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Cbd oil for arthritis and osteoperosis

CBD Oil for Osteoporosis

According to the International Osteoporosis Foundation 1 , this condition affects an estimated 75 million people in Europe, the United States, and Japan. It is estimated to affect 200 million women worldwide – approximately one-tenth of women aged 60.

What is Osteoporosis?

Also known as “porous bones”, Osteoporosis causes bone loss. It’s the loss of tissues, thus resulting in fragile and brittle bones. This means that patients with Osteoporosis have poor bone health as these parts have a lowered density. This makes them especially prone to fractures or other injuries. In worse cases, this disease might deform the normal physical structures. Osteoporosis can trigger issues such as spine deformities.

Symptoms & Causes for Osteoporosis

Symptoms

There are typically not many symptoms in the early stages of Osteoporosis. Once your bones have been weakened by the bone loss, you may have signs and symptoms that include:

  • Back pain, caused by a fractured or collapsed vertebra
  • Loss of height over time
  • A stooped posture
  • Bone fracture that occurs much more easily than expected

Risk Factors

Women are more likely to develop Osteoporosis. This is because they can quickly lose bone mass in the first couple of years after menopause.

Other risk factors could include:

  • Overactive adrenal glands
  • Overactive thyroid
  • Low level of sex hormones
  • Using corticosteroids for a long time
  • Medical issues like inflammatory or hormone-related conditions
  • A lower BMI than average
  • Heavy drinking and smoking
  • Frequent use of medications which affect bone strength, bone density or hormone levels negatively

Why can CBD oil work for Treating Osteoporosis?

Over the past few decades, researchers have found out the presence of some cannabinoid receptors such as CB1 and CB2 in bone tissues. Indeed, these elements play an essential role in bone health.

CB2 is expressed predominantly in osteoclasts (bone-resorbing cells) and osteoblasts (bone-forming cells). This kind of cannabinoid receptor is necessary for the regulation of your bone metabolism. Physiologically, it is important to keep a balance between osteoclasts and osteoblasts as it would maintain optimum bone health. As people age, this balance would be impaired, and result in bone fractures or loss of bone density.

CB2 agonists like cannabidiol (CBD) could be used to modulate the functions of these receptors 2 . They can improve the activity and count of osteoblasts while inhibiting the expression of osteoblasts and the proliferation of osteoclasts. These elements can also stimulate the formation of Endocortical bones, suppress bone losses and maintain a normal mass of bone. CB1 receptors, on the other hand, can be activated to inhibit a chemical known as norepinephrine 3 .

This element might delay the formation of your bones and the bone density, adjust the rate of reabsorption and lead to some bone issues.

Recent studies have proven that the use of Cannabidiol (CBD) oil can have positive effects on these receptors, thus alleviating symptoms as well as slowing the progression of osteoporosis.

CBD oil is available in various forms and concentrations, including liquid or thick paste, oil, capsules, gum or candy, salves, sprays or drops, and vapor.

What are the Benefits of Using CBD oil for Osteoporosis?

Over the years, studies have shown that CBD oil and other CBD products have 2 distinct benefits in osteoporosis treatments. Firstly, it would negatively modulate CB2 and CB1 receptors, thus reducing their capability of binding to agonists, a compound which activates them 4 . This is often called the entourage effect, meaning that using CBD oil can help reduce the effects of other compounds that serve as the same cannabinoid receptors.

What’s more, CBD can inhibit several enzymes such as FAAH and increase the effects that they would exert on these cannabinoid receptors. As a result of these effects, researchers have suggested that CBD is effective and helpful in lowering the risks of bone problems and enhancing health.

The Endocannabinoid System & Bones

The Endocannabinoid System (ECS) plays an essential role in the regulation of osteoclast and osteoblast activities 5 . This means if any problem happens in this area, it might lead to a number of conditions, including osteoporosis. There is also evidence to show your ECS might determine the development of a low bone mass 6 . Indeed, a lack of the endocannabinoid receptors in your brain has been linked to a higher turnover of bone.

Essentially, your body might keep “retiring” old bone cells without producing enough new ones for replacement. However, if these receptors could be stimulated with the help of cannabidiol (CBD), the bones are more likely to maintain its function even after many years.

In general, the ECS consists of cannabinoid receptors that are activated by several elements like CBD. The endocannabinoids are basically generated and degraded by a few types of enzymes, this giving this system a role in controlling some essential activities. Consequently, reduced numbers of endocannabinoid receptors are linked to the development of osteoporosis.

CBD oil dosage for Osteoporosis

As a rule of thumb, the dosage of CBD oil or for osteoporosis treatments can vary a lot depending on the level of intensity. It is advisable to start small and increase the CBD dosage gradually until you get the desired results. A standard dose of between 10mg and 100mg of CBD per day is recommended by the CBD experts Leinow and Birnbaum in thier book “CBD: A Patient’s Guide to Medicinal Cannabis”.

The Step-up Method

An in-depth guide of how to dose your CBD has been given in the book CBD: A Patient’s Guide to Medicinal Cannabis by Leinow and Birnbaum 7 . The authors have introduced their Step-Up Method, where they recommend different types of dosage according to weight and condition. To find out how to follow Leinow and Birnbaum’s guide, read our post on CBD dosage.

Is CBD good for Osteoporosis?

A study by French scientists has suggested that human bones come with a higher level of endocannabinoids and ligands than brain cells 8 . Also, a naturally generated cannabinoid in our body named Anandamide could have an effect on the bone tissues. Anandamide helps to bind to those CB2 receptors. They also pointed out that CBD can imitate Anandamide, thus positively affecting bone health in those people who suffer from osteoporosis.

Another study by Idris Al focused on the important part of cannabinoid receptors in treating osteoporosis 9 . The results suggested that CBD is likely to affect bone metabolism and ligands. Therefore, these products can be used for bone fractures and other issues as they may be applied to exploit the cannabinoid receptors for targeting anabolic therapy and anti-resorptive.

A published study in 2015 by researcher Kogan Niemand 10 has found that when mice were treated with CBD oil, the maximal loads on their bones significantly increased. Also, he discovered that using CBD could speed up the process of healing fractures or broken bones, as well as slow down the loss of bone density.

As reported by the World Health Organisation (WHO), cannabidiol is considered safe and has only few side effects and only in rare cases.

CBD for Osteoporosis: Can Hemp Oil Help Reverse Bone Loss?

Exciting new research has been exploring CBD’s powerful ability to speed fracture healing and preserve bone density.

Learn how it works and how to use CBD products for osteoporosis effectively.

Article By

Estimates suggest more than 200 million people have osteoporosis around the world [1].

According to the International Osteoporosis Foundation, osteoporosis is responsible for a staggering 8.9 million bone fractures annually — meaning there’s an osteoporotic fracture roughly every three seconds [2].

Often referred to as a “silent disease,” many people don’t realize they have the condition until a fracture occurs.

Here, we will discuss osteoporosis, current treatment options, and scientific research on how CBD can help.

MEDICALLY REVIEWED BY

Updated on June 05, 2021

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How Does CBD Help With Osteoporosis?

CBD (cannabidiol) is the primary non-psychoactive compound in cannabis. It’s been shown to support bone metabolism indirectly through its effects on the endocannabinoid system (ECS).

The ECS is a complex network of receptors that work to regulate various aspects of our health — including the formation and degeneration of bone [3]. Through this system, CBD is thought to help reduce bone loss and promote the regeneration of lost bone tissue.

CBD should always be used in combination with other therapies for maximum benefit. CBD is not a cure for osteoporosis, but can offer a powerful supportive role when used alongside other medications, supplements, and exercises.

The benefits of CBD oil for osteoporosis may include:

  • May improve the density of bones
  • Alleviates pain & inflammation
  • Supports hormone balance
  • Relieves pain from bone fractures

1. CBD May Improve Bone Density

Research has discovered that CBD appears to enhance the growth and strengthening of bones through accelerated osteoblast formation.

Researchers believe that osteoclasts — the cells that breakdown bone — have a cell receptor that, when activated, speeds up bone loss and degeneration. This receptor is known as GPR55. CBD has been shown to specifically block the activation of this receptor, reducing osteoclast activity [5].

Further, in a recent study in Israel, mice were given CBD or a combination of THC and CBD. The study found that the administration of CBD alone has significant effects on fracture healing with increased bone strength and toughness by stimulating Lysyl Hydroxylase — an enzyme involved in bone healing [5].

This research has given us a deeper insight into how CBD influences the body and opens up some exciting potential for further research.

2. CBD Alleviates Pain & Inflammation

CBD may have a therapeutic role in inflammation and healing. It has long been used by people with chronic pain and offers a non-habit-forming alternative to pain medications.

Many patients have reported replacing their prescription pain medications with CBD, with evidence that its use can help in the treatment of headaches, mental health disorders, insomnia, arthritis, and other chronic pain syndromes [6].

What’s The Dose of CBD Oil For Osteoporosis?

The key is to start low and go slow.

As yet, there are no standardized dosing guidelines for CBD use. CBD oil can come in many different strengths. As products vary greatly, it’s important to read the label of the specific product you are using.

When it comes to managing osteoporosis, the benefits will take several months before any change is noticed. We recommend starting with a moderate dosage (based on your weight using our CBD oil calculator below).

If you experience side-effects (more on this later), reduce the dose until they disappear.

CBD Oil Dosage Calculator

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Is CBD Oil Safe?

CBD is safe, even at high doses — but there are a few exceptions to be aware of.

According to the WHO, CBD oil, in its pure state, does not cause harm or have the potential for abuse — even at high doses [7].

If you’re using any prescription medications, or have underlying health issues, you should always speak with your doctor before taking CBD. Certain medications may interact with CBD and lead to side-effects.

What is Osteoporosis?

Osteoporosis means “porous bones.” It results in fragile bones. The weakness of the bones puts those affected at a higher risk of fractures.

As the bones become thinner, even a minor fall or bump can cause a serious injury.

Middle-aged women are at the highest risk — however, men are also affected.

The main concern most people have when talking about osteoporosis is the high risk of bone fracture. A fracture is a complete or partial break in a bone.

It’s estimated that 50% of women and 20% of men over the age of 50 will have an osteoporosis-related fracture in their lifetime [1].

With osteoporosis, the most common bones affected are the hip, wrists, and spine. Fractures and breaks can lead to chronic pain and mobility issues.

Understanding the Definitions
  1. Cortical bone — the hard outside layer of all bones and makes up most of your skull and ribs.
  2. Spongy bone — occurs inside the vertebrae and the ends of the long bones, such as the thigh bones.
  3. Osteoblasts — specialized cells involved in producing new bones.
  4. Osteoclasts — specialized cells involved in breaking down bones.
  5. Bone density — the amount of mineral content in a bone.

Symptoms of Osteoporosis

There are no specific symptoms of osteoporosis — the first sign is usually a bone fracture. There are other symptoms, but these can be difficult to identify.

Other signs and symptoms may include:

  • Back pain
  • Collapsed or fractured vertebra
  • Loss of height
  • Stooped posture
  • Lowered grip strength

Menopause & Osteoporosis

In osteoporosis, there is a thinning of the cortical bone and reduced bone density and structure in the spongy bone. Menopause is one of the main causes of the condition.

Bone tissue is continuously broken down and replenished. It’s a regular cycle, fluctuating on both a daily and monthly basis — affected by things such as time of day, diet, and season.

Specialist cells within the bones called osteoblasts and osteoclasts are essential for these fluctuations in healthy bones. From birth to adolescence, more bone is formed than broken down.

By the end of adolescence, bone growth has completed. By your mid to late 20s, peak bone mass has been achieved.

The sex hormones estrogen and testosterone have a major role in maintaining healthy bones in both men and women.

In menopause, as estrogen levels drop, the balance of hormones that were working to control bone density begins to fall apart. The result is an acceleration in bone loss. Women can lose up to 10% of their total bone mass within the first five years of menopause.

Risk Factors for Osteoporosis

  1. A family history of osteoporosis
  2. Previous bone fractures
  3. Age — people over 50 are at the highest risk
  4. Early menopause — before the age of 45
  5. Weight — being overweight is a major risk factor
  6. Vitamin D — important in the maintenance of bone tissue
  7. Calcium intake — calcium is a key mineral in bone architecture
  8. Lack of exercise — weight-bearing exercises directly lower the risk of osteoporosis
  9. Smoking (linked with osteoporosis)
  10. Alcohol intake — over three standard drinks per day increases the risk of osteoporosis [1]
  11. Medications — such as corticosteroid use
  12. Medical conditions — such as thyroid problems, celiac disease, chronic liver disease, kidney disease, or rheumatoid arthritis
  13. Conditions that affect the absorption of nutrients — such as Crohn’s disease, celiac disease, and other inflammatory bowel conditions

Diagnosing Osteoporosis

If osteoporosis is suspected, your doctor will most likely send you for a bone density scan.

This scan is used to measure bone mineral density (BMD). It is usually performed using a dual-energy x-ray absorptiometry (DEXA). This is a non-invasive process where, for 10 to 15 minutes, a machine passes over your body while you lie flat on a table.

The bone density scan will give you a T-Score and Z-Score, used to determine your risk of developing a fracture and whether further tests are needed.

According to the World Health Organization (WHO), your T-Score is classed as follows:

  • -1.0 or above is normal bone density.
  • Between -1.0 and -2.5 means you have low bone density or osteopenia.
  • -2.5 or below is a diagnosis of osteoporosis.

The following procedures can also be performed to determine bone injury or fractures as a result of osteoporosis:

1. Bone X-Ray

Bone x-rays produce images of bones that aid in the diagnosis of fractured bones, which are sometimes a result of osteoporosis.

2. CT Scan

CT scans of the spine are used to assess alignment and fractures. They can be used to measure bone density and determine whether vertebral fractures are likely to occur.

3. Magnetic Resonance Imaging (MRI)

An MRI of the spine is used to evaluate vertebral fractures for evidence of underlying diseases, such as cancer, and to assess the newness of the fracture.

How is Osteoporosis Treated?

Depending on how severe your osteoporosis is and your risk of bone fracture, your doctor may recommend lifestyle changes to strengthen your bones.

Lifestyle changes can help to ensure both men and women take steps to prevent the risk of developing osteoporosis.

1. Lifestyle & Diet Changes
  1. Incorporate a varied diet with plenty of fresh fruit, vegetables, and whole grains
  2. Avoid smoking
  3. Reducing alcohol intake
  4. Limit caffeine
  5. Do regular weight-bearing and strength-training activities
  6. Ensure adequate vitamin D and calcium intake

However, if your osteoporosis is more advanced, lifestyle changes alone may not be enough to help you strengthen your bones.

Prescription medications are standard care in the treatment of established osteoporosis. Their purpose is to either increase the formation of new bone or slow down the breakdown process.

However, they each come with their own set of side-effects and risks.

2. Bisphosphonate Medications

Bisphosphonates encourage bone density by slowing the breakdown of cells. You can take them with a combination of vitamin D and calcium supplements.

Side-Effects of Bisphosphonates:

3. Selective Estrogen Receptor Modulators (SERMs)

SERMs mimic estrogen in the body, reducing bone loss and increasing bone formation.

Side-Effects of SERMs:

4. Denosumab

This is given via an injection under the skin twice a year. It slows down the breakdown of bone, resulting in higher bone mineral density and reduced fractures. It is often used as an alternative to bisphosphonates.

Side-Effects of Denosumab:

5. Hormone Replacement Therapy (HRT)

Doctors prescribe HRT for women during menopause when there is a drop in estrogen levels, increasing the risk of osteoporosis. However, HRT is no longer routinely recommended due to the increased risks with long-term use.

Side-Effects of HRT:

6. Testosterone Therapy

When testosterone levels are low in men, doses of testosterone are given by injection to improve bone density.

Side-Effects of Testosterone Therapy:

  • Acne and oily skin
  • Worsening of sleep apnea
  • Increased risk of blood clots
  • Increased risk of prostate abnormalities
  • Enlarged breasts in men
  • Decreased testicular tissue
  • Increased aggression, mood swings
  • Increased risk of heart disease and stroke (maybe)

Final Verdict: Using CBD for Osteoporosis

Osteoporosis can be a debilitating disease, and the fear of bone fracture can have a significant effect on one’s lifestyle and mobility.

While there is no cure, there is good evidence that CBD may be an effective treatment for osteoporosis by slowing down the progression of the disease and relieving pain.

These are very exciting times, especially as we look at CBD and the clinical research that’s still in its infancy regarding verifying its use in reducing bone loss and fracture.

Based on this information, CBD is seen as a safe, effective, all-natural therapeutic treatment for osteoporosis.

Cannabidiol: A Brief Review of Its Therapeutic and Pharmacologic Efficacy in the Management of Joint Disease

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Cannabis use in the management of musculoskeletal diseases has gained advocacy since several states have legalized its recreational use. Cannabidiol (CBD), a commercially available, non-neurotropic marijuana constituent, has shown promise in arthritic animal models by attenuating pro-inflammatory immune responses. Additional research has demonstrated the benefit of CBD in decreasing the endogenous pain response in mice subjected to acute arthritic conditions, and further studies have highlighted improved fracture healing following CBD use in murine mid-femoral fractures. However, there is a lack of high-quality, novel research investigating the use of CBD in human musculoskeletal diseases aside from anecdotal accounts and retrospective reviews, perhaps due to legal ramifications limiting the enrollment of patients. The purpose of this review article is to highlight the extent of current research on CBD and its biochemical and pharmacologic efficacy in the treatment of joint disease, as well as the evidence for use of CBD and cannabis in patients undergoing joint arthroplasty. Based on available literature relying on retrospective data and case reports, it is challenging to propose a recommendation for CBD use in perioperative pain management. Additionally, a number of CBD products currently available as supplements with different methods of administration, and it is important to remember that these products are non-pharmaceuticals. However, given the increased social relevance of CBD and cannabis-based medicines, future, prospective controlled studies evaluating their efficacy are needed.

Introduction and background

With the ever-growing commercial market for cannabidiol (CBD), a derivative of cannabis, there is no doubt that its proposed therapeutic value merits high-quality and novel research, particularly in the management of joint pain. Osteoarthritis is the most common joint disorder in the United States, affecting approximately 27 million Americans [1]. Furthermore, the volume of total joint arthroplasty procedures in the United States has sustained continuous growth over the past two decades, with a projected increase in total hip and knee replacements nearing 71% and 85% over the next 10 years, respectively [2]. Therefore, in conjunction with other, well-studied non-opioid treatment options, CBD may prove to be a beneficial pharmacologic modality for the treatment of joint pain. CBD is a marijuana constituent that has pharmacologic benefits without the additive psychotropic effect of Δ9-tetrahydrocannabinol (THC), another major cannabis ingredient. Currently, anecdotal accounts citing relief of joint pain after smoking cannabis or using CBD exist in the literature, though these data are not corroborated by regulated clinical trials as the legal ramifications may inhibit enrollment in such studies [3]. The following review relays the currently held views on the biochemical efficacy of CBD for the management of inflammation and joint pain and highlights several previous studies that demonstrate a potential human application for CBD in this regard.

Review

Mechanism of action: cannabidiol

CBD, the major nonpsychoactive component of cannabis, has undergone a bevy of research in murine model organisms, though there is scant, well-vetted evidence of its efficacy in humans. In a study by Malfait et al. in 2000, DBA/1 mice underwent a collagen-induced arthritis (CIA) by immunization with type II collagen (CII) in complete Freund’s adjuvant (CFA) [4]. CBD was then administered after the onset of clinical symptoms, resulting in diminished CII-specific proliferation, IFN-gamma production, and release of tumor necrosis factor. Incidentally, in a separate murine line, the same authors found that CBD was capable of blocking the lipopolysaccharide (LPS)-induced rise in serum tumor necrosis alpha [4]. A subsequent review by Stephen Straus highlighted the aforementioned findings and suggested that CBD is effective when dosed orally or intraperitoneally, noting that it followed a sharp dose-response curve that limits its efficacy range [5]. Thereafter in 2004, Sumariwalla et al. explored the potential antiarthritic effects of a novel, synthetic cannabinoid acid pegged Hebrew University-320 (HU-320). In a prospective manner, these authors immunized DBA/1 mice with bovine CII, injected intraperitoneal HU-320, and assessed the outcomes both clinically and histologically [6]. The results of systemic, daily administration of 1 and 2 mg/kg HU-320 “ameliorated” the established CII-induced arthritis, without any noticeable adverse psychotropic effects [6]. Therefore, these data indicate that cannabinoids such as CBD, in both an anti-inflammatory and immunosuppressive manner, have potent anti-arthritic effects with a subjectively diminished adverse risk profile.

For the literature review, a PubMed Medical Subject Headings (MeSH; MEDLINE) search from 2000 to 2020 was conducted using the following terms: (“Cannabidiol”[MeSH]) and (“Joint Diseases”[Majr]). The search yielded 11 articles, and after reviewing each for accuracy, the focus was narrowed onto eight with the exclusion of those that did not involve CBD. Additionally, Google Scholar was queried using “cannabinoids, joint pain” as key phrases. While the search returned myriad articles from receptor classification to the effects of CBD in animal models, there were no relevant studies regarding any human, clinical data entertaining prospective CBD use and joint pain. In 2006, Blake et al. published an article on the preliminary assessment of the efficacy, tolerability, and safety of a cannabis-based extract called Sativex (GW Pharmaceuticals, Cambridge, UK) used in the treatment of pain from rheumatoid arthritis. Sativex is a cannabis-based pharmaceutical containing THC and CBD, and though a primary limitation of this study was that Sativex was not exclusively composed of CBD, the authors observed a significant analgesic effect with disease suppression following Sativex treatment [7]. In 2011, GW Booz wrote an article on CBD as an emergent therapeutic strategy, attempting to explore exactly how CBD mitigates oxidative stress. His results indicate the endogenous endocannabinoid system acts via CB1 and CB2 G-protein-coupled receptors via lipid ligands, a mechanism that Booz called “ripe for therapeutic exploitation” [8]. Interestingly, the author also notes that CBD has little affinity for the classic endocannabinoid receptor system. In a CB1- and CB2-independent fashion, the actions of CBD on immune cells appear to include the suppression of cell-mediated and humoral immunity. The effect is obtained via blockage of the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, the delayed wave of reactive oxygen species (ROS) formation, and the associated tumor necrosis factor alpha secretion, and p38 mitogen-activated protein kinases (MAPK) activation [8]. Furthermore, through an unidentified mechanism, CBD was reported to suppress pro-inflammatory signaling and LPS-induced microglial cell migration, while distinctly enhancing other anti-inflammatory pathways [9]. Therefore, given its attenuation of various pro-inflammatory responses in cell models, CBD may certainly have a role in the treatment of pain associated with rheumatoid arthritis via its effects on the immune cell.

Secondly, a more recent exploration into the role of cannabinoids in the treatment of non-rheumatoid arthritis pain suggests that CBD binds to and activates an atypical receptor system entirely. In their article on a novel endogenous receptor called G-protein coupled receptor55 (GPR55), Schuelert and McDougall investigated whether or not the synthetic GPR55 agonist 0-1602, a CBD analog, alters joint nociception in a rat model subjected to acute joint inflammation [10]. The authors induced acute (24-hour) joint pain by injecting male Wistar rats with intra-articular preparations of 2% kaolin and 2% carrageenan. Using extracellular recordings from afferent nociceptive fibers, they found that peripheral administration of 0-1602 reduced the firing of afferent C fibers in response to mechanical rotation of the knee [10]. Though not explicitly translatable to stress-induced osteoarthritic changes in a human knee, this study highlights the role of cannabinoid receptors in joint nociception and suggests a potential relationship between CBD and relief of joint pain in a non-immune fashion. Further evidence for the anti-arthritic role of CBD stems from additional animal studies that evaluate its route of administration and anti-inflammatory effects. Similar to the work produced by Schuelert and McDougall, Hammell et al. investigated a topical CBD application in an attempt to avoid gastric diminution of the drug, hepatic first-pass metabolism, and to achieve greater plasma drug levels outright. The authors describe a favorable transdermal absorption profile when dosed in 0.6-6.2 mg/day, and note that topical CBD significantly reduced joint swelling, limb posture scores, and thickening of the synovial membrane in a dose-dependent manner. Additionally, immunohistochemical analysis of spinal cord and dorsal root ganglia revealed dose-dependent reductions of pro-inflammatory biomarkers, without a concomitant rise in behavior alteration to suggest a psychotropic effect [11]. In light of these data, there emerges a theme. In rodent models, CBD administration has proven anti-inflammatory effects, with a seemingly sharp dose-response peak, no evidence of neurocognitive side effects, and a histologic regression of arthritis in the short term.

Clinical utility: cannabidiol

Currently recommended pharmacologic treatment options for the symptomatic management of osteoarthritis include non-steroidal anti-inflammatories (NSAIDs), low-dose steroids, and viscosupplementation. However, each of these modalities is fraught with side effects when used for long periods of time, and given the insidious time course of osteoarthritis, CBD may prove a useful drug for those with an aversion to other therapies. Additionally, the evidence for viscosupplementation relies on the results of controversial, randomized-controlled trials, and intra-articular preparations have notable contraindications to therapy. Therefore, it is reasonable to suggest that CBD is a safe, useful alternative or adjunct for the treatment of neuropathic joint pain due to secondary osteoarthritis. Osteoarthritis is a progressive disease that results in subchondral bone loss over the years, accelerated by a variety of environmental and genetic factors. In a study by Philpott et al. in 2017, osteoarthritis was induced in male Wistar rats via intra-articular injection of sodium monoiodoacetate (MIA; 3 mg). In addition to its therapeutic effect caused by a decreased joint firing rate and an increased threshold for weight-bearing, the authors demonstrate a prophylactic benefit of 100-300 mcg of CBD as evidenced by a statistically significant reduction of MIA-induced joint pain at a later time point [12]. Despite a small sample size (n = 8), these data are promising and suggest a possible role in prolonging the time course of osteoarthritis, either to the onset of clinical symptoms or to the need for pharmacologic or operative intervention. Therefore, one practical application of cannabinoids including CBD is in the primary prevention of osteoarthritis, or in its preoperative use. In a 2015 study by Kogan et al., CBD enhanced the biochemical properties of healing rat mid-femoral fractures via stimulation of mRNA expression of Plod1 in primary osteoblast cultures, a mechanism well-understood to be involved in collagen cross-linking and bony stabilization [13]. For this reason, along with the evidence presented herein, the orthopedic community has taken interest in CBD, along with other cannabis products, as a potential adjunct for musculoskeletal disease treatment, both in the preoperative and postoperative period.

Clinical utility: cannabis

Cannabis-based medicines have been employed in the orthopedic practice, though a lack of sufficient data precludes its widespread recommendation. A secondary literature review on cannabis-based therapy in orthopedics was conducted using a PubMed MeSH (MEDLINE) search: (“Cannabis”[Mesh]) and (“Fractures”[MeSH]) OR (“Arthroplasty”[MeSH]). The search yielded nine studies following the exclusion of two that did not meet inclusion criteria or were considered outside the realm of this study (Table 1 ). Additionally, Google Scholar was queried using the key phrases “cannabinoids, arthroplasty”, which yielded one more recent article by Runner et al. (2020) not found in the initial search.

Table 1

MeSH: Medical Subject Headings; OA: osteoarthritis; RA: rheumatoid arthritis; TKA: total knee arthroplasty; TSA: total shoulder arthroplasty; THA: total hip arthroplasty; RTKA: revision total knee arthroplasty; CBD: cannabidiol; BMD: bone mineral density; VTE: venous thromboembolism PROs: patient-reported outcomes; BMI; body mass index

Author, year Design Aims, methods, and endpoints Sample size Importance
Kogan et al., 2015 [13] N/A Whether CBD enhances the biomechanical properties of healing rat mid-femoral fractures N/A CBD stimulated mRNA expression of Plod1 in primary osteoblast cultures and collagen cross-linking
Richardson et al., 2008 [14] Cohort Synovial endocannabinoid expression between healthy and non-healthy (OA and RA) groups N = 45 total patients; 32 patients with a clinical diagnosis of OA, 13 patients with a clinical diagnosis of RA Increased CBD1 and CBD2 RNA levels in synovium suggests target for pain and inflammation associated with OA and RA
Best et al., 2015 [15] Retrospective, National Hospital Discharge Survey Drug misuse outcomes of primary total hip and knee arthroplasty N = 13,163 with no drug history; n = 8,366,327 with a drug history Drug misuse group had higher odds of in-hospital complications
Moon et al., 2019 [16] Retrospective, National Inpatient Sample, 2010-2014 Marijuana use and in-hospital mortality in commonly billed orthopedic surgeries N = 9,561,963 Marijuana use was associated with decreased mortality in patients undergoing THA, TKA, TSA, and traumatic femur fixation
Jennings et al., 2019 [17] Retrospective Self-reports of use in total joint arthroplasty (500 before and 500 after the legalization in Colorado) N = 1,000 Legalization of marijuana has led to more users or more patients willing to report its use
Roche et al., 2018 [18] Retrospective, PearlDiver Medicare database Effects of drug abuse on revision TKA N = 2,159,221 Drug abuse patients, including cannabis, are at increased risk for RTKA
Vakharia, et al., 2019 [19] Retrospective, database retrieval Whether patients with cannabis use disorder undergoing primary TKA have higher rates of VTE, readmissions; and costs N = 18,388 Patients with cannabis use disorder have higher rates of VTE complications, readmission rates, and cost
Jennings et al., 2019 [20] Retrospective Primary unilateral TKA PROs with minimum 1-year follow-up, who self-reported cannabis use N = 71 Cannabis use does not influence (adverse or beneficial) short-term outcomes in patients undergoing primary TKA
Sophocleous et al., 2017 [21] Cross-sectional case control, UK primary care database Heavy and regular cannabis smokers and BMD scores N = 56 moderate smokers, N = 144 heavy smokers; matched to 114 cigarette smokers Heavy cannabis use (>500 lifetime uses) is associated with low BMD, low BMI, high bone turnover, and an increased risk of fracture

CBD acts in a non-endocannabinoid fashion, distinguishing it from THC, the psychoactive ingredient of cannabis. Therefore, cannabis may have a distinct utility profile from CBD. Despite the clinical and preclinical evidence of cannabis-based medicines in combating inflammatory disease, legal ramifications of its use inhibit high-quality, prospective, controlled trials evaluating patient-reported outcomes as a primary endpoint. Retrospective studies have attempted to ascertain the relationship between drug use and postoperative complications following total arthroplasty. In a study by Best et al. in 2015, postoperative total hip and knee patients with a documented history of drug misuse (cocaine, cannabis, amphetamines, and opioids) had greater odds of incurring longer hospital lengths of stay, infection risks, and mortality [14]. Within large database claims such as this, though, cannabis use was likely not the sole culprit for risks of complications, and additional studies have attempted to understand the influence of specific marijuana use on postoperative outcomes in joint arthroplasty. In 2019, Moon et al. conducted a National Inpatient Sample (NIS) database study of 9.5 million inpatients undergoing five common orthopedic procedures: total hip, total knee, and total shoulder arthroplasties, spinal fusion, and traumatic femur fracture fixation. They identified a history of marijuana use disorder in 0.28% of total inpatients from 2010 to 2014, though only within patients undergoing total hip, knee and shoulder arthroplasties, and femur fixation do they describe a decreased odds of inpatient mortality [15]. Needless to say, the association between cannabis use and orthopedic surgical procedures remains unclear. Substance abuse can have a strong negative impact on the outcomes of arthroplasty, though cannabis and CBD both have demonstrated biochemical and therapeutic benefits. Therefore, given its increasing social relevance, prospective, randomized data is needed in this regard.

In orthopedic medicine, the benefit of adjunct CBD and cannabis is likely greatest in an otherwise healthy patient committed to a full, functional recovery, and these data cannot be derived from retrospective database studies. There is no doubt that its recreational use is growing, especially in states where it has been legalized. In a study by Jennings et al. in 2019, 1,000 records of patients undergoing primary total joint arthroplasty (500 consecutive before and 500 consecutive after the legalization of the commercial sale of marijuana in Colorado) were analyzed. The authors describe an increase in self-reported cannabis use from 1% to 11% following its legalization, attributable either to increased use, or increased self-reporting, given the lack of legal ramifications [16]. However, the significance of these results remains unclear. The potential clinical utility of cannabis-based medicines extends from the pre-operative period, following a diagnosis of osteoarthritis, into the peri-operative stage, including postoperative follow-up. No current evidence exists on whether or not cannabis-based medicines including CBD prolong time to total arthroplasty following a diagnosis of osteoarthritis. However, in a Medicare database study by Roche et al. in 2018, patients with a history of drug abuse including cannabis (cannabis use disorder) were at a significantly increased risk for revision total knee arthroplasty than a matched cohort [17]. Furthermore, retrospective studies by Vakharia et al. and Jennings et al. in 2019 note that patients with cannabis use disorder have statistically significant higher rates of venous thromboembolism (VTE) complications and costs, without an increase in postoperative range of motion or a mean improvement in mental and physical scores [18,19]. Similarly, in a prospective cohort of patients undergoing primary, unilateral THA/TKA enrolled in a single institution in California, where THC and CBD are legal, the authors describe a wide variety of usage patterns of THC/CBD; however, they note that between CBD/THC users and non-users, there was no significant difference in the length of narcotic use, narcotic pills consumed, average postoperative pain scores, the percentage of patients requiring a refill of narcotics, or length of stay [20]. In conjunction with sufficient literature that suggests that endocannabinoids have utility in mitigating the anti-inflammatory effects of osteoarthritis, these data highlight the potential pre-operative and preventative use for cannabis-based medicines as opposed to the postoperative utility.

Bone mineral health: endocannabinoids

In an orthopedic practice, joint replacement is quite prevalent, though fracture care is also a potential, high-volume area of interest for the use of cannabis or CBD. Though the current evidence is scant, in the aforementioned animal model study conducted by Kogan et al., THC was noted to potentiate the CBD-stimulated work-to-failure at six weeks post-fracture, followed by attenuation of the CBD effect at eight weeks, which would be a primary indication for use of cannabis in the setting of a fracture. Additionally, in a cross-sectional case-control study by Sophocleous et al. in 2017, heavy cannabis users (>500 lifetime uses) had lower hip and spine bone mineral density, lower BMI, and higher bone turnover, and increased fracture risk than a matched cohort who reported

Study limitations: the present study

The present study represents a brief literature review using MEDLINE (PubMed) and Google Scholar search engines. This review did not satisfy criteria set forth by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and additional databases such as EMBASE and Web of Science were not queried, which may decrease the guarantee of adequate and efficient coverage in the retrieval of articles. A time period from 2000 to 2020 was set forth in the literature review, and studies were excluded if they were not written in English, were duplicated, or lacked relevance to this review. The authors believed that searching MEDLINE and Google Scholar would highlight articles with relevance to CBD and joint pain, though it is possible that human clinical data may be uncovered via other search engines as well. The limitations of the articles within this review are discussed intermittently throughout.

Study limitations: collected articles

While animal-based model studies are important for the classification of endocannabinoids from a biochemical perspective, the preclinical and clinical human data presented herein have several limitations. First, to the knowledge of the authors, there is one study that attempts to prospectively ascertain the effects of CBD on peri-operative arthroplasty. However, in this study by Runner et al., CBD was not standardized among patients, meaning there was a wide variety of reported usage patterns, and the sample size was relatively small (n = 295) [22]. Future studies must prospectively enroll patients with the intent to monitor primary endpoints after standardized CBD doses and how they affect postoperative outcomes. With respect to the collected articles included in the review on cannabis-based medicine and arthroplasty, several limitations arise. six of the nine studies were retrospective in nature. None of the studies enrolled patients to receive CBD or cannabis-based products in a longitudinal manner, either pre-operatively with a diagnosis of osteoarthritis, or postoperatively in addition to their scheduled pain management plan. As mentioned earlier, legal ramifications likely inhibit high-quality prospective studies, and these studies are needed in the future before recommendations on THC/CBD use with arthroplasty can be made.

Conclusions

Cannabis has gained widespread popularity following the legalization of its recreational use in several states. CBD, a major non-neurotropic marijuana constituent that is also commercially available, has shown promise in mouse model studies by attenuating pro-inflammatory immune responses. Additionally, recent research has demonstrated the efficacy of CBD in decreasing the endogenous pain response in mice subjected to acute arthritic conditions, as well as improved fracture healing via collagen cross-linking in a murine mid-femoral fracture cohort. However, there is a lack of high-quality, novel research investigating the use of CBD in human musculoskeletal diseases aside from anecdotal accounts. This review highlights the extent of the current research on CBD and its biochemical and pharmacologic efficacy in the treatment of joint disease, as well as the current evidence surrounding cannabis-based medicine and orthopedic joint replacement. Currently, there are no approved pharmaceutical products that contain CBD alone for the management of pain. Based on available literature relying on retrospective data and case reports, it is challenging to propose a recommendation for CBD use in perioperative pain management. Additionally, a number of CBD products are currently available as supplements with different methods of administration, and it is important to remember that these products are non-pharmaceuticals. However, given the increased social relevance of CBD and cannabis-based medicines, future, prospective controlled studies evaluating their efficacy are needed.

Notes

The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.

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