Why Cannabis Holds Promise for Pain Management

By Benjamin Land, University of Washington Center for Cannabis Research

Drug overdose deaths from opioids continue to rise in the U.S. as a result of both the misuse of prescription opioids and the illicit drug market.

But an interesting trend has developed: Opioid emergency room visits drop by nearly 8% and opioid prescriptions are modestly lower in states where marijuana is legalized.

Marijuana is produced by the cannabis plant, which is native to Asia but is now grown throughout the world. Individuals use marijuana for both its psychoactive, euphoria-inducing properties and its ability to relieve pain.

Chemicals produced by the cannabis plant are commonly known as cannabinoids. The two primary cannabinoids that occur naturally in the cannabis plant are THC – the psychoactive compound in marijuana – and CBD, which does not cause the sensation of being high.

Many marijuana users say they take it to treat pain, suggesting that readily available cannabinoids could potentially be used to offset the use of opioids such as morphine and oxycodone that are commonly used in pain treatment. A safer, natural alternative to opioid painkillers would be an important step toward addressing the ongoing opioid epidemic.

Intriguingly however, research suggests that cannabis use could also lessen the need for opioids directly by interacting with the body’s own natural opioid system to produce similar pain-relief effects.

I am a neuropharmacology scientist who studies both opioids and cannabinoids as they relate to pain treatment and substance abuse. My research focuses on the development of drug compounds that can provide chronic pain relief without the potential for overuse and without the tapering off of effectiveness that often accompanies traditional pain medications.

How Opioids Work

Our bodies have their own built-in opioid system that can aid in managing pain. These opioids, such as endorphins, are chemicals that are released when the body experiences stress such as strenuous exercise, as well as in response to pleasurable activities like eating a good meal. But it turns out that humans are not the only organisms that can make opioids.

In the 1800s, scientists discovered that the opioid morphine – isolated from opium poppy – was highly effective at relieving pain. In the last 150 years, scientists have developed additional synthetic opioids like hydrocodone and dihydrocodeine that also provide pain relief.

Other opioids like heroin and oxycodone are very similar to morphine, but with small differences that influence how quickly they act on the brain. Fentanyl has an even more unique chemical makeup. It is the most powerful opioid and is the culprit behind the current surge in drug overdoses and deaths, including among young people.

Opioids, whether naturally produced or synthetic, produce pain relief by binding to specific receptors in the body, which are proteins that act like a lock that can only be opened by an opioid key.

One such receptor, known as the mu-opioid receptor, is found on pain-transmitting nerve cells along the spinal cord. When activated, mu-receptors tamp down the cell’s ability to relay pain information. Thus, when these opioids are circulating in the body and they reach their receptor, stimuli that would normally cause pain are not transmitted to the brain.

These same receptors are also found in the brain. When opioids find their receptor, the brain releases dopamine – the so-called “feel-good” chemical – which has its own receptors. This is in part why opioids can be highly addicting. Research suggests that these receptors drive the brain’s reward system and promote further drug-seeking. For people who are prescribed opiates, this creates the potential for abuse.

Opioid drugs, which include heroin, oxycodone and fentanyl, are highly addictive.

Opioid receptors are dynamically regulated, meaning that as they get exposed to more and more opioids, the body adapts quickly by deactivating the receptor. In other words, the body needs more and more of that opioid to get pain relief and to produce the feel-good response. This process is known as tolerance. The drive to seek more and more reward paired with an ever-increasing tolerance is what leads to the potential for overdose, which is why opioids are generally not long-term solutions for pain.

How THC and CBD Relieve Pain

Both THC and CBD have been shown in numerous studies to lessen pain, though – importantly – they differ in which receptors they bind to in order to produce these effects.

THC binds to cannabinoid receptors that are located throughout the central nervous system, producing a variety of responses. One of those responses is the high associated with cannabis use, and another is pain relief. Additionally, THC is believed to reduce inflammation in a manner similar to anti-inflammatory drugs like ibuprofen.

In contrast, CBD appears to bind to several distinct receptors, and many of these receptors can play a role in pain reduction. Importantly, this occurs without the high that occurs with THC.

Because they target different receptors, THC and CBD may be more effective working in concert rather than alone, but more studies in animal models and humans are needed.

Cannabinoids may also be helpful for other conditions as well. Many studies have demonstrated that cannabinoid drugs approved for medical use are effective for pain and other symptoms like spasticity, nausea and appetite loss.

Along with the pairing of THC and CBD, researchers are beginning to explore the use of those two cannabinoids together with existing opioids for pain management. This research is being done in both animal models and humans.

These studies are designed to understand both the benefits – pain relief – and risks – primarily addiction potential – of co-treatment with cannabinoids and opioids. The hope would be that THC or CBD may lower the amount of opioid necessary for powerful pain relief without increasing addiction risk.

For example, one study tested the combination of smoked cannabis and oxycontin for pain relief and reward. It found that co-treatment enhanced pain relief but also increased the pleasure of the drugs. This, as well as a limited number of other studies, suggests there may not be a net benefit.

However, many more studies of this type will be necessary to understand if cannabinoids and opioids can be safely used together for pain. Still, using cannabinoids as a substitution for opioids remains a promising pain treatment strategy.

The next decade of research will likely bring important new insights to the therapeutic potential of cannabinoids for chronic pain management. And as marijuana legalization continues to spread across the U.S., its use in medicine will undoubtedly grow exponentially.

Benjamin Land, PhD is a Research Associate Professor of Pharmacology at the University of Washington School of Medicine and the UW Center for Cannabis Research. Land receives funding from the National Institutes of Health for cannabinoid research, and has received cannabinoid related funding from the University of Washington Addiction and Drug Abuse Institute and SCAN Design Foundation.

This article originally appeared in The Conversation and is republished with permission.

The Conversation

Controversy Grows over Journal Article on Pain Treatment

By Pat Anson, Editor

It’s not uncommon for colleagues in the medical profession to disagree. Egos and different medical backgrounds can sometimes lead to heated discussions about the best way to treat patients. But those arguments are usually kept private. 

That is why it is so unusual for a prominent pain physician to publicly call for another doctor to resign or be fired from her faculty position at a prestigious medical school.

“I believe she should resign her academic post,” says Forest Tennant, MD, referring to Jane Ballantyne, MD, a professor at the University of Washington School of Medicine, who recently co-authored a controversial article in the New England Journal of Medicine (NEJM) that said reducing pain intensity should not be the goal of doctors who treat chronic pain. The article also suggests that patients should learn to accept their pain and move on with their lives.

“For somebody in her position as a professor at a university to call for physicians to quit treating pain – or pain intensity – whether acute, chronic, whether rich, poor, disabled or what have you, is totally inappropriate. And it’s an insult to the physicians of the world and an insult to patients. And frankly, she should not be a professor.” Tennant told Pain News Network.

“To suggest that physicians should no longer treat pain intensity and let patients suffer goes beyond any sort of decency or concern for humanity.”

Tennant is a pain management specialist who has treated patients for over 40 years at his pain clinic in West Covina, California. He’s authored over 300 scientific articles and books, is editor emeritus of Practical Pain Management, and is highly regarded  in the pain community for accepting difficult, hard-to-treat patients that other doctors have given up on.

dr. forest tennant

dr. forest tennant

Tennant was surprised the influential, peer-reviewed New England Journal of Medicine, which reaches over 600,000 people each week, even published the article.

I know that they’re biased and they’ve got all their medical device people there and all their academia and all that, but I think they have a responsibility also. They are supposedly representing medicine,” says Tennant. “Why do I have a medical degree if I’m not supposed to treat pain intensity? Give me an answer to that. She didn’t have an alternative did she?”

dr. jane ballantyne

dr. jane ballantyne

Exactly what Ballantyne and co-author Mark Sullivan, MD, meant to say is open to interpretation. Pain News Network has been unable to get comment from either about the controversy.

They began their article by saying “pain that can be relieved should be relieved,” but then veer off in another direction, stating that chronic pain should not be treated with opioid pain medication.

“Is a reduction in pain intensity the right goal for the treatment of chronic pain? We have watched as opioids have been used with increasing frequency and in escalating doses in an attempt to drive down pain scores — all the while increasing rates of toxic drug effects, exposing vulnerable populations to risk, and failing to relieve the burden of chronic pain,” they wrote, dismissing the pain intensity scales that are widely used by physicians to measure pain levels.

“We propose that pain intensity is not the best measure of the success of chronic-pain treatment. When pain is chronic, its intensity isn't a simple measure of something that can be easily fixed.”

Ballantyne and Sullivan offered no alternative “fixes” for pain treatment, other than patients learning to live with pain and sitting down for a chat with their doctors.

“Nothing is more revealing or therapeutic than a conversation between a patient and a clinician, which allows the patient to be heard and the clinician to appreciate the patient's experiences and offer empathy, encouragement, mentorship, and hope,” they wrote.

Angry Comments from Readers

The article infuriated both patients and physicians, including dozens who left angry comments on the NEJM website.

“Great job. I will be going into the coffin business thanks to these believers that people should suck it up. How NEJM even recognizes these people as doctors and not quacks is beyond me,” wrote Michael Shabi, who identified himself as a family practice physician.

“I take just enough narcotic pain meds to cut the edge off of my pain to be coherent enough to love my wife and respond to your constant misinformation. I have had 21 neurological surgeries and procedures and live in constant pain. So why in the heck do you people have such a problem in hearing us?” asked pain patient Kerry Smith.

“Only an idiot might conclude that one can dismiss the effects of living with a healthcare problem that reminds you of its presence with every move you make,” wrote Terri Lewis, PhD, a specialist in rehabilitation.

Both Ballantyne and Sullivan have lengthy careers in medicine and have been active in organizations that discourage the use of opioids. 

According to the University of Washington website, Ballantyne received her medical degree from the Royal Free Hospital School of Medicine in London and trained in anesthesiology at John Radcliffe Hospital in Oxford. She moved to Massachusetts General Hospital in Boston in 1990 and then to the University of Washington in 2011, as a Professor of Education and Research and as Director of the UW Pain Fellowship. 

Last year Ballantyne was named president of Physicians for Responsible Opioid Prescribing (PROP), an advocacy group funded by Phoenix House, which operates a chain of addiction treatment centers. She also serves as an expert adviser to the Centers for Disease Control and Prevention (CDC) as it develops controversial new guidelines that discourage primary care physicians from prescribing opioids. Ballantyne is one of five PROP board members who are advising the CDC on the guidelines.

Sullivan is a Professor of Psychiatry and Behavioral Sciences -- also at the University of Washington School of Medicine -- and is executive director of Collaborative Opioid Prescribing Education (COPE), a program that educates healthcare providers about safe opioid prescribing practices. He is also a PROP board member.

Sullivan has authored several research articles on opioids, including a recent one warning about the co-prescribing of sedatives and opioids.

“He’s not as well known,” says Tennant. “He doesn’t carry the public influence that she does. She’s sitting on federal committees, advising CDC that pain patients should not be treated and the intensity scale should not be used. I cannot imagine anyone making that statement. I can’t imagine the New England Journal of Medicine publishing it. The atrocity here is just awful.

dr. mark sullivan

dr. mark sullivan

“Any semblance of decency left among physicians in PROP, if that’s what they believe, then I think the whole organization ought to close its doors. I didn’t know they were going to say we didn’t want pain treated at all. They said they wanted to use opioids responsibly. Well, that’s fair. But that’s not what she said.”

Tennant is urging the pain community to contact Paul Ramsey, the CEO of UW Medicine and Dean of the School of Medicine to ask that Ballantyne be fired. He’s gotten a few takers, including Becky Roberts, who suffers from arachnoiditis.

“I do not feel she should be teaching new medical students. Professor influence is big when you are a student. I am sure if any one of them read her article, most were probably shocked,” Roberts said in an email to Pain News Network.

“They did not get into medicine because they are uncaring. Compassion for other human beings is why they went to medical school. To help heal human beings is their goal. I really do think she needs to be removed from that position. How long has she been teaching this kind of logic?”

The UW School of Medicine has about 4,500 students enrolled in undergraduate, professional, and post-graduate programs.