Daily use can have unintended long-term consequences

[00:00:00] Host Amber Smith: Upstate Medical University in Syracuse, New York invites you to be "The Informed Patient" with the podcast that features experts from Central New York's only academic medical center. I'm your host Amber Smith. Many people who use cannabis for medical reasons are seeking pain relief. Medical cannabis is currently used as an off label pain treatment without Food and Drug Administration approval. Is cannabis a natural herb that is safe to use? Today, I'll be talking about risks that may be associated with the daily use of cannabis with two guests. Dr. Brian Johnson is a clinical professor emeritus of psychiatry and behavioral Sciences and the recently retired director of addiction medicine at Upstate. And Dr. Yanli Zhang-James is a research associate professor of psychiatry and behavioral sciences. Welcome, both of you, to "The Informed Patient."

[00:00:53] Yanli Zhang-James, MD, PhD: Thank you, Amber. Good to be here.

[00:00:56] Host Amber Smith: Your research was published in the American Journal of Addictions. Let's start with your conclusion first, and then talk about how you got there. You say that daily cannabis use may make chronic pain worse over time, by reducing pain tolerance, so that people who use cannabis daily may be risking addiction without long term benefit for chronic pain. Is that right?

[00:01:20] Yanli Zhang-James, MD, PhD: That's absolutely correct, Amber. That's the most important message that we wanted to convey through this study.

Reduced tolerance to pain is not new for other drugs like opioids, alcohol and nicotine. But it's a first time that we reported that this also happens to people who chronically use cannabis. And this is really important because it's becoming increasingly widely accepted and considered relatively safe drugs to use for pain, but people should still be aware that it comes with certain risks, like we showed.

And I do want to highlight that one of the most important things that made the study possible is the incorporation of cold pressor time tests into the clinical practice that Dr. Johnson had for over 10 years at the department of psychiatry. This was a pain service. He saw over 2,000 patients with all kinds of pain and various addictions. So with almost all of the patients that he had tested for cold pressor time, which is an objective measure of their pain tolerance, and we were able to see that for people who use cannabis chronically, that this system is also compromised.

[00:02:45] Host Amber Smith: Let me, if I may... You mentioned the cold presser test. Dr. Johnson, can you explain what that is and how it's done?

[00:02:52] Brian Johnson, MD: It's a fancy name for a very simple procedure. It's a beer cooler full of ice water. There's an aquarium circulating pump. The patient puts their completely normal forearm in, and it really hurts. And then we just time how long the patient is able to keep their arm under the ice.

[00:03:20] Host Amber Smith: Interesting. Very simple to understand. Now, for this study, you were focused on people who were using cannabis for chronic pain. Does that mean, would it be treated differently if someone was using it for acute pain?

[00:03:37] Brian Johnson, MD: Yes. It's called opponent process. And it's true of alcohol, nicotine, and opioids, as well as marijuana. Anything that reduces pain short term increases it if you use it constantly.

[00:03:56] Host Amber Smith: Dr. Zhang-James, how many patients were included in this study, and over what period of time were you focused on?

[00:04:05] Yanli Zhang-James, MD, PhD: So, this is a retrospective review of patient medical records. We had records from over 10 years, so we had over 2,000 patients total. It was difficult to find people who only used cannabis without other drugs, but we were able to find 47 that had used the cannabis, without opioid or alcohol. Thirty-seven of them also used nicotine. So in order to tease apart that effect, fortunately we were able to find also 32 patients who used only nicotine, no cannabis, and no any other drugs. And we were also able to find 30 of them who had actually did not use any of these drugs. So it is a relatively small study, but we were able to see the effect. And definitely would be interesting (to see) future studies that can replicate this finding in a larger sample size.

[00:05:03] Host Amber Smith: Let me ask you, I don't understand why you included tobacco use, or nicotine. What difference does that make or what impact does that have? Dr. Johnson?

[00:05:14] Brian Johnson, MD: This is a little known thing, but we've got wonderful colleagues at Syracuse University who are important researchers on nicotine and pain. So, Professor Joe Ditre would be the leader of that group, and they've published several studies showing that if you inhale tobacco, you've got more pain.

[00:05:44] Host Amber Smith: Interesting.

[00:05:45] Brian Johnson, MD: The context here is... We've got a database of about 2, 000 patients who came to the pain service, and we were so careful to find people who only used nicotine, only used marijuana. Of course using marijuana and nicotine together is common, so that was the third group. And then we could only find 30 people who did not have a history of exposure to any addictive drugs.

[00:06:22] Host Amber Smith: Did the cannabis users in your study ingest the cannabis by smoking?

[00:06:29] Brian Johnson, MD: Yes. Eating marijuana is unusual in our population. Most people inhale the drug, and of course, that's a weird route of administration. I'm always saying, when you take an aspirin for pain, do you smoke it, inject it, snort it, or eat it? Almost everyone eats their drugs. To use your lung to get drugs into your brain is just weird.

[00:07:01] Host Amber Smith: Well, you looked at daily cannabis use. How much cannabis were they using though, daily?

[00:07:10] Brian Johnson, MD: OK, so this is another thing about studies. Studies don't indicate anything about one particular person. We've got to agglomerate people into categories. So if you used one joint or if you had two joints for breakfast, two blunts for lunch, and five cigars full of marijuana for dinner, you went into the "daily use" category.

[00:07:43] Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith. I'm talking with Dr. Brian Johnson and Dr. Yanli Zhang-James, who both work in Upstate's department of psychiatry and behavioral sciences. And we're talking about whether daily use of cannabis provides chronic pain relief.

Now, Dr. Johnson, can you explain how the body develops hyperalgesia?

[00:08:07] Brian Johnson, MD: OK, well, one idea to mention is just like the way we got to daily marijuana use is daily opioid use. Every drug that comes from a plant -- so of course, nicotine comes from the tobacco plant; morphine comes from the poppy plant; and marijuana comes from the marijuana plant -- these are natural substances. And we all make hormones, we make cannabinoids, we make nicotinic acetylcholine, and we make endogenous morphine or endorphins. That's why we've got a receptor system. When you pour huge amounts of these hormones into your body by either taking opioid medications, inhaling cigarettes or marijuana, you change the receptor system.

[00:09:16] Host Amber Smith: Dr. Zhang-James, does that receptor system, does that mean that all types of pain are going to be affected, then? Not just the chronic pain that the person has, but, for instance, if they get a paper cut, is that going to hurt more because they've become more sensitized? Is that how that works?

[00:09:37] Yanli Zhang-James, MD, PhD: Yes. In some sense, yes, exactly, because all the pains that we receive from peripheral stimulations -- either it's headache or muscle ache, injury, post-surgical pain or paper cuts -- all mediated through our brain's central pain system.

We don't know exactly how different drugs act on this, but we do know that when the system gets sensitized and when patients have reduced tolerance, all kinds of pains get amplified. That is actually why we were able to use cold pressor time to measure the health of the central pain system.

[00:10:20] Host Amber Smith: How soon after you start using marijuana on a daily basis, is this likely to develop, where you have this increased sensitivity?

[00:10:29] Brian Johnson, MD: No one knows. We just discovered this. So, if we had a million dollars, we could take people and have them start to use marijuana or placebo and answer your question. But all we can tell you right now is anything that helps with pain short term is going to worsen it long term.

[00:11:00] Host Amber Smith: What if a person stops taking cannabis? Will their pain sensitivity, will it go back, or is the damage done already?

[00:11:09] Brian Johnson, MD: Same answer. We just discovered this.

So we can answer that about opioids. And unfortunately, a lot of opioid-induced hyperalgesia looks like it's permanent. Other people seem to get better over months and years. So the message here is be careful. Don't use something that helps your pain every day. You want to use it once in a while. You want to take an oxycodone to help you sleep because your back is really hurting -- fine. You want to smoke a joint -- no problem. Just be careful that drugs that you use frequently cause this opponent process.

[00:12:02] Host Amber Smith: A lot of patients and even medical providers are seeing cannabis as a treatment for pain. Is there evidence showing that it can help with that? Or, where did they get the idea of using cannabis for pain control in the first place?

[00:12:17] Brian Johnson, MD: Well, it's a flavor-of-the-week phenomenon. You know, anything that makes you feel good should be good for everything, right?

But unfortunately, it's like opioids were 20 years ago. Everyone was saying, gee, we've got a great drug, Oxycontin, that is magnificent for pain. Everyone should be on it. Twenty years later, unfortunately, they're saying the same thing about marijuana.

Are there good long term studies? There are a few. Ours is one, and we could find four other studies, and they all show the same thing.

[00:13:08] Host Amber Smith: Are recreational users of cannabis likely to develop increased pain sensitivity also, just like the daily users?

[00:13:18] Brian Johnson, MD: Yes, it happens. If you use heroin for fun, or if you use heroin because your back hurts, you're going to do the same thing to your brain. And that's true of marijuana too. If you use it every day or frequently, you're going to attack your own pain dampening cannabinoid system, and you're going to make more pain for yourself.

[00:13:47] Host Amber Smith: I know that you focused on chronic pain, but people also turn to medical cannabis for anxiety and depression. Is there evidence that it can help or that it might hurt in those situations?

[00:14:01] Brian Johnson, MD: The way I'd describe it is, the human brain seems to be set up to have all of us be slightly miserable. It's a survival thing. It makes you go out and do stuff to feel better. So whether it's anxiety, depression, pain, those are the three drivers of misery.

If you're slightly miserable and you win the lottery and you have a billion dollars, you'll be happy, but a year later, you'll be slightly miserable. So, if you use marijuana, for anxiety, depression, or pain, if you use it constantly, a year later, you'll be even more miserable with whatever you're using it for.

And there are good studies about that. There's more depression. There's more suicidality. There's even that prospective Australian study that took a baseline at zero and then looked four years later, the people who use marijuana were not only in more pain, but they were more anxious.

[00:15:17] Yanli Zhang-James, MD, PhD: Especially for people who use cannabis for long term, if you stop, the withdrawal symptoms include increased anxiety and all those bad feelings, right?

[00:15:29] Brian Johnson, MD: Yeah, so one way to put it is, withdrawal unmasks the opponent process. If you're in opioid withdrawal, you have more pain. If you're in marijuana withdrawal, you have more pain. In both cases, you've got more anxiety. It unmasks the changes that you've created in your own brain.

[00:15:55] Host Amber Smith: Is there a risk of becoming addicted to marijuana if you're using it daily?

[00:16:01] Brian Johnson, MD: Yes, absolutely. And, you know, it's interesting. What does it mean if you are addicted to marijuana? Well, the standard definition of addiction is repeated harm from use. So if you drink and it's always fun, that's great. Have a good time. If you drink and it keeps making trouble for you, alcoholism is repeated harm from drinking.

It's the same thing with marijuana. If you use it and it's always fun, have a great time. If you start to develop that amotivational syndrome, if you get the hyperemesis so that you're vomiting constantly, if it makes you psychotic, if it changes your blood vessels and you start to have strokes, if it makes you stupid and you can't remember anything, you're a high school student and as a freshman you got A's and now you're getting C's as a sophomore and you're headed for straight F's, the denial system says, whoa, I couldn't be vomiting because of marijuana. The doctor should look for what's really wrong. Or, I can't be flunking out of high school because of marijuana; I'm just not studying anymore.

It's the marijuana.

[00:17:43] Host Amber Smith: Well, what do you recommend be done for patients who have chronic pain and have been using cannabis daily, and now they've got this increased pain sensitivity. What can be done for them?

[00:17:58] Brian Johnson, MD: They should come to our addiction medicine service. It's terrific. It uses the cold pressor test. Psychotherapy is the main modality of treatment, but we can treat anything else. If you've got anxiety, pain, depression, ADHD (Attention Deficit Hyperactivity Disorder), those are immediately recognized and treated along with your pain. So just call up (315) 464 3130. And make an intake appointment and get some expert feedback.

[00:18:37] Host Amber Smith: Does the treatment typically include weaning the person off of cannabis?

[00:18:42] Brian Johnson, MD: No. You know, weaning is, you were smoking eight joints a day, so smoke seven for a week and then six for a week.

We routinely ask people and their support people, who are required to come with them, to stop the drugs and let us help you stop. You're going to go through marijuana withdrawal if you've been using it every day. And it's unpleasant. But there are medications that help, and we'll talk you through it. You'll come twice a week. And when you're in distress, every visit you see someone who can prescribe medication. And you have a 50-minute psychotherapy hour, so we'll collaborate with you and find our way through it.

[00:19:39] Host Amber Smith: Well, that's good to know. I appreciate both of you making time for this interview.

[00:19:45] Brian Johnson, MD: Well, thank you for having us.

[00:19:47] Yanli Zhang-James, MD, PhD: Thank you.

[00:19:49] Host Amber Smith: My guests have been Dr. Brian Johnson, a clinical professor emeritus of psychiatry and behavioral sciences and the recently retired director of addiction medicine at Upstate, and Dr. Yanli Zhang-James, a research associate professor of psychiatry and behavioral sciences. "The Informed Patient" is a podcast covering health, science, and medicine, brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe. Find our archive of previous episodes at upstate.edu/informed. This is your host, Amber Smith, thanking you for listening.