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mellowsong
11-02-07, 11:17 PM
October 31, 2007 One of the first dose-response studies of cannabis in humans has found a window of efficacy within which healthy volunteers experienced relief from experimentally induced pain. But although mid-range doses provided some pain relief, high doses appeared to exacerbate pain.
"This study suggests that there is a window of modest analgesia for smoked cannabis, with lower doses decreasing pain and higher doses increasing pain," the researchers, with first author Mark Wallace, MD, professor of anesthesiology at the University of California, San Diego (UCSD), conclude in their report.
The study is published in the November issue of Anesthesiology.
Mimicking Neuropathic Pain
The study included 15 male and female occasional pot smokers (they had been exposed to cannabis in the past 6 months but not in the past 30 days). In 4 separate sessions, the volunteers randomly smoked a low-, medium-, and high-dose marijuana cigarette (2%, 4%, and 8% respectively of delta-9-tetrahydrocannabinol [THC] by weight) or a placebo cigarette that smelled and tasted like marijuana but did not contain THC.
Five minutes after subjects smoked each cigarette, Dr. Wallace injected capsaicin, a derivative of hot chili pepper, under the skin of each volunteer's right arm. Capsaicin mimics neuropathic pain a brief, intense pain followed by a longer-lasting secondary pain that plagues many patients with HIV/AIDS, diabetes, and shingles. He then took blood samples, pain reports (spontaneous and elicited), and other data from the subjects. Forty-five minutes after smoking, subjects were "stung" again on their left arm and the same information was collected.
There was no effect on pain levels 5 minutes after smoking, regardless of the dose, although patients tended to report a fair degree of "highness," said Dr. Wallace, who is also program director for the UCSD Center for Pain Medicine. After 45 minutes, volunteers reported lower levels of highness and varying degrees of pain relief. "The low dose had no effect there was no difference from placebo, while the medium dose reduced their pain and the high dose increased their pain," he told Medscape Neurology & Neurosurgery.
A significant negative correlation was seen between pain perception and THC levels after adjustment for the overall dose effects, the authors note.
Mechanism Unclear
Dr. Wallace said he is not sure why the volunteers reported more pain with higher THC blood levels. "Maybe the high doses were causing a little more paranoia," which counteracted the analgesic effects, he said. Or the cannabis may contain a compound not measured in the study that led to pain at the higher dose. Dr. Wallace also did not know whether the pain relief would have eventually kicked in with the high dose, because subjects were tested only to 45 minutes.
The study shows that cannabis does work to curb pain at certain doses. However, it does not mean it will work in multiple sclerosis patients, cancer patients, or others who suffer pain on a regular basis, he said. "My study does not tell us one way or another that this is going to work in clinical pain. We still have a way to go," said Dr. Wallace.
However, it provides valuable information to use in future studies. Dr. Wallace has received a grant from the Center for Medicinal Cannabis Research, which also funded this study, to look at effects of inhaled (vaporized) cannabis in pain patients.
In general, pain studies are difficult to carry out because there is such a wide range of responses among pain patients, Dr. Wallace said. To date, most pain research has been limited to animal studies. Studies that have involved human subjects "are few and far between," he said, and have generally been very small, poorly controlled, and included only single doses. "This was one of the first studies looking at the dose-response effect," he added.
Precise Dosages Required
Researchers for this study also looked at neuropsychological functioning in the 15 subjects. "Although patients were reporting highness, there were no significant effects on their neurocognitive functioning," said Dr. Wallace. This, he noted, would be an advantage over currently marketed pain relievers that have mind-altering effects or, like opioids, come with a myriad of problems related to abuse, dependence, and withdrawal.
For this and other reasons, Dr. Wallace said, cannabis is a valuable tool in modern pain control. But he was critical of the current system that allows cannabis for medicinal purposes but does not involve pharmacists in dispensing it. "Cannabis is a medicine that should be in the hands of a pharmacist," said Dr. Wallace, "I'm not comfortable prescribing it, not because I think it's harmful or don't think it's useful, but I wouldn't prescribe any medication if I didn't know where it came from."
The cannabis that Dr. Wallace used in his study came from government sources. "I knew exactly what I was giving them. I knew the concentration of each cigarette, the exact dose," he said.

The research was supported by a grant from the University of California Center for Medicinal Cannabis Research, La Jolla, California.
Anesthesiology. 2007;107:785-796.

mellowsong
11-02-07, 11:21 PM
I have never smoked pot personally BUT when I was working Hospice, there was one patient with end stage pancreatic cancer who smoked it regularly. He was on Oxycontin and all kinds of other stuff, but he said nothing helped him like a "joint", I could see the difference in him and it wasn't just because he was "high". I just thought this article was interesting, because, he had the THC capsules, but he said smoking the joint did a lot more for him. THC is used to increase appetite and control nausea in terminal patients.