Patients with chronic pain find relief with cannabis, despite varying evidence
Cannabis has become an integral part of pain medicine despite the lack of clear evidence to support its use, an expert said at the 2021 American Academy of Pain Medicine virtual meeting.
“Some patients with chronic pain clearly benefit from medical cannabis,” said Elon Eisenberg, MD, of Rambam Health Care and the Technion Israel Institute of Technology in Haifa, during a special session on cannabis.
The endo-cannabinoid system is involved in pain control at the peripheral, spinal and supra-spinal levels, Eisenberg observed. “The activity of cannabinoid receptors inhibits ascending nociceptive transmission, activates inhibitory descending pathways, and alters the emotional component of pain that is important in itself.”
Most clinical trials with medical cannabis have involved neuropathic pain, Eisenberg noted, and experts disagree that there is enough evidence to support cannabis as a pain treatment. In March 2021, the International Association for the Study of Pain (IASP) released a statement saying it did not endorse the general use of cannabinoids to treat pain due to a lack of evidence from high quality research.
“On the other hand, an opposing opinion came from the National Academies,” Eisenberg noted. After an extensive review of the data, the National Academies of Science, Engineering and Medicine concluded in 2017 that there is “substantial evidence that cannabis is an effective treatment for chronic pain in adults.”
About 10% of medicinal cannabis users experience adverse events that include psychotomimetic effects, anxiety and psychosis, cognitive dysmotivation syndrome, or addiction, Eisenberg said. Other effects include risks from smoking, pregnancy and motherhood, hyperemesis effects of cannabis, safe driving and vascular events.
Driving and cardiovascular events are of particular concern, he noted. In Colorado, where cannabis is legal for medical and recreational purposes, 13.5% of drivers involved in fatal crashes in 2018 tested positive for cannabis. An analysis of nine epidemiological studies linking marijuana use to the risk of a car crash gave an OR of 2.66. More recently, a simulator study in the Netherlands demonstrated that when young, healthy, occasional users vaporized cannabis with 13.75 mg of tetrahydrocannabinol (THC), they had driving problems, including lane weaving, deviations and overcorrection.
Traditionally, cannabinoids have not been viewed as life-threatening compounds, but changes in blood pressure and heart rate soon after marijuana use have been recorded, Eisenberg said. Reports of possible associations between cannabinoid consumption and stroke or myocardial infarction have emerged.
“What is worrying is that these events are occurring in young patients who are otherwise healthy; they don’t have cardiovascular risk factors, ”he noted. A review of all the cannabis-related complications reported in France showed that almost 2% were cardiovascular and mainly affected men in their 30s.
Cannabis strains now contain up to 20% THC, Eisenberg pointed out. Smoking 1 g of cannabis per day – the equivalent of two cigarettes – could expose a patient to up to 200 mg of THC per day. In contrast, the THC content of cannabis strains in 1999 was less than 6%.
“Doses above 20-30 mg THC may increase adverse events or induce tolerance without improving efficacy,” said Eisenberg. The question for patients with chronic pain who may use cannabis multiple times a day for prolonged periods then becomes “what are these high levels of THC doing to them?” It is an open question which remains to be answered ”.
Recent studies have shown that lower doses of cannabis can be effective in treating chronic pain. In a small study in Israel, a metered dose inhaler that exposed patients with neuropathic pain to precise doses of low-dose THC showed a significant reduction in pain intensity that remained stable for 150 minutes. A post-market survey suggested that patients using this device felt about 20% less pain for at least 120 days, Eisenberg noted. (The device, known as the Syqe inhaler, got Health Canada approval for medical cannabis this week.)
Some patients benefit from medical cannabis in a way that they have not benefited from any other pain intervention, Eisenberg noted. “The problem is, we can’t yet find predictors of good answers,” he said. “Which patients will respond? What types of pain? What constituents will give us the best results? We don’t know.”
Eisenberg said he received research grants from Rafa Laboratories, Syqe Medical Ltd., Israel Pain Association, and Teva Israel Ltd.