Whether marijuana helps with pain is unclear
Daily users with severe pain report worsening health
April 8, 2020
Science Daily/Ohio State University
Medical marijuana users who say they have high levels of pain are more likely than those with low pain to say they use cannabis three or more times a day, a new study finds.
However, daily marijuana users with severe pain also reported their health had become worse in the past year.
The results don't necessarily mean that marijuana is not effective in treating at least some kinds of pain, according to the researchers. But it suggests more research is needed before marijuana is accepted as an effective treatment for severe pain.
"It's not clear if marijuana is helping or not," said Bridget Freisthler, co-author of the study and professor of social work at The Ohio State University.
"The benefits aren't as clear-cut as some people assume."
The study was published recently in the International Journal of Drug Policy.
One issue is the complex relationship between pain, marijuana use and self-reported health, said Alexis Cooke, lead author of the study and postdoctoral scholar in psychiatry at the University of California, San Francisco.
"Having high chronic pain is related to poorer health, so it may be that people who are using marijuana more often already had worse health to begin with," Cooke said.
"There are still a lot of questions to answer."
The study involved a survey of 295 medical marijuana dispensary patients in Los Angeles. The surveys were conducted in 2013, when California allowed marijuana use only for medical purposes.
All participants were asked how often they used marijuana; rated how their current health compared to one year ago (on a five-point scale from "much better" to "much worse"); and were asked two questions about their pain levels. Based on their answers, the researchers rated participants' pain as low, moderate or high.
Among those surveyed, 31 percent reported high pain, 24 percent moderate pain, and 44 percent were in the low-pain category.
Daily marijuana use was reported by 45 percent of the sample, and 48 percent said they used three or more times per day.
The percentage of participants who used marijuana every day did not differ by pain categories. But about 60 percent of those who reported high pain used the drug three or more times a day, compared to 51 percent of those with moderate pain and 39 percent of those in the low-pain group.
Findings showed no association between daily marijuana use and change in health status among those with low levels of pain. But daily marijuana use was linked to worsening health status among those reporting high levels of pain.
However, strangely, there was no association between how often participants used marijuana per day and changes in health status. There's no easy explanation for this, Freisthler said.
"It shows how little we know about marijuana as medicine, how people are using it, the dosages they are receiving and its long-term effects," she said.
People use marijuana for a variety of different types of pain, including cancer, joint pain, HIV and nerve pain. Researchers don't know if marijuana has different effects on different causes of pain, Cooke said.
"Chronic pain is also associated with depression and anxiety. Marijuana may help with these problems for some people, even if it doesn't help with the pain," she said.
In addition, marijuana use seems to help people who have lost their appetite due to pain or nausea caused by cancer drugs.
"It may not be the pain that patients are trying to address," Cooke said.
The results do suggest we need to know more about the link between marijuana and pain relief, Freisthler said.
"Particularly since the opioid crisis, some people have been touting marijuana as a good substitute for opioids for people in pain," she said.
"But our study suggests we don't know that marijuana is helping to address pain needs."
https://www.sciencedaily.com/releases/2020/04/200408145805.htm
Medical marijuana could help patients reduce pain with opiates
December 6, 2011
Science Daily/University of California - San Francisco
A UCSF study suggests patients with chronic pain may experience greater relief if their doctors add cannabinoids -- the main ingredient in cannabis or medical marijuana -- to an opiates-only treatment. The findings, from a small-scale study, also suggest that a combined therapy could result in reduced opiate dosages.
More than 76 million Americans suffer from chronic pain -- more people than diabetes, heart disease and cancer combined, according to the National Centers for Health Statistics.
"Pain is a big problem in America and chronic pain is a reason many people utilize the health care system," said the paper's lead author, Donald Abrams, MD, professor of clinical medicine at UCSF and chief of the Hematology-Oncology Division at San Francisco General Hospital and Trauma Center (SFGH). "And chronic pain is, unfortunately, one of the problems we're least capable of managing effectively."
In a paper published this month in Clinical Pharmacology & Therapeutics, researchers examined the interaction between cannabinoids and opiates in the first human study of its kind. They found the combination of the two components reduced pain more than using opiates alone, similar to results previously found in animal studies.
Researchers studied chronic pain patients who were being treated with long-acting morphine or long-acting oxycodone. Their treatment was supplemented with controlled amounts of cannabinoids, inhaled through a vaporizer. The original focus was on whether the opiates' effectiveness increased, not on whether the cannabinoids helped reduce pain.
"The goal of the study really was to determine if inhalation of cannabis changed the level of the opiates in the bloodstream," Abrams said. "The way drugs interact, adding cannabis to the chronic dose of opiates could be expected either to increase the plasma level of the opiates or to decrease the plasma level of the opiates or to have no effect. And while we were doing that, we also asked the patients what happened to their pain."
Abrams and his colleagues studied 21 chronic pain patients in the inpatient Clinical and Transitional Science Institute's Clinical Research Center at SFGH: 10 on sustained-release morphine and 11 on oxycodone. After obtaining opiate levels from patients at the start of the study, researchers exposed them to vaporized cannabis for four consecutive days. On the fifth day, they looked again at the level of opiate in the bloodstream. Because the level of morphine was slightly lower in the patients, and the level of oxycodone was virtually unchanged, "one would expect they would have less relief of pain and what we found that was interesting was that instead of having less pain relief, patients had more pain relief," Abrams said. "So that was a little surprising."
The morphine group came in with a pain score of about 35, and on the fifth day, it decreased to 24 -- a 33 percent reduction. The oxycodone group came in with an average pain score of about 44, and it reduced to 34 -- a drop of 20 percent. Overall, patients showed a significant decrease in their pain.
"This preliminary study seems to imply that people may be able to get away perhaps taking lower doses of the opiates for longer periods of time if taken in conjunction with cannabis," Abrams said.
Opiates are very strong powerful pain medicines that can be highly addictive. They also can be deadly since opiates sometimes suppress the respiratory system.
As a cancer doctor, Abrams was motivated to find safe and effective treatments for chronic pain. Patients in the cannabis-opiates study experienced no major side effects such as nausea, vomiting or loss of appetite.
"What we need to do now is look at pain as the primary endpoint of a larger trial," he said. "Particularly I would be interested in looking at the effect of different strains of cannabis."
For instance, Delta 9 THC is the main psychoactive component of cannabis but cannabis contains about 70 other similar compounds with different effects. One of those is cannabidiol, or CBD. It appears to be very effective against pain and inflammation without creating the "high" created by THC.
"I think it would be interesting to do a larger study comparing high THC versus high CBD cannabis strains in association with opiates in patients with chronic pain and perhaps even having a placebo as a control," Abrams said. "That would be the next step."
Abrams is the lead author of the paper; co-authors are Paul Couey, BA, and Mary Ellen Kelly, MPH, of the UCSF Division of Hematology-Oncology at SFGH; Starley Shade, PhD, of the UCSF Center for AIDS Prevention Studies; and Neal Benowitz, MD, of the UCSF Division of Clinical Pharmacology and Experimental Therapeutics.
The study was supported by funds from the National Institutes on Drug Abuse (NIDA), a subsidiary of the National Institutes of Health (NIH).
Major Components of Cannabis
· Delta-9 Tetrahydrocannabinol (Delta-9 THC)-- It is the main psychoactive component of cannabis with mild to moderate painkilling effects. It also helps treat nausea associate with cancer chemotherapy and to stimulate appetite. It induces feelings of euphoria. Potential side effects include accelerated heartbeat, panic, confusion, anxiety and possible paranoia.
· Cannabidiol (CBD)- It is a major, non-psychoactive component of cannabis that helps shrink inflammation and reduce pain without inducing the euphoria effects of THC. It has been used to treat rheumatoid arthritis, inflammatory bowel diseases, psychotic disorders and epilepsy. Larger amounts of CBD can relax the mind and body without causing negative side effects associated with THC.
· Cannabinol (CBN)-- It is a secondary psychoactive component of cannabis. It is not associated with painkilling effects of THC or CBD. CBN is formed as THC ages. Unlike the euphoria effects of THC, CBN can induce headaches and a sense of lethargy.
· Tetrahydrocannabivarin (THCV) -- It is found primarily in strains of African and Asian cannabis. THCV heightens the intensity of THC effects and the speed in which the component is delivered, but also causes the sense of euphoria to end sooner.
https://www.sciencedaily.com/releases/2011/12/111206151448.htm
Cannabis pain relief without the 'high'
Mechanism of cannabidiol for safe pain relief without side effects
October 24, 2018
Science Daily/McGill University Health Centre
In the wake of cannabis legalization, a team of scientists at the Research Institute of the McGill University Health Centre (MUHC) and McGill University have delivered encouraging news for chronic pain sufferers by pinpointing the effective dose of marijuana plant extract cannabidiol (CBD) for safe pain relief without the typical "high" or euphoria produced by the THC. The findings of their study have been published in the journal PAIN (The Journal of the International Association for the Study of Pain).
Cannabis indica and sativa are the two main cannabis strains that produce the pharmacological principles known as tetrahydrocannabinol (THC) and cannabidiol (CBD). Dr. Gabriella Gobbi's team demonstrated that CBD does not act on the CB1 cannabinoid receptors like THC but through the mechanism that binds specific receptors involved in anxiety (serotonin 5-HT1A) and pain (vanilloid TRPV1). Researchers were able to extrapolate the exact dosage of CBD displaying analgesic and antianxiety properties without the risk of addiction and euphoria classically produced by the THC.
"We found in animal models of chronic pain that low doses of CBD administered for seven days alleviate both pain and anxiety, two symptoms often associated in neuropathic or chronic pain," says first author of the study Danilo De Gregorio, a post-doctoral fellow at McGill University in Dr. Gobbi's laboratory.
Lead author Dr. Gobbi, a researcher in the Brain Repair and Integrative Neuroscience (BRaIN) Program of the RI-MUHC, sees this as advancement for the evidence-based application of cannabis in medicine with CBD offering a safe alternative to THC and opioids for chronic pain, such as back pain, sciatica, diabetic, cancer and post-trauma pain.
"Our findings elucidate the mechanism of action of CBD and show that it can be used as medicine without the dangerous side effects of the THC," says Dr. Gobbi, who is also Professor of Psychiatry at the Faculty of Medicine at McGill University and staff psychiatrist at the MUHC. "This research is a new advancement for an evidence-based application of cannabis in medicine."
Despite widespread public usage, little clinical studies exist on CBD, which became legal in Canada on October 17, 2018, following the passage of Canada's Cannabis Act.
"There is some data showing that CBD provides pain relief for humans but more robust clinical trials are needed ," says Dr. Gobbi, a recent grant recipient for her study of the pharmalogical effects of CBD.
https://www.sciencedaily.com/releases/2018/10/181024163625.htm
An alternative to medical marijuana for pain?
March 4, 2015
Science Daily/Elsevier
Medical marijuana is proliferating across the country due to the ability of cannabis ingestion to treat important clinical problems such as chronic pain. However, negative side effects and the development of tolerance limit the widespread therapeutic use of Δ9-tetrahydrocannabinol (Δ9-THC), the major psychoactive ingredient in cannabis.
THC's side effects are produced via its actions at cannabinoid CB1 receptors in the brain. Thus, scientists theorized that an agent with similar mechanistic actions, but that activate CB2 receptors instead, may eliminate the unwanted side effects while maintaining an equivalent level of efficacy.
Dr. Andrea Hohmann and her colleagues at Indiana University tested this strategy and found that, unlike Δ9-THC, repeated dosing with the cannabinoid CB2 agonist AM1710 suppresses chemotherapy-induced pain in mice without producing tolerance, physical withdrawal, motor dysfunction, or hypothermia. Moreover, the therapeutic effects of AM1710 were preserved in mice lacking CB1 receptors but absent in mice lacking CB2 receptors.
Their findings are reported in the current issue of Biological Psychiatry.
"Our study is important because it demonstrates beyond doubt that activation of cannabinoid CB2 receptors suppresses neuropathic pain without producing signs of physical dependence (i.e., a withdrawal syndrome) or other unwanted side effects associated with activation of CB1 receptors in the brain," said Hohmann.
Their studies used animals that were treated with a chemotherapeutic agent (paclitaxel) to produce pain. When animals were given AM1710, a CB2 agonist, its pain-suppressive effects were fully preserved and its therapeutic effects were maintained even after repeated dosing.
Alternatively, and as expected, when animals were given Δ9-THC, they developed complete tolerance to the pain-suppressing effects of THC and with repeated dosing, THC was no longer effective in suppressing neuropathic pain.
When the THC-treated animals were challenged with a drug that blocks CB1 receptors in the brain, the animals showed a prominent withdrawal syndrome, indicating signs of physical dependence following removal of THC. Strikingly, this was not the case with the CB2 agonist; blocking either CB1 or CB2 receptors produced no signs of withdrawal in animals treated chronically with the CB2 agonist.
Hohmann added, "We think our data suggests that CB2 receptors are an important target for suppressing chronic pain without unwanted side effects (e.g. psychoactivity, addiction)."
"It is important to know whether the benefits of cannabis ingestion for pain could be attributed in large part to the stimulation of CB2 receptors," commented Dr. John Krystal, Editor of Biological Psychiatry. "CB2 agonists, in theory, would present less risk regarding addiction and intoxication than the ingestion of cannabis or THC."
More work will be necessary before CB2 receptor agonists could be prescribed for use in humans, but for now, these data support the therapeutic potential of CB2 agonists for managing pain without the adverse effects associated with cannabis.
https://www.sciencedaily.com/releases/2015/03/150304075336.htm