cbd oil for pain from bone fractures

Cannabinoid Use in Musculoskeletal Illness: a Review of the Current Evidence

The use of cannabinoids has increased since legalization of recreational and medical use in the USA. It is likely that many orthopaedic patients consume cannabinoid products during the traumatic or perioperative period. The purpose of this study was to investigate the pre-clinical data evaluating the mechanism of action of cannabidiol (CBD) and Δ 9 -Tetrahydrocannabinol (Δ 9 -THC) and to evaluate the current clinical data on the use of cannabinoids in musculoskeletal illness.

Recent Findings

Recent pre-clinical studies have demonstrated that cannabinoid use and the endocannabinoid system (ECS) has an important role in bone healing and bone homeostasis. There is data that suggests that the use of cannabidiol (CBD) may increase bone healing, whereas the use of Δ 9 -Tetrahydrocannabinol (Δ 9 -THC), the major psychoactive ingredient in marijuana, likely inhibits bone metabolism and repair. The clinical implications and consumption of marijuana by orthopaedic patients have not been thoroughly evaluated. Studies have demonstrated concern for negative cardiovascular and psychiatric effects caused by marijuana use, but have not yet elucidated outcomes in the orthopaedic literature.

Summary

With the recent increase in advertising of CBD products and legalization of marijuana, it is likely that many orthopaedic patients are consuming cannabinoid products. The clinical implications and consumption of these products are unclear. We need more robust and well-designed clinical studies prior to making further recommendations to our patients on the consumption of these products.

Introduction

Marijuana, otherwise known as Cannabis sativa, is the most commonly used illicit drug in the USA [1]. Self-reported use of cannabinoids has increased since legalization of recreational and medical use [2••, 3•]. Approximately 3.1 million individuals reported daily use in 2013 and 8.1 million reporting using marijuana most days in the last month in 2013 [4]. Data demonstrates that the number of marijuana users has steadily increased from 2002 and that in 2016 it was estimated that over 22 million Americans over the age of 12 used marijuana [2••].

Cannabidiol (CBD) is an active ingredient in marijuana, but has recently gained popularity due to extensive marketing and advertising. The Food and Drug Administration has only approved highly purified CBD for the treatment of epilepsy. However, many companies make unproven claims that CBD can treat a variety of medical maladies including acne, anxiety, opioid addiction, pain, and menstrual problems [5•]. With the increased popularity of marijuana use and advertising surrounding CBD, it is likely that many orthopaedic patients consume cannabinoid products during the perioperative period [5•, 6•].

It is known that cannabinoids have a number of effects on the body and specifically on the musculoskeletal system. There is a growing body of literature on cannabinoid use, its biomechanical impacts on the musculoskeletal system and on the effect of cannabinoids in orthopaedic surgical outcomes. The primary purpose of this review is to critically analyze the current data on cannabinoid mechanism of action on the musculoskeletal system and its use in the treatment of musculoskeletal illness.

The Endocannabinoid System Positively Affects Bone Mass and Cellular Differentiation

The endocannabinoid system (ECS) is comprised of two G protein–coupled receptors: CB1 and CB2, activation of which inhibit adenylyl cyclase activity. Current research suggests that both receptors serve a common role in the modulation of chemical messengers from various cell types [7]. High concentrations of CB1 receptors have been identified on neurons and CB2 receptors on immune cells, suggesting their role in both neuro- and immunomodulation. Furthermore, the CB1 and CB2 receptors and their associated endogenous cannabinoid ligands have been shown to be cytoprotective in many cell types [8, 9].

CB1 and CB2 receptors are associated with endogenous ligands, termed endocannabinoids. These are eicosanoids, derived from fatty acids, and include anandamide and 2-arachidonoylglycerol and their degradative enzymes fatty acid amide hydrolase and monoacylglycerol lipase [7, 10]. The endocannabinoids along with their corresponding receptors make up the endocannabinoid system (ECS).

Recent studies suggest that the ECS affects regulation of bone mass maintenance through CB1 and CB2 receptor activity. Another G protein–coupled receptor, GPR55, is activated by certain endocannabinoids and antagonized by CBD, and appears to inhibit CB1 and CB2 receptor activity. Inactivation of the GPR55 receptor in male mice produces phenotypes with increased bone mass and increased bone resorption [11]. The complete physiologic function of the GPR55 receptor at this time is yet largely unknown [12, 13].

CB1 receptor activity appears to serve a protective role in regulating bone mass and osteoporosis through adipocyte and osteoblast differentiation, as well as expression of multiple intracellular signaling proteins [14]. CB1 deactivation in knockout mice has demonstrated short-term in vivo increased bone mass with ovariectomy-induced bone loss [15]. Further investigations have shown age-related osteoporosis at 12 months in CB1 knockout mice. It is believed the increased bone mass at 3 months is secondary to reduced osteoclast activity and at 12 months, the osteoporotic changes are the result of defects in osteoblast differentiations and the accumulation of adipocytes in the bone marrow [13, 16]. Cannabinoid receptor deficiency in mouse models is confounded by the fact that the effects of cannabinoid receptor deficiency are age and sex dependent [13].

CB2 receptor function also appears to affect bone mass maintenance, first through direct stimulation of osteoblasts and stromal cells, and second through inhibition of RANKL expression [17]. CB2-deficient mice have a low bone mass phenotype, similar to CB1 knockout mice at 12 months. Conversely, activation of the CB2 receptor has been shown to increase bone mass by increasing the number and activity of osteoblasts, inhibiting osteoclast proliferation and stimulating fibroblastic colony formation by bone marrow cells [17–19].

The ECS also appears to affect mesenchymal stem cell (MSC) differentiation through cannabinoid receptors on mesenchymal stem cells [16, 17, 20]. Research has demonstrated a functional increase in the CB1 receptor during osteogenesis. Based on an in vivo model, it is likely that the CB1 receptor also has a functional role in the survival of the differentiated MSCs [7].

ESC activation may enhance not only MSC survival but also migration and chondrogenic differentiation of MSCs. Among other benefits, this has potential for use in mesenchymal stem cell–based tissue-engineered cartilage repair strategies; however, data on the role of the cannabinoid system in cartilage tissue is currently lacking [21].

Δ 9 -THC Activates CB1 and CB2 but Has Cytotoxic Properties

The Cannabis sativa plant otherwise known as marijuana contains more than 100 cannabinoids; the major constituents are Δ 9 -Tetrahydrocannabinol (Δ 9 -THC) and cannabidiol (CBD) [10, 20]. The psychoactive ingredient in cannabis is Δ 9 -THC and although it also has analgesic and anti-emetic effects, it is best known for its psychoactive effects [10, 22].

Δ 9 -THC is a partial agonist of the CB1 and CB2 receptors, but has higher affinity for the CB1 receptor. The effects of Δ 9 -THC are largely due to the activation of CB1 receptors in the nervous system affecting control of synaptic activity, motor function, pain perception, and appetite [23]. This nervous system activation gives rise to marijuana’s euphoric effects, but carries the frequent side effect of memory impairments and an increased risk of psychosis [23].

Despite its activation of CB1 receptors, Δ 9 -THC may have a detrimental effect on bone healing. Δ 9 -THC has a dual toxicity profile that prevents osteogenesis and induces cell death in a number of cell types, including neurons and mesenchymal stem cells, likely via a proapoptotic downstream signaling mitochondrial pathway [7]. For this reason, Δ 9 -THC is being investigated for possible use as an anti-tumoral agent [7, 23–26].

Cannabis smoke inhalation, similar to tobacco smoke, has been shown to reduce bone healing around titanium implants in a rat fracture model [27]. This raises concerns for implant survival and bone healing in patients after fracture fixation. In particular, the impact of Δ 9 -THC on mesenchymal stem cell differentiation suggests a negative effect on osteogenic potential and resultant bone healing [7].

The effects of marijuana on bone homeostasis and fracture healing are under current investigation. Heavy cannabis use has been linked to low bone mineral density, low BMI, high bone turnover, and increased risk of fracture [13]. It is currently unclear to what extent this is caused solely by the ingestion of Δ 9 -THC.

Cannabidiol Antagonizes GPR55 Thereby Facilitating CB1 and CB2

Cannabidiol (CBD) is another popular cannabinoid of the Cannabis sativa plant. CBD has no psychoactivity and is primarily an anti-inflammatory [1, 28]. CBD has been well studied for a number of illnesses including neurodegenerative disease, epilepsy, and immune disorders such as multiple sclerosis, arthritis, and cancer [29•]. Currently, it is FDA approved only for the treatment of epilepsy [29•].

CBD antagonizes cannabinoid receptor GPR55, and is thus an inverse agonist of the CB2 receptor. Compared with Δ 9 -THC, CBD has lower affinity to the CB1 and CB1 receptors. In vivo studies have demonstrated that CBD can inhibit bone resorption via modulation of GPR55 signaling and activation of CB2 receptors. It is unknown whether Δ 9 -THC acts on the GPR55 receptor, and if so, whether it has similar or opposing effects to CBD.

The effect of CBD in fracture healing has been investigated in a rat model evaluating callus formation about femur fractures. This data demonstrated enhanced biomechanical properties of healing rat mid-femoral fractures in rats given CBD compared with a control group. This effect was not shared by rats given only Δ 9 -THC; moreover, attenuation of the osteogenic CBD effect was seen in rats given equal amounts of CBD and Δ 9 -THC. This favorable biological effect of CBD is believed to occur via enhancement of osteoblastic expression of lysyl hydroxylase 1, a collagen crosslinking enzyme [28]. Similar in vivo research has shown that CBD incorporated into an osteoconductive scaffold can stimulate MSC migration and osteogenic differentiation [28]. Further studies are needed to better evaluate the role of CBD in human bone healing and metabolism, as well as the long-term effects of CBD ingestion [30•].

Minimal Evidence Regarding Orthopaedic Surgical Outcomes in Marijuana Users

While recent pre-clinical data has demonstrated promising effects of CBD on bone healing and bone metabolism, clinical studies are insufficient and inconclusive. A retrospective review of the National Hospital Discharge Survey (NHDS) evaluated patients who underwent primary total joint arthroplasty and found that patients who abused substances preoperatively had higher rates of surgery-related complications. Significantly, this study was not limited to marijuana users and included patients using opioids, cocaine, cannabis, amphetamines, inhalants, and sedatives [31].

Research surrounding marijuana in the total joint arthroplasty cohort is contradictory. In a recent series, Law et al. performed a retrospective review of the Medicare database on total knee arthroplasty (TKA) patients evaluating those who used marijuana compared with those who did not. This study found a significant increase in reoperation rate due to infection in the cohort that used marijuana. This study was limited as they relied on accurate coding for data collection and further did not stratify patients based on additional risk factors [32••].

In comparison, a recent retrospective cohort study using a matched control and selected patients only using marijuana versus other substances found no difference in complications after primary TKA in patients that did and did not use marijuana [3•]. The limitations of this study must be appreciated as well, as not all patients report use of substances, and frequency and type of use may not be properly recorded [3•].

A recent review analyzed data from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) database to evaluate the effect of marijuana use by orthopaedic patients on inpatient mortality, heart failure, stroke, and cardiac disease. A decreased mortality rate was seen in patients who used marijuana compared with those who did not [2••]. Similar to previous studies, this study did not stratify by comorbidities, nor by demographics of marijuana users. Furthermore, the heart failure, stroke, and cardiac disease codes generated during hospital visits were likely in part preexisting conditions rather than complications of hospitalization.

Marijuana use does not only affect the musculoskeletal system, nor is marijuana ingestion limited to CBD and Δ 9 -THC. The smoke from cannabis has been shown to contain many of the same carcinogens as tobacco, and heavy cannabis use has been associated with an increased risk of developing lung cancer [1]. Patients using marijuana are at increased risk of psychiatric effects including anxiety, agitation, and even acute psychosis [33]. Other studies report potential increased risk of cardiac events, atherosclerosis, and even stroke in patients that smoke marijuana [34–38].

The current conflicting data on marijuana use in an orthopaedic surgical population demonstrates the need for future well-designed prospective studies evaluating outcomes and potential complications. It is possible that the perioperative use of marijuana or CBD alone may significantly impact healing, recovery, and complication rates after orthopaedic procedures.

Cannabinoid Use for Musculoskeletal Pain

Opioid over-consumption among patients with musculoskeletal pain is of top concern to orthopaedic surgeons given recent trends in morbidity and mortality associated with chronic narcotic use [3•]. Accordingly, alternatives to narcotic use have recently gained substantial attention. Many patients with complicated surgical history, large-scale procedures, or multiple comorbidities require multimodal pain medication regimens [3•]. Cannabinoids, if effective for pain relief, could potentially reduce the opioid burden [3•, 39•].

Pre-clinical studies demonstrate that cannabinoid signaling has an integral role in the nociceptive system and that CB1 and CB2 receptor agonists have antinociceptive properties. Δ 9 -THC has also been shown to have euphoric and psychoactive effects, both of which have a role in pain modulation and experience [7]. Clinical evidence has not demonstrated similar findings in human experiments [40•]. No clear benefit from the use of cannabinoids has been shown to be better than placebo [41•]. This result is due in part to a lack of high-quality evidence to support the use of medical marijuana therapy for acute or chronic pain indications [41•]. The paucity of high-quality data is not only an issue in musculoskeletal pain, but is part of the larger lack of evidence supporting the common use of marijuana for chronic rheumatologic, oncologic, or arthritic pain [33, 39•,41•].

Conclusion

Pre-clinical studies demonstrate that the ECS has an important role in bone healing and bone homeostasis. There is promising evidence that CBD may increase bone healing through activating cannabinoid receptors, whereas Δ 9 -THC likely inhibits bone metabolism and repair. Current mouse and rat models are age and sex dependent, limiting generalizability and applicability to human cannabinoid receptor function [13]. It is currently unclear whether the pre-clinical evidence demonstrated in this review will correlate with clinical evidence in bone formation and homeostasis in humans.

The perioperative consumption of marijuana by orthopaedic patients has more relevant factors to consider than only the ingestion of specific cannabinoids. Marijuana smoke contains carcinogens similar to tobacco smoke, and has not been thoroughly evaluated as a cause of perioperative or long-term complications. Studies have demonstrated concern for negative cardiovascular and psychiatric effects caused by marijuana use, but have not elucidated similar orthopaedic complications. Future areas for research include age- and comorbidity-stratified analysis of clinical outcomes in marijuana users to non-users. The consumption of CBD alone or in combination with Δ 9 -THC as conventional marijuana may have significant clinical effects in the realm of bone metabolism and fracture healing.

Compliance with Ethical Standards

The study has been performed in accordance with the ethical standards in the 1964 Declaration of Helsinki and has been carried out in accordance with relevant regulations of the US Health Insurance Portability and Accountability Act (HIPAA).

This work was performed at The Albany Medical Center, Albany, NY.

Casey M. O’Connor, Afshin A. Anoushiravani, Curtis Adams, Joe Young, Kyle Richardson, and Andrew J. Rosenbaum declare that they have no conflicts of interest.

This article does not contain any studies with human or animal subjects. Informed consent was not required for this study as it did not study human subjects.

Footnotes

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Cannabis (CBD) Cannabidiol Helps bone health and heals fractures… Research suggests.

Cannabis (CBD) Cannabidiol Helps bone health and heals fractures… Research suggests.

Marijuana has been a controversial treatment among medical professionals. Recently, a study published by The Journal of Bone and Mineral Research suggests that cannabinoid cannabidiol (CBD), the chemical in marijuana, could strengthen the bone and help heal fractures. According to an online interview Yankel Gabet, the researcher of the study, CBD is effective in developing more mineralization in the bone tissue in the animal model. “CBD alone is sufficiently effective in enhancing fracture healing.” Another gradient in marijuana is tetrahydrocannabionol (THC), which causes the marijuana high. Adding THC does not affect the healing of the bones.

However, marijuana is still not widely accepted for medical use due to its concerning psychoactive effect. CBD extracts alone, on the other hand, is used as an experimental treatment for the Dravet syndrome, a rare form of child epilepsy. There has been encouraging literature on CBD in suppressing seizures, inhibiting cancer metastasis, and soothing chronic pain. However more robust clinical human trials are needed. We look forward to following more research into potential beneficial effects of CBD including bone related diseases like osteoarthritis and fractures.

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CBD for Bones: Pain, Healing and Growth!

Studies dating back to the early 2000s have sought to answer the question ‘is it safe to use CBD for bones?’ The preliminary clinical trials indicate that the natural elements within CBD oil have the potential to vastly improve the strength and duration of human bone structures. However, more studies are necessary for the results to prove conclusive.

That being said, there is promising evidence that CBD can strengthen bone integrity. CBD has become well-known in the health and wellness industry as a natural remedy that improves one’s overall quality of life. Doctors have recommended CBD doses to treat autism, anxiety, depression, muscle soreness, gout, and even to reduce blood pressure. Treatments are available in small doses in the form of oils, lotions, skin creams, and other CBD products.

So how does CBD help treat bone strength? Let’s look into it.

CBD and Bone Growth

In an article published to the American Society for Bone and Mineral Research, researchers determined that CBD enhances the biomechanical properties of healing mid-femoral bone fractures in rats. Human trials are still necessary to analyze if similar results will occur. But the doctors behind the trial were confident in proclaiming CBD as a net benefit for bone growth and healing of bone fractures.

The lab rat results mirror similar studies conducted on both humans and animals in using CBD to treat symptoms of arthritis and muscle pain. In fact, these studies concluded that CBD could alleviate the pain suffered by arthritis patients by relieving chronic pain within the bones.

CBD and Broken Bones

Similar to the bone growth study, a broken bone study was conducted in Israel. The test subject was also a rat, which received controlled doses of CBD oil to treat a broken bone.

The bones did show signs of healing, but the scientists were unable to definitely prove if the pain associated with the broken bones had diminished due to the treatment. However, there is room to suspect the overall levels of pain did improve.

CBD has the ability to substitute for the body’s natural endocannabinoids, which empower the endocannabinoid system. These endocannabinoids attach to receptors in the body that help minimize the effects of pain through anti-inflammatory activity. The brain receives a signal from these receptors to minimize the feelings of pain and, therefore, improve the overall quality of life in the patient.

Studies are still necessary to determine if CBD also minimizes the pain of broken bones.

CBD Oil and Bone Cancer

Pain resulting from cancer is caused by excessive inflammation treatments, nerve injuries, or invasion of bone and other pain-sensitive structures. CBD has the ability to treat cancerous pain with anti-inflammatory properties contained within the remedy.

CBD is particularly effective as an anti-inflammatory treatment. The receptors in the body responsible for mediating pain and sensory perception are triggered by anti-inflammatory treatments, like CBD. The cannabinoids within CBD oil latch onto these receptors and prevent the body from succumbing to excessive inflammation, which actually increases levels of pain.

Doctors have recommended CBD oil as a natural way to alleviate pain in the body. CBD has helped minimize cancer-induced pain, particularly for conditions like pancreatic cancer. It’s also been used to reduce the pain associated with arthritis, menstrual cramps, and even common headaches.

Research still needs to enter the clinical trial stage to determine if there’s possible therapy in using CBD oil for bone cancer treatments. But there is potential that it could provide relief.

CBD Dosage for Bone Cancer

While official clinical trials are still pending for CBD dosages for bone cancer, doses used to treat other underlying conditions help paint a picture on the recommended dosage for bone cancer-related pain.

Many people using CBD to treat their conditions will use a minimum of 5mg of CBD oil per day. In some cases, the treatment can rise as high as 100mg per day, or even higher. The overall size and mass of the body in question plays a role in defining the optimal dosage.

Medical history is also important. It helps to consult with your primary doctor if you plan on taking CBD for bones or any other conditions. Your doctor can prescribe the ideal dosage based on the history in your medical file to ensure there will be no notable side effects to the treatment.

Can CBD Oil Help Osteoporosis

Like bone cancer, osteoporosis is a condition caused by the deterioration of the body’s bone structure. It occurs when the integrity of the bones weakens as a result of the body producing too much bone, too little bone, or both.

An early test determined if CBD oil can be used to treat symptoms of osteoporosis. Scientists prescribed 5mg of CBD oil to a lab rat that was suffering from alveolar bone loss. The trial lasted for 30 days and results were measured at the end of the testing timeline. The tests showed decreased alveolar bone loss in the rat and the doctors also confirmed decreased neutrophil migration in the gingival tissues.

Similar to the treatments for bone growth and bone cancer, more studies are required to draw medically approved conclusions. In particular, studies must proceed to human trials to gain greater insight into how CBD will improve the lives of patients with osteoporosis.

Final Thoughts

It remains to be seen how effective CBD for bones will be in treating bone-related injuries and conditions. More research is necessary to draw enough conclusions from the treatments to definitively rule CBD as a viable treatment for bones.

That being said, if you feel intense, lingering pain in your bones, speak with your doctor about CBD for bones as a possible solution for the pain. While no medical positions are officially on the record, doctors will likely have some knowledge as to whether CBD can help remedy the pain associated with your specific condition. This is your best way to test a natural remedy without inadvertently causing additional pain.