The review formed the basis for an international guideline with a weak recommendation from an expert panel to offer a trial of non-inhaled medical cannabis or cannabinoids, in addition to standard care and management (if not sufficient) to people living with chronic cancer or non-cancer pain.
"We were surprised to find that use of cannabis for chronic pain was associated with very modest benefits, given its widespread use and the enthusiasm that some of our patient partners expressed for medical cannabis," Dr. Jason Busse and Dr. Li Wang of McMaster University in Hamilton, Ontario told Reuters Health by email. "However, an associated review of patients' values and preferences for medical cannabis found that people who live with chronic pain place very high value on small improvements in their symptoms." (https://bit.ly/3CAKLV0)
"Research exploring factors that may allow for more targeted use of medical cannabis (e.g., identifying patients more likely to benefit, and less likely to be harmed) is needed," they said.
As reported in The BMJ, the team analyzed randomized clinical trials of medical cannabis or cannabinoids versus any non-cannabis control for chronic pain at least one month follow-up.
Thirty-two trials with 5,174 adult patients were included, 29 of which compared medical cannabis or cannabinoids with placebo. Medical cannabis was administered orally (30 studies) or topically (two).
Indications were non-cancer-related pain (28) and cancer-related pain (four). Follow-up ranged from 1 to 5.5 months.
Compared with placebo, non-inhaled medical cannabis probably results in a small increase in the proportion of patients experiencing at least the minimally important difference (MID) of 1 cm (on a 10 cm visual analogue scale) in pain relief (modeled risk difference of 10%).
Medical cannabis taken orally results in a very small improvement in physical functioning (4% modeled RD) for achieving at least the MID of 10 points on the 100-point SF-36 physical functioning scale, and a small improvement in sleep quality (6% modeled RD) for achieving at least the MID of 1 cm on a 10 cm VAS.
Medical cannabis taken orally does not improve emotional, role, or social functioning (high certainty evidence) and probably (moderate certainty) results in a small increased risk of transient cognitive impairment (RD 2%), vomiting (RD 3%), drowsiness (RD 5%), impaired attention (RD 3%), and nausea (RD 5%), but not diarrhea; high certainty evidence shows greater increased risk of dizziness (RD 9%) for trials with <3 months follow-up versus RD 28% for trials with at least three months follow-up.
Dr. Edeltraut Kroger of Laval University in Quebec, coauthor of a related editorial, commented in an email to Reuters Health, "The guidance combines evidence from trials of cannabis/cannabinoids in patients with all types of chronic pain. (Yet) musculoskeletal pain, the most frequent type of chronic pain, was studied only in a minority of the studies."
Because evidence on medical cannabis effectiveness in chronic musculoskeletal pain is sparse, previous guidelines did not recommend it. However, she noted, "The new BMJ guidance took patient views into account: given limited therapeutic options, patients may want to try treatment with cannabis even if it offers only small benefits and despite possible harms."
"But listening to patients also means watching out for harms," she added. "Specific vulnerable populations may be at a higher risk. Knowledge is just emerging on the effects of cannabis products on the young brain and possible psychotic episodes, or on major harms for the heart."
After additional research on safety and effectiveness, she said, "standardization and optimal dosing of cannabis products will be necessary before cannabis could be used more widely in medicine."
Dr. Mark Calarco, National Medical Director of American Addiction Centers, also commented by email. "It is premature to advocate for universal adoption of cannabinoids for chronic pain based on this one study as the findings were very weak. In particular, the authors found no reduction in the use of opioids when cannabis products were added to the treatment regimen."
Regarding the weak evidence on pain improvement, Dr. Calarco suggests that subjects may have been underdosed in many of the trials; both tetrahydrocannabinol and cannabidiol were used in some studies, making it difficult to know which compound was responsible for pain control (or lack thereof); and only oral and topical cannabinoids, which can have delayed absorption, delayed onset of action, and suboptimal efficacy compared to smoked/vaped cannabinoids, were evaluated.
He also noted that in people with substance abuse disorders, "administration of any drug that causes a dopamine spike - including cannabis - can result in relapse or addiction. Therefore, clinicians must proceed with great care when treating this population."
SOURCE: https://bit.ly/3CAKPUK, https://bit.ly/3CLiZFc and https://bit.ly/3i6Qrhz The BMJ, online September 8, 2021.
By Marilynn Larkin
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