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Cannabis has become an integral part of pain medicine despite a lack of clear evidence to support its use, an expert said at the 2021 virtual American Academy of Pain Medicine 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, in a special .

The endo-cannabinoid system is involved in pain control at the peripheral, spinal, and supra-spinal levels, Eisenberg observed. "Cannabinoid receptor activity inhibits the ascending nociceptive transmission, activates the inhibitory descending pathways, and modifies the emotional component of pain which is important by itself."

Most clinical trials with medical cannabis have involved , Eisenberg noted, and experts don't agree on whether there's enough evidence to support cannabis as pain treatment. In March 2021, the International Association for the Study of Pain 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 view came from the National Academies," Eisenberg noted. After a substantial review of data, the 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 dysmotivational syndrome, or addiction, Eisenberg said. Other effects involve smoking hazards, pregnancy and maternity, cannabis hyperemesis effects, driving safety, and vascular events.

Driving and cardiovascular events are especially concerning, he noted. In Colorado, where cannabis is legal for medical and recreational purposes, involved in fatal crashes in 2018 tested positive for cannabis. An analysis of nine epidemiologic studies relating yielded an OR of 2.66. More recently, a simulator study in the Netherlands demonstrated that when healthy young occasional users vaped cannabis with 13.75 mg of tetrahydrocannabinol (THC), they had problems driving, including lane weaving, swerving, and overcorrecting.

Traditionally, cannabinoids are not viewed as life-threatening compounds, but changes in blood pressure and heart rate soon after consuming marijuana have been recorded, Eisenberg said. Reports on possible associations between cannabinoid consumption and stroke or myocardial infarction have emerged.

"What's worrisome is that these events occur in young patients who are otherwise healthy; they don't have cardiovascular risk factors," he noted. A review of all reported cannabis complications in France showed that nearly and involved mainly men in their 30s.

Cannabis strains now contain up to 20% THC, Eisenberg pointed out. Smoking 1 g of cannabis a day -- the equivalent of two cigarettes -- could expose a patient to up to 200 mg of THC a day. By contrast, the THC content of cannabis strains in 1999 was less than 6%.

"Doses exceeding 2o to 30 mg of THC may increase adverse events or induce tolerance without improving efficacy," Eisenberg said. The question for chronic pain patients who may use cannabis several times a day for extended periods then becomes "what do these high concentrations of THC do to them? This is an open question yet to be answered."

Recent studies have shown that lower doses of cannabis may be effective to treat chronic pain. In a small study in Israel, a metered dose inhaler that exposed neuropathic pain patients to showed a significant reduction in pain intensity that remained stable for 150 minutes. A post-marketing survey suggested that patients using this device experienced about 20% less pain that lasted at least 120 days, Eisenberg noted. (The device, known as the Syqe Inhaler, won for medical cannabis this week.)

Some patients benefit from medical cannabis in ways they have not benefited from any other pain interventions, Eisenberg noted. "The problem is that we cannot find predictors for good responses yet," he said. "Which patients are going to be responsive? What pain types? What constituents are going to give us the best results? We don't know."

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