Searching for Medical Marijuana’s ‘Therapeutic Window’

Dr. Mark Ware is one of the world’s leading experts on medical marijuana. Ware is an associate professor in Family Medicine and Anesthesia at McGill University in Montreal and director of clinical research at the Alan Edwards Pain Management Unit at McGill University Health Centre. He practices pain medicine at Montreal General Hospital.

Although medical marijuana is legal throughout Canada, and in 23 U.S. states and the District of Columbia, mainstream medicine still frowns upon its use. Research into the therapeutic benefits of cannabis -- particularly for pain management -- has also been limited.

Pain News Network editor Pat Anson recently spoke with Ware at the annual meeting of the American Pain Society. The interview has been edited for content and clarity.



Anson: You’ve called medical marijuana an “incredible social experiment.” What do you mean by that? 

Ware: I think what we’re seeing is the lid coming off something that’s been going on for a long time. I think people have been self-experimenting with marijuana for years and years. People have been growing it in their basements and backyards. So there’s been a social experiment with cannabis since the 1960’s in the Western world.

I think the medical aspect of it has kind of followed through with that, because as you get thousands of people using cannabis, eventually somebody with an illness is going to stumble upon it. Lester Grinspoon (a marijuana researcher) reported on this in 1971. So that’s how long we’ve known or suspected the potential medical properties. The fact that the drug has been illegal has suppressed the possibility of there being much in the way of good quality research. So the experiment has been going on underground, out of sight and out of the public eye.

What we’re seeing now is that suddenly we’re able to talk about it. We’re able to look at this seriously. And we’re beginning to realize how much was already going on. So I think it’s an experiment that’s been going on for a long time and we’re beginning to put some parameters around it now, which allow us to track it more carefully. And hopefully it can yield some important results that can help inform the patient and the physician about what to do with this.

Anson: Some doctors have told me they don’t think marijuana will ever go mainstream until big companies like Pfizer and Purdue Pharma start backing marijuana research and doing clinical studies. Would you agree with that?

Ware: I don’t know if I would agree with that. That’s true for new pharmaceutical drugs. If you’re developing a molecule from the lab up, you need Big Pharma to come along and take that and move it to the point where they can do the big clinical trials.

With an herbal medicine, I think you almost don’t want to look at the pharmaceutical model for drug development. It’s more like how we regulate natural health products in Canada. We want good quality cultivation techniques, we want good quality processing, and we want to know what it is that we’re giving to patients.

I think fundamentally what we have to figure out is what we want to know about this drug. What is it that we need to know and how do we go about getting that information?

I think if we wait for Big Pharma to come along it’s going to be a long wait.  They would have been on this long ago if they thought this was important.

It’s a plant based medicine that’s already in our society at some level and we need to recognize the reality that mainstream doesn’t mean mainstream prescription availability. It’s going to mean mainstream figuring out how to put cannabis in a safe place in our society.

Anson: Medical marijuana is so widely available today, it’s like we’re already past the clinical trial phase.

Ware:  Exactly.  And to go back and do the Phase III study now, it’s expensive and would take hundreds of millions of dollars. And that requires knowing whether you’re going to get your money back. Companies invest that money when they know they’ve got a patent and they can make money back on the drug in the ten years after it’s launched. It’s much harder to see that happening with an herbal material like cannabis.

Why invest the money? It’s already available. You can already buy it at the dispensary. So now the question is how do we improve that process? How do we improve the quality of the product? How do we label them so people know what’s in them? How do we provide information to the patients that are buying them? What they should be looking for and what they should be careful about?

And how do we inform the physicians and health professionals who should be managing that whole process or at least informing it? What kinds of patients should be avoiding this? This isn’t for young kids. This isn’t for women who are pregnant. Some of this is obvious, but some of it needs to be specified and mandated.

I don’t think there’s strong enough evidence to start using cannabis in younger people. I think that the risks of cannabis on the developing brain in teenagers is significant enough that, unless there is a very real reason like a younger person with a severe intractable illness, this is a drug that should be held for the 25 and older crowd.

I would caution people who have unstable heart problems against using cannabis. It does increase your heart rate, can open up your blood vessels, and that could precipitate some heart problems.

Anson: What are the pain conditions that you think medical marijuana can be beneficial for?

Ware: I think for sure it’s more likely effective for chronic pain than acute pain. It’s never been reported for acute pain syndromes, but it has been reported for chronic pain.  There are clinical trials now that bear out that chronic neuropathic pain is one of the relieved conditions that it seems to respond to. We’ve seen reports for spinal cord injury, fibromyalgia, and PTSD (post-traumatic stress disorder). Cannabinoids appear to have some signals in some of these conditions.

And then you go beyond that to abdominal pain with Crohn’s disease, diabetic neuropathy, and so on. The list of conditions where it looks like it may work is as long as your arm.  There are individual case reports of cannabis being used on a huge range of conditions.

Anson: What is the most effective delivery system? Everyone thinks of smoking, but there are plenty of other ways to ingest marijuana.

Ware: There are. And I think the key thing is the difference between inhaling and taking it by mouth. The inhaled route is a very quick onset, has a very rapid effect on the patient, and then a fairly quick half-life; whereas the oral route takes much longer to absorb and takes a longer time for the patient to feel the effects. But then it lasts a lot longer. 

courtesy drug policy alliance

courtesy drug policy alliance

So it’s almost like a short acting versus a long acting medication. I don’t think there’s any way of saying one is more effective than the other. I think they’re effective in different ways.

If I was vomiting because of chemotherapy, I’d want something I could inhale to control the vomiting quickly. But if I’m not able to sleep because of my chronic pain, I want something that would be longer lasting so I could sleep through the night.  I don’t want to wake up three hours later and have to do it again. So I think we just have to figure out how to use the different administrative techniques for different clinical conditions.

Anson: Most of our readers are pain patients and when this subject comes up many of them say, “I’ve never tried marijuana. I’m curious about it and I’d like to try it, but I’m worried about getting high.” Can they get pain relief without getting high?

Ware: We’ve done studies where we kept the doses very, very small -- to the point where people have read the protocols and said you’re not giving these patients enough to feel the effect. And in fact, what happens is patients are still able to find analgesic benefit and avoid that euphoric or psychoactive effect.

That’s important for most patients. They want to be able to use a drug or any kind or a therapy that doesn’t impair them from doing the things that they need to do. They need to drive. They need to work. They need to hang out with their families. They need to do their sports and their activities. And this is part of pain management generally. We want people to be living as full and as active a life as possible. We don’t want them collapsing on the couch all day long.

So can we find that window, what we call that therapeutic window, that dose where you get the benefit but you don’t get the sedative or psychoactive effect? And I think we can. I think for patients who are considering this approach, they really have to learn to be very patient and use very, very small doses. Try very small amounts first and allow your body to feel what the drug is doing to you. And if nothing happens, that’s okay. You’ve started with a low enough dose that you felt nothing. You gradually work your way up.

The interesting thing about cannabis is that there are two ways of thinking about dose. One is the amount of the drug itself, the number of grams, joints or pipes, if you will. The other is the THC level of the cannabis itself.

courtesy drug policy alliance

courtesy drug policy alliance

If patients have access to material where the THC level has been standardized or has been measured, they should be trying to use THC cannabis that is as low as possible, because the likelihood of having a psychoactive reaction to a high THC cannabis is much higher.

If it’s high in THC, it doesn’t take much to get that effect, where if they use very low THC levels, less than 10 percent THC, and they use a small quantity of the material, then potentially they can find that therapeutic window that can be effective.

Anson: What about taking marijuana with opioids? Can you do that?

Ware: You can. There’s no medical reason why you shouldn’t. I think the key thing for patients who are doing that, and again I emphasize with the knowledge and support of their physician, is that they can reduce the doses of other medications which may not be helping as much.

Cannabis use can be seen in terms of improving patients in two ways. One is in reducing the medications that they’re already taking, which may have side effects. And the other is in improving their functioning state so that they’re doing more. This is where I think the responsibility lies with the patient to prove to the doctor that this drug is helping. And you do that by reducing your other medications with the doctor’s support, by increasing your functioning and by showing that you’re doing things that you weren’t doing before. That is what doctors want to see.

There appears to be evidence, at least in animal studies, that opioids and cannabinoid drugs work synergistically. So if you take the two separately and you take the two combined, you get a greater effect with the combination than if you took either of the others by themselves.

This synergism, we’ve seen it in patients who started using cannabis successfully and they were able to reduce their other medications. In some cases they find that the dose of opioids they were taking, they can lower it and get a similar effect with much lower doses. With others, they don’t need the opioids any longer and they can taper off it and stop completely. 

Anson: One fear of using medical marijuana is that it could make you more prone to abusing other substances.

Ware: I think patient selection is very important when you’re considering as a physician whether to authorize or prescribe cannabis, because cannabis is a drug with a known risk of abuse and dependence by itself. There are people who struggle with their marijuana use and withdrawal when they try to get off it. Physicians need to be sure they’re not making things worse for a patient that has a dependency disorder by authorizing cannabis.

Screening for dependence means looking for abuse of other substances, such as alcohol. If you’ve done that carefully, prescribing cannabis to a patient who doesn’t have that addiction risk appears to be fairly safe.

Medical cannabis should be used as an option only when all the conventional therapies have failed; when all of the other approaches to pain management, and I’m not just talking about pharmacology, but when all of the non-pharmacological approaches have all been considered and tried. Cannabis is not at the point where it can be thrown in as a first line agent for a patient struggling with pain management.

Anson: Thank you, Dr. Ware.