Adding medical cannabis to standard analgesic treatment for fibromyalgia: a prospective observational study.

Image result for Clin Exp Rheumatol. “To assess any clinical improvement attributable to the addition of medical cannabis treatment (MCT) to the stable (>3 months) standard analgesic treatment of fibromyalgia (FM) patients, the retention rate and any changes in the concomitant analgesic treatment over a period of six months.

METHODS:

The study involved 102 consecutive FM patients with VAS scores ≥4 despite standard analgesic treatment. Patients were prescribed two oil-diluted cannabis extracts: Bedrocan (22% THC, <1% CBD), and Bediol (6.3% THC, 8% CBD). FM severity was periodically assessed using Fibromyalgia Impact Questionnaire (FIQR), Fibromyalgia Assessment Scale (FAS), FACIT-Fatigue score, Pittsburgh Sleep Quality Index (PSQI), and Zung Depression and Anxiety Scales. During the study, patients were allowed to reduce or stop their concomitant analgesic therapy.

RESULTS:

The 6-month retention rate was 64%. A significant improvement in the PSQI and FIQR was observed in respectively 44% and 33% of patients. 50% showed a moderate improvement in the anxiety and depression scales. Multiple regression analysis showed a correlation between the body mass index (BMI) and FIQR improvement (p=0.017). Concomitant analgesic treatment was reduced or suspended in 47% of the patients. One-third experienced mild adverse events, which did not cause any significant treatment modifications.

CONCLUSIONS:

This observational study shows that adjunctive MCT offers a possible clinical advantage in FM patients, especially in those with sleep dysfunctions. The clinical improvement inversely correlated with BMI. The retention rate and changes in concomitant analgesic therapy reflect MCT efficacy of the improved quality of life of patients. Further studies are needed to confirm these data, identify MCT-responsive sub-groups of FM patients, and establish the most appropriate posology and duration of the therapy.”

https://www.ncbi.nlm.nih.gov/pubmed/32116208

Cannabis and Cannabinoids in the Treatment of Rheumatic Diseases.

 Logo of rmmj“Chronic pain is a common complaint among patients, and rheumatic diseases are a common cause for chronic pain. Current pharmacological interventions for chronic pain are not always useful or safe enough for long-term use.

Cannabis and cannabinoids are currently being studied due to their potential as analgesics. In this review we will discuss current literature regarding cannabinoids and cannabis as treatment for rheumatic diseases.

Fibromyalgia is a prevalent rheumatic disease that causes diffuse pain, fatigue, and sleep disturbances. Treatment of this syndrome is symptomatic, and it has been suggested that cannabis and cannabinoids could potentially alleviate some of the symptoms associated with fibromyalgia. In this review we cite some of the evidence that supports this claim. However, data on long-term efficacy and safety of cannabinoid and cannabis use are still lacking.

Cannabinoids and cannabis are commonly investigated as analgesic agents, but in recent years more evidence has accumulated on their potential immune-modulatory effect, supported by results in animal models of certain rheumatic diseases. While results that demonstrate the same effect in humans are still lacking, cannabinoids and cannabis remain potential drugs to alleviate the pain associated with rheumatic diseases, as they were shown to be safe and to cause limited adverse effects.”

https://www.ncbi.nlm.nih.gov/pubmed/32017684

Safety and Efficacy of Medical Cannabis in Fibromyalgia

jcm-logo“Chronic pain may be treated by medical cannabis. Yet, there is scarce evidence to support the role of medical cannabis in the treatment of fibromyalgia. The aim of the study was to investigate the characteristics, safety, and effectiveness of medical cannabis therapy for fibromyalgia.

Results: Among the 367 fibromyalgia patients, the mean age was 52.9 ± 15.1, of whom 301 (82.0%) were women. Twenty eight patients (7.6%) stopped the treatment prior to the six months follow-up. The six months response rate was 70.8%. Pain intensity (scale 0–10) reduced from a median of 9.0 at baseline to 5.0 (p < 0.001), and 194 patients (81.1%) achieved treatment response. In a multivariate analysis, age above 60 years (odds ratio [OR] 0.34, 95% C.I 0.16–0.72), concerns about cannabis treatment (OR 0.36, 95% C.I 0.16–0.80), spasticity (OR 2.26, 95% C.I 1.08–4.72), and previous use of cannabis (OR 2.46 95% C.I 1.06–5.74) were associated with treatment outcome. The most common adverse effects were mild and included dizziness (7.9%), dry mouth (6.7%), and gastrointestinal symptoms (5.4%).

Conclusion: Medical cannabis appears to be a safe and effective alternative for the treatment of fibromyalgia symptoms. Standardization of treatment compounds and regimens are required.”

https://www.mdpi.com/2077-0383/8/6/807

“Medical cannabis appears to be a safe and effective alternative for the treatment of fibromyalgia symptoms.”  https://www.ncbi.nlm.nih.gov/pubmed/31195754

Cannabidiol, cannabinol and their combinations act as peripheral analgesics in a rat model of myofascial pain.

Archives of Oral Biology

“This study investigated whether local intramuscular injection of non-psychoactive cannabinoids, cannabidiol (CBD), cannabinol (CBN), cannabichromene (CBC) and their combinations can decrease nerve growth factor (NGF)-induced masticatory muscle sensitization in female rats.

RESULTS:

In behavioral experiments, CBD (5 mg/ml) or CBN (1 mg/ml) decreased NGF-induced mechanical sensitization. Combinations of CBD/CBN induced a longer-lasting reduction of mechanical sensitization than either compound alone. No significant change in mechanical withdrawal threshold was observed in the contralateral masseter muscles and no impairment of motor function was found with the inverted screen test after any of the treatments. Consistent with behavioral results, CBD (5 mg/ml), CBN (1 mg/ml) and the combination of CBD/CBN (1:1 mg/ml) increased the mechanical threshold of masseter muscle mechanoreceptors. However, combining CBD/CBN (5:1 mg/ml) at a higher ratio reduced the duration of this effect. This may indicate an inhibitory effect of higher concentrations of CBD on CBN.

CONCLUSIONS:

These results suggest that peripheral application of these non-psychoactive cannabinoids may provide analgesic relief for chronic muscle pain disorders such as temporomandibular disorders and fibromyalgia without central side effects.”

https://www.ncbi.nlm.nih.gov/pubmed/31158702

https://www.sciencedirect.com/science/article/pii/S0003996919302249?via%3Dihub

An experimental randomized study on the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia.

 

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“In this experimental randomized placebo-controlled 4-way crossover trial, we explored the analgesic effects of inhaled pharmaceutical-grade cannabis in twenty chronic pain patients with fibromyalgia.

We tested four different cannabis varieties with exact knowledge on their [INCREMENT]-tetrahydrocannabinol (THC), and cannabidiol (CBD) content: Bedrocan® (22.4 mg THC, < 1 mg CBD), Bediol® (13.4 mg THC, 17.8 mg CBD), Bedrolite® (18.4 mg CBD, < 1 mg THC) and a placebo variety without any THC or CBD.

Following a single vapor inhalation, THC and CBD plasma concentrations, pressure and electrical pain thresholds, spontaneous pain scores and drug high were measured for 3 hours. None of the treatments had an effect greater than placebo on spontaneous or electrical pain responses, although more subjects receiving Bediol® displayed a 30% decrease in pain scores compared to placebo (90% vs. 55% of patients, p = 0.01), with spontaneous pain scores correlating with the magnitude of drug high (ρ = -0.5, p < 0.001). Cannabis varieties containing THC caused a significant increase in pressure pain threshold relative to placebo (p < 0.01). CBD inhalation increased THC plasma concentrations but diminished THC-induced analgesic effects, indicative of a synergistic pharmacokinetic but antagonistic pharmacodynamic interactions of THC and CBD.

This experimental trial shows the complex behavior of inhaled cannabinoids in chronic pain patients with just small analgesic responses after a single inhalation. Further studies are needed to determine long-term treatment effects on spontaneous pain scores, THC-CBD interactions and the role of psychotropic symptoms on pain relief.”

https://www.ncbi.nlm.nih.gov/pubmed/30585986

https://insights.ovid.com/crossref?an=00006396-900000000-98794

Effect of adding medical cannabis to analgesic treatment in patients with low back pain related to fibromyalgia: an observational cross-over single centre study.

Image result for Clin Exp Rheumatol.

“Low back pain (LBP) occurs in many patients with fibromyalgia (FM). The current study aimed to assess the possible pain and function amelioration associated with medical cannabis therapy (MCT) in this setting.

METHODS:

31 patients were involved in an observational cross-over study. The patients were screened, treated with 3 months of standardised analgesic therapy (SAT): 5 mg of oxycodone hydrochloride equivalent to 4.5 mg oxycodone and 2.5 mg naloxone hydrochloride twice a day and duloxetine 30 mg once a day. Following 3 months of this therapy, the patients could opt for MCT and were treated for a minimum of 6 months. Patient reported outcomes (PRO’s) included: FIQR, VAS, ODI and SF-12 and lumbar range of motion (ROM) was recorded using the modified Schober test.

RESULTS:

While SAT led to minor improvement as compared with baseline status, the addition of MCT allowed a significantly higher improvement in all PRO’s at 3 months after initiation of MCT and the improvement was maintained at 6 months. ROM improved after 3 months of MCT and continued to improve at 6 months.

CONCLUSIONS:

This observational cross-over study demonstrates an advantage of MCT in FM patients with LBP as compared with SAT. Further randomised clinical trial studies should assess whether these results can be generalised to the FM population at large.”

The Consumption of Cannabis by Fibromyalgia Patients in Israel.

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“OBJECTIVE:

To report on the habits of cannabis consumption among fibromyalgia patients in Israel.

RESULTS:

Of 2,705 people, 383 (14%) responded to the questionnaire, with a mean age of 42.2±14.2 years. Of the responders, 84% reported consuming cannabis, and 44% were licensed for MC. The mean amount per month of cannabis consumed was 31.4±16.3g, and 80% of cannabis consumers (CC) smoked pure cannabis or cannabis mixed with tobacco. Pain relief was reported by 94% of CC, while 93% reported improved sleep quality, 87% reported improvement in depression, and 62% reported improvement in anxiety. Of MC-licensed CC, 55% bought cannabis beyond the medical allowance on the black market. Adverse effects were reported by 12% of CC. Only 8% reported dependence on cannabis. Most CC (64%) worked either full- or part-time jobs, and 74% reported driving “as usual” under cannabis use.

CONCLUSIONS:

Cannabis consumption among fibromyalgia patients in our country is very common and is mostly not licensed. Nearly all CC reported favorable effects on pain and sleep, and few reported adverse effects or feeling of dependence on cannabis.”

“The results of our study should encourage both the Rheumatology Association in our country and the MCA to reconsider their stand on cannabis and include fibromyalgia among the indications for MC under certain restrictions.”

The relationship of endocannabinoidome lipid mediators with pain and psychological stress in women with fibromyalgia – a case control study.

“Characterized by chronic widespread pain, generalized hyperalgesia, and psychological stress fibromyalgia (FM) is difficult to diagnose and lacks effective treatments.

The endocannabinoids – arachidonoylethanolamide (AEA), 2-arachidonoylglycerol (2-AG), and the related oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA) – are endogenous lipid mediators with analgesic and anti-inflammatory characteristics, in company with psychological modulating properties (e.g., stress and anxiety), and are included in a new emerging “ome”, the endocannabinoidome.

This case -control study compared the concentration differences of AEA, OEA, PEA, SEA, and 2-AG in 104 women with FM and 116 healthy controls (CON). All participants OEArated their pain, anxiety, depression, and current health status. The relationships between the lipid concentrations and the clinical assessments were investigated using powerful multivariate data analysis and traditional bivariate statistics. The concentrations of OEA, PEA, SEA, and 2-AG were significantly higher in FM than in CON; significance remained for OEA and SEA after controlling for BMI and age. 2-AG correlated positively with FM duration and BMI, and to some extent negatively with pain, anxiety, depression, and health status. In FM, AEA correlated positively with depression ratings.

The elevated circulating levels of endocannabinoidome lipids suggest that these lipids play a role in the complex pathophysiology of FM and might be signs of ongoing low-grade inflammation in FM. Although the investigated lipids are significantly altered in FM their biological roles are uncertain with respect to the clinical manifestations of FM. Thus, plasma lipids alone are not good biomarkers for FM.

PERSPECTIVE:

This study reports about elevated plasma levels of endocannabinoidome lipid mediators in FM. The lipids suitability to work as biomarkers for FM in the clinic were low, however their altered levels indicate that a metabolic asymmetry is ongoing in FM, which could serve as basis during explorative FM pain management.”

https://www.ncbi.nlm.nih.gov/pubmed/29885369

https://www.jpain.org/article/S1526-5900(18)30197-4/fulltext

Endogenous systems involved in exercise-induced analgesia.

Image result for J Physiology Pharmacology

“Exercise-induced analgesia is a phenomenon discussed worldwide. This effect began to be investigated in the early 1970s in healthy individuals and rodents during and after an acute or chronic session of running or swimming. Thereafter, studies found this effect was also induced by resistance exercises. Over the years, many studies have demonstrated the importance of exercise-induced analgesia in relieving pain caused by different conditions, such as fibromyalgia, low back pain, neuropathy, and osteoarthritis. This review aims to provide the reader with an in-depth description of the main endogenous systems, substances, neurotransmitters, receptors and enzymes that are thought to be involved in the analgesic effect induced by exercise. Many hypotheses have been proposed to elucidate the mechanisms responsible for exercise-induced analgesia. One of the most accepted hypotheses has been the activation of several endogenous systems described as analgesics. Studies have demonstrated that during and after exercise different endogenous systems are activated, which release substances or neurotransmitters, such as opioids, nitric oxide, serotonin, catecholamines and endocannabinoids, that may modulate the pain perception.”  https://www.ncbi.nlm.nih.gov/pubmed/29769416

http://www.jpp.krakow.pl/journal/archive/02_18/pdf/jpp.2018.1.01.pdf

“Exercise activates the endocannabinoid system.”  https://www.ncbi.nlm.nih.gov/pubmed/14625449

Medical Cannabis for the Treatment of Fibromyalgia.

Image result for J Clin Rheumatol.

“Fibromyalgia is a chronic pain syndrome, characterized by chronic musculoskeletal pain, fatigue, and mood disturbances. There are nearly no data on the effect of medical cannabis (MC) treatment on patients with fibromyalgia.

Data were obtained from the registries of 2 hospitals in Israel (Laniado Hospital and Nazareth Hospital) on patients with a diagnosis of fibromyalgia who were treated with MC. After obtaining patient consent, demographic, clinical, and laboratory parameters were documented. All the patients also completed the Revised Fibromyalgia Impact Questionnaire regarding the period before and after MC treatment.

Thirty patients were identified, and 26 patients were included in the study. There were 19 female patients (73%), and the mean age of the study group was 37.8 ± 7.6 years. The mean dosage of MC was 26 ± 8.3 g per month, and the mean duration of MC use was 10.4 ± 11.3 months. After commencing MC treatment, all the patients reported a significant improvement in every parameter on the questionnaire, and 13 patients (50%) stopped taking any other medications for fibromyalgia. Eight patients (30%) experienced very mild adverse effects.

 

CONCLUSIONS:

Medical cannabis treatment had a significant favorable effect on patients with fibromyalgia, with few adverse effects.”

https://insights.ovid.com/crossref?an=00124743-900000000-99352