Accurate Education – Marijuana (Cannabis): Fibromyalgia

Finally, another 2021 review article concluded: “Although the studies reviewed in this article suggest that medical cannabis is a safe and effective treatment for fibromyalgia pain, several limitations regarding dosage, length of treatment, adverse effects, long-term follow-up, and dependence needs further investigation.”

 

That being said, many retrospective trials and patient surveys suggest that cannabis provides significant improvement of pain, improvement in sleep, and reduction of other associated symptoms.

 

There were no serious adverse effects in this study. The patients reported a few mild adverse effects, including dry mouth, redness of the eyes, and feeling hungry. These symptoms appeared at the start of the treatment but were usually transient, lasting only a few weeks, and were mainly associated with smoking the cannabis. Many patients adapted to feeling hungry by eating prior to the use of cannabis. 

 

Finally, A Systematic Review of Fibromyalgia and Recent Advancements in Treatment published in 2021 concluded “that cannabinoids can be a low-cost and well-tolerated therapy to reduce symptoms and increase the quality of life of patients with fibromyalgia. Results concluded patients have improved pain scores over 12 months. Moreover, cannabis treatment is not associated with increases in the frequency of undesired adverse events, but rather there is a decrease in the frequency of headaches, fatigue, feelings of anxiety, and nausea.

 

 

 

Fibromyalgia Treatment with THC

In an early 2006 trial in only nine patients, THC was administered in doses of 2.5–15 mg a day for 3 months although all but four patients left the study early due to THC side effects. The remaining five subjects had marked reductions in their overall pain but no benefits for touch-evoked allodynia, nor pinprick hyperalgesia.

Another 2006 study evaluated electrically induced pain in subjects provided THC. It was concluded a sub-population of fibromyalgia patients reported significant benefit from delta-9-THC monotherapy. Based on evaluation of the nerves, the study authors concluded the analgesic benefit of THC was not due to direct effect of THC on the peripheral nerve being stimulated but it was due to a central mode of action in the brain.

 

Another study assessed nabilone, a semi-synthetic THC analog and CB1 agonist believed to work in the same way as THC but it is 10-times stronger than THC.  Forty fibromyalgia patients received nabilone 1 mg 2x/day for 4 weeks (roughly equivalent to 10 mg THC 2x/day. Overall pain and anxiety were improved as well as generalized improvement in daily activities.

 

Fibromyalgia Treatment with CBD

Studies are lacking that directly evaluate the use of CBD for treating fibromyalgia. Nevertheless, patients with fibromyalgia commonly use CBD for symptomatic relief. In a 2021 publication, it was found that “patients use CBD for numerous fibromyalgia-related symptoms (most commonly pain), and generally reported slight to much improvement across symptom domains. Around half of participants reported side effects, which were typically minor.” No assessment of terpene content of CBD products was available unfortunately and it is likely that terpenes offer definitive benefits for many different symptoms.

A recent 2022 study assessed CBD use comparing those who also used marijuana and those who did not. The past-year HTC group used inhalation routes far more frequently than those who did not (39.8% vs 7.1%). For those using CBD tinctures or edibles, the average dose was 16 mg and 24 to 27 mg per day respectively, ]although about one-third of participants did not know what dose of CBD they used. Patients using both inhalation and non-inhalation methods reported greater symptom relief than those using non-inhalation methods alone. It was also noted that there was no consistent relationship between CBD dose and reported benefits.

 

Fibromyalgia Treatment with Sublingual Cannabis Extracts

A 2020 study evaluated the benefit of an oral extract of a White Willow strain with a 24.44-mg/mL concentration of THC and 0.51 mg/mL of CBD (a proportion of 48/1 THC/ CBD), including small quantities of other cannabinoids including as CBG (cannabigerol), THCV (tetrahydrocannabivarin), CBN (cannabinol), and cannabicromen. Although the product used was not analyzed for terpenes, the White Willow strain typically has myrcene, caryophyllene (BCP), and pinene.

This double-blind, randomized, placebo-controlled clinical trial was conducted for eight weeks in 17 women (mean age 52 years) with fibromyalgia (FM) to determine the benefit of this product on symptoms and quality of life based on use of the the Fibromyalgia Impact Questionnaire (FIQ). The FIQ is a well established standardized evaluation that assesses the impact of FM symptoms on daily activities and quality of life including:“physical function,” “feel good,” “work missed,” “job ability,” “pain,” “fatigue,” “morning tiredness,” “stiffness,” “anxiety,” and “depression.”

The initial dose was one drop (1.22 mg of THC and 0.02 mg of CBD) a day with subsequent increase doses every 10 days as. needed according to symptoms. The mean dose at post-intervention evaluation was 3.6 drops of cannabis oil (4.4 mg of THC and 0.08 mg of CBD).

After the intervention, the cannabis group achieved a significant decrease in FIQ score in comparison with the placebo group and in comparison with their baseline scores.  Analyzing individual items on the FIQ, the cannabis group presented significant improvement on the “feel good,” “pain,” “do work,” and “fatigue” scores.  There were no intolerable adverse effects. The authors concluded the product to be a low-cost and well-tolerated therapy effective in reducing symptoms and increasing the quality of life of patients with fibromyalgia.

Of interest about this study is that the “feel good” item demonstrated the greatest improvement in the cannabis group while there was no change in the placebo group. The importance of this subjective feeling of well-being lies in the context of the World Health Organization definition of health: a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity. Here the “feel good” reflects a perception of well-being, a particularly valuable therapeutic benefit.

While this particular product is not commercially available, another product (Carolina Cannabinoids) recommended here offers similar constituents at similar concentrations and would likely provide a reasonably similar alternative that would be expected to provide similar, and likely even better benefits due to the presence of other constituents (including high dose BCP) with definitive therapeutic benefits in fibromyalgia.

Fibromyalgia Treatment with Terpenes

 

 

Safety and Efficacy of Medical Cannabis in Fibromyalgia – 2019

Perhaps the most helpful study that supports the potential benefit for medical marijuana is a 2019 Israeli study evaluating 298 patients with fibromyalgia who were treated with medical cannabis for six months. Of these, only 211 responded with the follow-up questionnaire. although out of the 87 patients who did not respond to the six months questionnaire, 76 patients (87.3%) were still using cannabis at six months.

 

The majority of the patients in this study were 40–60 years old (181 patients, 49.3%) and female (301 patients, 82.0%). Patients had reported previous experience with recreational cannabis in the past in 45.2% of cases. The median length of fibromyalgia symptoms was 7 years, and 320 (87.2%) patients reported constant daily pain. In 283 patients (77.1%), fibromyalgia was the primary pain-related indication to initiate medical cannabis therapy. Fibromyalgia was the secondary indication to initiate cannabis therapy in 35 (9.5%) patients with the primary pain condition of cancer, 22 (6.0%) patients, post-traumatic stress disorder (PTSD) in 27 (7.4%) patients and others with other indications.

 

The route of administration was oil in 74 patients (20%), inhalation of marijuana flower (vaped or smoked) in 247 patients (67%) both oil and inhalation in44 patients (12%). The actual dosing employed in this study is, unfortunately, confusing. The median cannabis plant dosage was 670 mg/day  at initiation of the study and 1000 mg/day at six months. The calculated median THC and CBD dosages at six months were 140 mg/day (ranging from 90–200 mg) for THC and 39 mg/day (ranging from 10–69 mg) for THC. When comparing dose at six months between patients with fibromyalgia as a primary or secondary indication, the primary fibromyalgia patients utilized the similar THC and CBD dosages as the secondary patients. However, it is not clear at all how these doses were calculated and no comparism was provided between oil vs. inhalation doses. Therefore, applying these doses as a means of recommending doses to patients with FM appears to be very speculative.

 

Overall, treatment was successful in 194 out of 239 patients (81.1%), defined as at least moderate improvement in their condition while receiving medical cannabis without experiencing serious adverse events. The likelihood of treatment success was reduced in patients who expressed concerns about cannabis treatment, whereas spasticity at treatment initiation and previous use of cannabis were variables associated with increased likelihood of treatment success.

 

Regarding pain intensity, prior to treatment initiation 193 patients (52.5%) reported a high level of pain scale (8–10). However, after six months of follow-up, only 19 patients (7.9%) reported similar pain intensity. Overall pain intensity reduced from a median of 9.0 at baseline to 5.0 (range 4.0–6.0) after six months.

 

Regarding quality of life (QOL) assessment, prior to treatment initiation only 10 patients (2.7%) reported good or very good QOL, whereas after six months of treatment 148 patients (61.9%) reported their QOL to be good or very good. When analyzing QOL components, sleep quality, appetite, and sexual activity significantly improved at six months while other components (e.g., mobility, dressing, and concentration) did not improve. The sleep problems reported by 196 patients (92.9%) at intake improved in 144 patients (73.4%) and disappeared in 26 patients (13.2%). Depression-related symptoms reported by 125 patients (59.2%) at the baseline improved in 101 patients (80.8%).

 

The patients in this study used 14 different strains of cannabis, which prevented evaluation of a comparison between THC and CBD strains and products in terms of effectiveness or side effects. Of the regimens used by the patients in this study, 56% used THC-rich regimens compared to 22% who used CBD-rich regimens. This suggests that a THC-rich regimen was more popular and therefore more effective, but no direct analysis was performed comparing effectiveness of one regimen vs. the other nor did the study offer an analysis of side-effects comparing the two regimens. Furthermore, no comparism was made between inhaled regimens vs. oral or buccal regimens either related to dosing, effectiveness or side effects.

 

Regarding the use of other drugs for the treatment of fibromyalgia after six months, most patients ceased, reduced, or at least did not change the dosage of their chronic drugs for fibromyalgia while receiving medical cannabis. At six months, 28 out of 126 patients (22.2%) stopped or reduced their dosage of opioids, and 24 out of 118 (20.3%) reduced their dosage of benzodiazepines. When stratifying the analysis to patients with fibromyalgia as the primary vs. secondary pain source, both groups showed the same improvement at six months in terms of pain intensity and overall quality of life.

 

With respect to side effects, the most commonly reported adverse events after six months were dizziness (7.9%), dry mouth (6.7%), and vomiting/nausea (5.4%). This is consistent with the findings of other studies.

 

The final conclusion of this study is therefore limited to the fact that the use of cannabinoids appears to offer significant benefit for those with fibromyalgia on multiple levels but no specific recommendations can be made for route of administration or dosing regarding THC or CBD.

 

Pharmaceutical Cannabinoids – THC

THC (delta-9-tetrahydrocannabinol), the major cannabinoid constituent of cannabis, has only limited research as a singular agent for treating fibromyalgia. A 2006 study evaluated just nine fibromyalgia (FM) patients who received a daily dose of 2.5-15 mg of THC, starting with a 2.5mg/day dose with a weekly dose increase of 2.5 mg up to a maximum 15 mg/day dose, as long as no side effects were reported. Daily-recorded pain of the FM patients was significantly reduced but researchers recommended further studies be done prior to concluding definitive effectiveness.

 

In 2009 a multicenter survey was performed evaluating 172 patients treated with an average of 7.5 mg/day of THC over 7 months. Of these, 48 patients prematurely withdrew due to side effects, insufficient analgesia, or expense of therapy. In the end, 124 patients were assessed for changes in pain intensity,  quality of life, anxiety and depression. Pain intensity improved significantly with the THC treatment. Opioid doses were reduced and patients perceived THC therapy was effective with tolerable side effects. About 25% of the patients, however, did not tolerate the THC treatment.

 

Pharmaceutical Cannabinoids – Nabilone (Cesamet)

Nabilone is a synthetic cannabinoid intended for oral use that is different from THC, but is structurally similar. Nabilone is FDA-approved in the United State but indicated only for the treatment of the nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments. Nabilone is also approved for use in Canada, Mexico, and the United Kingdom for the treatment of severe nausea and vomiting associated with chemotherapy.

 

Evidence is emerging for the use of nabilone in the management of different pain conditions including fibromyalgia. A systematic review of the Cochrane Library databases (updated July 23, 2015) identified eight randomized controlled trials, two prospective cohort trials, and one retrospective chart review evaluating cancer pain, chronic noncancer pain, neuropathic pain, fibromyalgia, and pain associated with spasticity. Nabilone was most commonly used as adjunctive therapy but overall nabione treatment led to small but significant reductions in pain. The most common side effects included euphoria, drowsiness, and dizziness but nabilone was rarely associated with severe side effects that required discontinuation of use. The likelihood of abuse was considered low. Although the optimal role of nabilone in the management of pain is yet to be determined, nabilone is generally considered to be a third-line agent.

 

A Cochrane review article published in 2016 reviewed randomised controlled trials of at least four weeks’ duration that evaluated any formulation of cannabis products used for the treatment of adults with fibromyalgia. Highest quality evidence was obtained from studies with at least 200 participants and of eight to 12 weeks duration. Lesser quality evidence was obtained from smaller studies that were considered at some risk of bias. The primary outcomes in the review were participant-reported pain relief of 50% or greater.

 

Nabilone was compared to placebo and to amitriptyline in two small studies with 32 and 40 participants and study duration of four to six weeks. Nabilone was provided with a bedtime dosage of 1 mg.  Neither study reported participants experiencing at least 30% or 50% pain relief or who were very much improved.

 

Some studies, though of very low quality, provided evidence of greater reduction of pain and limitations of health-related quality of life compared to placebo. There were no significant differences to placebo found for fatigue and depression. Better effects of nabilone on sleep than amitriptyline (Elavil) were reported. More participants dropped out due to adverse events in the nabilone group (4/52 participants) than in the control groups (1/20 in placebo and 0/32 in amitriptyline group). The most frequent side effects were dizziness, nausea, dry mouth and drowsiness (six participants with nabilone). There were no reported serious side effects.

 

The authors of the Cochrane review concluded that there is no convincing, unbiased, high quality evidence that nabilone is of value in treating people with fibromyalgia and the tolerability of nabilone was low.