Arthritis: Cannabinoids and CBD Research Overview. by ECHO Overview of Arthritis. Arthritis is a States That Have Approved Medical Cannabis for Arthritis. Osteoarthritis, the most common type of arthritis, is the wear and tear of joint cartilage. Studies have shown cannabis helps reduce osteoarthritic. Dustin Sulak, DO, is a doctor on the front lines of medical marijuana. at the Mayo Clinic and author of a review of medical marijuana research. fibromyalgia, multiple sclerosis, HIV, rheumatoid arthritis, and spinal injuries.
Overview Marijuana Research Arthritis – Medical
We did not include synthesized, pharmaceutically prepared cannabinoids, such as dronabinol or nabilone, because they are not available in dispensaries, and the efficacy of synthetic cannabinoid preparations for chronic pain was examined in 2 recent reviews 10 , We broadly defined plant-based cannabis preparations to include any preparation of the cannabis plant itself for example, cannabis cigarettes and oils or cannabis plant extracts to capture the variety of products available in U.
To address the efficacy of cannabis for treating chronic pain, we included controlled clinical trials and cohort studies. This review focuses specifically on pain outcomes, although our larger report and search were designed to include other outcomes, such as sleep and quality of life 8. Because data about harms in the general population might be applicable to chronic pain populations, we examined harms broadly and reported whether the data were derived from studies of the general population or populations with chronic pain.
Disagreements were resolved by a third reviewer. Given the broad scope of this review, we summarized data from existing systematic reviews. We included only reviews that clearly reported their search strategy, reported inclusion and exclusion criteria, and appraised the internal validity of the included trials We prioritized the most recent reviews and those with the broadest scope. In addition, we included individual studies that met inclusion criteria and either were published after the end search date of the included review or were not included in a prior systematic review.
For all reports, 2 investigators abstracted details of study design, setting, patient population, intervention, and follow-up, as well as important co-interventions, health outcomes, health care use, and harms. Two reviewers independently assessed each trial including those that were identified from a prior systematic review as having low, high, or unclear risk of bias ROB for the pain outcome using a tool developed by the Cochrane Collaboration Disagreements were resolved by consensus.
To assess the ROB of observational studies for the pain outcome, we considered potential sources of bias most relevant to this evidence base and adapted existing assessment tools 15 , 16 Supplement 3. We assessed the magnitude of statistical heterogeneity among the studies using the standard Cochran chi-square test, the I 2 statistic Clinical heterogeneity, variation in outcomes reported, and the small number of trials precluded meta-analysis for other subgroups and outcomes, so we reported these qualitatively.
After group discussion, we classified the overall strength of evidence for each outcome as high, moderate, low, or insufficient on the basis of the consistency, coherence, and applicability of the body of evidence as well as the internal validity of individual studies 19 , Department of Veterans Affairs Quality Enhancement Research Initiative supported the review but had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review, and approval of the manuscript; or decision to submit the manuscript for publication.
Table 1 provides study-level details and the ROB rating for each of the chronic pain trials. Table 2 summarizes findings, including the ROB rating, by pain subgroup. Table 3 summarizes the harms in both pain and general populations. Supplement 5 provides additional study-level data from pain studies not included in prior reviews and from studies on general harms. We identified 22 RCTs 21—42 from 2 recently published systematic reviews 10 , 11 and an additional 8 studies 5 RCTs [ 43—47 ] and 3 cohort studies [ 48—50 ] that met our inclusion criteria and were not included in prior reviews.
The primary methods of continuous pain assessment were a visual analogue scale from 0 to mm and a numerical rating scale NRS from 0 to 10 where 0 indicated no pain and 10 indicated the worst possible pain. Thirteen trials examined the effects of cannabis-based preparations on neuropathic pain Table 1.
Participants had central or peripheral neuropathic pain related to various health conditions. Overall, we found low-strength evidence that cannabis may alleviate neuropathic pain in some patients Table 2. Studies generally did not find clinically significant between-group differences on continuous pain scales, but a higher proportion of intervention patients had clinically significant pain relief up to several months later.
Most studies were small, few reported outcomes beyond 2 to 3 weeks, and none reported long-term outcomes. In the largest RCT, patients with peripheral neuropathic pain self-titrated nabiximols up to a maximum dosage of 24 sprays per day or received a placebo Those who completed the study 79 in the nabiximols group and 94 in the placebo group and responded positively to the intervention had a significant decrease in pain odds ratio, 1. However, among all participants, including those who did not have an intervention response, the reduction in the NRS pain score did not reach clinical or statistical significance.
Cannabis users had a reduction in average pain intensity using a visual analogue scale from 0 to 10 that was stable across 4 time points over 1 year, but the change was small and not clinically significant 0.
Nine trials examined the effects of cannabis-based preparations on pain among patients with multiple sclerosis MS Table 1. Participants generally had intractable body pain or neuropathic pain related to a clinically confirmed diagnosis of MS. Overall, we found insufficient evidence to characterize the effects of cannabis on pain in patients with MS Table 2 because of the small number of methodologically rigorous studies, inconsistent findings across studies, lack of long-term outcomes, and small number of patients included in the trials.
Of the 3 low-ROB trials, 1 found small but clinically nonsignificant alleviation of pain at 5 weeks, 1 foundno difference in outcome, and a larger trial found that more intervention patients reported relief from body pain at 12 weeks Participants had moderate to severe intractable pain related to a clinically confirmed diagnosis of cancer, although the exact cause of pain was unspecified.
Overall, these trials provide insufficient evidence because of the small number of studies and their methodological limitations, including high attrition, exclusion of patients with variable pain scores, use of some nonvalidated measures, and lack of clarity about randomization and blinding procedures Table 2.
Two trials 21 , 46 and 3 cohort studies 48—50 examined the effects of cannabis-based preparations on pain among patients with other or mixed pain conditions, including fibromyalgia, rheumatoid arthritis, and inflammatory abdominal pain Table 1.
Overall, evidence was insufficient because of the inconsistent results and the paucity of methodologically rigorous studies Table 2. Limitations of individual studies include lack of follow-up, inadequate allocation concealment, selection bias, high attrition, and lack of inclusion of nonnaive cannabis users. Data from 2 systematic reviews examining cannabis for chronic pain suggest that cannabis use may be associated with a higher risk for short-term adverse effects 10 , However, the rates of adverse events did not significantly differ between groups in the additional pain trials we reviewed.
Although most reported adverse events were mild, such as dizziness and lightheadedness, some were serious, such as suicide attempts, paranoia, and agitation Table 3. An additional prospective observational study did not detect a difference in serious adverse events between a cannabis group Moderate-strength evidence from 2 well-designed cohort studies 52 , 53 suggests that low levels of cannabis smoking do not adversely affect lung function over about 20 years in young adults, but some evidence suggests that daily use may cause adverse pulmonary effects over an extended period Table 3.
Because of methodological limitations, including a lack of longitudinal exposure measurement and potential recall bias, 2 studies 55 , 56 give insufficient evidence about the effect of cannabis use on the risk for cardiovascular events. A meta-analysis 59 of 9 case—control studies provides low-strength evidence that cannabis use is not associated with an increased risk for head and neck cancer odds ratio, 1. Another meta-analysis 57 of 6 case—control studies provides low-strength evidence of no elevated risk for lung cancer with cannabis use odds ratio, 0.
Insufficient evidence exists about the effects of cannabis on testicular 60 or transitional cell cancer 61 Table 3. One systematic review 64 and 8 studies 65—71 , 74 consistently found an association between cannabis use specifically related to THC content and the development of psychotic symptoms low strength of evidence Table 3.
The association was seen both in populations at risk for psychotic spectrum disorders and in average-risk populations. The possibility that cannabis contributes directly to the development of psychotic symptoms is supported but not proved by biological plausibility, evidence of a dose—response relationship, prospective cohort studies, and small experimental studies. A systematic review of 6 longitudinal studies provides low-strength evidence of an association between cannabis use and exacerbation of manic symptoms in patients with known bipolar disorder.
The review found higher incidence of new-onset mania symptoms among populations without a diagnosis of bipolar disorder pooled odds ratio, 2. Two systematic reviews of studies in general populations provide moderate-strength evidence that active, long-term cannabis use is associated with small to moderate negative effects on many domains of cognitive function, but evidence on cognitive effects in past users is insufficient 72 , A meta-analysis of 4 epidemiologic studies found significantly increased odds of suicide death pooled odds ratio, 2.
However, our confidence in the findings is limited by inconsistent findings among included studies, inadequate assessment of exposure, and inadequate adjustment for confounding among the studies insufficient strength of evidence 62 , Moderate-strength evidence from a recent meta-analysis of 21 multinational observational studies suggests that acute cannabis intoxication is associated with a moderate increase in collision risk odds ratio, 1.
Long-term cannabis use has been associated with a severe form of cyclic vomiting called cannabinoid hyperemesis syndrome 75— Serious infectious diseases, including aspergillosis 83—86 and tuberculosis, have also been associated with smoking cannabis 87 , Evidence of the effects of cannabis on violent behavior is mixed 89 , Cannabis use was associated with incident cannabis use disorder adjusted odds ratio, 9. In a cross-sectional study of patients receiving daily opioid therapy for chronic pain, the prevalence of cannabis use disorder was 2.
The prevalence of cannabis use disorder among the subgroup of current users, however, was not reported In our systematic review, we found limited evidence on the potential benefits and harms of cannabis use in chronic pain populations Tables 2 and 3. We found low-strength evidence that cannabis preparations with precisely defined THC—cannabidiol content most in a 1: Most studies are small, many have methodological flaws, and the long-term effects are unclear given the brief follow-up of most studies.
Among neuropathic pain studies, we found a discrepancy between continuous and dichotomous pain outcomes. Possible interpretations are that cannabis is simply not consistently effective or that, although cannabis may not have clinically important effects on average, subgroups of patients may experience large effects. We did not find data to clarify which subgroups of patients are more or less likely to benefit.
Our findings complement several recent reviews. In 1 review, the authors concluded that low- to moderate-strength evidence supports the efficacy of cannabis in chronic pain populations, limited mainly to those with MS or neuropathic pain. However, a separate group reviewed and reanalyzed a similar set of published articles and determined that insufficient to low-strength evidence supports the use of cannabis to treat chronic noncancer pain A recent report from the National Academies of Sciences, Engineering, and Medicine examined the biological and clinical effects of cannabis across a broad range of indications and concluded that there is substantial evidence of benefit for patients with chronic pain.
Although the overall conclusions seem to differ from our findings, the authors stipulated that the clinical improvements were modest and limited to neuropathic pain 93 , and they underscored the urgent need for better research clarifying the effects of cannabis. Our review augments this report by using a systematic approach on a more focused topic chronic pain and harms as well as standard terminology for describing the strength of the body of evidence Even though we did not find strong, consistent evidence of benefit, clinicians will still need to engage in evidence-based discussions with patients managing chronic pain who are using or requesting to use cannabis.
Therefore, clinicians must understand what is known and unknown about its potential harms. We found moderate-strength evidence that light to moderate cannabis smoking does not adversely affect lung function over about 20 years.
However, the limited data on the effects of heavy use suggest a possible deleterious effect on lung function over time 52 , We found low-strength evidence that light to moderate cannabis use is not associated with lung cancer or head and neck cancer diagnoses independent of tobacco use, but the data are limited to case—control studies and do not address heavy use.
We found insufficient evidence examining whether cannabis use is associated with cardiovascular events over the long term. Cannabis use has potentially serious mental health and adverse cognitive effects, although data are insufficient to characterize the magnitude of risk or in whom the risk is highest.
Cannabis seems to be associated with at least small, short-term deleterious effects on cognition in active users, but long-term effects in past users are uncertain. We found a consistent association between cannabis use and the development of psychotic symptoms over the short and long term. A large prospective cohort study in the United States found that cannabis use was associated with a substantial risk for incident cannabis use disorder and a smaller risk for incident alcohol and other substance use disorders Finally, we found some adverse effects that seem to be related to cannabis use and are important for clinicians to know for example, infectious disease complications, cannabis hyperemesis syndrome, and violent behavior , but the incidence of these effects has not been well-characterized.
Evidence-based nonpharmacologic and nonopioid pharmacologic therapies are the preferred initial methods for treating chronic pain Clinicians may struggle with treating chronic pain in patients who have not responded to first-line treatment, and cannabis may be perceived as a safer strategy in these patients The scale and severity of adverse events, including death, seen with opioids have not been described with cannabis in the literature although less research is available on cannabis than on opioids However, no studies have directly compared cannabis with opioids, and no good-quality data exist on how cannabis use affects opioid use and opioid-related adverse effects.
Cross-sectional studies suggest an association between co-occurring cannabis use and adverse opioid-related events that is, misuse or more refills among patients prescribed opioids 6 , 7 , 96— By contrast, an open-label study found that pain scores and opioid use decreased over 6 months in participants with chronic pain who initiated cannabis treatment, although confidence in the findings is limited by the large number of participants lost to follow-up The applicability of study data to current practice is limited in several ways.
The patient populations in many studies were highly selected, and some studies included a run-in period after which patients who did not respond were excluded from further study. The data on effectiveness largely come from trials examining formulations with precisely defined THC and cannabidiol content, which differs from the reality of clinical practice. Even though dispensaries are increasingly labeling products' content, discrepancies often exist between labeled and measured content Moreover, the dose of THC assessed in many of the studies is substantially lower than that in products commonly available in dispensaries for example, 2.
Finally, the evidence base on harms is limited because studies include relatively few patients who are older, are chronically ill, or have a history of heavy and prolonged cannabis use. In observational studies, the exact dose of exposure to cannabis was rarely known because of recall bias, and the potency that is, in estimates of cannabis cigarettes smoked per day was impossible to assess.
On the other hand, this imprecision probably mirrors the uncertainty clinicians will face in discussing benefits and harms with their patients. Our approach to synthesizing the literature also has limitations. Given the broad scope of our review, we relied on existing systematic reviews to identify the best available evidence.
However, we also comprehensively searched for and included newer primary studies, included only good-quality systematic reviews, and reassessed the quality of primary pain studies included in prior reviews.
We excluded studies of synthetic prescription cannabinoids, in part because these were included in recent reviews and are not available in cannabis dispensaries. Regardless, inclusion of these studies would not have changed our overall findings because so few studies were available, they were methodologically flawed, and they had very small sample sizes.
We examined harms in both chronic pain and general populations, although the degree to which harms data in general populations apply to patients with chronic pain is uncertain. Finally, we focused specifically on pain outcomes in patients with chronic pain, but we acknowledge that other outcomes are also important in the treatment of chronic pain.
In our larger report, we describe low-strength evidence that cannabis may reduce spasticity and improve sleep in patients with MS. We found insufficient evidence regarding the effects of cannabis on these outcomes in other patient populations and regarding effects on quality of life and functional status in any population 8.
Virtually no conclusive information exists about the benefits of cannabis in chronic pain populations, and limited information is available on harms, so methodologically strong research in almost any area is likely to add to the strength of evidence see Table 8 of Supplement 5 for a list of important research gaps and Table 9 of Supplement 5 for a list of ongoing studies. Of note, many of the studies we found were done in European countries, suggesting that there may be fewer barriers to conducting cannabis-related research there than in the United States, where barriers are substantial.
Although cannabis is increasingly available for medical and recreational use, little methodologically rigorous evidence examines its effects in patients with chronic pain. Limited evidence suggests that it may alleviate neuropathic pain, but evidence in other pain populations is insufficient. Evidence is also limited on its association with an increased risk for nonserious short-term adverse effects and potentially serious mental health adverse effects, such as psychosis. National Conference of State Legislatures.
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In the U.S., cannabis was widely utilized as a patent medicine during the 19th and . Cannabinoid pharmacokinetic research has been challenging; low analyte . A systematic review of published trials on the use of medical cannabinoids over with preliminary evidence of efficacy in fibromyalgia and rheumatoid arthritis. I wanted to find out more about the weed-arthritis connection, so I figured strain review websites to find out what people suffering from arthritis. Can medical marijuana help your arthritis pain? in Arthritis Care & Research advises doctors to discourage arthritis patients from using medical marijuana.