Cannabis for Pain? An Expert's Guidance

John Watson


January 05, 2021

Mark Steven Wallace, MD

Many have put forth medical cannabis as a promising treatment for chronic pain that can potentially replace opioids. However, although it's never been easier for patients to access medical cannabis, those researching its use say that the structural challenges inherent to studying a Schedule 1 drug remain formidable.

Medscape recently spoke with Mark Steven Wallace, MD, a pain management specialist and chair of the Division of Pain Medicine at UC San Diego Health, about the latest data on medical cannabis and the challenges in studying its clinical use in pain management.

What is the current legal status of medical cannabis in the United States, and what disorders is it approved for?

It's still illegal at the federal level, which means there's no medical use of it that's authorized or approved. It's very different at the state level, where more and more states are legalizing it. Federal law can overrule state law, but the federal government has elected not to do this, and I don't think they will. They're just letting it take its course.

There is no approved condition for cannabis. Most of the evidence for it is with the treatment of pain. There's almost no evidence for it to treat other nonpainful conditions, such as psychiatric conditions (eg, depression or anxiety). There are certain neurologic conditions, such as essential tremor, that they're studying it for, but there's really just no evidence for it.

With that stipulation, can we say that doctors are prescribing medical cannabis in states where it is legal?

The question is, how do you define "prescribe"? At the federal level, because it's a Schedule 1 drug, it's illegal to prescribe. With a prescription, the physician is writing out the medication, the dose, the frequency of administration, and the quantity to be dispensed. We don't do that for cannabis.

What most states allow is for a physician to medically authorize it, but that isn't necessarily prescribing it. That's the problem with the laws that we're under. You often don't know what the source is, what the patients are receiving, and what the quality control of it is.

California is way ahead of the other states. As of January 1, 2018, the Bureau of Cannabis Control kicked in. They oversee the quality control of the products that hit the shelves of the dispensaries that patients are accessing. Before distributing the products, the manufacturers have to batch test it for quantity and such things as contaminants and water content. We can now ask for that certificate of analysis at the dispensary to make sure it's had that testing.

I take the extra step of actually recommending dosing to my patients, because we've learned a lot about it. We have a doctor of naturopathic medicine affiliated with our pain clinic who does the dosing consultations for us. I know how to dose it, but I don't have the time to keep up with the quality control. Then the patients follow up with me to determine how they're doing.

How has the availability of cannabis changed your approach to prescribing opioids for pain?

One of the drivers of my interest in medical cannabis is using it to replace opioids. I've been doing pain medicine for over 25 years and have been very concerned over the mess we've created with opioids.

Initially I'd tell patients, "I will not allow you to do both. You have to get completely off your opioids before I will allow you to use cannabis." Many were very motivated and wanted off their opioids. I would put them on a very slow taper schedule. I found that many patients were very compliant in reducing their opioids and would be having increased pain and some withdrawal symptoms.

Then I thought, you know what, let's introduce the cannabis. What I saw was that they would kind of chill out and continue weaning off their opioids. The difference between an opioid user and a cannabis user is that with the former, their life revolves around that opioid, their next refill, anxiety over how many pills they have left. When I can move an opioid user to cannabis, that behavior goes away. Many are soon so stable that they don't even follow up with me until they're ready for their annual cannabis renewal.

How strong is the body of evidence for the efficacy of medical cannabis in the treatment of pain?

It's low to moderate. The reason for that is that it's impossible to do multicenter randomized controlled trials with large numbers of patients, because you can't transport cannabis across state lines.

We've started studies here at the UC Center for Medicinal Cannabis Research back in 1999-2000 from state money allocated for that purpose. We've conducted a lot of double-blinded, placebo-controlled, randomized trials in a number of different pain syndromes, and all of them were positive. They did show better effects for cannabis vs placebo. However, they were small single-site studies with limitations.

The only way you're going to get the stamp of high-level quality is to have larger numbers of patients, but we can't because it's Schedule 1. It's very, very challenging.

What are the different effects of the psychoactive and neuroactive components of cannabis on pain?

We have no evidence for the effects of cannabidiol (CBD) on pain. All the evidence is with tetrahydrocannabinol (THC).

The dose of CBD that would be required to have a beneficial effect is probably cost prohibitive. If you look at the biphasic effect of CBD, going from low to higher doses, the range is from 10 mg to 800 mg. The doses that are probably going to actually be beneficial for reducing pain are likely in the 200-400 mg range. That would cost thousands of dollars a month for a patient. Most patients who are using CBD are using doses that are 100 mg, maybe around 20 or 30 mg.

The dosing range for THC is much narrower, from 1 mg to 20 mg. With 1 mg, you'll have beneficial effects — maybe pain reduction — and increasing it a little will get improvement in sleep. If you get to 10 mg, you start getting paranoia. If you get to 20 mg, you get psychosis.

I ask lot of patients that come to me, "Have you tried medical cannabis?" It's not unusual for them to respond, "I tried it, but it was horrible. I didn't like it." And I say, "Did anybody help you with dosing?" Well, no, they just went to the dispensary, where they were handed these high doses of THC. If we can get them to start over and use lower doses, most of them actually report beneficial effects.

Is there an ideal ratio of active compounds? 

This is anecdotal, but we do find that with the combination of the two, CBD reduces the psychoactive effects of the THC. The ratios we use during the daytime range around 20 mg of CBD to 1 mg of THC. I instruct them to take maybe a quarter of a droplet of oil, drop it under their tongue, let it sit there for a minute or two, and then swallow it.

At night we go to a 1:1 ratio, because we want to bump up that THC. They take a full droplet, which is probably around 4 or 5 mg of THC. That gives them a good quality of sleep. If they take that same 1:1 ratio during the day, sometimes there's a little bit too much psychoactive effects, and they don't like it.

I did a crossover study on THC levels in diabetic neuropathy. There was a dose-dependent reduction in pain, but the high doses started to go in the opposite direction. We showed that as the THC level goes up, the pain reduces until you reach about 16 ng/mL; then it starts going in the opposite direction, and pain will start to increase.

Using cannabis is all about starting low and going slow. Titrate it very slowly, because if you don't, you'll blow right through the beneficial effects and get into the negative effects.

How safe is medical cannabis? What are the common side effects?

It's hard to say. We don't have clinical trials that are looking at safety. But there are clearly safety issues with the inhalation of smoke and a higher instance of pulmonary disease. There may be some safety issues in patients with preexisting psychosis or psychiatric disease. Overall, I have not run into any significant safety issues.

There are concerns with CBD though. High doses of CBD affect the liver metabolism pathways and can interact with certain medications. You have to be careful with some patients that may be on blood thinners, anticoagulants, or maybe antiseizure or hypoglycemic medications.

How do you decide in which patients to prescribe cannabis?

I evaluate them as I would any of my other patients with pain. I'm looking at what their pain diagnosis is, what their psychosocial status is — do they have depression or anxiety? Then I look at treatments they tried, because a lot of patients come to me and think cannabis is their cure-all. And I say, "Wait a minute, you haven't tried some very conservative treatments." I would rather go with something simple to use, such as gabapentin and some of the other low-risk medications, and maybe physical therapy, psychological support therapies, and even integrative therapies. I try to get them to use conservative therapies first.But I'm a pain specialist. Most of the patients who hit my door have already tried all those things, so it's much more likely that I'll move onto cannabis.

Besides pain, which lines of research into medical cannabis look promising in neurologic disease?

There's a number of trials we're moving along here at UC San Diego. There is one looking at the effects of CBD on autism. There is some evidence that the behavior of autistic children drastically changes when they start using CBD. There's a study looking at CBD/THC in essential tremor. Also, one of my colleagues got a grant from the Migraine Research Foundation to conduct a placebo-controlled, randomized crossover trial of THC, CBD, CBD/THC, and placebo for migraine. It's going to be powered for about 80 or 90 participants. It will be a very important study because there's almost no research on the effects of cannabis on migraine, although I commonly have patients who report that they've been using it to avoid migraines.

John Watson is a freelance writer in Philadelphia, Pennsylvania.

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