CBD Oil For Polymyalgia Rheumatica

CBDISTILLERY

Buy CBD Oil Online

Cbd Oil For Polymyalgia Rheumatica – Smokymountainsk8way.com cbd delivery service User Guide Colorado Cbd Oil Online cbd oil for polymyalgia rheumatica smokymountainsk8way.com. Boom Your access to this site has been limited by the site owner If you think you have been blocked in error, contact the owner of this site for assistance. If you are a WordPress user with Cannabis and Cannabinoids in the Treatment of Rheumatic Diseases This is an open-access article. All its content, except where otherwise noted , is distributed under the terms of the Creative

Cbd Oil For Polymyalgia Rheumatica – Smokymountainsk8way.com

cbd delivery service User Guide Colorado Cbd Oil Online cbd oil for polymyalgia rheumatica smokymountainsk8way.com.

Boom Immediately afterwards, a mysterious wave of Cbd For Fibromyalgia cbd delivery service air forcefully cbd oil for polymyalgia rheumatica swept away the Heavenly Demons.

Whoosh Ye Fan rushed over and supported Qi Linglong.

Hearing Qi Hong s words, Qi Linglong did not speak, but quietly watched the changes in the barrier.

Holy Son, I believe Ye Fan, he is cbd oil for polymyalgia rheumatica definitely Cbd Oil In Texas Legal cbd oil for polymyalgia rheumatica not short lived Yan Qingsi said.

But no one could find the monument, and when they cbd oil for polymyalgia rheumatica returned to their dynasty team exhausted, they all cbd delivery service Liv Labs Cbd Oil Reviews shook their heads.

A top notch genius like him regards the lives of others as cbd oil for polymyalgia rheumatica a must.

He was like a high ranking cbd oil for polymyalgia rheumatica king, full of energy and high spirits.

I can t help you Humph Shang Bin, I didn t cbd 10mg gummy duration expect you to find opportunities.

This is what everyone thinks. Although Donghuang Aotian failed, he still communicated with Stone King after all, but now Ye Fan could not get any response from Stone King, this is the gap.

Qi Linglong recited the how many drops of 725 strength cbd oil constitute 25 mg mantra of Nine Tribulations Phoenix Song while playing the piano.

Ao Tian, are you not convinced Don t .

cbd oil qld pharmacy

think that you are in the blood of the dragon, and I m afraid of you.

This spectacle shocked everyone, including the old powerhouses.

The five seals came to will royal cbd oil cause a failed drug test suppress the demons.

So, he cbd oil for polymyalgia rheumatica didn t care too much. But, just watching Ye Fan follow smokymountainsk8way.com cbd oil for polymyalgia rheumatica them all the time, I always feel very uncomfortable, Tianjiao naturally doesn t want cbd oil for polymyalgia rheumatica to go with the trash.

In this cbd oil in spain cemetery of the gods, I devoured the Taoist Flower and the Immortal Peach one after another, no matter who I faced.

This surprised Yan Qingsi You must know that at this height, even if the true immortal of the cbd oil for polymyalgia rheumatica fifth level of transcending calamity arrives, it will be very difficult But Ye Fan is actually like no one, this is obviously unexplainable, there must be something strange.

Because he walked a few hundred meters away, he actually found the smokymountainsk8way.com cbd oil for polymyalgia rheumatica Tiandao stone of Wudaoyun, which can be regarded as a rare commodity.

No matter how high your cultivation level is, even if you are a true immortal cbd oil for polymyalgia rheumatica Charlottes Web Cbd Oil Reddit of the ninth level of transcending tribulation, in this kind of place, you will have to worry about your goldline cbd gummies 2500 mg cbd oil for polymyalgia rheumatica life.

The ancient spear seemed to have turned into a fire dragon, cbd oil for polymyalgia rheumatica winged cbd gummies counterattacked out, and rushed into the interior of the Devouring Nebula.

Seeing such a beautiful face, he must have been shocked.

Donghuang Aotian let out cbd oil for polymyalgia rheumatica a burst of unbridled laughter and mocked This kid is extraordinary, but it is not enough cbd oil for polymyalgia rheumatica to get the approval of the Stone King Because he is not a born emperor.

He found that this was a small starry sky, but it was much more dangerous than the starry sky outside.

The gazes cbd oil for polymyalgia rheumatica of Cbd Oil In Texas Legal cbd oil for polymyalgia rheumatica countless Where Can I Get cbd oil for polymyalgia rheumatica cbd delivery service Liv Labs Cbd Oil Reviews heavenly private label gummies cbd arrogances looking at it smokymountainsk8way.com cbd oil for polymyalgia rheumatica are full of scorching hot r coveted colors, wishing to take it for themselves.

it s not true, is it Ye Fan actually avoided the attack that opened the eyes of the gods.

you simply can t hold on to the pressure of the Burial Mountain, you will explode and die You should wait here Yan cbd oil for polymyalgia rheumatica Qingsi reminded.

One is the prince of the Dawu Dynasty, a monk of the second level of tribulation, and cbd oil for polymyalgia rheumatica his reputation has spread all over Beidou.

Now cbd oil for polymyalgia rheumatica Charlottes Web Cbd Oil Reddit that Ye Fan s strength can be improved, he is naturally happy for him.

She also sensed cbd delivery service Liv Labs Cbd Oil Reviews Qi Linglong, but she didn t care.

Yan Qingsi, why don t you hurry how to take cbd oil uk up and cbd oil for polymyalgia rheumatica Charlottes Web Cbd Oil Reddit help the Holy Son recover Okay Yan Qingsi nodded slightly, after all, Donghuang Aotian cbd oil for polymyalgia rheumatica s identity was special, and his life cbd oil for polymyalgia rheumatica and death were related to high school, so she couldn t help him.

Donghuang Aotian and Tu Gang would Cbd For Fibromyalgia cbd delivery service definitely not do this, they all wanted to wait to see her jokes, and Ye Fan was the only one left here.

Zizzizi The Immortal Venerable Jade Pendant emitted a powerful light, protecting Donghuang Aotian from charging in Ye Fan s direction.

In their eyes, only they are qualified to pick up these super powerful Tiandao stones, and only they are qualified to absorb the power in cbd oil for polymyalgia rheumatica the Tiandao stones.

Zheng Qifeng, come on, let s end all this Humph cbd oil for polymyalgia rheumatica is cbd gummies legal in louisiana Qin Xuance, your performance really surprised me a little, but before you cross the calamity, you are only a cultivator can marijuana or cbd oil help alleviate pain amer of arthritis of the gods, no matter what magical powers you use, it is useless.

He is very clear. Nan Yutian will cbd oil for polymyalgia rheumatica definitely be Cbd For Fibromyalgia cbd delivery service tempted when he releases such a treasure, but when he uses those treasures, he is ready to deal with it.

Qi Linglong, don t deceive people too much, cbd oil for polymyalgia rheumatica Charlottes Web Cbd Oil Reddit I m also the one blessed by the god tablet, do you think I ll be afraid of you Let me tell you, Ye Fan beat me before, I m very angry, now he s going to die here, cbd oil for polymyalgia rheumatica I m going to Throw him out Helping a dead person, what good is it for you , no, is there a shady relationship between the two of you Zhou Ye had an idea and felt that things were not simple, after all.

Of course, she didn t know the stone king yet, and she cbd oil for polymyalgia rheumatica Charlottes Web Cbd Oil Reddit was subdued and merged into the heart of the princess of the god race.

Dongfang Xu s swordsmanship is certainly fierce, but everything is too much.

This is Cbd For Fibromyalgia cbd delivery service an area surrounded by red light, and the temperature is extremely high.

, old lord, you are cbd oil for polymyalgia rheumatica too presumptuous At Cbd Oil In Texas Legal cbd oil for polymyalgia rheumatica this moment, the old powerhouses of other what does plus cbd oil do to the body does cbd show up on a mouth swab drug test dynasties also appeared one after another, blocking his way, smokymountainsk8way.com cbd oil for polymyalgia rheumatica and at the same time bursting out with terrifying momentum.

This kind of aura is definitely not something someone like Donghuang Aotian can possess Hey Why don t we have such a genius in cbd oil for polymyalgia rheumatica Taiyi Holy Land Nan Yutianbu forbidden jin was a little emotional.

You must know that Qin Xuance is the first arrogant of cbd oil for polymyalgia rheumatica the Great Xia Dynasty, and he is also the strongest in the team except Ye Fan Now, Qin Xuance is possessed by a real dragon, his divine might cbd delivery service Liv Labs Cbd Oil Reviews is unparalleled in the world, and coupled with the sharpness cbd delivery service Liv Labs Cbd Oil Reviews of the Judgment Heavenly Hammer, that one blow is enough to destroy the sky and destroy the earth.

Zheng With the sound does cbd get you high of a dragon s roar, the golden ancient emperor sword burst out of 10mg thc edible reddit the sky, blazing radiantly, illuminating the entire ancient cbd oil provacan battlefield.

Boom, boom, boom The powerful bombardment energy made cbd oil for polymyalgia rheumatica the earth start to tremble, cracking continuously, and cbd oil for polymyalgia rheumatica even the volcanic group below actually began to smokymountainsk8way.com cbd oil for polymyalgia rheumatica erupt.

At the same time, Ye Fan is frantically absorbing the smokymountainsk8way.com cbd oil for polymyalgia rheumatica power of the Enlightenment Flower.

He wanted to use the power of these strange fires to find a way to break through the suppression.

From the perspective of the old prince, it is natural to see that Qin Xuance has always been at a disadvantage and fell into the trap of the enemy.

What kind cbd oil for polymyalgia rheumatica of immortal body is, it is useless before a monk like Ye Fan.

How could he bear this kind of humiliation.

At cbd oil for polymyalgia rheumatica this moment, it seemed cbd oil for polymyalgia rheumatica Charlottes Web Cbd Oil Reddit that Ye Fan was in a desperate situation.

See also  CBD Oil And Methadone

Bah He shouted loudly, madly urging the cbd oil for polymyalgia rheumatica heavenly hegemony body, exuding a mighty aura, trying to get rid of this invisible control, but it was still difficult to do.

After an hour of rest, the cbd oil for polymyalgia rheumatica divine rune barrier around Ye Fan gradually dissipated, and then he stood up.

Once Donghuang cbd oil and fertility Aotian cbd oil for polymyalgia rheumatica is completely angered, and he may even use the power of Immortal Venerable to deal with Ye Fan, then things cbd oil for polymyalgia rheumatica will be troublesome It s cbd oil for polymyalgia rheumatica just that Ye Fan has made all the preparations.

Level 2 The power is definitely not his limit, cbd oil for polymyalgia rheumatica he has this confidence.

Is it It s ridiculous cbd oil for polymyalgia rheumatica The demon will be surrounded by the magic wind.

The more Ye Fan stimulated her potential, the stronger her determination to kill.

Immediately, Kanglong exited the border, turning the world around, and the powerful rays of light big oil calculator instantly suppressed the black clouds.

Zila, zila, zila Boom, boom, boom The mighty power of thunder is like the summoning of the god of death, cbd oil for polymyalgia rheumatica and cbd oil for polymyalgia rheumatica every landing can cut open a space.

Where. Originally, he thought that this Dao Enlightenment Flower was taken away by a strong man, and he went a step late.

No matter how Qi Hong attacks, he cannot break its defense.

Then it goes without saying that this is a high quality medicinal Where Can I Get cbd oil for polymyalgia rheumatica pill made by the father himself, even if the general elders don t have it Dong Huang said proudly.

Presumptuous Dongfang Xu exclaimed, the pair of pupils under the cloak became more and more red, and the momentum on cbd oil for polymyalgia rheumatica his body suddenly rose, as if it .

mayo clinic on cbd oil for copd

cbd delivery service Liv Labs Cbd Oil Reviews had risen to the extreme.

Such a breach of responsibility would make him the target of Wan Fu.

Suddenly, a cbd oil for polymyalgia rheumatica dark halo appeared behind the Heavenly Demon General, and then, countless voices resembling a spell appeared high in the sky, filling the surroundings continuously.

In his eyes, murderous aura boiled. cbd oil for polymyalgia rheumatica Ye Fan, you re crazy, what are you going to do Don t come here Shang Bin was frightened and retreated quickly, but where could he escape Ye Fan, I cbd oil for polymyalgia rheumatica beg you

Ah What Cbd For Fibromyalgia cbd delivery service Shang Bin was startled. He didn t expect Qi Hong to think it wasn t enough, but in order to survive, 75 mg cbd gummies he didn t dare to resist at all.

These noises were like the cbd oil for polymyalgia rheumatica roars of beasts from hell, constantly cbd oil for polymyalgia rheumatica corroding the hearts of the monks.

At this moment, Ye Fan is very close to the peak, and he can even see the scenery above the peak.

so. Just use this method to ease the atmosphere first, cbd oil for polymyalgia rheumatica hoping that Nan Yutian is not the kind of person who is difficult to talk.

Suddenly, a python sparrow shot out of her body, and an incredible change took place.

Although he was very arrogant, he was still unable to face the power of Immortal Venerable Law.

He is the real ants Let him go. Die Countless cultivators began to roar loudly, although they were suppressed by the divine light and could not see does cbd oil interact with alcohol clearly, they could feel the trembling and fear of the demon general.

He slowly got up benefits of indica edibles sh n , and then held out a cbd oil for polymyalgia rheumatica hand.

Although Ye Fan took the Taoist Flower and the Peach of Immortality, he cbd delivery service Liv Labs Cbd Oil Reviews was only a cbd oil for polymyalgia rheumatica cultivator of the Nine Ranks of Spirit Transformation.

Only with softness overcomes rigidity can we win the battle Once Dongfang Xu s moves are flawed, that s his chance.

, Ye Fan, you really know broad spectrum cbd gummies smilz how to put money on your face What kind of skills do you have, just say it, why do you use this kind of lie to cbd oil for polymyalgia rheumatica deceive us After Cbd For Fibromyalgia cbd delivery service Cbd Oil In Texas Legal cbd oil for polymyalgia rheumatica the curse of the monument, now I still want to confuse the public, damn it Zhou Ye laughed, he would never believe Ye Fan s words.

Okay, you are too fast cbd oil for polymyalgia rheumatica Ye Fan responded casually, but this made the front cast a contemptuous look smokymountainsk8way.com cbd oil for polymyalgia rheumatica at him.

This sacred mountain is too terrifying, and it may even have something to do with the origin of the Big Dipper Galaxy.

The wind accompanies the walk, the devil is indeed a person from a a cure for wellness dvd cover small dynasty, so cowardly Cowardly I think you are thinking the same question, if Ye Fan can really deprive other people of the power of the divine monument, who is there at the scene Aren t you worried The words of Feng s accompaniment made everyone s heart tremble.

my father has made great contributions to Da smokymountainsk8way.com cbd oil for polymyalgia rheumatica Xia Even if it cbd oil california s for my father, give me another Where Can I Get cbd oil for polymyalgia rheumatica chance Shang Bin began to take advantage of it again.

How Ye Fan was able to avoid his own attack from the God s Eye, which was completely beyond his expectations.

This Beidou No. 1 beauty is actually cbd oil for polymyalgia rheumatica Charlottes Web Cbd Oil Reddit cbd oil for polymyalgia rheumatica Charlottes Web Cbd Oil Reddit strong to this level, I don t know how high her vision is, and what level of arrogance can get her heart

On the ground, running internal strength to fight cbd oil for polymyalgia rheumatica against the magic sound.

Zhou Ye had always paid great attention to what others thought of him.

This road is difficult and dangerous, full of thorns.

The Kamikaze Dynasty has all been smokymountainsk8way.com cbd oil for polymyalgia rheumatica wiped quality cbd oil for purchase cbd delivery service out, and now it s their turn Even cbd delivery service Liv Labs Cbd Oil Reviews a prince level arrogant like cbd oil for polymyalgia rheumatica Charlottes Web Cbd Oil Reddit Feng Xingxing can t fight against the magic wind, let alone other people.

This idiot, his face cbd oil for polymyalgia rheumatica is thicker than the city wall If Duke Dingguo of Daxia cbd oil and ms saw his son, he was so brazen, he would be so angry that he would vomit blood Shang Bin is like a clown who exists for cbd oil for polymyalgia rheumatica everyone s entertainment.

Damn Ye Fan was furious, but helpless. This was originally a predicament that he cbd oil for polymyalgia rheumatica had to face alone, but he suddenly encountered Qi Linglong, but instead dragged him down.

He did not expect that Ye Fan would come everyday optional cbd gummies thc back cbd oil for polymyalgia rheumatica alive after going smokymountainsk8way.com cbd oil for polymyalgia rheumatica through such a dangerous situation.

I saw a smear of red cbd oil for polymyalgia rheumatica blood on the tip of her cbd gummies 500mg side effects index finger shocking On the Jiuxiao Huanpei Guqin, a string was also broken.

Many of them have profound cultivation and have seen too many big scenes, but what they saw today is enough to cbd oil for polymyalgia rheumatica Charlottes Web Cbd Oil Reddit make them unforgettable forever.

If you want to fight me, you have to deal with this catastrophe as well as me, hahaha, your cultivation is impossible to stand up to.

Qiang Suddenly, the swords finally intersected.

Qi Linglong s expression did not change, but her eyes were suddenly sharp, and there was a breathtaking Cbd For Fibromyalgia cbd delivery service sharpness in her cbd oil for polymyalgia rheumatica Charlottes Web Cbd Oil Reddit eyes.

How is this possible, what s going on with this kid Donghuang Aotian couldn t believe what he saw.

It cbd delivery service Liv Labs Cbd Oil Reviews s a young woman There was a huge wave in Ye Fan s heart, and he was beyond cbd oil for polymyalgia rheumatica surprised.

Boom cbd oil for polymyalgia rheumatica Charlottes Web Cbd Oil Reddit With a roar, the move of the Purple Emperor s Colossal Sword cbd oil for polymyalgia rheumatica Cbd Oil In Texas Legal cbd oil for polymyalgia rheumatica was broken cbd oil for polymyalgia rheumatica again.

she is cbd oil for polymyalgia rheumatica Where Do You Buy Cbd Oil already dead, just a corpse Qi Linglong s tone was filled with regret.

Tu Gang also noticed Ye Fan s situation. He began to think that Ye what type of cbd oil should i use to treat anxiety Fan was hiding his strength, but he was unwilling to believe it.

so sublingual thc not working that he can carefully look for cbd oil for polymyalgia rheumatica a suitable Tiandao stone.

The power is infinite and the energy is so great that even he himself is a little out of control.

No matter what kind of powerhouse, seeing such a terrifying move, I am afraid they will be frightened.

Jiuzhong Zhenxian, or even

Many people didn t know what cbd delivery service Liv Labs Cbd Oil Reviews it was, but many of those old strongmen stood up directly.

He didn t expect that Donghuang Aotian would actually use such a magic weapon in order to gain smokymountainsk8way.com cbd oil for polymyalgia rheumatica the approval of this celestial stone.

Ye Fan replied. Seeing Ye Fan s 9th rank cultivation level, he could actually withstand Nan Yutian s invisible aura.

Nine tribulations are born, heaven and earth are lost, ten thousand stars are dim and life is dim

See also  Fx CBD Oil For Dogs

Ye Fan felt the powerful power of the Heavenly Dao Stone, cbd oil for polymyalgia rheumatica and as time passed, the power of the eight dragons gradually .

can you use expired cbd oil

condensed, as if an ancient dragon was about to be born.

You should know it clearly Yan Qingsi said.

In an instant, cbd delivery service Liv Labs Cbd Oil Reviews the entire field smokymountainsk8way.com cbd oil for polymyalgia rheumatica seemed to be transformed into cbd oil or hemp oil is there a difference between a sea of sword energy, and endless sword energy emerged, tearing the sky, smashing the space, and sweeping out long ravines in the sky, which was extremely terrifying.

Suddenly, a voice appeared cbd oil for polymyalgia rheumatica in the sky, making Ye Fan cbd oil for polymyalgia rheumatica feel familiar, but with a strange aura.

Ah With smokymountainsk8way.com cbd oil for polymyalgia rheumatica a scream, the old man was severely injured.

Only in this way can he have a chance of life.

how is this possible It s too powerful Ye Fan s face changed wildly, and he broke out in a cold sweat, secretly thinking that he underestimated the strength of Nine Tribulations Phoenix .

isolate direct cbd oil

No I m not going, I m giving up, I don t want to die

The power of thunder and lightning in the sky gradually began to condense.

Although Qi Hong .

glaucoma and royal cbd oil

is not cbd oil for polymyalgia rheumatica a member of the Wanlong Dynasty, Ao Zhan still feels pity for him, which is the pity of the entire Big Dipper galaxy.

They cbd oil for polymyalgia rheumatica are also very clear that all fetishes have spirituality and can do this Have you found it I still haven t.

it is good Yan Qingsi walked slowly to the center, her beautiful eyes Cbd Oil In Texas Legal cbd oil for polymyalgia rheumatica closed tightly, and an invisible spiritual power emanated from her delicate body.

Yan Qingsi and Tu Gang both felt that domineering, this was due to luck.

Although it was broken by Qi Hong before and there were cracks, the Ancestral Emperor Mirror was Qin Baxian s magic weapon after all, and cbd oil for polymyalgia rheumatica it carried the imperial luck of Daxia.

people think that Ye Fan can return to the peak, if it is true cbd oil for polymyalgia rheumatica If it smokymountainsk8way.com cbd oil for polymyalgia rheumatica is like that, this behavior will cbd oil for polymyalgia rheumatica make a lot of money.

At this moment, the momentum is like a rainbow.

Seeing Donghuang Aotian cbd oil for polymyalgia rheumatica s confident appearance, Yan Cbd For Fibromyalgia cbd delivery service Qingsi shook her head.

I don t know how many soldiers have fallen on the ancient battlefield.

What happened Suddenly, Ye Fan felt that the pulsation came from the position of the goddess s chest, and it was very rhythmic.

The blood continued to gather on the blood finch she summoned, and the entire space fell into the shroud of blood light.

No one could imagine that he still cbd delivery service had such magical cbd oil for polymyalgia rheumatica powers, making Qi Hong s moves a joke.

Your access to this site has been limited by the site owner

If you think you have been blocked in error, contact the owner of this site for assistance.

If you are a WordPress user with administrative privileges on this site please enter your email in the box below and click “Send”. You will then receive an email that helps you regain access.

Block Technical Data

Block Reason: Access from your area has been temporarily limited for security reasons
Time: Wed, 14 Sep 2022 7:20:31 GMT

Cannabis and Cannabinoids in the Treatment of Rheumatic Diseases

This is an open-access article. All its content, except where otherwise noted, is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.

INTRODUCTION

Chronic pain is commonly defined as pain that lasts for longer than three to six months and is a common complaint among many patients seeking medical attention. 1 The prevalence of chronic pain among the adult population in certain countries is estimated to be as high as 30%, 2 and rheumatic diseases are a leading cause for chronic pain. 3 Analgesia in rheumatic diseases is often an important part of treatment, especially since disease remission and response to therapy do not always entirely eliminate pain. In rheumatoid arthritis (RA) patients, it had been shown that pain can persist even with the achievement of clinical targets, and that pain was also the most common residual symptom associated with RA remission or low disease activity. 4 In this review, we will discuss the potential of using cannabis and cannabinoids in the treatment of rheumatic disease, based on the literature existing on this issue.

Management of chronic pain is difficult, and patients are often unsatisfied with the effect of treatment. 5 Drug options that are currently available may not be very safe for certain patient populations. Opioids are a problematic long-term solution for chronic pain, due to the risk they carry of significant adverse events, addiction, and overdose. 6 Opioid use was also found to be associated with more severe symptoms and unemployment in fibromyalgia. 7 Other drugs used to treat chronic pain, such as antidepressants (e.g. serotonin-norepinephrine reuptake inhibitors [SNRIs], tricyclic antidepressants [TCAs]), have been shown to be useful for this indication but have certain side effects (e.g. increased risk of cardiovascular events and falls with TCAs) that might limit their use in older patients. 8 One solution for long-term pain that has been studied in the context of pain relief in rheumatic diseases—but not thoroughly enough—is the use of cannabis or cannabinoids, which may potentially show therapeutic qualities as well. 9

CANNABINOIDS

It is assumed that the plant Cannabis sativa exerts its effects on human physiology through substances it contains, termed phytocannabinoids (over 100 of them have already been isolated so far). Those phytocannabinoids are thought to bind cannabinoid receptors throughout the human body, to which endocannabinoid (i.e. cannabinoids produced by human tissue) bind as well. Of the phytocannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most well-studied and are used as medications. Tetrahydrocannabinol is considered to be the more psychoactive component in cannabis, while CBD is considered to be the major non-psychoactive component. Cannabinoid receptors are found in a variety of tissues throughout the body—from neurons in the frontal cortex, to the gastrointestinal tract and immune cells as well. 9 According to the “entourage theory,” the combination of THC and CBD creates a synergistic effect in which other phytocannabinoids possibly take part as well, suggesting that there could be a benefit in using cannabis rather than synthetic cannabinoids as analgesic or therapeutic agents. 10

FIBROMYALGIA

Fibromyalgia is a common chronic pain syndrome causing diffuse pain, tenderness, fatigue, and sleep disturbances. Other complaints include cognitive symptoms, as well as headaches. 11 The prevalence of fibromyalgia is estimated at 2.7% globally. 12 Without a known pathophysiology and etiology, and therefore in the absence of disease-modifying or definitive treatment, analgesia is a significant part of fibromyalgia symptomatic treatment. Fibromyalgia patients may respond to certain pharmacological agents (e.g. antidepressants and anticonvulsants) or to other interventions such as aerobic exercise, physical therapy, and rehabilitation programs (non-pharmacological interventions were recommended as the first line of treatment in recent European League Against Rheumatism [EULAR] guidelines 13 ).

Fibromyalgia pain shares certain common characteristics with neuropathic pain, 14 and both are thought to involve a mechanism of central sensitization. 15 It should also be noted that current guidelines recommend treating it with similar agents to those used in neuropathic pain. 13

Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID) usually used for the treatment of musculoskeletal pain, was not found to be an effective treatment option, 16 and a randomized double-blinded study that compared the addition of etoricoxib, a selective COX-2 inhibitor, to pre-existing medical therapy with the addition of placebo in female fibromyalgia patients found that etoricoxib did not improve patients’ pain, sleep, or disability parameters. 17 While tramadol (a weak opioid with mild SNRI activity) was found to be potentially effective in alleviating fibromyalgia pain, 13 opioids in general may cause an exacerbation of symptoms in this patient population. 7 Cannabis and cannabinoids were recommended for the treatment of neuropathic pain, 18 and, due to the similarities between neuropathic pain and fibromyalgia, as previously mentioned, it is not unreasonable to hypothesize that cannabis or cannabinoids might be effective for fibromyalgia-associated pain as well.

Data regarding the use of cannabinoids in the treatment of fibromyalgia consist of several studies investigating the use of nabilone—a synthetic analog of THC—and fewer in which cannabis was used. Two studies evaluating the use of nabilone in fibromyalgia were included in a Cochrane review that found that nabilone was not superior to placebo or amitriptyline (a TCA) in relieving fibromyalgia symptoms, 19 – 21 as neither study provided high/moderate-quality evidence for efficacy. However, one study included in this Cochrane review did show very low-quality evidence that nabilone compared with placebo led to a decrease in pain and anxiety as well as to an improvement in health-related quality of life. 21 In the other study included in this Cochrane review, very low-quality evidence that nabilone was superior to amitriptyline in improving sleep was found. 20 While cannabinoids were not suggested as treatment for fibromyalgia in the aforementioned Cochrane review, The National Academies of Science, Engineering, and Medicine suggested in their 2017 report that there was moderate evidence that cannabis or cannabinoids are effective for fibromyalgia. 22

See also  CBD Oil Brain Cancer

In an observative study in which 28 fibromyalgia patients treated with cannabis were compared with 28 controls, significant pain relief, reduction of stiffness, and increase in relaxation and perception of well-being were all found, and were evaluated by visual analog scale (VAS) before and 2 hours after cannabis self-administration. 23 More compelling results emerge from a study that included fibromyalgia patients in Israel. In a recent publication by Sagy et al., 24 a prospective observational study was conducted, in which 367 fibromyalgia patients were treated with medical cannabis and followed up at six months. A total of 81.1% of patients achieved treatment response, and pain intensity decreased significantly from a median of 9 at baseline to 5 at six months (on a numeric rating scale of 0 to 10, with 0 being no pain, and 10 being worst pain imaginable). Dizziness, dry mouth, and gastrointestinal symptoms were among the most common side effects of the treatment. In a recent retrospective review, Habib and Artul 25 assessed 26 fibromyalgia patients treated with medical cannabis, using the Fibromyalgia Impact Questionnaire. The mean duration of cannabis treatment was 10.4 months, and the mean dose of cannabis was 26 g per month. Significant improvement was reported in every item of the questionnaire after cannabis treatment, and 50% of patients stopped using any other medical therapy for fibromyalgia. Adverse effects were mild and were reported by 30% of patients.

In another study, Habib and Avisar employed questionnaires on social media to reach out to Israeli fibromyalgia patients using cannabis 26 and found that, of 383 responders, 323 (84%) reported consuming cannabis; 142 (44%) of these were licensed to do so. The majority of patients reported pain relief (94%) and improved sleep quality (93%). Depression and anxiety were both also reported to improve under cannabis use by the patients. Most of the reported adverse effects were mild (e.g. eye or throat irritation); 12% reported experiencing adverse effects.

In another recent study that assessed the analgesic effect of inhaled cannabis with varying concentrations of THC and CBD, pressure and electrical pain thresholds, spontaneous pain scores, and drug high were measured before and after cannabis inhalation. The results showed that cannabis strains containing THC led to a significant increase in pressure pain threshold compared with placebo. However, no strain of cannabis was found to be superior to placebo’s effect on spontaneous or electrical pain responses. Drug high was assessed by the Bowdle questionnaire and was found to occur in 40%–80% of the subjects treated with inhaled cannabis, compared to 10% of the subjects in the placebo group. 27

RHEUMATOID ARTHRITIS, OSTEOARTHRITIS, AND SYSTEMIC SCLEROSIS

Cannabis and cannabinoids were investigated as substances that can ameliorate chronic pain and other symptoms associated with rheumatic disease. However, it had also been suggested that cannabinoids have an inflammatory-modulating quality that could exert a therapeutic effect in such conditions, as cannabinoids were shown to have an overall anti-inflammatory effect on immune cells; these results were reinforced by studies in animal models of RA and systemic sclerosis (SSc). 9

In RA and osteoarthritis (OA), for example, the hypothesis that cannabinoids may have a disease-modifying quality is based on animal models, as well as in vitro studies that have shown that the synovia of RA and OA patients contained two endocannabinoids that the synovia of healthy controls did not. Results of the same study showed that, in fibroblast-like cells obtained from RA and OA patients, cellular receptors ERK-1 and ERK-2 underwent phosphorylation in response to cannabinoid stimulation, an effect which was attenuated by a cannabinoid receptor antagonist. 28

In another study, synovial tissue obtained from RA patients was shown to undergo attenuation and inhibition of cytokine production in response to a cannabinoid binding a cannabinoid receptor. 29 Animal models also suggest a possible therapeutic quality for cannabinoids in RA, with three studies using a murine model with collagen-induced arthritis showing a beneficial effect of the cannabinoids CBD, JWH-133, and HU-308. These substances were found to be associated with clinical improvement: CBD was associated with a decrease in cytokine release and production as well as a decrease in lymphocyte proliferation 30 ; JWH-133 was associated with a decrease in serum antibody levels, decreased cytokine production, and reduced bone destruction 31 ; and HU-308 was associated with less joint swelling and destruction, reduced synovial inflammation, along with a decrease in serum antibody levels. 32 Despite these promising results, clinical research focusing on cannabinoids’ disease-modifying qualities is still lacking.

The use of cannabinoids for the relief of pain associated with RA has been assessed by one study 33 which showed that, in comparison with placebo, the cannabis-based drug was associated with significant improvements in certain pain parameters and quality of sleep. With regard to drug safety, the study found no serious adverse effects in the active treatment group, with most adverse effects being mild or moderate.

In OA, a murine model with surgically induced OA showed that the severity of the disease was reduced in wild-type compared with mice that have undergone gene-deletion for a presumed relevant cannabinoid receptor. The same study also showed that treatment of wild-type mice with an agonist for the same cannabinoid receptor resulted in a partial protection against OA that did not occur in the gene-deletion group or in the wild-type placebo group. 34 In another study, the activity of an enzyme suspected of causing cartilage breakdown was reduced by the treatment of chondrocytes from OA patients with a cannabinoid. 35 Only one clinical trial assessed the use of an endocannabinoid modulator in OA for pain relief, and this was not found to be significantly more beneficial for OA-associated pain than placebo. 36 Other clinical trials assessing the use of cannabis and cannabinoids for OA are currently ongoing or are yet to be published. 37

Several studies have also shown that cannabinoids and cannabinoid receptors might play a role in SSc, as cannabinoid receptors have been shown to modulate SSc in murine models, 9 and were also found to be over-expressed in SSc fibroblasts. 38 A study on a murine model also found that treatment with cannabinoids prevented the development of cutaneous and pulmonary fibrosis and decreased the proliferation of fibroblasts and antibody development. 39 A clinical trial of a novel oral selective cannabinoid receptor agonist is currently in phase 3, after showing a statistically significant effect on skin fibrosis. 40

Research from recent years has shown some promising results regarding the potential of cannabinoids as disease-modifying therapeutics in rheumatic disease. To further investigate this theory, clinical trials should be conducted to evaluate the disease-modifying quality of cannabis in certain rheumatic diseases.

However, despite the evidence on the potential of cannabis and cannabinoids in the treatment of rheumatic disease and the pain associated with it, the literature regarding the use of cannabis as treatment for chronic pain in general contains conflicting reports. While The National Academies of Science, Engineering, and Medicine found in their 2017 report that there was substantial evidence that cannabis or cannabinoids effectively managed chronic pain in adults, 22 and in 2015 an updated review of randomized controlled trials suggested that cannabinoids are a reasonable treatment option for chronic non-cancer pain, being safe and “modestly effective,” 41 other reviews were less supportive of those claims.

An overview of systematic reviews on the efficacy and safety of cannabis-based medications for chronic pain concluded that there was insufficient information to recommend cannabinoids as treatment for chronic pain in rheumatic disease, 42 and a systematic review and meta-analysis from 2018 on the treatment of non-cancer chronic pain with cannabis and cannabinoids claimed that the number needed to treat to benefit was high and the number needed to treat to harm was low, and that the evidence for effectiveness of cannabinoids for chronic non-cancer pain was insufficient. 43 It should be emphasized that while the reviews cited in this paragraph evaluated studies and systematic reviews in which cannabis was used to treat chronic pain of many etiologies, in this article we wish to focus on the potential of cannabis as treatment for chronic pain caused by rheumatic diseases only. In a recent review of this topic, Sarzi-Puttini et al. 44 discussed the pros and cons of medical cannabis in the treatment of rheumatic diseases, claiming that, given the evidence currently available, cannabis should only be used as complementary treatment in rheumatic diseases at the moment, until high-quality evidence is found.

CONCLUSION

In conclusion, we believe that the use of cannabis and cannabinoids for pain relief in rheumatic diseases (and fibromyalgia in particular) shows great potential and may be a source of hope for those suffering from chronic pain associated with those conditions, and for the physicians treating them. More research into this question should be conducted, especially among larger cohorts of patients and for longer periods of time, to assess for long-term efficacy and adverse effects. 45 At this point, the data suggest that the use of cannabinoids and cannabis carries limited side effects in the treatment of rheumatic disease, 46 although drug interactions should always be kept in mind. 9 Research also suggests that cannabis and cannabinoids can improve some common and debilitating symptoms of rheumatic disease, thus making them an adequate potential treatment option in our opinion, when other treatment lines have been exhausted.

How useful was this post?

Click on a star to rate it!

Average rating 3 / 5. Vote count: 1

No votes so far! Be the first to rate this post.