Meet the Experts is a series of interviews conducted by experts from the field of Cannabis to world leaders in research and clinical practice of Cannabis as medicine.
Zach Walsh, PhD, is a clinical psychologist and an Associate Professor of Psychology at the University of British Columbia, where he directs the Therapeutic Recreational and Problematic Substance Use lab.
He has published and presented widely on topics related to medical cannabis use and cannabis and mental health. He is the lead investigator for several ongoing studies of the therapeutic use of cannabis including a clinical trial of cannabis for PTSD.
Zach Walsh: Canada's funding agencies are becoming more open to diverse forms of cannabis research. There has been priority setting meetings with cannabis scientists across Canada, and I believe they are consistent with what the scientific community would prioritize as well. The changing attitudes within the general healthcare community will hopefully inspire those who were interested in cannabis research but thought that it was too stigmatized before. I believe this will accelerate funding with potential researchers.
Our research group has a couple of studies that look at the effects of legalization on a variety of outcomes in young adults. We are following participants both before and after legalization. It is very exciting to be able to look at it from a multifaceted perspective that isn't overly obsessed with harms to the exclusion of potential benefits. We will examine how it affects relationships, and the use of other substances. If we don't look at cannabis in the form of a substitution for alcohol and opioids, then we have a biased picture that would miss the potential public health benefits. I'm looking forward to figuring out how legal cannabis affects people's choices around substance use and behavior, and how this relates to health and wellbeing.
SR: Can you discuss the difference between getting approval to do a cannabis based clinical trial in Canada as opposed to other countries (like the USA)?
ZW: Canada has had licensed producers since 2014, and researchers have had access to pretty good cannabis for their studies. The cannabis is close to what people use in the real world. Some would still argue that it differs from the diversity that you see in dispensaries. But it isn't like the USA, which is reliant on NIDA cannabis.
I haven't done research in the USA, but I believe there are a couple levels of clearance in order to get to work with cannabis. When you are allowed to study it, there is still essentially a monopoly. You are restricted to one producer which isn't equivalent to the cannabis people typically use. There was a recent study out of Colorado that compared NIDA cannabis to the dispensary cannabis and found some pretty substantial differences.
That's a big deal, since it can strongly impact the results of the clinical trial. It makes it a different kind of study. It is different in Canada. I would say that Health Canada (the regulatory body that oversees clinical trials) generally looks at it as they would with any other medication. There is variability in herbal cannabis that makes it a bit different than studying other things. But Health Canada is used to regulating it. They know they don't need to overdo it in terms of safety. I think the challenges in doing research in cannabis are distinct to the plant and not with Health Canada.
We have strict safety and security protocols we have to follow. Cannabis used in research is kept in a safe which is bolted to the ground. There has to be records of who is coming and going. But as compared to some places where you can't access cannabis at all for research purposes, Health Canada has been supportive and helpful. People in Canada are very enthusiastic and curious about cannabis research and recognize that it needs to be done.
SR: Can you briefly discuss the clinical trial that you are conducting on cannabis for PTSD?
ZW: Our study is a randomized controlled trial (RCT) of cannabis for PTSD. We have two types of cannabis and a placebo group. One variety is 10% THC, with very little CBD. The other is a balanced 10% CBD / 10% THC. People are given a week supply at a time as seven 2 gram vials of milled cannabis from Tilray, who is the study sponsor. Participants are supposed to open a new vial every day and use as much as they'd like from the two grams. They return the remaining vials, which are weighed so we can get an idea of how much they used. Participants also get a vaporizer. Our study is one of the first studies that looks at vaporized administration, and also examining THC versus a balanced CBD/THC preparation. There still are some basic questions that we need to examine of cannabis, such as the impact of chemovars for different conditions. Two varieties doesn't give you the full range, but I think it is a step forward.
A clinical trial with cannabis produces some unique challenges. Usually in a clinical trial the study drug is something that someone hasn't heard of or can't get. In the case of cannabis, it has a reputation as being effective for various conditions. It is readily available, which limits the enthusiasm people have to go into a clinical trial and completing all the necessary paperwork.
At the same time, a lot of people are enthusiastic about cannabis science. They want to contribute, which is such an admirable approach. If people are using cannabis regularly and it is helpful for them, they want to share the news. But those people aren't ideal for a trial either. If they come into our study, they are used to getting different cannabis. Who is to say that the cannabis we have is better than what they were getting before? They may have found a particular variety that was effective for them. Even after a cessation period, it then becomes a study of cannabis withdrawal rather than a study on the effectiveness of cannabis. Other clinical trials are going to come up against the same issue. In some ways we are in a Phase 4 with cannabis. We should be looking at how it works in society, as opposed to treating it like some new drug that we are trying to understand at a more basic level.
The placebo cannabis for the study is the leaves of the plant that don't have high levels of cannabinoids, but still has its odor and appearance. The trial uses milled cannabis placed in vials. Setting and expectancy has so much to do with drug effects. In clinical trials of cannabis, or psychedelic substances, people may believe they are in an active condition when they received a placebo. It's more rare for people in the active condition think they got the placebo.
I think that cannabis science gives the opportunity to ask questions about that methodology of scientific research and to find alternatives beyond the normal ways things are done. RCT's are absolutely important, but I don't think it has to be the only approach to meaningful research. It sometimes seems like the medical establishment would say there is no other way. Cannabis and psychedelic research, have the potential to expand our ways of knowing and understanding that aren't reliant on placebo blind control.
SR: Can you share a bit about your involvement with the Multidisciplinary Association for Psychedelic Studies?
ZW: I am interested in medicines that have been stigmatized and taken out of the mainstream. I worked on the MDMA for PTSD clinical trial. We recently published a paper (not directly with MAPS) on psychedelics and partner violence that was published in Journal of Psychopharmacology. It demonstrated that men who used psychedelics have reduced domestic violence in the community. We also discovered that prison inmates are less violent when using psychedelics.
Both cannabis and MDMA have medicinal applications for PTSD, but they work differently. MDMA facilitates the reintegration of memories, which with a therapist, can allow people to revisit the memories and integrate them. I think cannabis is more likely to reduce PTSD symptoms, particularly with nightmares, sleep disturbances, irritability, and hyper arousal. If you reduce the symptoms, people start to sleep better, and can get their life on track. This would help them with relationships and social interactions. Cannabis could be a longer term therapy to get people back on their feet. MDMA that is like an intensive surgery, where people can feel better as soon as they have experienced the direct effects.
Some people may continue to use cannabis to moderate symptoms for as long as they see fit. The hope would be that cannabis would be a part of a cure for their PTSD. Cannabis can help build a virtuous cycle. When someone has a positive shift in your life, they can start talking about recovering from PTSD.
SR: Can you talk a bit about the claim that cannabis use can impair memory?
ZW: There is evidence, at least in naive users, that cannabis can disrupt short term memory formation. Everything in your consciousness and cognition works together. The ability to engage in complex tasks and self monitor is connected to short term memory. You can't monitor yourself if you can't remember what you are supposed to be doing. Memory is part of functioning. Medical use studies show improved executive function when people use medical cannabis. If cannabis effectively reduces your symptoms, it may improve your executive functioning rather than decrease it. Regular cannabis users develop a tolerance to a lot of the cognitive effects of cannabis.
Short term memory might have different meanings in the popular consciousness than it does in neuropsychology. Scientifically, short term memory is the span of a few seconds or less, like when remembering a series of different numbers. Long term memory is anything someone can remember from before, even recalling what they ate for breakfast that morning.
It is certainly adaptive to forget things. We take in much more information than we can use or need. We are always forgetting and cleaning out our memory to make room for new things. So I think getting away from those narrow constructs and examining what cannabis does specifically is important.
SR: The use of cannabis for those with bipolar or schizophrenia has been a matter of debate. Have you been able to draw any conclusions whether or not it would be potentially beneficial or harmful for these conditions?
ZW: When we look at the real risks of cannabis, psychosis has to be one that really sticks out. Cannabis can potentially make it worse, or could trigger psychosis. Bipolar disorder that has psychotic like features, may lead to psychosis as well. I think it is certainly a risk for some people who may already have a psychotic disorders. Cannabis could maybe exacerbate it. CBD may help reduce the potential issues of THC in this regard. We definitely need more research on that.
We do know that some people with psychotic disorders use cannabis and it makes them feel better. We have to honor that and try to understand why they are having a positive experience. You don't hear of someone at the age of 50 using cannabis for arthritis and then all of a sudden becoming schizophrenic. It may be happening, but I am not hearing about it.
My perspective as a healthcare provider is to support the patients and walk beside them in health. If someone perceives benefit from using cannabis, perhaps we can reduce harms by helping them use it in a safe way. Maybe they can use higher levels of CBD, and be closely monitored for psychosis symptoms. Like anything else with a potential risk or benefit, it means finding ways to mitigate risks.
SR: Thank you for your insight, Zach.