know they are trying to help, but so far none of the prescription medications have worked.49

  1. 2.52 Similar sentiments were expressed by Shirley Humphris about her granddaughter, Cambrie, who has intractable epilepsy. Cambrie has been trialled with ‘over 12 antiepileptics all with frightening side effects and some with unknown long-term risks for children’. 50
  2. 2.53 People with adult epilepsy also expressed interest in trying medicinal cannabis. Derek Spence told the Commission about his wife, Elyse, who suffers from intractable epilepsy. He stated she ‘has tried every drug available and they’re all crap and don’t work plus have numerous side effects.’51 Jan Hartwich told the Commission about her 55-year-old daughter, Karyn, who has suffered from epilepsy since birth. Ms Hartwich said that her daughter is on a number of drugs, which do not fully control her symptoms and have numerous side effects, such as blurred vision, anxiety and depression. They also cause her to sleep for more than 18 hours each day. Ms Hartwich advised that Karyn’s neurologist believed cannabis could be of assistance to her but ‘because [of] its illegal status we are unable to use it’.52
  3. 2.54 A couple who attended the public consultation in Shepparton told the Commission about their adult son who suffers from epilepsy. He has seizures all day, and is severely incontinent. His condition has ‘taken away the lives of three people’—his and his parents—and has the potential to break up families. If cannabis could reduce or eliminate his symptoms, they said, they might be able to get their lives back.53
  4. 2.55 Mark Eastick, who experiences pain and muscle spasms as a result of a spinal cord injury, told the Commission he wished to try medicinal cannabis for his symptoms.54
  5. 2.56 Another person told the Commission about his wife, who ‘has been in constant pain for over 15 years’, which has been categorised as fibromyalgia, and more recently as a type of pain believed to be nerve-based. He stated that she has received various forms of medical help, including pain medication, pain counselling and physiotherapy, but ‘nothing seems to be working’, leaving her confined to a wheelchair. She considered using morphine but her apparent drug sensitivities have left few options as regards medication. Although desperate for some relief, the person’s wife has not yet tried cannabis:

The use of cannabis may or may not work, but given media reports that it has worked in unusual cases, it is [her] desire to at least test it to see if it can make a difference. Her current medical condition is now pushing us to look at what may be considered extreme approaches which may entail a measure of risk but we often wonder if it will be much worse than current efforts and associated risks. Given that all known conventional help has been exhausted with little relief from symptoms, an opportunity should be given anyone seeking help without undue hindrance to at least test the efficiency or otherwise when all other options are not proving effective.55

  1. 2.57 The Commission also received a submission from a person suffering from a number of medical conditions, including a rare condition known as Idiopathic CD4 Lymphocytopenia, otherwise known as ‘non-HIV AIDS’—a form of AIDS which is not caused by HIV. The person described a grave illness, which has left them largely bedridden and causes a range of debilitating symptoms, including ‘chronic unrelenting’ pain. They cannot tolerate a number of medications, and experimental treatments have been suggested which would come at a high cost and require overseas travel. After researching cannabis online, the person has formed the view that ‘medicinal cannabis is the only realistic and comparatively safe treatment option available’. Notwithstanding this, the person has elected not to access cannabis because it is unlawful:

I have been tormented by thoughts of unlawful activity, experiencing feelings of great despair and loss that I have found myself in a position of having to choose between everything that I have believed in and stood for (the law) and trying to save my own life. The unlawful status surrounding cannabis, does not only affect me, it also affects those I live with. If prosecuted, my partner would stand to lose his current professional licence.56

Research support for efficacy

Breadth and variety of data

  1. 2.58 The Commission’s issues paper posed the question: ‘For what conditions is there sufficient knowledge of the therapeutic benefits, dangers, risks and side effects of cannabis to justify allowing sufferers to use it lawfully in Victoria?’
  2. 2.59 In response, the Commission received submissions that, together, asserted that a wide variety of conditions can be cured or assisted by medicinal cannabis and thus should be viewed as ‘exceptional circumstances’ for the purpose of determining who should have access to medicinal cannabis under a Victorian scheme. These included asthma/breathing disorders,57 HIV/AIDS,58 Ebola,59 cancer,60 nausea from cancer,61 Crohn’s disease/gastrointestinal disorders/colitis,62 diabetes,63 epilepsy,64 glaucoma,65 hepatitis C,66 migraines/headaches,67 muscle spasms and pain due to multiple sclerosis,68 pain,69 fibromyalgia,70 arthritis,71 inflammation,72 menstrual pain,73 menopause,74 stress and anxiety,75 insomnia/sleep disorders,76 bipolar disorder,77 depression,78 psychotic illnesses,79 attention deficit hyperactivity disorder (ADHD),80 Tourette syndrome,81 nymphomania,82 post-traumatic stress disorder,83 Alzheimer’s disease and dementia,84 Parkinson’s disease,85 autism and Asperger’s disorder,86 thyroid disorders,87 ageing,88 back pain, scoliosis, neck pain and spinal cord injury,89 cardiovascular health and blood pressure,90 eating disorders,91 haemorrhoids,92 heavy metal toxicity,93 phlebitis and venous ulcerations,94 skin conditions, dermatitis and psoriasis,95 scars, ulcers, warts and moles,96 weight management,97 wounds, cuts, corns, acne, furuncles and nail fungus.98
  3. 2.60 The supporting evidence for each of these claims varies in quality and quantity. Certainly the volume of information is vast. Matthew Pallett pointed out in his submission that:

The current literature base available in the recognised medical libraries and medical journals of the world amounts to over 30,000 peer reviewed studies and journal articles on Cannabis.99

  1. 2.61 In determining what the eligibility criteria should be for a scheme that allows people to be treated with medicinal cannabis in exceptional circumstances, and when making clinical decisions about a patient’s treatment, not all evidence is of equivalent value.
  2. 2.62 A threshold consideration when making these types of decisions regarding medicinal cannabis is the clinical evidence for its efficacy in treating particular conditions and symptoms. The associated risks must also be taken into account.
  3. 2.63 Partly as a result of the broadly stated, often divergent, claims made regarding medicinal cannabis, it is important that, prior to introducing any kind of medicinal cannabis scheme, the available evidence is evaluated to determine which claims can be substantiated, and to what degree. The conventional means of doing so is by reference to evidence-based medicine.

Evidence-based medicine and the quality of evidence

  1. 2.64 Evidence-based medicine is an approach to the practice of medicine that has been described as the ‘conscientious, explicit, and judicious use of current best practice in making decisions about the care of individual patients.’100It aims to improve decision making by medical practitioners about the provision of treatment, by emphasising a systematic approach that critically appraises the available clinical evidence.
  2. 2.65 A cornerstone of evidence-based medicine is the hierarchical system of classifying evidence, often referred to as ‘levels of evidence’. This approach is used by the National Health and Medical Research Council (NHMRC). Medical practitioners are encouraged to find the highest level of evidence to answer clinical questions, including whether they should prescribe or encourage access to particular forms of medication.101
  3. 2.66 As Justice Perry observed in Australian Competition and Consumer Commission v Consumer Plus! Australia Pty Ltd:

The standard taxonomy of levels of evidence for intervention studies based on the NHMRC guidelines and starting with the highest quality of evidence, is as follows:

Level I: evidence obtained from a systematic review of Level II studies;

 

Level II: evidence obtained from at least one properly designed randomised controlled trial of appropriate size;

Level III-1: evidence obtained from well-designed pseudo-randomised controlled trials;

Level III-2: evidence from comparative studies (including systematic reviews of such studies) with concurrent controls being a non-randomised experimental trial, a cohort study, an interrupted time series or matched case-controlled study;

Level III-3: evidence from a comparative study without concurrent controls, being a historical control study, two or more single arm studies (i.e. case series from two studies), or a well-designed interrupted time series trial without a parallel control group from more than one centre or research group or from case reports; and

Level IV: evidence obtained from a case series, either post-test or pre-test/post-test outcomes.102

  1. 2.67 The evidence-based medicine hierarchy ranks clinical evidence according to the authoritativeness of the results. At the top of the hierarchy (at Level I) are systematic reviews and meta-analyses. These studies draw conclusions in a systematic way, based on high-level published studies in the literature.
  2. 2.68 Next are randomised, double-blind, placebo-controlled studies (Level II). These studies are particularly valuable because they are designed to be unbiased, and to have the lowest risk of errors.
  3. 2.69 Further down the hierarchy are ‘cohort studies’ and then ‘case control’ studies (Level III), considered to be less valuable because fewer controls are placed on the conduct of the research, making it more difficult for conclusions to be drawn from the findings.103
  4. 2.70 Case series (Level IV) and case examples follow. They are at the lowest level of the hierarchy and do not normally form the basis of decision making about proposed drugs to be administered to patients.
  5. 2.71 The evidence cited in support of the medicinal properties of cannabis ranges across a number of these categories. In the next section, an overview is given of the status of current knowledge about the efficacy of cannabis for conditions regarding which particular claims have been made to the Commission.104 The overview emphasises outcomes at the highest level of clinical evidence: systematic reviews and meta-analyses.

The quality of cannabis research

  1. 2.72 A substantial body of evidence now exists in relation to the efficacy of certain forms of cannabis for particular medical conditions. AMA Victoria, for instance, acknowledges that there is ‘some evidence to suggest that cannabinoids are effective for the treatment of neuropathic pain, muscle spasticity for patients with MS, and in controlling nausea for cancer patients.’105
  2. 2.73 However, while this body of evidence exists—and, indeed, is rapidly expanding—it is of inadequate quality for definitive statements to be made about the therapeutic efficacy of cannabis for many conditions. This causes consternation in many quarters of medicine about claims of the legitimacy or advisability of prescribing medicinal cannabis. The Senate Legal and Constitutional Affairs Legislation Committee observed that: ‘there remain significant gaps in our scientific understanding’ and that ‘it is important that medicinal cannabis is used to treat identified medical conditions where it has been proven to be safe and effective.’106
  3. 2.74 In an editorial in the Journal of the American Medical Association published in June 2015, for instance, D’Souza and Ranganathan argued that for most conditions that have been regarded as appropriate for medicinal cannabis:

approval has relied on low-quality scientific evidence, anecdotal reports, individual testimonials, legislative initiatives, and public opinion. … For most of the conditions that qualify for medical marijuana use, the evidence fails to meet [Food and Drug Administration] standards.107

  1. 2.75 In May 2015 the College of Physicians and Surgeons of British Columbia prefaced its position on medicinal cannabis with the observation that: ‘Few reliable published studies are available on the medical benefits of marijuana’. However, it accepted that:

there are sometimes circumstances in medical practice where exceptions to strong relative contraindications may be appropriate. When physicians utilize a therapeutic agent despite strong relative contraindications, the standard of care mandates detailed documentation of their rationale.108

  1. 2.76 The Royal Australasian College of Physicians also expressed concern about the quality of the research base available as of 2015:

the majority of the trials that have taken place on this issue have been small and weak and have not been tested against standards of care. Randomised controlled trials are required to establish the efficacy and benefits of treating particular conditions with medicinal cannabis and evidence of any harm that may arise as side effects.109

  1. 2.77 A refrain of the credible scholarly literature is that further suitably controlled, high quality studies need to be undertaken to evaluate whether the claims, anecdotes and aspirations for the efficacy of medicinal cannabis can be justified. An example in this regard is the extensive review of the literature published in 2015 by Belendiuk, Baldini and Bonn-Miller who lament ‘the dearth of rigorous research on the effects of marijuana for the most common conditions for which it is currently recommended’.110 They observed that:

It is paramount that well-designed [randomised controlled trials] with larger sample sizes be conducted to determine the actual medical benefits and adverse effects of marijuana for each of the [conditions for which claims of efficacy have been made].111

  1. 2.78 It can be difficult to reconcile belief in medicinal cannabis with the strength of the clinical evidence. Views of the evidence for the efficacy of medicinal cannabis vary, and perceptions based on faith, hope and experience with cannabis, on the one hand, can depart substantially from views based on the assessment of the clinical trials.112 A possible exception is in respect of multiple sclerosis.
  2. 2.79 To this must be added that there are obstacles to the accumulation of high-quality cannabis research which do not exist for other drugs. For example, conducting research with cannabis or cannabinoids tends to attract much more onerous regulatory complexity than for other drugs. To adapt the conclusion of an American writer describing this difficulty, ‘[t]his creates a vicious circle: marijuana is [a schedule 9 drug] and has no currently accepted medical use in treatment because there is no data on its safety and efficacy there is no data because marijuana is [schedule 9] and clinical testing is restricted.’113
  3. 2.80 Further, whole-plant forms of cannabis generally do not have a ‘sponsor’ with a financial interest in funding clinical trials, possibly resulting in fewer or smaller studies.

Determining efficacy

  1. 2.81 The Commission’s issues paper reviewed the state of the clinical literature as of early 2015 regarding a number of the conditions asserted to be responsive to the administration of medicinal cannabis as a therapeutic agent. The following section isolates particular conditions that were identified in submissions and have also been the subject of recent systematic reviews, meta-analyses and other significant evaluations.

Multiple sclerosis

  1. 2.82 The results of a meta-analysis by Whiting et al published in the Journal of the American Medical Association in June 2015 indicate that there is ‘moderate-quality evidence to suggest that cannabinoids may be beneficial for the treatment of spasticity due to [multiple sclerosis]’.114 The authors identified 11 placebo-controlled trials meeting the selection criteria, and concluded that:

Studies generally suggested that cannabinoids were associated with improvements in spasticity, but this failed to reach statistical significance in most studies.115

  1. 2.83 Results of trials on the efficacy of cannabis to treat multiple sclerosis are complicated somewhat because there are a number of ways to measure spasticity. Some of these rely on objective measures of spasticity, while others rely on subjective measures,116 with subjective measures sometimes said to be more informative but complicating the interpretation of trial results.117 Often research findings depend upon patient self-reports.
  2. 2.84 On 26 November 2012 the TGA registered Sativex oromucosal spray118 to treat the symptoms of patients with moderate to severe spasticity due to multiple sclerosis, and included it in Schedule 8 of the Standard for the Uniform Scheduling of Medicines and Poisons.119 However, Sativex was denied listing on the Pharmaceutical Benefits Scheme, which would have enabled it to be sold at a subsidised price.
  3. 2.85 Sativex was not listed on the Pharmaceutical Benefits Scheme because the Pharmaceutical Benefits Advisory Committee considered that there was insufficient evidence of its efficacy and its relative effectiveness compared to standard care. In summary it found:
  • There is insufficient evidence to establish comparative effectiveness and safety compared with standard care alone in patients who are intolerant to anti-spasticity medication.
  • There is no evidence of efficacy and safety provided in comparison with high dose baclofen alone, or in combination with dantrolene or diazepam as the second-line therapy.
  • The nominated comparator was not appropriate (the second-line therapy of oral baclofen dose escalation alone or in combination with dantrolene or diazepam should have been included at least as a secondary comparator).
  • Although the results of the key trial showed an improvement in the average rating of spasticity, the design of the trial meant that it was difficult to extrapolate this benefit to patients likely to be treated in the Pharmaceutical Benefits Scheme population.
  • The clinical relevance of the benefit was not adequately substantiated; the claim for superior efficacy over standard care was inadequately supported; and nabiximols appeared to be inferior over standard care in terms of comparative safety.120
  1. 2.86 Although not conclusive, there is a reasonable level of research support for the effectiveness of cannabis in relieving pain and spasticity for those suffering multiple sclerosis.

Epilepsy

  1. 2.87 The state of epilepsy research at the time of writing is characterised by uncertainty and change with respect to the efficacy of medicinal cannabis. The research collected to date has delivered results of limited significance. At the same time, considerable research energy is being committed to the further study of cannabinoids as a treatment for refractory epilepsy, particularly in juvenile patients.
  2. 2.88 In 2013, Canada Health issued this guidance for medical practitioners: ‘Increasing evidence points to a role for the endocannabinoid system in the modulation of neuronal tone and excitability and possibly in epilepsy.’121 However, this does not mean that the evidence is yet clear. In 2014, the authors of an article in a medical journal on epilepsy argued that: ‘Until data from well designed clinical trials are available and reliable, and standardised CBD products that are produced using good manufacturing practices are available, caution must be exercised in any consideration of using CBD for the treatment of epilepsy.’122 Also in 2014, the American Society of Neurology expressed the view that the use of oral cannabinoids is of unknown efficacy in epilepsy and that there was not sufficient evidence to prescribe CBD or to recommend self-treatment with medicinal cannabis.123
  3. 2.89 A Cochrane Review124 published in 2014 on ‘Cannabinoids for Epilepsy’125 reviewed research literature to assess the efficacy and safety of cannabinoids when used as a single therapy or add-on treatment for people with epilepsy. It was very reserved in its findings. It found that ‘no reliable conclusions’ could yet be drawn regarding the efficacy of cannabinoids as a treatment for epilepsy. It identified only four studies from 1978 to 1990 that met the selection criteria of randomised controlled trials. All used CBD as the treatment agent. It observed that patient numbers in the studies were small (48 patients in total) and that there had been varying reports of reduction in seizure frequency and/or seizure freedom. The review’s authors also expressed the view that, as the studies ran for short periods of time (four weeks to 18 months) the safety of long-term cannabidiol treatment could not be reliably assessed.
  4. 2.90 In addition, a systematic review of the efficacy and safety of medical marijuana in treating selected neurological disorders, including epilepsy, was published by the American Academy of Neurology in 2014. It concluded that oral cannabinoids are of unknown efficacy in epilepsy, that the risks and benefits of medical marijuana should be weighed carefully, and that the comparative effectiveness of medical marijuana as against other therapies for epilepsy are unknown.126
  5. 2.91 The position of Epilepsy Australia in relation to the efficacy of medicinal cannabis is also reserved:

There have been several reports in the media of dramatically positive responses to derivatives of cannabis, medical marijuana in children with severe forms of epilepsy that have not responded to available therapies. While these reports give reason for hope, we must be mindful that these are anecdotal reports only. However such reports have brought attention to the potential for cannabis to provide a new anti-epileptic therapy and help us understand how epilepsy occurs.127

  1. 2.92 However, there is optimism that research currently underway will deliver positive results, supportive of the efficacy of cannabis for treating severe forms of epilepsy.128 Researchers from the United States presented results at the 2015 Annual Meeting of the American Academy of Neurology from an open-label trial on the treatment of children and young adults suffering from drug-resistant forms of epilepsy129 with purified CBD (Epidiolex). The trial recruited 213 participants, of whom 123 were included in efficacy calculations. The data showed a median reduction in seizure frequency of 46 per cent by the twelfth week. Patients with Dravet Syndrome had a reduction in seizure frequency of 51 per cent by week 12, while those with Lennox-Gastaut Syndrome experienced a median reduction of 52 per cent. The researchers concluded that:

CBD showed reductions in seizure frequency across multiple drug-resistant epilepsy syndromes and seizure types and was generally well tolerated in this open-label cohort. Controlled trials are indicated to characterize efficacy and safety.130

  1. 2.93 Two Phase III trials using Epidiolex to treat Lennox-Gastaut Syndrome have also commenced, with data expected to become available in early 2016.131 The Commission notes that a particular component of the trials to be conducted in New South Wales, with the participation of Victoria and Queensland, is intended to be in respect of the efficacy of medicinal cannabis for paediatric epilepsy.
  2. 2.94 Therefore, there is emerging research support for the effectiveness of cannabis in relieving the symptoms of epilepsy, especially for those with juvenile syndromes.

 

Chronic pain

  1. 2.95 Assessment of the experience of pain is complex. It incorporates complicated overlaps between the physical and the psychological. The concept of exclusively ‘physical pain’ is no longer accepted in light of our understanding of the neurophysiology and psychology of pain as it has evolved over the past 80 years. The contemporary understanding of pain is now embodied in the definition adopted by the International Association for the Study of Pain:

Pain is always subjective. Each individual learns the application of the word through experiences related to injury in early life. Biologists recognize that those stimuli which cause pain are liable to damage tissue. Accordingly, pain is that experience we associate with actual or potential tissue damage. It is unquestionably a sensation in a part or parts of the body, but it is also always unpleasant and therefore also an emotional experience.132

  1. 2.96 Importantly, according to the Association’s definition,

Many people report pain in the absence of tissue damage or any likely pathophysiological cause; usually this happens for psychological reasons. There is usually no way to distinguish their experience from that due to tissue damage if we take the subjective report. If they regard their experience as pain, and if they report it in the same ways as pain caused by tissue damage, it should be accepted as pain.133

  1. 2.97 The fact that pain is both physical and psychological results in its intensity being difficult to measure and its impact upon different patients in terms of both subjective suffering and functionality being highly variable. As a result, a significant element of the contemporary therapeutic response to pain is that its management is more than just pharmacological; it incorporates multimodal and multidisciplinary forms of intervention, tailored to the needs of the individual patient and an assessment of what is most efficacious for the individual patient.134
  2. 2.98 In evaluating the potential contribution of medicinal cannabis to alleviating the experience of patients’ pain, it is fundamental to acknowledge that it should only form part of an overall strategy for pain management—it is not the complete answer. Thus it should be integrated, and regulated as necessary, within a broad-based approach to the suffering caused by the experience of pain.
  3. 2.99 It is also important to distinguish between the potential effect of the THC component of cannabis in inducing euphoria and any effect it may have in relieving or alleviating pain.135
  4. 2.100 A systematic review and meta-analysis of cannabis treatment for chronic pain was published in 2009.136 It reviewed 18 trials and concluded that the evidence suggested that cannabis treatment was moderately efficacious for treatment of chronic pain but observed that its beneficial effects may be partially (or completely) offset by potentially serious harms. It concluded that more evidence from larger, well-designed trials was needed to clarify the true balance of benefits to harms.137
  5. 2.101 A more recent systematic review and meta-analysis, published in June 2015 and including 79 trials with 6,462 participants, concluded that there is evidence of moderate quality to support the use of cannabinoids for the treatment of chronic pain.138
  6. 2.102 In May 2015 Mark Ware, the Executive Director, Canadian Consortium for the Investigation of Cannabinoids and Director of Clinical Research at the Alan Edwards Pain Management Unit, McGill University Health Center, argued to the American Pain Society Annual Scientific Meeting that:

much of what we know about medical marijuana is anecdotal, so the challenge is to recognize that patients who say they get pain relief by self medicating with marijuana may be right, and move forward in conducting more scientific studies to better understand its analgesic benefits and overall safety.139

  1. 2.103 A 2011 systematic review of randomised controlled trials examining cannabinoids in the treatment of chronic non-cancer pain reported that 15 of the 18 trials that met the inclusion criteria demonstrated a significant analgesic effect of cannabinoids as compared with placebos and several reported significant improvements in sleep. No serious adverse effects were reported. This led the authors to conclude that there was evidence that cannabinoids were safe and modestly effective in neuropathic pain (nerve pain) with preliminary evidence of efficacy in fibromyalgia and rheumatoid arthritis. It called for further large studies of longer duration examining specific cannabinoids in homogeneous populations.140
  2. 2.104 As discussed in the issues paper,141 a number of studies have suggested that medicinal cannabis, variably taken by vaporiser,142 oromucosal spray143 or smoking,144 may be efficacious for neuropathic and non-cancer pain. A Canadian review of the literature in 2014 recommended that smoked cannabis be prescribed by doctors only for severe neuropathic pain syndromes that have not responded to adequate trials for pharmaceutical cannabinoids and other analgesics.145
  3. 2.105 The current status of the research indicates moderate, albeit emerging, support for the proposition that chronic non-cancer pain, incuding neuropathic pain, can be alleviated to some degree by medicinal cannabis. However, the Commission notes that medicinal cannabis generally has the potential only to be part of an overall and preferably multimodal strategy for medical management of a patient’s chronic pain.
Palliative control of pain
  1. 2.106 There are many assertions that cannabis oil and other forms of cannabis are able to assist in reducing the severity of pain experienced by persons dying of terminal illnesses, in particular cancer and HIV/AIDS.146 There is some research evidence which supports the capacity of medicinal cannabis (specifically cannabis with a significant THC content) to provide relief in these circumstances.

 

  1. 2.107 There is evidence that cannabis (particularly smoked cannabis) is an effective treatment for pain caused by HIV-associated sensory neuropathy. A systematic review of treatments for the condition published in 2010 located two randomised controlled trials showing superior results for pain relief from cannabis as compared to the placebo.147
  2. 2.108 In relation to cancer, there is limited high-quality research literature on the subject. The position of the American Cancer Society remains that it supports the need for more scientific research on cannabinoids for cancer patients, and recognises the need for better and more effective therapies that can overcome the often debilitating side effects of cancer and its treatment.148
  3. 2.109 In 2013 Health Canada also observed a need for more research:

establishing the effectiveness of cannabis as a viable treatment option in a palliative care context requires a careful assessment of its effects in a wide range of conditions; such evidence is not yet abundant and further research is needed.149

  1. 2.110 A 2014 review called for caution:

the effectiveness of cannabinoids for the treatment of chronic cancer pain remains unclear, although any benefit is likely to be modest. The available evidence indicates a risk of potentially serious adverse effects, including alterations in perception, motor function, and cognitive function.150

  1. 2.111 Research is ongoing. Sativex is currently undergoing trials for the treatment of cancer pain in the United States, but results to date have been equivocal.151 In 2015, medicinal cannabis will be administered in Chile to 200 patients with cancer to assess its analgesic effects.152 For the present, what can be said is that there is some evidence of the capacity of medicinal cannabis to alleviate the symptoms of patients with high levels of pain and discomfort from cancer and HIV/AIDS.

Relief from nausea and vomiting

  1. 2.112 The evidence indicates that medicinal cannabis in a variety of forms can assist in relieving nausea and vomiting and in enhancing appetite.153 This has the potential to be of particular utility for chemotherapy-induced nausea and vomiting (CINV) and for persons with wasting (cachexia) caused by HIV/AIDS. For instance, a 2008 meta-analysis found that a synthetic cannabinoid was superior to a number of other options for reducing nausea. A variety of studies summarised by Kramer in 2015 have identified efficacy in both respects.154
  2. 2.113 However, as Cancer Council Victoria pointed out in its submission, the research support is not unequivocal:

a systematic review that considered cancer patient perceptions of the effectiveness of synthetic cannabinoids and natural cannabinoid extract products in comparison to traditional anti-emetic treatments showed that patients perceive these products as only slightly more effective than traditional anti-emetics; however, they also preferred cannabinoid use to alleviate the side effects of future chemotherapy.155

  1. 2.114 Therefore, there is a modest level of research support for the capacity of medicinal cannabis to reduce nausea and vomiting caused by chemotherapy and to reduce the wasting caused by HIV/AIDS.

Spinal cord injury

  1. 2.115 There is some research evidence to suggest that medicinal cannabis can assist with the symptoms associated with spinal cord injury, particularly pain and spasticity. Double-blind, placebo-controlled trials156 ‘suggested modest improvements in pain, spasticity, muscle spasms and sleep quality in patients with spinal cord injury’.157
  2. 2.116 Although there is some evidence to support the contention that medicinal cannabis can alleviate some symptoms associated with spinal cord injury, at this stage the research on the issue is at a comparatively early juncture.

Post-Traumatic Stress Disorder

  1. 2.117 In a 2015 review of 46 articles in relation to treatment of Post-Traumatic Stress Disorder (PTSD) with medicinal cannabis, Yarnell noted thatit has been suggested on a significant number of occasions that those with less perceived ability to withstand emotional distress were more likely to attempt to ‘self-soothe’ with cannabis in response to distressing emotions related to trauma.158
  2. 2.118 Additionally, those with PTSD-related symptoms have been asserted to be more likely to use cannabis with the explicit purpose of coping.159 It has been suggested too that patients with more severe PTSD symptoms may have an even stronger motivation to use cannabis. The literature establishes that the fact that a person is diagnosed with PTSD significantly increases his or her chance of using cannabis at some point in life.160
  3. 2.119 Yarnell’s conclusion was not positive:

To date, there is no large-scale, randomized, controlled study investigating efficacy of marijuana and PTSD symptomatology; however, the literature that exists suggests that it may have an effect on decreasing PTSD symptoms, and the neurobiological and animal studies seem to suggest potential underlying mechanisms consistent with these findings. However, PTSD may also be related to problematic, pathological use of cannabis. Additionally, the overall literature may be limited by publication bias, and the lack of standardized, large-scale controlled trials at this time makes any final conclusions on the efficacy uncertain. As the number of people seeking medical marijuana as well as those self-medicating for PTSD continues to rise, there is a clear need for more research trials and monitoring of the long-term effects of using cannabis for the treatment of PTSD and other medical conditions.161

  1. 2.120 As yet it is premature to conclude that research has established that medicinal cannabis can alleviate the symptoms of PTSD.

 

Schizophrenia

  1. 2.121 In 2014 a Cochrane Review reviewed the correlation between cannabis and schizophrenia, including the potential for medicinal cannabis to be used for treatment of psychotic illnesses such as schizophrenia. The study identified eight previously conducted randomised trials, involving 530 participants, which met the rigorous selection criteria of the Cochrane Collaboration. It particularly had regard to the contention that CBD has an antipsychotic effect and compared whether CBD was more effective as a treatment than the antipsychotic, amisulpride. It found the evidence ‘insufficient’ for such an assertion.162
  2. 2.122 As yet it is premature to conclude on the basis of research that medicinal cannabis can inhibit the experience of the symptoms of schizophrenia. However, as noted below, there is concerning evidence that it can be detrimental for some persons who have a vulnerability to develop psychotic illnesses such as schizophrenia.

Anti-cancer properties

  1. 2.123 A number of people who made submissions or attended consultations asserted that cannabis has the capacity to reduce tumour size across a number of cancer types.163 The ‘antitumorogenic’ properties of cannabinoids have been known for some time, with animal studies conducted as early as the 1970s.164
  2. 2.124 Since that time, a ‘vast range of cancer cell and tumour models’ have been used to evaluate the anti-tumour properties of cannabinoids, and increased quantities of endocannabinoid receptors have been detected in various cancer cell lines, supporting the empirical findings. While these studies have shown cannabinoids in some cases reduce tumour cell growth, in others they have caused it to increase.165
  3. 2.125 The authors of a 2013 review article concluded that:

It is a distinct possibility that the cannabinoids may have a place in the future treatment of cancer. Several reports have shown that the synthetic cannabinoids in particular have the potential to show sufficient specificity and efficacy to be precursors to clinical treatments. However, at this point in time, the results from studies are lacking sufficient depth of understanding to allow this transition to occur. The contradictory nature of reports around the efficacy of compounds highlights our lack of detailed understanding of mechanisms of action. The resolution of the conflicting evidence around cannabinoid action will continue to be a research priority in the near future, and it is expected that developing a more robust understanding of the mechanisms of action underlying cannabinoid action will facilitate the acceptance of cannabinoid use in a clinical setting.166

  1. 2.126 Significant human studies on the cancer-fighting properties of cannabis are yet to occur. However, a number of clinical trials are on the horizon for specific cancer types.167 Cancer Council Victoria submitted that the available evidence does not support the use of cannabis as a treatment for cancer.168 The National Cancer Institute in the United States supports this position.169 The Clinical Oncology Society of Australia and the Cancer Council Australia stated their view clearly in a recent joint submission:

There is no current evidence that cannabinoids are effective at inhibiting tumour growth or treat or cure cancer in humans. In addition, there is no current evidence that cannabis or cannabinoids reduce risk or prevent cancer occurrence or promote good health.170

  1. 2.127 On this evidence it is premature at yet to conclude that research has established that medicinal cannabis is able to reduce or curtail the progression of cancer.

Other conditions

  1. 2.128 The Commission received evidence that a number of other conditions can be assisted by the use of medicinal cannabis. For reasons of space it is not possible to set out in detail the most recent clinical research findings regarding each of these conditions. However, a few important conditions merit specific note and these are discussed briefly below.
Tourettesyndrome
  1. 2.129 The 2015 meta-analysis by Whiting et al concluded that there was ‘low-quality evidence’ (two small, placebo-controlled studies) demonstrating the efficacy of cannabinoids for Tourette syndrome.171 An earlier Cochrane Review considering these same studies concluded that there was currently insufficient evidence to support the use of cannabinoids in treating Tourette syndrome.172
Arthritis
  1. 2.130 There is a large incidence of patients using cannabis to treat the symptoms of arthritis. As at June 2013, 65 per cent of Canadian patients authorised to receive cannabis reported ‘severe arthritis’ as their diagnosis.173 Many forms of arthritis are due to inflammation, and cannabinoids have potential anti-inflammatory properties, particularly those which act on the CB2 receptor.174 However, there is scant research support for the efficacy of cannabinoids for pain caused by rheumatoid arthritis, with a 2014 review concluding that: ‘In light of other available treatment options for the management of arthritis pain, lack of sound evidence for effect, and potential for harm, herbal cannabis cannot be recommended for arthritis pain management at this time.’175 Preliminary studies using Sativex found a small but significant analgesic effect in patients with rheumatoid arthritis,176 but it does not appear that follow-up studies were conducted. A clinical trial that reviewed the efficacy of vaporised herbal cannabis for painful osteoarthritis of the knee (a non-rheumatoid form) has been approved to take place in Canada and is currently recruiting patients.177
 
Motor-neurone disease (also known as amyotrophic lateral sclerosis)
  1. 2.131 Cannabis has been suggested as a potentially useful treatment for motor-neurone disease because it possesses many properties with potential relevance to the disease (such as analgesia, muscle relaxation, saliva reduction and sleep induction).178 Animal studies have shown that cannabinoids could delay progression of the disease.179 A recent review concluded that ‘Based on the currently available scientific data, it is reasonable to think that cannabis might significantly slow the progression of amyotrophic lateral sclerosis (ALS), potentially extending life expectancy and substantially reducing the overall burden of the disease. … clinical trials with cannabis are the next logical step.’180
Glaucoma
  1. 2.132 The progression of glaucoma has been shown to be slowed by the lowering of intraocular pressure. Many glaucoma drugs cause side effects which patients find unacceptable. THC is believed to reduce intraocular pressure, and a possible mechanism has been identified.181 Other studies have shown promising results using cannabinoids.182 However, it appears that the effects of cannabis on intraocular pressure are of short duration,183 by contrast with other therapeutic options, and not sustained over time.184 There are also other medications that address intraocular pressure. Use of cannabis for glaucoma has been dismissed due to the adverse effects associated with smoking cannabis,185 the high quantities required to be consumed and because other available therapies provide ‘round-the-clock’ reductions in intraocular pressure without the psychoactive effects.186 However, researchers have shown some interest in topical and oral cannabinoid preparations, composed of isolated cannabinoids or synthetic agonists.187 According to a 2004 review article, cannabinoids have the ‘potential of becoming a useful treatment for glaucoma’, as they seem to have neuroprotective properties and effectively reduce intraocular pressure, but noted that difficulties associated with side effects and administration methods needed to be overcome.188 It therefore appears that the most promising avenue of inquiry for glaucoma treatment is pharmaceutical preparations. The position of the American Glaucoma Society is that while medicinal cannabis can lower intraocular pressure, its short duration of action (3–4 hours), its side effects and the lack of evidence that its use alters the course of glaucoma preclude its being recommended.189
 
Parkinson’s disease
  1. 2.133 The issues paper noted Parkinson’s disease as a condition for which cannabis may provide relief, by reference to a number of clinical trials.190 However, a systematic review published in 2014 concluded that oral cannabis extract is ‘probably ineffective for treating levodopa-induced dyskinesias in patients with Parkinson disease’.191
Inflammatory bowel disease
  1. 2.134 Some studies192 have been conducted on the use of cannabis for inflammatory bowel disease. One placebo-controlled trial, conducted on sufferers of Crohn’s disease in 2013, found that a short course of smoked THC-rich dried cannabis produced ‘significant clinical, steroid-free benefits to 10 out of 11 patients in the treatment group, with some able to be weaned from steroid dependency. There were no significant side effects’.193 The author of a recent review concluded that: ‘During the forthcoming years, the plant might be widely used in the treatment of [inflammatory bowel disease] patients. … It is, however, necessary to accurately confirm the safety and effectiveness of the plant by performing large clinical studies.’194
Sleep disorders
  1. 2.135 Whiting et al concluded that there was ‘low-quality evidence’ to support the use of cannabinoids in the treatment of sleep disorders. The authors located two studies, one considering sleep apnoea and the other insomnia. The first trial, which was identified as having a high risk of bias, found that nabilone had a greater effect than a placebo. The second trial suggested that nabilone had a greater effect than placebo, but that it was less effective than amitriptyline in terms of sleep restfulness.195
Anxiety and depression
  1. 2.136 Whiting et al found no research support for the use of cannabis as a treatment for depression. It did consider studies targeted at other conditions but where effects on depression were measured found that cannabinoids were no better than placebo.196 In relation to anxiety, the authors located one ‘small parallel-group’ trial that found CBD to have a greater effect than placebo on generalised social anxiety disorder, but considered that this trial was ‘at high risk of bias’. This trial was described by the authors as ‘very low quality’ evidence.197

Issues for policy-makers

  1. 2.137 As summarised above, the evidence base for the clinical efficacy of medicinal cannabis remains of at best moderate quality for most conditions in respect of which claims of efficacy are made. There are several reasons for this. Many of the studies which are commonly cited in support of its efficacy are low in the evidentiary ‘hierarchy’ because they:
  • rely on case reports
  • make claims arising from small patient cohorts
  • lack controls and methodological rigour.
  1. 2.138 As of 2015 few systematic reviews or meta-analyses strongly support the efficacy of medicinal cannabis.
  2. 2.139 Some studies which might otherwise be regarded as promising are of limited utility because they were conducted on animals or cell lines, not humans. For the most part, systematic reviews and meta-analyses have been discouraging or have identified potential rather than actual efficacy in medicinal cannabis.
  3. 2.140 There is also a great level of variability in the type of medicinal cannabis used in the reported studies. Many studies are based on smoked cannabis leaf rather than medicinal cannabis products of known constituency—in terms of THC and CBD content—and known amounts of consumption. THC, CBD, THCA, and the entourage effect are claimed to be explanations for reported efficacy. However, there has been little correlation of successful outcomes with particular aspects, strains or constituents of the cannabis plant. This presents a difficulty when assessing the available evidence in relation to its prospective utility for Victorians in exceptional circumstances. Most of the anecdotal information communicated to the Commission arises from use of cannabis grown in a variety of unregulated circumstances and containing unknown and/or variable constituents.
  4. 2.141 Comparatively few research trials have been undertaken under close medical supervision, using medicinal cannabis of known constituency, for instance using cannabis oil of identified strength, with double-blind techniques or with effective placebo-controls. Some trials using pharmaceutical medicinal cannabis products (such as Sativex and Epidiolex198) have been undertaken. However, for many conditions, the results of these trials have been equivocal at best.
  5. 2.142 The submission by the Drug Policy Modelling Program observed that most clinical trials have been conducted with one or another of the pharmaceutical-grade cannabis products, rather than with herbal cannabis:

To date, cannabinoids other than CBD and THC have not been isolated into pharmaceutical preparations, and thus the synergistic effect has only been observed when herbal cannabis or its compounded extracts are used medically.199

  1. 2.143 Put another way, little research has been done as yet in respect of the use of products such as cannabis oil or tinctures. AMA Victoria has also observed that most research conducted on cannabis has used pharmaceutical preparations, rather than ‘crude cannabis’.200
  2. 2.144 In principle, on the basis of anecdote and some trials, there is reason for optimism in relation to the efficacy of medicinal cannabis. The orthodox research-derived position is that medicinal cannabis shows promise201 but it is too soon to state definitively that it is therapeutically efficacious for any medical condition. It seems likely that these deficits will be addressed in current or future research. When these results become available, scientific discussion about the efficacy of medicinal cannabis will be significantly more informed than it is now.

 

Evidence of side effects

  1. 2.145 A major reason for concern about the creation of a medicinal cannabis scheme is the identification of the risk of adverse health effects.
  2. 2.146 All medicines come with some risk of adverse side effects or toxicity. What is of interest is whether the medicine’s benefits outweigh its risks. A medicine can be very risky—for example, because it is very toxic—and still be justified because it is necessary to treat a serious condition. What is of concern, particularly to medical practitioners, is that the risks of cannabis are inadequately known and so no assessment can be made of its benefit to a patient on balance. In particular, while there is reasonable knowledge of the risks posed by recreational use of cannabis, there are very few studies as yet on the side effects of medicinal cannabis, including non-smokable forms. This is especially so in respect of medium-term and long-term risks for different categories of patients with different vulnerabilities.
  3. 2.147 For instance, AMA Victoria has contended that ‘the potency and safety of crude cannabis is unknown, variable and unregulated’. In addition, it has argued that the negative side effects produced by cannabis should not be disregarded ‘merely because of a patient’s age or health status, such as approaching the end of life.’ It has also raised the issue of ‘psychological side effects including psychosis-like symptoms in some patients’.202
  4. 2.148 Another expression of concern was from theFaculty of Pain Medicine of the Australian and New Zealand College of Anaesthetists, which said it was ‘very concerned about the adverse event profile in cannabis users, especially in young people, including impaired respiratory function, psychotic symptoms and disorders, and cognitive impairment’.203
  5. 2.149 However, the point made by many submissions to the Commission is that the proven level of adverse effects, even from unmonitored recreational abuse of herbal cannabis, is of relatively well known and modest dimensions.204 Unlike in respect of opiate drugs, no deaths have been attributed to cannabis overdose or abuse.205
  6. 2.150 Most studies on the adverse effects of cannabis have focussed on unregulated, illegal cannabis used recreationally, rather than a quality-controlled supply intended for medical use, and may be of limited application to identifying the risks of the latter.206 There are important limitations on the extent to which it is legitimate to extrapolate from risks relating to recreational use of cannabis to risks arising from medicinal cannabis, in particular when use of medicinal cannabis is suitably supervised by a medical practitioner.
  7. 2.151 A systematic review conducted in 2008 looking at the medical use of cannabinoids, as distinct from the recreational use of cannabis, concluded that short-term use of cannabinoids increased the risk of non-serious adverse events compared to a control group, but not the risk of serious adverse events. However, the authors concluded that further research was needed before long-term risks could be accurately characterised.207

 

Types of side effects

  1. 2.152 As the submission made on behalf of the cannabis community of Victoria acknowledged: ‘Cannabis … is not “harmless”’.208 Cannabis use carries a range of known side effects which, while well described, are of disputed magnitude. The most important of these are summarised below.
Respiratory effects
  1. 2.153 If cannabis is smoked, particularly in combination with tobacco, a range of potentially carcinogenic effects may arise, as well as ones which are adverse for respiratory function.209
Psychotic effects
  1. 2.154 There is a small and relatively unresearched incidence of recreational users who have experienced psychoses in the context of cannabis use. This has been manifested in the commission of some violent crimes.210 Cannabis use is a risk factor for developing schizophrenia211 and for the development of psychotic symptoms in young people.
  2. 2.155 While cannabis use is associated with precipitating and exacerbating schizophrenia, it is not clear whether the correlation is causative or due to a tendency for the affected group to use cannabis.212 Some submissions have argued that the presence of CBD in cannabis may counteract the psychotogenic properties of THC. As a result, a percentage of the cannabis psychoses which have been identified may well be attributable to very high THC-content cannabis, known as ‘skunk’, and used by some recreational users.213
  3. 2.156 The relevance of this phenomenon to a scheme which is properly clinically monitored by medical practitioners, where the amount of THC ingested by the patient is known, is very limited. In addition, it is likely that some categories of patients, such as those with epilepsy, will receive medicinal cannabis with very low or no THC content. This removes the risk of THC-induced psychosis for these patients.
Mood effects
  1. 2.157 A further concern identified has been the potential for cannabis to impact adversely upon users’ moods, including by making them anxious, depressed or paranoid. However, while often seen among new users, these effects are uncommon in regular users and tend to disappear after a few months of abstinence.214 Again, this is a phenomenon that has been identified for a small percentage of recreational users but there is little information on the issue in respect of individuals who receive cannabis for medicinal purposes.
Impairment of learning ability, memory and motivation
  1. 2.158 Adults who use marijuana chronically have demonstrated poorer performance on tests of learning and memory, attention, visuospatial skills, processing speed, and executive functions. However, some studies have found no performance deterioration among heavy cannabis users. A meta-analysis examined 11 studies that met strict inclusion criteria, and ascribed impaired learning and memory to chronic recreational cannabis consumption, but determined that other cognitive domains remained unaffected.215 Particular issues arise in this context in respect of children, whose brains are developing. Care would need to attend the monitoring of children by medical practitioners in this regard.
Dependency
  1. 2.159 An issue that has arisen in respect of recreational users of cannabis and that may be relevant in relation to long-term users of medicinal cannabis is the potential for them to become physically or psychologically dependent on it. In general, cannabis is not a highly addictive or habit-forming drug216 but the potential does exist for a small percentage of users, at least in the recreational context, to become dependent on it to a point where they experience withdrawal symptoms for a time when they stop using. Symptoms may include craving for cannabis, decreased appetite, sleep difficulty and weight loss, as well as aggression, irritability, restlessness and strange dreams.217 The American Psychiatric Association identified the diagnosis of ‘cannabis withdrawal’ in its 2013 edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).218 However, it has been suggested that its severity is similar to withdrawing from smoking tobacco.219
Cardiac effects
  1. 2.160 Cannabis consumption is known to induce tachycardia, and can increase the risk of myocardial infarction (heart attack). However, these effects tend to be problematic only in conjunction with other cardiac risk factors, such as existing heart disease or arrhythmias.220
Pregnancy complications
  1. 2.161 Cannabis use during pregnancy has been found to be associated with a number of undesirable effects, but these findings are disputed.221
Impairment of concentration and psychomotor response:
  1. 2.162 The evidence is compelling that using cannabis retards concentration and response to stimuli.222 Critical tracking tests, reaction times, divided attention tasks, lane position variability and speeding have all shown cannabis-induced impairment in the driving context.223Psychomotor performance generally is impaired by cannabis.224 It is also common for subjects not to appreciate their level of impairment.225Impairment is exacerbated when combined with the consumption of alcohol.226This has important ramifications for safety for those driving under the influence of medicinal cannabis and for safety in the workplace.227
Guidance by College of Physicians and Surgeons of British Columbia
  1. 2.163 This combination of factors led the College of Physicians and Surgeons of British Columbia to conclude in May 2015 that dried cannabis is generally not appropriate for patients who:
  • are under the age of 25
  • have a personal history or strong family history of psychosis
  • have a current or past cannabis use disorder
  • have an active substance use disorder
  • have cardiovascular disease (angina, peripheral vascular disease, cerebrovascular disease, arrhythmia) or respiratory disease
  • are pregnant, planning to become pregnant or are breastfeeding.
  1. 2.164 In order to address such identified risks and ‘the paucity of evidence to support the use of marijuana for medical purposes’, it also required physicians to adopt the following measures:

Document that conventional therapies for the condition for which the authorization of marijuana for medical purposes was provided have been attempted to assist the patient in the management of his/her medical condition and have not successfully helped the patient.

Assess the patient for addiction and/or risk of addiction. For the latter, use a validated addiction risk tool and retain a copy in the patient record.

Discuss with the patient the risks of using marijuana and record in the patient’s medical record that a discussion occurred.

Review the patient’s PharmaNet information prior to issuing an authorization for marijuana for medical purposes and in any reassessment of patients receiving marijuana for medical purposes.

Retain a copy of the document provided for the authorization of marijuana for medical purposes in the patient’s medical record.

Include processes to identify any misuse/abuse/diversion by the patient in any reassessment of patients receiving marijuana for medical purposes.

Not sell or dispense marijuana for medical purposes to any patient.

Not complete a document for the authorization of marijuana for medical purposes for a patient unless

- the physician has a longitudinal treating relationship with the patient, or

- the physician is in direct communication with another physician or nurse practitioner who has a longitudinal treating relationship with the patient and both are in well-documented agreement with the issuance of a document for the authorization of marijuana for medical purposes. 228

 

Managing risk

  1. 2.165 It is important that any medicinal cannabis scheme acknowledges the reality of a diverse range of actual and potential side effects for patients. For the most part, such risks were recognised by submissions made to the Commission.
  2. 2.166 However, such side effects generally arise from cannabis with a significant THC content and thus do not arise or are significantly less relevant in the context of cannabis that has a high CBD content.
  3. 2.167 Many potential side effects can be minimised by avoiding uncertain and excessive levels of consumption arising from self-administration and also by establishing a scheme that does not include smoked forms of cannabis.
  4. 2.168 Most prescribed medications have side effects for which appropriate warnings are given to patients by their medical practitioners (as well as by pharmacists) so that the consent that patients (or those responsible for them) provide is properly informed. In addition, a fundamental responsibility of medical practitioners is to review the condition of patients for whom they prescribe in order to identify not only the correct level of medication to address patients’ symptoms but also the onset of any side effects, so that these can be addressed. Medicinal cannabis is no different from other medications in this regard, save that for the most part the side effects arising from the use of medicinal cannabis are unlikely to be life-threatening provided that suitable steps to avoid misuse are taken by medical practitioners.


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