Proceedings of the Subcommittee on
Issue No. 16 - Evidence - May 23, 2018
OTTAWA, Wednesday, May 23, 2018
The Subcommittee on Veterans Affairs met this day at 12:02 p.m. to continue its study on the services and benefits provided to members of the Canadian Forces; to veterans; to members and former members of the Royal Canadian Mounted Police and their families (Topic: Study On Cannabis Use For Medical Purposes by Canadian Veterans).
Senator Jean-Guy Dagenais (Chair) in the chair.
The Chair: Honourable senators, welcome to the Subcommittee on Veterans Affairs. Before we get to our subject, I would like to give you a chance to introduce yourselves, starting on my right.
Senator Boniface: Gwen Boniface, Ontario.
Senator Wallin: Pamela Wallin, Saskatchewan.
Senator McIntyre: Paul McIntyre, New Brunswick.
Senator Richards: Dave Richards, New Brunswick.
Senator Griffin: Diane Griffin, Prince Edward Island.
The Chair: I am Senator Dagenais, chair of the subcommittee. I would like to thank our two witnesses, Mr. James MacKillop and Dr. Albert Wong, for accepting our invitation. Today, we are continuing our study on the use of cannabis for medical purposes by Canadian veterans.
James MacKillop is the Director of the Michael G. DeGroote Centre for Medical Cannabis Research at McMaster University. Dr. Wong is a research scientist and staff psychiatrist at the Centre for Addiction and Mental Health. Gentlemen, I welcome you once again. We’ll hear your presentations, and then we’ll go to questions. Thank you, gentlemen. Go ahead.
James MacKillop, Director, Michael G. DeGroote Centre for Medical Cannabis Research, McMaster University, as an individual: Good afternoon, honourable senators. I appreciate the opportunity to address this committee.
At McMaster University and St Joseph’s Healthcare Hamilton, I direct both the Peter Boris Centre for Addictions Research and the Michael G. DeGroote Centre for Medicinal Cannabis Research. With regard to the Centre for Medicinal Cannabis Research, central operations are funded by philanthropy, not industry, and its mission is to develop an evidence-based understanding of cannabis, both in terms of its positive, therapeutic effects and negative side effects.
We do this using three strategies: creating a web portal that provides scientifically sound information about cannabis; conducting new research studies to gather much-needed data; and creating a network comprising both internal and external partners, such as Dr. David Pedlar the Scientific Director of the Canadian Institute for Military and Veterans Health Research.
Our highest priority is the objective study of medical cannabis, just like any other drug in medicine. Importantly, the centre does not exist because we categorically believe cannabis is or is not effective medicine, but because we are certain there is a need for more rigorous research. Our goal is to follow the data wherever it takes us.
As a preface to my comments on the science of cannabis, I am mindful of the sacrifices made by veterans. Part of my training was in the U.S. at the Providence Veterans Administration Hospital, working directly with veterans. I’m fully aware that many of the medical conditions for which veterans seek cannabis, such as chronic pain and PTSD, are direct results of their service.
Moreover, over 7,000 veterans are currently authorized for medical cannabis in Canada. I know decisions about these policies are not hypothetical and will affect real lives. This testimony is given from the perspective of using the best possible evidence to advance the health and well-being of veterans in Canada.
Now to the questions at hand. The first is the scientific basis for Veterans Affairs Canada policies for reimbursement of up to 3 grams of cannabis in general and up to 10 grams of cannabis with approval for exceptional cases. Unfortunately, precise dosing is not available from the existing medicinal cannabis research. This is one of the ways medicinal cannabis is different from traditional medicine.
The reason for imprecision when it comes to dosing is because of the product itself. It’s a plant, not a pill, and a plant that contains dozens of compounds that act on the body’s internal cannabinoid system. Furthermore, these diverse compounds are hypothesized to interact to confer medical benefits. In addition to the complexity of the medicine itself, the plant can be consumed in a variety of ways. This affects how much of the active ingredients are consumed and the time course of consumption.
To put these amounts in context, however, in non-medical consumers, 3 grams daily would be considered heavy consumption, and 10 grams daily would be extremely heavy. In research, we standardize 1 gram as reflecting four joints or cannabis cigarettes. The current authorizations would permit up to 12 or 40 cannabis cigarettes per day.
Importantly, pharmacology does not make distinctions between medical and non-medical use. The higher the volume of use, the higher the risk for side effects. For example, the likelihood of an individual consuming 10 grams of cannabis daily developing physical dependence would be very high, just as it would for a person taking high doses of opioids or anxiety medications. As a result, withdrawal symptoms would be more likely in high-dose patients, as would other side effects, such as motor impairment, cognitive difficulties and risk for developing addicted use.
It is worth noting VAC policies are not excessively conservative relative to reimbursement in other countries, such as Israel or the Netherlands, and were based on recommendations by the College of Family Physicians of Canada. Collectively, my perspective is that VAC’s policy was determined using a reasonable process and generally leans toward more access rather than less.
The second issue I would like to address is the level of evidence supporting medical cannabis. Unfortunately there’s widespread agreement that medical applications have substantially outpaced the science. It is important to remember that medical cannabis came into being by way of the legal system; it did not run the usual gauntlet of clinical trials for specific indications the way other drugs do. It does not have a drug identification number, DIN, like other pharmaceuticals. It is authorized, meaning permission is given, but it is not prescribed. Also, as noted before, its dosing is vastly less specific than for other medications, where an exact amount is given with a specific time interval.
There are some applications where the evidence is moderately supportive, such as reducing chemotherapy-induced nausea, chronic pain and muscle spasticity in multiple sclerosis. In general, however, there is insufficient evidence to judge its effectiveness for other conditions. This includes PTSD, where there are intriguing observational findings but a dearth of randomized control trials.
For veterans, there is supportive evidence when it comes to pain, but insufficient evidence when it comes to PTSD or other conditions.
In this situation, I would argue there is a need for both caution and compassion in considering veterans who are currently using medical cannabis. Abruptly reducing access or making policy changes that dramatically increase costs could have serious adverse consequences. Instead, it will be important to engage veterans who are using cannabis with their treatment providers, closely monitor their progress and side effects, and make changes in a graduated and deliberative way to avoid unintended consequences.
How will legalization affect medical cannabis for veterans? My expectation is overall there will be both benefits and risks to legally regulated cannabis. For veterans using medical cannabis, a risk is that individuals will pursue medical applications outside consultation with a physician or will augment their authorized amount with legal recreational products.
A reality is that cannabis is a psychoactive drug with a number of established risks, and the more that’s consumed, the higher the risks. Medical use should always take place in consultation with a health professional. It will be important for Health Canada’s dual system for medical and recreational cannabis to be fully implemented and supported.
Some have argued legalization will reduce stigma and encourage veterans to consider medical cannabis. I am unsure about this because of the equivocal evidence. If a treatment has not been shown to work, does it make sense to encourage patients to seek it?
My hope is that clinicians and patients will be guided by the evidence.
In this case, the evidence supports cannabis for pain but is insufficient for PTSD. Furthermore, a number of studies have linked cannabis use to self-harm and suicide in U.S. veterans. Caution is warranted. Excessive optimism can lead to serious harm.
Where do we go from here? We need more randomized controlled trials because observational studies simply can’t speak to the effectiveness of a treatment compared to a placebo condition. I have personally treated veterans with concurrent PTSD and alcohol use disorder, and by self-reports, alcohol helps with the symptoms. We know alcohol is not the answer. Alcohol provides a short-term solution that leads to problems in the long term. We need to make sure that is not the case for cannabis. However, RCTs take time, and what should we do in the interim?
We need more real-world longitudinal research. We need to engage veterans and other medical cannabis users in research cohorts to monitor and evaluate patterns of change, both positive and negative. We need more active knowledge translation and guideline development to make sure veterans are aware of potential applications and the realities of risks and to give clinicians clear guidance based on the best available evidence.
Of note, Canada and the world often rely on U.S.-based research in the development of pharmaceuticals, but because of regulatory contradictions there, the U.S. has not played a leadership role. As a result, the current environment in Canada provides the opportunity to be a world leader in cannabis research. This would be dependent on major investments, but it’s an issue of widespread relevance to Canadian society. I recognize this may seem self-serving, but it’s also a practical reality that funding is critical to high-quality research, especially clinical trials.
Perhaps most important going forward will be engaging veterans and other medical cannabis users in the health care system prior to and following legalization. This will be essential to avoid creating a shadow system that does an end-run around health care providers and is guided by myth and lore rather than evidence.
Thank you for the opportunity to serve as a witness for this committee.
The Chair: Thank you for your presentation. We will now hear from Dr. Albert Wong.
Dr. Albert Wong, Neuroscientist and Psychiatrist, Centre for Addiction and Mental Health, as an individual: Thank you for inviting me. I thought I would begin with a brief summary of my background so you know where my area of expertise is and where it isn’t.
I am a neuroscientist, as you’ve heard, and a full professor at the University of Toronto in the Department of Psychiatry as well as the Departments of Pharmacology and Toxicology and the Institute of Medical Science. That is where my research occurs, about 75 per cent of my time.
The other 25 per cent of my time I am a psychiatrist at the Centre for Addiction and Mental Health. It is the largest psychiatric hospital in Canada. In my clinical work, I work mostly in the emergency department. It’s the largest emergency department for psychiatry in Canada. We see about 10,000 unique visits per year.
I also work in the brain stimulation clinic, where we do electroconvulsive therapy and magnetic seizure therapy. I also do psychopharmacology consults.
My research in general is quite eclectic. I work on genetic mutant models to understand how genes are implicated in psychiatric disorders that affect brain development, behaviour, circuit formation and brain anatomy. I also do clinical research with virtual reality as a kind of environment where we can probe cognitive function in a naturalistic way.
In terms of my research related to PTSD and veterans, I did a study a long time ago on suicide in Canadian peacekeeping troops, and more recently, I have several PTSD-related projects. The first one is most relevant to this committee, which is in collaboration with Lakshmi Kotra, who is a medicinal chemist at the University of Toronto. Our study has a simple question, which is what is in cannabis that people with PTSD claim is helpful? That study involves recruiting patients with PTSD — civilians mostly — in Toronto and doing a number of questionnaires to characterize their PTSD symptoms and severity and then collecting a sample of their cannabis as well as a blood test to try to determine what is in the cannabis they are using and what is in their body.
Briefly, there are two other studies related to PTSD. One is an unusual study looking at memory reconsolidation disruption in PTSD. This is a randomized clinical trial. If you have ever seen the movie Eternal Sunshine of the Spotless Mind, Jim Carrey is the actor who plays this person who has a bad relationship and wants to delete that memory from his past. He finds somebody to do this for him. It’s sort of a science-fiction comedy.
The idea with our study is that ECT, electroconvulsive therapy, involves inducing seizures for the treatment of depression. It is a very effective treatment for depression but of course has memory impairment in the form of short-term amnesia around the time of ECT as a side effect. That is because it disrupts memory formation. It also disrupts memory reconsolidation; when you recall a memory, you have to restore it each time. The idea is to randomize people to either reactivate their traumatic memory or a neutral memory before each treatment, with the hypothesis that reactivating the traumatic memory will allow the seizure to disrupt that memory each time. Exploit the side effect of ECT as a therapeutic effect.
The last study I want to tell you about is one that I’m doing with Fang Liu, another scientist colleague at U of T. We have discovered a protein complex that we think is involved in PTSD. We have a therapeutic peptide that targets this complex. We think, at least in animal models, this can both prevent and treat PTSD. This is an interesting paradigm because it would mean that after trauma exposure, one could get the peptide and this would prevent later PTSD. It is an antidote or kind of mental first aid, if you will.
Moving from that, I want to say that I agree with James’ comments. I think we need a lot more knowledge about cannabis, both in terms of the basic science and the pharmacology of it. The two known cannabinoid receptors were only discovered less than 20 years ago. These are early days for understanding how this drug works and what it is doing in the brain. We don’t understand much about the endogenous cannabinoid system. Those receptors in the brain, just like opioid receptors, are not there, we think, primarily for a drug to activate but because the body has its own system. This is not well understood.
I also agree with James there are no clear randomized, double-blind clinical trials showing the efficacy of cannabis. I also agree with James on a very important point that if you think of cannabis, it is like wine; every wine is different, and saying this wine is better than that wine or this wine goes with fish or beef, it is quite complicated. It is the same thing with cannabis. There are many strains and dozens of psychoactive chemicals within each cannabis plant. It is very difficult to make broad conclusions about cannabis as a thing. It’s not. Pharmacologically, it’s a collection of many different psychoactive compounds.
There is some evidence — of course, not gold standard randomized controlled trial evidence, but there is clinical evidence that cannabis can be effective for PTSD. I suspect randomized trials will show there is some benefit, but I doubt it will be curative.
My last point is while I think we should be exploring and considering how we use cannabis to treat PTSD, it is probably like the rest of the drugs we use in psychiatry, which is no different than alcohol or benzodiazepines. All of these drugs and medications have psychoactive compounds that change the way people feel, think and behave. In some cases, that can be therapeutic; in other cases, it can be problematic.
There is a lot we need to learn before we can come up with treatments that are curative rather than just adjusting somebody’s symptoms, counteracting perhaps what they find problematic. I think that is a reasonable and basic approach. That is where we are at. That is the level of technology we have in psychiatry. I think we really need to look forward to the horizon and see where we could do better. I would make a plug for supporting basic research, of which research into cannabis could be an important part, because clearly cannabinoid receptors have a powerful effect on symptoms related to PTSD. I think this is a useful neurobiological entry point but just the beginning. Thank you.
The Chair: Thank you, Dr. Wong. We are going to continue with questions.
Senator McIntyre: Gentlemen, thank you for your fine presentations and for sharing your knowledge on the state of research on the use of cannabis for medical purposes regarding veterans.
My first question concerns gender differences in using medical cannabis. Are there gender considerations to take into account with respect to use of medical cannabis? For example, are there indications that cannabis could affect men and women differently?
Mr. MacKillop: In the context of medical cannabis, we know less than what we know in basic preclinical research looking at male and female rodent models, for example. There, we see clearly there are sex differences. These are probably going to be important considerations in terms of medical applications. In particular, in some of the research we are doing currently at McMaster in looking at novel cannabinoids for treating pain in animal models, we see very different reactions in male rats versus female rats, using a rat model.
We know this is the case in experimental paradigms where we have a lot of control. We know less about what this looks like in terms of what people are actually consuming in the real world. It is an important consideration and one of the unanswered questions out there.
Senator McIntyre: Men and women face different barriers with regard to the use of medical cannabis.
Mr. MacKillop: I wouldn’t describe it as “barriers.” Rather, the drug acts differently in the different sexes’ bodies and can be harmful or helpful in ways we don’t fully understand.
Dr. Wong: I agree with James: We don’t know enough from direct clinical studies in humans, but there are clear sex differences in animal models. This is true for virtually every drug that affects the brain. The effects on male and female animals are different. There are important gene environment and gene-gene interactions in the origins of PTSD and all psychiatric disorders, as well as all brain and behaviour phenotypes. There is not enough information.
A parallel but important gender aspect is the nature of PTSD that presents in men and women is often quite different. I typically see civilian patients with PTSD; the vast majority are female. Their PTSD history and origin is very different than veterans.
Women with PTSD in the civilian population typically have a history of childhood abuse and neglect, and often sexual trauma, that is over a long period of time in childhood. That interacts with further adult events, often sexual abuse again or some kind of sexual assault.
That is a different picture than the military/first-responder type of PTSD where it is a majority male population who are screened to be mentally and psychologically well as much as possible before exposure to combat trauma. Those incidents are very remote and distinct from childhood events.
It’s two different pictures, both in terms of the clinical presentation and the neurobiology. There is very clear evidence early childhood trauma changes the way the brain receives and processes adult trauma. These are important considerations.
They may not directly be the result of sex differences; they might be interactions between sex in the environment and sex in society that lead to different clinical pathways. That’s important, because you can’t separate them in reality. We could do so in a lab with animals. The clinical reality with adult patients is you can’t separate all of these conflating factors associated with sex but may not arise directly from the biology. Some arise from biological sex and others don’t.
Senator McIntyre: In your view, should the federal government play a larger role in advancing knowledge about the use of cannabis for medical purposes, expressly with respect to veterans?
Dr. Wong: The simple answer is “yes.” The government could work with commercial interests to provide financial support for further research. There is a big gap of knowledge. This is a situation where popular usage and culture is far ahead of scientific knowledge and clinical expertise. It is an important gap.
There are many areas of science that might be interesting and a priority from a knowledge standpoint, but there may not be such a practical public need. In this case, people are using cannabis, and legalization is coming up. Also, veterans with PTSD are using cannabis. I think that increases the priority for getting to know more about what is going on, whether it works and what part of it is working for what purpose.
Senator McIntyre: Are there specific recommendations that you would like to make to the Government of Canada?
Dr. Wong: I would like to reinforce what I said earlier. It is obvious we need to have clinical studies to look at the efficacy of cannabis and different types of cannabinoid constituents. That is a practical, obvious question. My position is we also need a lot of upstream knowledge about the basic biology of cannabis and PTSD. Those two elements are important. Otherwise, it is a black box, and we are trying to see whether it works. That is the end question. From a practical standpoint, that is important, but it is not enough.
Senator McIntyre: Thank you.
Mr. MacKillop: I echo the comment that it would be entirely appropriate for the federal government to invest in research in this area, because this is an issue that is truly of nationwide relevance at the level of both recreational and medical use.
With regard to priority areas, in some ways, the horse is already out of the barn. There is a need for research on what is happening now among people who are already using cannabis for medical purposes in the veteran community and also in the non-veteran community.
It is important that, over the course of legalization and its aftermath, there be surveillance and evaluation of what the impact is on Canadians’ lives. That is not at the exclusion of more basic research or full-scale trials that will give us black-and-white answers in terms of the effectiveness and whether this is a possible treatment.
Senator Griffin: Thank you for being here today, both of you. It has been really interesting.
I have in my hand something that will look familiar. It was produced by the McMaster University Michael G. DeGroote Centre for Medical Cannabis Research. It is a news item, and it says that, in 2014, the College of Family Physicians of Canada advised doctors not to authorize medical cannabis to patients who are under the age of 25.
We have a lot of veterans in our country who are under the age of 25. What is your impression of this advice and the impact it would have on those young veterans?
Mr. MacKillop: That is one of our knowledge products. I am delighted you saw it. We sometimes wonder how many people are reading. It is great to see someone take it up.
The point you raise illustrates perfectly the quandary of many physicians. The guidance is murky, the areas are grey and decisions are difficult when it comes to people who fall outside of clear recommendations.
When we don’t know whether something is really effective as a treatment and a person may have a high-risk background, it becomes a difficult clinical decision whether cannabis is appropriate. It would be hard to make a blanket statement that under no circumstances it would be appropriate, but caution would be warranted.
This does illustrate the challenges faced by health care providers where a treatment is available without having been vetted the way we typically vet medical care.
Dr. Wong: The core neurobiological point here is the human brain doesn’t finish developing until about age 30. Maybe some of you have children who are at university age. The reason why an 18- or 21-year-old cannot rent a car or has to pay five times higher insurance is because their brain is not mature. The frontal lobes mature last. Those are the parts that make important judgment decisions, for example, while driving.
The point is any psychoactive substance can affect the way the brain develops. This is especially problematic earlier in development, especially in utero, and then in childhood and adolescence. It is less so as the person gets older; it’s a curve that asymptotes. There is less and less to be developed as the person ages.
That is where that is coming from.
I agree with James that we really don’t know enough. The concern about adolescent use of cannabis is related to the risk of psychotic illness, like schizophrenia. That is still an unanswered question; it is still unclear whether it is causal or whether people who are more susceptible to psychotic illness are more drawn to use, or whether it’s a self-medication: a co-inheritance or a causal relationship. Simple questions like that remain unanswered.
Without knowing those things, as James said, it is difficult to translate into a concrete clinical recommendation. The first line of the Hippocratic oath is to not do anything harmful. When we don’t know, the tendency for physicians, appropriately so, is to be conservative and not recommend something without knowing for sure it will help more than it hurts. On the other hand, people are using cannabis anyway, especially when it becomes legal and certainly someone who is an adult, and people under 25 will have full access.
For example, none of the medications I prescribe have approval from the manufacturer to use with alcohol. The reality is that most patients drink alcohol, and they often ask if they can drink on their medication. My answer is always like this: “Officially, no, you can’t. I know you’re probably going to drink anyway, so just try not to drink excessively. Try to be careful and cautious.” That’s the realistic message. If I say to the average patient that, no, they cannot drink at all when on antidepressants, they are more likely to stop the antidepressant than stop drinking alcohol.
Mr. MacKillop: I echo Albert’s comments, and they also point out the paradox that the highest rates of cannabis use are among people in their late teens and early 20s. As a clinician, there is a pragmatic choice about making a recommendation that may be mindful of the neurobiology, which is completely accurate, but equally recognizing there will be access and that many patients are already using cannabis. Would it be preferable to do so under a doctor’s care?
Senator Griffin: Okay, thank you.
Senator Wallin: I have a two-part question, Dr. MacKillop. You are talking about the need for clinical trials and proper testing. Have you no arrangement with Veterans Affairs Canada on using that 7,000-person base as a place to start? Are there privacy concerns? To me, that seems a natural place to go.
Mr. MacKillop: We have been actively discussing collaborations with Veterans Affairs Canada and also with the Canadian Institute for Military and Veterans Health Research. Those are critical resources. That is the constituency clearly most affected.
It is a difficult group to think of in terms of existing trials, because in many ways, a trial has to be experimentally balanced and would involve engaging people who have not already had experience with the drug, for example, and would have certain eligibility requirements. On the other hand, should we be trying to understand the patterns of use and potential misuse among existing users? Absolutely. That’s what I really was alluding to in terms of the need of doing real world, real-time research now so we understand the positive impacts and the negative impacts, recognizing it might not be that a trial is the right design for existing medical cannabis users.
Senator Wallin: One of the issues we are dealing with here — and this is applicable to medical marijuana, but it will become a real issue when legalization becomes a reality — and that is functional impairment tests. How do we establish that? I’ll ask this of Dr. Wong: I think we told last week there are 87 chemical compounds or components in marijuana. Is it different in recreational marijuana where THC is higher, CBD, et cetera?
First, this other question: What do we do at this point about functional impairment tests both in the existing community and what will happen post-legalization?
Mr. MacKillop: Functional outcomes are critical in evaluating medical cannabis. It is not just about symptom reduction; it’s about recovery of functioning. One of my colleagues at Saint Joseph’s Health Care London, Don Richardson, who has given testimony before the committee also, has seen in some of his patients that although there can be symptom reduction, that does not mean that people are getting healthy. They aren’t getting well, necessarily; there may be some masking of the symptoms.
We need to use multiple channels. In the pilot trials we’re now designing, we’re looking at symptoms, functional outcomes, neuropsychological tests and biomarkers so we can use a multichannel approach to evaluate whether there are positive impacts and, if so, what are the mechanisms that underlie those impacts?
Within the veterans community of existing medical cannabis users, we need to be looking more broadly, not just at symptoms but at functional recovery and other domain areas like cognition to understand what is happening.
Senator Wallin: It goes to our question that, when there are already being prescribed this — as you say, we don’t know what they are being prescribed, but they are prescribed this — how do we know whether they should be going to work or driving?
Mr. MacKillop: Exactly.
Dr. Wong: To pick up on that point, I would broaden the answer to include all of the psychoactive substances we prescribe and use recreationally.
Impairment and functional outcomes are related but different questions. We already have a present issue with many of the other psychoactive compounds we use — antipsychotics, antidepressants, mood stabilizers, anticonvulsants — each have sedating potential and can affect motor reaction times, perception — things important for driving that can make it unsafe. I don’t think we have a good answer for that.
Alcohol is convenient, because there is a Breathalyzer test. As we all know, there is a huge variation between blood-alcohol level and a person’s function. Often in the emergency department, I see someone who seems mildly impaired, and I’m shocked to see that their blood-alcohol level is four or five times the legal driving limit, yet we are having a coherent conversation. If I were at a party or if I were a bartender, I would never question their ability to drive. Other people can have a single drink and be completely incoherent.
That’s one important thing — the functional test for whether someone is safe to operate a machine or be driving. We don’t have those. I’m not sure how we will do that. That’s a difficult question. It’s not just about cannabis and the dozens of chemicals in cannabis.
Senator Wallin: To clarify on that other point, in terms of chemical or psychotropic effects, you don’t see much difference between medical marijuana and recreational marijuana?
Dr. Wong: In a sense, there is no difference, because each plant varies from batch to batch and from plant to plant. The certain grapes that made a great wine in one year may not do so the next year, and it is for the same reasons there are so many variables that affect the chemical constituents of any plant.
Any strain with an average combination of components could be taken recreationally or prescribed. Just to give you some preliminary data from our study, what we found was already kind of surprising. We assumed, as I think in the literature, people assume, there are two well-known cannabinoids: delta-9-tetrahydrocannabinol, THC, and cannabidiol, CBD. There are many others, but these are the two that were best studied. The THC is the one that seems to cause people who use recreationally to get high. It’s also what, in higher doses, can produce social anxiety and sometimes overt paranoia. The CBD has more sedating, more calming properties.
In the literature, people assume that higher CBD would be better for treating something like PTSD. That’s not what we’ve found so far. We are aiming to recruit about 50 or 60 subjects. We are halfway there. We’ve done a preliminary analysis just on the THC and CBD. These are PTSD patients using cannabis who report it is helpful for them, and they are using much higher THC strains than we expected.
In terms of functional outcomes of treating people with PTSD with cannabis, I agree it’s not clear to me how much it will change. I think people report symptom reduction, and that’s probably what the clinical trials will say. I don’t know.
However, I would also say this is true of pretty much all medications we use in psychiatry. There is a big problem that we, collectively as a society, need to work on — antipsychotics are very good at treating psychotic symptoms; 90 per cent of patients have a significant reduction in symptoms or the symptoms are gone. However, that doesn’t change their outcomes in life. As Freud said, the marker of function is love and work. That means social relationships, family and intimate relationships, and the ability to function, have gainful employment, professional success, et cetera. This is not happening with schizophrenia anywhere.
We should have a high standard for evaluating treatments for illness, including cannabis for PTSD. Keep in mind that standard is not really met for any illness in psychiatry at this time. That’s to be realistic while still being ambitious.
Senator Wallin: Thank you.
I have a thousand more questions. I’ll go on a second round.
Senator Boniface: Thank you very much for being here. This is fascinating to me.
One of the things we all heard for some time was cannabis for medical use would reduce the use of opioids for pain, as well as other drugs for insomnia and anxiety. Veterans Affairs Canada stated it has not observed that correlation among its clients yet, as such trends could take years to emerge.
Do you think that using marijuana for therapeutic purposes may lead to a decline in the use of opioids or other medications? Are you seeing anything in a trend yet?
Mr. MacKillop: There are two recent studies that were just published in JAMA Internal Medicine that focused on U.S. catchment areas and provided further support for reductions, at least in opioid prescriptions, in states where cannabis was made legal for medical purposes. Now there does seem to be a growing literature, but it’s from the 10,000-foot perspective. These are very high-level studies that cannot speak to whether there is actual substitution happening and cannot account for overall prescribing practice changes because of the appreciation of the danger around opioids and their habit-forming properties.
We do not have data that speaks to this. It could well take a lot of time within the VAC to detect that because these are small effects only detectable in vast data sets, and I think they are also simply observational associations. They can’t speak to whether medical cannabis is the cause. I’m both persuaded by accumulating data and cautious because I recognize it’s correlation and not causation.
Dr. Wong: I agree with James, and would add a couple of points.
The first is if we’re talking about pain as the target — I don’t treat pain primarily. That’s not my area of specialty, but regardless of symptom targets, it is possible cannabis could augment, for example, the pain-relieving properties of opiates. One way of looking at the outcome is a possible decrease in opiate prescription or use. There might also be a scenario where the dose of opiates doesn’t change but the patient has better pain relief. It’s important to keep that in mind. It’s complicated.
On the other hand, just to give you an example of a patient whom I saw a couple of weeks ago. This patient came with new onset ADHD in adulthood, which I don’t think is a thing when there is no childhood history of it. She had done a lot of reading and was convinced that she had ADHD based on all kinds of stuff on the Internet.
The onset of her ADHD coincided with the onset of her beginning to smoke large amounts of cannabis. That is the other side. Every drug has side effects as well as beneficial effects. In this case, I think this person’s attention and focus had been impaired by using this high level of cannabis. I don’t think the answer is to add amphetamines to this cocktail. Rather, I would suggest decreasing the cannabis, which is not what the patient was looking for.
Just to keep in mind this kind of thing can happen and there are synergistic effects of drugs, but also, people may start to chase side effects with more drugs, which cause more side effects. We see that all the time in medicine in general. Definitely in psychiatry sometimes patients come in with shockingly large lists of medications which presumably have been added piecemeal by different doctors to address new symptoms that arise that could have been better treated by reducing a different drug.
Senator Richards: Thank you very much for being here. A lot of my questions have been answered by now. I generally ask the same question to the witnesses.
It’s not a cure. It’s a mask. It’s a cover. In a way, it’s like alcohol. Marijuana has always been a companion drug to alcohol where I grew up. This is what kids did and they continue to do. I’m worried about medical marijuana, the effects of having 12 joints a day. If you have 40 joints a day, you are comatose, at least most people I know would be. With 12 joints a day, you are probably an addict.
Where is the benefit in allowing this as a treatment? I’m not so naive as to know there are not addicts and that alcohol and marijuana won’t be used together. I’m just wondering about the ongoing treatment at the same time. Is there a way you try to wean people off of this over time to get their lives straightened out so they can function without this amount of marijuana in their bloodstream?
The idea they are only using marijuana is pretty naive too because we know it’s a companion drug to alcohol and perhaps opiates as well. I am being compassionate. I’m concerned about these kids coming home, suffering in this way and growing up with First World War veterans who were raging alcoholics because they went through gas. When I was a little boy watching them on the seats, this is different, but it’s not different in kind. It might be different in degree, but it’s the same kind of effect. Do you have any answers or ideas about that?
Dr. Wong: James and I were talking earlier on this topic. I think all of the drugs humans in general know about that alter brain function, that change the way we feel, think, behave and so on, I don’t think there is any difference between any of them. If someone feels anxious and they take a Valium or a Ativan or they have a martini, all of these things have very similar effects. The drugs we use in psychiatry are very straightforward. There is this joke about psychiatry that it’s like dermatology because there are a thousand rashes but only three creams.
Psychiatry is straightforward sometimes. I’m being facetious. If you have depression, we treat with an antidepressant; if one has psychosis, then one is treated with an antipsychotic. These are symptomatic treatments, all of them, and so might cannabis be for the symptoms of PTSD. I see no difference there. I think it’s an important point, a good question, but one we should also see as being broadly applicable to all the treatments we currently use in psychiatry, not just this context.
Mr. MacKillop: I agree with Albert’s point. I think the issues you raised are at the heart of this question: Are we really helping people by providing greater access to this drug?
The body doesn’t make a distinction between legal and illegal drugs, drugs that are prescribed by a physician or drugs they buy off the street. Where I think it is critical that health providers are involved is that a skilled clinician helps a person have access to the psychoactive drugs that can be helpful and ultimately hopes the person will no longer need to use them and will experience full functional recovery. The big question is whether cannabis should be part of that tool kit to help people with PTSD, pain and other conditions. I think that is such a critical question to answer.
For myself, I come at this as an addiction researcher first and as a medical cannabis researcher more recently. I’m very aware of the harms that are associated.
I’m also hardened that the animal models can’t lie to us. The rats don’t know if it’s a drug to get high or a drug to treat their pain or the other conditions we simulate. The data are persuasive that there appears to be a therapeutic signal. The question is, can that be delivered to real-world human patients in ways that maximum benefit and minimize harms? That’s where I think the real hard work needs to be done.
Senator Richards: I’ll follow up briefly. There can be a good day with cannabis and then a really bad day with cannabis. It can be with same person. It can be a day later. Just like there can be a good day with alcohol and a then a hell of a terrible day with alcohol. That’s something we have to realize too, and I’m sure you know that. Thank you.
The Chair: Before we start the second round of questions, I would like to ask a few questions myself. Mr. MacKillop, are there any more advanced studies that have been done on cannabis use among veterans in other countries?
Mr. MacKillop: Unfortunately, that work does not exist, to a large extent. In part, that is because the largest amount of research on health outcomes on veterans takes place in the U.S. via the coordinated VA system. The contradiction between federal and state laws means there has been relatively little research on cannabis as a medical treatment.
To my knowledge, there is also scant evidence from other countries. This is really, to a large extent, uncharted territory.
The Chair: In your studies, have you observed any adverse personal or family effects associated with marijuana use?
Mr. MacKillop: Certainly we’ve heard anecdotally that positive effects have very powerful ripple effects throughout families.
If a person can get traction on their pain or psychiatric symptoms, that has tremendous downstream positive consequences. What is less clear is the extent to which that is simply anecdote versus a reliable effect based on the drug itself, as opposed to expectancies or the general positive trajectories people often experience once they have entered treatment.
The Chair: Thank you, Mr. MacKillop.
I have two questions for Dr. Wong. What relationship might you make between suicide and cannabis use? Can cannabis use lead to suicide in some cases?
Dr. Wong: If I understand the question correctly, it’s about the relationship between suicide and cannabis use and whether it’s causal. This is a difficult area in the literature in general with psychiatric treatments and how psychiatric treatments might be related to suicide.
You will probably know there was a controversy in the media, perhaps 10 years ago, to do with adolescents and antidepressant prescriptions where there was an observation that sometimes there was an association between the prescription and taking of antidepressants and, later, suicide.
I would like to point out why this question is difficult. The first is if you were to study patients who were taking Propranolol, a beta blocker and an old heart drug, you would note that they have a much higher incidence of heart attacks than the general population. This is most likely because they are prescribed this medication to protect their heart when it is already damaged and they have heart disease. They are more likely to have adverse cardiac outcomes, but not because the drug causes it.
I think this is the most likely explanation during treatment for a psychiatric illness for which suicide is a possible adverse outcome because, obviously, when it is the core cause of mortality for most psychiatric disorders, one will see patients commit suicide. It’s difficult to say whether that treatment caused it or not.
I want to make a further point it’s complicated because, for example, in the case of anti-depressants, this relates to what James brought up earlier about functional versus symptom improvement.
Antidepressants may improve some of the symptoms of depression. There is a transition zone between when someone is depressed and when they recover where the symptoms do not all respond at the same time. It’s possible the person has more energy and motivation and is better able to initiate activity while their mood still remains low. Their mood might perhaps improve later, but there may be different weeks, to what Senator Richards was saying. There are good days and bad days. It’s not just a monotonic improvement and each symptom does not respond with the same trajectory.
In the case of depression and antidepressants, sometimes patients might get more energy first, before their mood improves, and the suicide attempt they have been planning actually occurs not because the antidepressant is not effective, but because there is that window while they are improving where symptoms are changing. That could be what happens.
I wouldn’t say that’s causal; there is a relationship. What is important is the overall outcome. Suicide is, of course, a possible bad outcome of all psychiatric disorders, including PTSD. It is difficult to disentangle the causal the relationship with any treatment or adjunctive recreational use of any substance.
The Chair: This is my last question for Dr. Wong. In your research, did you assess the potential danger for a veteran to mix cannabis for medical purposes with cannabis that will be legalized if Bill C-45 is passed? I imagine that between medical and recreational cannabis, there are all kinds of cannabis that can be found. Have you assessed the danger between using one and the other?
Dr. Wong: That question is part of our study because, as you said, if someone is using more than one strain of cannabis, two different sources or even two different batches, that alters what chemicals and drugs they are ingesting and then it becomes difficult to tell what might be therapeutic or not.
Yes, that is a problem and that’s something we need to try and sort out. Patients will make their own decisions and may not always take our advice. It’s an important factor to consider that whatever they are prescribed, they may find a cheaper or more convenient alternative. They may prefer the effects of mixing different strains together. It does muddy the picture from a neurobiological standpoint.
Senator Wallin: I want to make a distinction from research on people and the impact which we all agree is crucial, and then the research on the drugs and where that stands. We’ve heard testimony here at this committee that really the only way to safely administer this and also assess the impact is if you have some pharmaceutical version of marijuana where you can then have consistent quantities of THC, CBD or whatever it is and put it into some form.
As long as you are getting it off the street or buying it at the store and every strain is different, we will never be able to test. As you’ve just said, there are too many variables. Is that research reasonably underway so we will have some pharmaceutical version of marijuana that could be then used and monitored more accurately?
Mr. MacKillop: There has been a lot of progress made in that domain. You are exactly correct that the plant form, especially taken by inhalation, is incredibly difficult to measure because people can take more or fewer puffs and they can inhale for longer. The composition issue is one we have touched on at length.
Now that there are oils and formulations that can include encapsulation of oils, for example, the drug can be delivered in more standardized forms. The industry seems to be interested in developing devices that would permit more standardized delivery and in turn would lend themselves to more rigorous evaluation.
This question of standardization is at the heart of what has prevented a lot of research from being funded. There has been a stigma against cannabis research because it has been difficult to identify what the optimal strain or comparative strain would be. It doesn’t mean it’s an impossible question; it just means you would have to have the resources to systematically characterize multiple strains and use some of these new formulations that are increasingly available to get closer to less metaphorical medicine and more traditional medicine.
Dr. Wong: I agree. I think some of these new formulations, like the oils, can definitely improve the standardization of what the patient is using. I think it’s also possible to do that with the whole plant. It’s akin to the special kind of tomatoes that come from a certain part of Italy at a certain time of year. They are not always exactly the same but they are better than other tomatoes.
There is the possibility of a reasonable standardization. It’s not clear to me that fine variation will have major therapeutic effects. That’s something we don’t know yet. That’s an important question, whether the level of standardization that is realistically achievable from a commercial growing operation is sufficient. It might well be. The problem, as James has said, is really what is out there is a mess and we have a hard time now even knowing what components — or which combination of components — in this so-called entourage effect are important and which are therapeutic or not.
Senator Wallin: I’m back to the issue of research on people versus research on the substance. Do you think you could, if you had access to control groups and user groups and whatnot, isolate what component of the 87 is actually impacting PTSD or migraine headaches or whatever it might be?
Dr. Wong: This is a general question as well with botanical treatments for illness. I think the story has been varied with other treatments. Often, though, it’s not just a single ingredient of a plant that might be therapeutic. I think cannabis is a likely candidate for this eventual conclusion. A different conclusion would be reached, for example, with artemisinin, the plant-derived antimalarial drug that was the subject of the Nobel Prize a year or two ago.
In that case, it was probably just that single chemical. I suspect with cannabis it’s not just a single chemical. From a pharmaceutical and scientific standpoint, it is much better to have a single compound that you deliver, do clinical trials on and conduct neurobiology tests.
Considering the long cultural use of cannabis, it’s probably an entourage effect. That is more complicated because it is the combination of chemicals at certain ratios. There’s probably an optimum. To further complicate it, there’s probably significant inter individual variation as well. What is optimal for one person is different for another. I think this is where the field, hopefully, will go in medicine in general; that is, where this is true for cancer chemotherapy and management for hypertension or diabetes as well. Each person has their own biological idiosyncrasies and this would affect the combination of drugs and the ratio of different components in their treatment — and so it should. However, we’re not there yet.
For simplicity and from a pragmatic standpoint, we want to start with a single compound. I don’t know how in the real world that would happen.
Mr. MacKillop: I agree with all those points. To your question, at the heart of it is should we throw our hands up and say this is an impossible undertaking or could we fundamentally identify the ingredients/combination of ingredients? I think we can. It is a matter of resources and rigorous experimental methods that start with the compounds we know have the most promise from evidence. Start with THC and CBD, then start working through the cannabinoids that have some but less evidence, such as CBG, CBN, CBC. It’s a laundry list and an acronym farm, for lack of a better word, but it’s not an unlimited number. Although the entourage effect is hypothesized, it is fundamentally a hypothesis not a certainty and we can test it. It’s a matter of starting with smaller questions and adding to them. From an experimental standpoint it is trackable. It is a matter of it being a large undertaking.
Senator Wallin: Let me ask the larger question for the community and in general. Will the legalization of marijuana help your research or confuse it even more?
Mr. MacKillop: We are embarking on a national natural experiment in cannabis legalization. We will have the capacity to ask questions many other countries have not been able to. We will be able to advance the knowledge of cannabis — medicinal, recreational and otherwise — in a lot of different ways as a result. It is a limited time opportunity because of the tremendous transition that is happening. It is a matter of marshalling all the available resources to take advantage of that, I think.
Dr. Wong: I agree this looming legalization is a great natural experiment. That’s probably not its intention, but it provides an amazing opportunity. Often in science and medicine, this is when things progress, namely when there is accidental opportunity.
I agree with James that things will change in a dramatic way. That may not have been the deliberate experimental approach. Here we have one variable that is changing and we now have an opportunity to see how everything else changes, in this particular context, with veterans and soldiers who are using cannabis for their PTSD. Their access and patterns of use will potentially change and we should avail ourselves of the knowledge that could generate.
Senator Wallin: Thank you very much, gentlemen.
Senator McIntyre: My question is a follow up to the question asked by Senator Dagenais on the correlation between the use of cannabis and suicide.
For 25 years, I acted as chair person for the New Brunswick Criminal Code Board of Review. The board derives its authority under section 672 of the code, “mental disorder.” It deals with individuals who have committed a criminal act, following which they are found either unfit to stand trial or fit, not criminally responsible, on account of mental disorder.
In the majority of cases, the board observed a direct correlation between mental disorder and the use of illicit drugs, particularly cannabis.
You may have already answered this: How do we address the issue of mental disorder generally and the excessive use of cannabis?
Dr. Wong: I mentioned one of the studies I did in the introduction, namely, the study of suicide in Canadian peacekeepers. I raise that because that study was prompted by the unfortunate incidents that occurred in Somalia with our Canadian peacekeepers and the death of a Somali prisoner and then some prominent and well-publicized suicides among Canadian military personnel.
The approach we took was called a psychological autopsy in which we reviewed the medical examiner reports, medical history, which included Canadian Forces, UN, sometimes local police reports and sometimes very large files with a lot of information, to try to reconstruct as possible what led up to this suicide to answer this question of what was it that tipped this patient over into killing themselves.
It’s usually difficult to come up with a single answer. I want to point out suicide rates across the globe vary greatly. They are high in some countries and low in some neighbouring countries which superficially are similar to the other country. There are a lot of factors that contribute to suicide. It is difficult to parse out a specific factor.
I agree substance use and mental illness are both major risk factors for suicide, but so are things like legal challenges for a person, for example if there is a looming charge; or loss of a business; divorce; loss of a spouse. In some cultures, certain types of dishonour are expected to be met with suicide. That is actually the expectation rather than a negative mental health outcome that we might frame it as in the West.
I don’t think there is a clear answer. Substance abuse and mental illness certainly increase the risk of suicide. However, whether it is causal is difficult to say. It’s possible these three things arise from the same origin. That is, the person is using substances because of their mental illness and whatever led to that is also driving the suicide. It is not that it is a stepwise progression, but that they all occur in parallel.
Senator McIntyre: One thing I learned from the board is that a mixture of a mental disorder with the use of illicit drugs makes a strange cocktail, let me tell you. When that explodes, that’s it.
Dr. Wong: From my experience in the emerge, the CAMH emergency room is right downtown between the business district, Chinatown and the university district it is central downtown. What you said is exactly what causes the most problems. The patient with a pre-existing mental illness, whether it is bipolar disorder or schizophrenia, who is using a large number of street drugs — usually something like crystal methamphetamine, smoked methamphetamine or crack cocaine, or injected drugs, or hallucinogens. Patients who do that come in. Often they are violent and out of control and they are brought in by the police. That is the most difficult, dramatic presentation we have in emergency. I agree. That is a bad combination. Although that occupies my time almost every time I’m there, overall it is a rare beast. This is the tiny tip of the iceberg.
Mr. MacKillop: I would add those are exactly the concerns that come up in our forensic psychiatry unit at St. Joe’s because many of individuals are there in part because of actions that happened in the presence of a variety of mental disorders but also cannabis use.
I am very troubled by the associations between cannabis use and suicide. Even though they may be correlational, in some individuals we see these links of violence either against themselves or others. I agree with Albert’s point that we need to dig into whether that is simply an artifact of other things and a symptom of very high psychiatric complexity and severity or whether it has a causal role.
If we think of having a unilateral, positive therapeutic effect, we wouldn’t expect to see that association. I am troubled, but that is why we need to study it more closely and not just look at cannabis narrowly in relation, for example, to PTSD or pain but also to suicide, depression, anxiety and more broadly within the context of veterans’ health.
The Chair: Mr. MacKillop, Dr. Wong, thank you for your testimonies. I’m sure that they will help us a great deal in preparing our report.
That concludes this meeting of our committee. Thank you, honourable senators.