From Flower to Function: Medical Cannabis Modalities in Orthopedic Practice

Introduction

Medical cannabis (MC) and its derivatives, cannabinoids, have been used throughout history, with records dating back to ancient China, India, Egypt, and Greece.¹ However, there has historically been stringent regulation in the United States (U.S.), including the Marihuana Tax Act of 1937 and the Controlled Substances Act of 1970, with the latter designating MC as Schedule I, thereby preventing its medical use.^1–3 Despite the past restrictions in the U.S., there has recently been increased interest in MC and cannabinoids due to their potential therapeutic effects. Since the 1980s, when the Food and Drug Administration (FDA) approved the synthetic cannabinoid dronabinol, forty states, three territories, and the District of Columbia now allow the use of MC, with state-specific restrictions.^2–4

Following MC’s increasing acceptance, research has shown its efficacy in the management of chronic pain, chemotherapy-induced nausea and vomiting, spasticity with multiple sclerosis (MS), and human immunodeficiency virus (HIV)-related neuropathic pain symptoms.^3,5–9 While MC has broad applications, its role in orthopedic surgery is of particular interest. Orthopedic patients frequently experience acute postoperative pain and chronic musculoskeletal pain. Given the significant contribution of orthopedic surgeons to national opioid prescribing practices, MC offers a potential adjunct that could reduce reliance on opioids while providing effective analgesia. This Current Concepts narrative review aims to summarize the administration routes, pharmacology, and common indications of MC, while discussing its relevance to orthopedic practice and treating musculoskeletal pain. This review will also describe the evolving regulatory and prescribing considerations most pertinent to surgeons.

Tetrahydrocannabinol and Cannabidiol Compositions

MCs can be classified based on their chemical composition and distinct formulations. Clinically, the most relevant and recognized therapeutic cannabinoids are tetrahydrocannabinol (THC) and cannabidiol (CBD).^10–13 Other cannabinoids, such as tetrahydrocannabivarin (THCV), cannabigerol (CBG), cannabichromene (CBC), and cannabinol (CBN), are lesser studied but may also exert pharmacological effects.^10–13

THC is the principal psychoactive component of cannabis, exerting its effects by acting as a partial agonist at endocannabinoid type 1 (CB1) and type 2 (CB2) receptors in the central nervous system, leading to cognitive impairment and feelings of euphoria.¹⁴ CBD, the principal non-intoxicating cannabinoid, modulates endocannabinoid signaling primarily through negative allosteric effects at CB1 receptors and antagonism at CB2 receptors, influencing inflammation and nociception.^13,15–18 In contrast to THC, CBD is not known to produce potent adverse cognitive effects. THC and CBD can both be used independently as therapeutics, but MC can have varying ratios of both components, including high-THC, balanced THC/CBD, and high-CBD/low-THC.¹⁹ There may also be a synergistic or interactive dynamic between these two cannabinoids,^20,21 with CBD potentially being able to reduce the cognitive and psychotropic effects associated with THC.²² However, these findings are still inconsistently defined and may depend on the specific dose and administration method, requiring further investigation.^20–22

Inhalation Administration (Smoking and Vaporization)

Inhalation is the most common route of MC administration and includes smoking or vaporization. When cannabis is inhaled, the cannabinoids are absorbed into the bloodstream through the pulmonary alveoli in the lungs. This method results in a rapid onset of analgesic effects and a peak concentration within 15 minutes of inhalation.^19,23–26 However, the specific absorption and bioavailability of cannabinoids will depend on inhalation depth, duration, and THC or CBD content.²⁶ Smoked MC involves inhaling the combusted smoke of dried cannabis flower through cigarettes, pipes, bongs, or other similar devices. Vaporization, or vaping, which involves heating cannabis flower or oils to produce an aerosol or gas, is an alternative that avoids the combustion products and has been quickly growing as a means of risk-reduction.^23,27 However, both chronic vaping and smoking can cause airway irritation, symptoms of bronchitis, and long-term lung function deficiencies.^28,29

Inhaled cannabis is used for a wide range of indications that reflect its uniquely rapid speed of action. Smoked and vaped MC products are primarily used for pain syndromes where the immediate onset of effects is desirable, including chronic and neuropathic pain. In meta-analyses and randomized controlled trials of patients with neuropathic and chronic pain, inhaled cannabis was found to provide significant short-term relief with a tolerable safety profile.^7,8,30,31 In the oncologic setting, patients have also reported high usage of inhaled MC and relief in several cancer and treatment-related symptoms.^32,33 Despite these findings, the analgesic and therapeutic effects of MC will differ across conditions, and further research is needed to confirm these results. Given the inhaled nature of this modality, physicians and patients should also weigh the potential benefits and risks, especially for patients at increased risk of respiratory complications.^27–29

Oral Administration (Capsule, Sprays/Tinctures, Edible Gummies)

MC can also be ingested. The most commonly available encapsulated cannabis products include hemp seed capsules, dronabinol, and nabilone. Compared to inhalation, the onset of effects for oral methods is more prolonged and may depend on concurrent or past food intake.³⁴ Despite this variability, the onset is typically 30 minutes to one and a half hours after ingestion, with the concentration peaking around two to four hours and lasting upwards of five hours.^19,23–26 These delayed effects are in part due to the poor gastrointestinal absorption and hepatic first-pass metabolism, which can significantly reduce the bioavailability.³⁴ The indications for capsule cannabis are evolving and broad. Hemp-derived CBD capsules have been shown to significantly improve chronic musculoskeletal symptoms and quality-of-life measures, such as low back pain from lumbar spine stenosis.³⁵ According to the American Society of Clinical Oncology, oral cannabinoids such as dronabinol, nabilone, and quality-controlled 1:1 THC:CBD extracts may be potentially useful as adjuncts alongside guideline-concordant antiemetics for refractory nausea and vomiting in patients with cancer.³

The oromucosal administration method involves the vascularized buccal and sublingual surfaces of the oral mucosa. Oromucosal formulations most commonly include sprays, tinctures, and dissolvable capsules or tablets.²³ Sprays, including nabiximols (Sativex^®), are metered-dose medications applied as an aerosol.³⁶ Tinctures and drops are liquid-based cannabis extracts applied to the underside of the tongue, and dissolvable tablets are placed under the tongue for disintegration.³⁷ The mechanism of action of these drugs is to allow the cannabinoids to enter the systemic circulation directly through the highly vascularized sublingual and buccal mucosa in the mouth.^37–40 This method of administration, similar to inhalation, avoids poor gastric absorption and hepatic first-pass metabolism, offering higher THC and CBD bioavailability and a quicker therapeutic onset compared to ingested formulations.^37–40 However, the specific absorption can still vary depending on other factors, like drug composition, saliva pH and flow, and the permeability of the mucosal vasculature.^37–40 The main indications for these formulations are chronic pain and MS spasticity. Evidence has shown that nabiximols and sprays, when used as an adjunct, can significantly improve chronic pain and spasticity-related symptoms, including muscle spasms, fatigue, and sleep quality, with minimal physical and cognitive adverse effects.^36,41,42 However, more research is still needed to confirm long-term efficacy and safety.

MC edibles are THC and CBD products in a chewable form. They are an alternative to traditional inhalation, oral, or oromucosal formulations. Once cannabis edibles are ingested, the cannabinoids are absorbed through the gastrointestinal tract, which contributes to a delayed onset of effects due to poor gastric absorption, degradation, and hepatic metabolism.³⁴ Edibles are available in a wide range of THC and CBD concentrations and thus can have significant variabilities in dosing and labeling, especially in the unregulated and commercial market.^43,44 Furthermore, the concentration of THC or CBD in edible products may be unsuitable for medical use.⁴⁴ A recent study conducted by Khak et al⁴⁵ further confirmed inconsistencies in dosing, with 46.5% and 47.2% of respondents being unaware of their exact THC or CBD dosage, respectively, which raises concerns about the regulation and patient education regarding these MC formulations. Although not FDA-approved, patients continue to use edibles for chronic pain. More research is needed to confirm their analgesic efficacy and to justify broader clinical use.

Topical Administration (Creams, Lotions, Ointments, Gels)

Topical formulations, such as creams, lotions, ointments, or gels that contain cannabinoids, can be applied directly to the skin.^23,46,47 These medications contain THC and CBD extracted into vehicles designed to permeate the skin barrier and exert the therapeutic effects. Given their topical nature, these formulations offer more targeted relief than inhalation or oral methods. The main benefit of topical administration is delivering cannabinoids directly to affected areas, such as the skin, joints, or peripheral nerves. Thus, they are designed for local action and have limited systemic absorption, lowering the risk of central nervous system side effects such as euphoria or cognitive intoxication.^46–49 The topical delivery of medicinal cannabis also avoids hepatic metabolism and poor gastrointestinal absorption, preserving bioavailability.^47,48

The main indications for topical MC would be localized musculoskeletal pain and dermatologic conditions. Current research into the use of topical CBD for hand arthritis has indicated a favorable safety profile with significant improvements in pain and disability.⁵⁰ Studies have also shown that topical and transdermal cannabinoids can improve pain and function for musculoskeletal and rheumatic conditions, including osteoarthritis.^45,51,52 However, topical cannabinoids are not limited to joint pain, as they have also shown promise in treating certain skin condition symptoms. Research indicates that topical cannabinoids can improve acne and pruritus, as well as erythema and scaling, in atopic dermatitis, contact dermatitis, and psoriasis.^53–55 Nanoformulated forms of CBD, such as emulsions, cryogels, lipid nanoparticles, and nanomicelles, were also identified to potentially offer improved skin delivery and enhanced efficacy for treating various skin conditions.⁵⁶ Despite these promising findings, the current landscape of evidence is still growing, and future research should investigate whether topical MC can serve as a viable adjunct or alternative to traditional therapies in musculoskeletal and dermatologic contexts.

MC in Orthopedic Conditions

While MC has demonstrated efficacy in managing symptoms across a range of conditions, its role within orthopedics and postoperative pain is paramount. Orthopedic patients frequently experience both acute and chronic pain, and the current treatment paradigms rely on opioids, which can carry significant adverse effects.⁵⁷ MC is a potential alternative that can effectively provide analgesia without the typical risks associated with opioid use. Khak et al.⁴⁵ found that the majority of patients using MC for musculoskeletal pain had positive views of the therapy, with 93.7% agreeing or strongly agreeing that MC was effective in relieving their main symptoms. In an observational study conducted by Bakewell et al,³⁵ patients with lower back pain caused by lumbar spinal stenosis who took hemp-derived CBD gel caps with 0.3% THC experienced a clinically and statistically significant two-point decrease in the mean Pain Numeric Rating Scale (NPRS) over the study period. These improvements in pain also corresponded to improvements in quality-of-life measures and sleep. Glare et al⁵⁸ further confirmed MC’s effectiveness in managing chronic back and neck pain, finding that medium (1.0 mL) and high (1.5 mL) dose oromucosal-administered MC, Cybis^®, significantly reduced NRPS pain scores by 28.8% and 34.1%, respectively, over the study period.

In the management of osteoarthritis, MC has also indicated efficacy. In a randomized controlled trial evaluating CBD’s effectiveness for managing thumb basal joint arthritis, Heineman et al⁵⁰ found that Visual Analog Score (VAS) pain and disability scores were significantly improved from baseline for the topical CBD group compared to the control group. Bawa et al.⁵¹ also investigated the use of transdermal CBD for hand osteoarthritis. They found that patients’ pain scores were significantly lower during the CBD gel application and washout phases compared with baseline. Patients’ grip strength also increased during treatment compared with baseline. Another open-label study found that athletes who received topical CBD for their lower extremity injury experienced significant improvements in pain and their ability to return to normal life activities, highlighting a potential sports medicine application.⁵⁹

The breadth of studies highlights MC’s therapeutic potential but also underscores the heterogeneity of formulations and their specific use cases [Table 1]. While orthopedic patients most often turn to topical, oral, and inhaled MC,⁴⁵ there is no clear consensus as to which modalities are most appropriate for any musculoskeletal indication. In the absence of clear guidelines on how to offer MC to orthopedic patients, surgeons must exercise discretion, considering their patients’ specific needs and how these align with the modalities’ pharmacokinetic and clinical characteristics.

MC and Postoperative Orthopedic Pain

In the context of immediate postoperative orthopedic pain relief, there is currently contradicting evidence and an overall paucity of literature. One randomized controlled trial by Haffar et al⁶⁶ found that postoperative topical application of CBD following total knee arthroplasty did not reduce pain or improve sleep scores. However, another randomized controlled trial by Alaia et al.⁶⁰ found that patients undergoing arthroscopic rotator cuff repair who received an oral, buccally absorbed CBD tablet three times per day experienced a significantly lower VAS pain score than the placebo group on postoperative day one. Patients in the CBD group also reported higher satisfaction with pain control compared to the control group on postoperative days one and two. In the one-year follow-up analysis from this research group, they confirmed that patients in the perioperative CBD group did not have any significant deficits in pain or self-reported satisfaction and outcomes compared to the placebo control group.⁶⁷ These findings validate the considerable heterogeneity in the existing literature, particularly with regard to the formulations, dosing regimens, and routes of administration of MC for postoperative orthopedic pain. Accordingly, future studies must prioritize procedure-specific trials to delineate the efficacy of different modalities and establish evidence-based dosing strategies that can be standardized in clinical practice.

MC’s Role in Combating the Opioid Crisis

MC is particularly relevant to the ongoing opioid crisis in the United States, defined by the misuse of prescription opioids, incidence of opioid use disorder, and increasing overdose deaths.⁶⁸ Orthopedic surgeons are among the highest prescribers of opioids⁶⁹ and they are at the front line of managing chronic nonsurgical and acute postoperative musculoskeletal pain, so reducing opioid use for orthopedic pain is crucial.

Opioid risks have led to a shift towards multimodal pain management strategies and increased use of non-opioid analgesics. Within this shifting landscape, MC has emerged as a promising adjunctive strategy that can mitigate opioid reliance. In a study by Greis et al,⁶¹ patients with chronic lower back pain certified for MC had fewer filled opioid prescriptions and significantly reduced opioid consumption regardless of their baseline opioid usage. These opioid reductions were also accompanied by improvements in pain scores and daily function. Similarly, Renslo et al.⁶² found that patients with osteoarthritic pain experienced a 43.6% average decrease in MME/day between six months pre-MC and six months post-MC use. This study also demonstrated clinically significant improvements in pain scores and Global Physical Health scores at 3 months post-MC initiation. Supporting these findings, a systematic review conducted by Okusanya et al.⁶³ revealed between a 64% to 75% reduction in opioid dosage for MC users with non-cancer chronic pain, and complete opioid cessation was achieved in up to 59.3% of patients. Therefore, MC as an adjunct in a multimodal pain management regimen could be key in mitigating the opioid crisis, particularly in orthopedic contexts with historically high opioid prescribing.

Changes in Patient Attitudes Towards MC

Despite the caution and stigma surrounding cannabis, recent surveys have shown that patients are increasingly receptive to MC to manage pain. Karakash et al.⁶⁴ found that 81.3% and 90.1% of orthopedic sports medicine patients were amenable to receiving THC or CBD-based products for their musculoskeletal pain, respectively. Additionally, 85.3% of the surveyed patients felt that cannabis-based products would be effective in combating the opioid crisis. In a cross-sectional survey conducted by Fones et al.,⁶⁵ approximately 10% of hand surgery patients used MC, and 80.9% of the remaining patients reported that they would consider its use to manage their chronic pain. The most common orthopedic conditions that patients considered using MC for included arthritis, back pain, tendon pain and inflammation, as well as postoperative pain. These findings highlight a growing willingness among orthopedic patients to consider MC as an alternative to traditional therapies to manage their musculoskeletal pain conditions.

MC’s Evolving Legal Landscape

MC’s rapidly evolving legal landscape in the U.S. presents a challenge for orthopedic surgeons and other physicians. MC remains a Schedule I controlled substance under federal law. However, MC has been approved for medical use in 40 states, three territories, and the District of Columbia, creating a complex legal landscape in which state and federal laws conflict.⁴ Further complicating this is the fact that MC’s regulation differs across states and their various policies. As such, the feasibility and practicality of endorsing MC are significant concerns, particularly for practicing surgeons. Therefore, surgeons must remain educated on the current laws surrounding MC in their specific state, as well as be prudent regarding any new federal regulation changes. While surgeons may not be able to formally prescribe MC, they can play a critical role in discussing and expanding the current evidence base, outlining the potential benefits and risks, and helping patients navigate the various state-specific access pathways. Providing clear, informed communication can foster informed decision-making between patients and surgeons, ensuring that MC, when an option, can be implemented as part of a safe and effective multimodal approach to pain management.

Conclusion

MC has various modalities, pharmacokinetic considerations, and indications. However, its unique role within orthopedic surgery remains a crucial area of discussion. Evidence supports its potential in managing musculoskeletal and postoperative pain, and surveys suggest that orthopedic patients most often turn to topical, oral, and inhaled formulations. Still, the literature remains highly heterogeneous, therefore precluding consensus and making concrete conclusions difficult. This lack of standardization reveals the pressing need for clinical trials to help establish clear guidelines. MC may also reduce opioid consumption, which has significant public health implications related to the ongoing opioid crisis. As patient demand and legal acceptance expand, orthopedic surgeons must remain informed about local regulations and engage in patient-specific dialogue to advance the safe, evidence-based integration of MC into multimodal pain management plans.

Declaration of conflict of interest

The authors do not have any potential conflicts of interest in the information and production of this manuscript.

Declaration of funding

The authors received no financial support for the preparation, research, and publication of this manuscript.

Declaration of ethical approval for study

Given the review nature of the manuscript and the lack of patient information, there was no ethical approval process.

Declaration of informed consent

There are no patient names, initials, hospital identification numbers, photographs, or any other form of protected health information in the submitted manuscript. Given the review nature of this manuscript, no formal informed consent process was conducted.