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

New guideline warns pain benefits of medical cannabis overstated

University of Alberta led guideline warns health risks may outweigh benefits, provides guidance on when (and when not to) prescribe.

February 15, 2018

Science Daily/University of Alberta Faculty of Medicine & Dentistry

A new medical guideline published today suggests Canada's family physicians should take a sober second thought before prescribing medical cannabis to most patients.

Published in Canadian Family Physician, "Simplified Guideline for Prescribing Medical Cannabinoids in Primary Care" states there is limited evidence to support the reputed benefits of medical marijuana for many conditions, and what benefits do exist may be balanced out or even outweighed by the harms.

"While enthusiasm for medical marijuana is very strong among some people, good-quality research has not caught up," said Mike Allan, director of evidence-based medicine at the University of Alberta and project lead for the guideline.

The guideline was created after an in-depth review of clinical trials involving medical cannabis and will be distributed to roughly 30,000 clinicians across Canada. It was overseen by a committee of 10 individuals, supported by 10 other contributors, and peer reviewed by 40 others, each a mixture of doctors, pharmacists, nurse practitioners, nurses and patients. The review examined cannabinoids for the treatment of pain, spasticity, nausea and vomiting, as well as their side-effects and harms.

Researchers found that in most cases the number of randomized studies involving medical cannabis is extremely limited or entirely absent. The size and duration of the studies that do exist are also very narrow in scope.

"In general we're talking about one study, and often very poorly done," said Allan. "For example, there are no studies for the treatment of depression. For anxiety, there is one study of 24 patients with social anxiety in which half received a single dose of cannabis derivative and scored their anxiety doing a simulated presentation. This is hardly adequate to determine if lifelong treatment of conditions like general anxiety disorders is reasonable."

According to the guideline, there is acceptable research for the use of medical cannabinoids to treat a handful of very specific medical conditions. They include chronic neuropathic (nerve) pain, palliative cancer pain, spasticity associated with multiple sclerosis or spinal cord injury, and nausea and vomiting from chemotherapy. Even in those specific cases, the benefits were found to be generally minor.

For nerve pain, 30 per cent of patients given a placebo saw a moderate improvement in their pain while 39 per cent experienced the same effect while on medical cannabinoids. In patients with muscle spasticity, 25 per cent of those taking a placebo saw a moderate improvement compared to 35 per cent on medical cannabis. The use of medical cannabis was best supported in its use for chemotherapy patients experiencing nausea and vomiting. Just under half of patients using cannabinoids for their symptoms had an absence of nausea and vomiting compared to 13 per cent on placebo.

"Medical cannabinoids should normally only be considered in the small handful of conditions with adequate evidence and only after a patient has tried of number of standard therapies," said Allan. "Given the inconsistent nature of medical marijuana dosing and possible risks of smoking, we also recommend that pharmaceutical cannabinoids be tried first before smoked medical marijuana."

While the researchers found evidence supporting the use of medical cannabinoids to be limited, side-effects were both common and consistent. About 11 per cent of patients were not able to tolerate medical cannabinoids, versus three per cent of those taking placebo. Common effects included sedation (50 per cent versus 30 per cent), dizziness (32 per cent versus 11 per cent) and confusion (nine per cent versus two per cent).

"This guideline may be unsatisfactory for some, particularly those with polarized views regarding medical cannabinoids," said Allan.

He added that those who oppose the use of cannabinoids for medical therapy may be disappointed that the guideline considers medical cannabinoids in specific cases. Others, who feel cannabinoids are highly effective and don't pose any risk, may be frustrated that the guideline doesn't advocate their use sooner or for a broader range of conditions.

"Better research is definitely needed -- randomized control trials that follow a large number of patients for longer periods of time. If we had that, it could change how we approach this issue and help guide our recommendations."

https://www.sciencedaily.com/releases/2018/02/180215153923.htm

Smoking marijuana provides more pain relief for men than women

August 18, 2016

Science Daily/Columbia University Medical Center

Men had greater pain relief than women after smoking marijuana, a new study has found. Despite differences in pain relief, men and women did not report differences in how intoxicated they felt or how much they liked the effect of the active cannabis.

Researchers from Columbia University Medical Center (CUMC) found that men had greater pain relief than women after smoking marijuana.

Results of the study were recently published online in Drug and Alcohol Dependence.

"These findings come at a time when more people, including women, are turning to the use of medical cannabis for pain relief," said Ziva Cooper, PhD, associate professor of clinical neurobiology (in psychiatry) at CUMC. "Preclinical evidence has suggested that the experience of pain relief from cannabis-related products may vary between sexes, but no studies have been done to see if this is true in humans."

In this study, the researchers analyzed data from two double-blinded, placebo-controlled studies looking at the analgesic effects of cannabis in 42 recreational marijuana smokers. After smoking the same amount of either an active or placebo form of cannabis, the participants immersed one hand in a a cold-water bath until the pain could no longer be tolerated. Following the immersion, the participants answered a short pain questionnaire.

After smoking active cannabis, men reported a significant decrease in pain sensitivity and an increase in pain tolerance. Women did not experience a significant decrease in pain sensitivity, although they reported a small increase in pain tolerance shortly after smoking.

Despite differences in pain relief, men and women did not report differences in how intoxicated they felt or how much they liked the effect of the active cannabis.

The authors noted that additional studies in both men and women are needed to understand the factors that impact the analgesic effects of cannabinoids, the active chemicals in cannabis products, including strength, mode of delivery (smoked versus oral), frequency of use and type of pain measured.

"This study underscores the importance of including both men and women in clinical trials aimed at understanding the potential therapeutic and negative effects of cannabis, particularly as more people use cannabinoid products for recreational or medical purposes," said Dr. Cooper.

https://www.sciencedaily.com/releases/2016/08/160818165936.htm