However, we have to keep in mind that a certain cannabinoid invention can be referred into more than one patent category. For instance, cannabinoids are highly hydrophobic by nature and thus they have low bio-availability in the human body. As a result, a new class of cannabinoid-glycosides has been created,whose representatives are produced through enzymatic glycosylation. This novel strategy led to increased aqueous solubility of the target cannabinoids and resulted in four patents . Recently a new method of producing one or more cannabosides by feeding an insect a cannabinoid was patented . These new classes of cannabinoid glycosides generated vast structural diversity and have greatly improved water solubility,enabling new pharmaceutical formulations, and multiple administration routes .The discovery of the genes encoding glycosyl transferases may belong to different categories of the cannabinoid patent family, that is, genes, enzymes, delivery technology, etc.The exponential enhancement of the patent number during recent years in the diverse areas of cannabinoid applications is indicative of the increased commercial interest in this class of natural compounds.The various pharmaceutical applications will continue to shape primarily the the path of the future invention cannabinoids. Pain management remains a major challenge in orthopedics.Surgeons employ a multitude of strategies to combat this challenge,including multimodal pain regimens and preoperative opioid counseling.1e3 A recent review of medical cannabis  in orthopedic surgery proposed that MC may provide an additional pain management option for patients with chronic pain.Chronic pain,defined as pain that fails to respond to traditional pain control regimens and lasts greater than 3 to 6 months, is one of the most widely recognized indications for MC use and has been reported to be the primary indication for MC use in two-thirds of patients presenting to MC dispensaries in the northeast.

MC use has become more widespread in recent years and is currently legal in 36 states and 4 United Sates territories.This has been paralleled by a decreased perceived risk of marijuana grow system use reported in a nationwide survey of United States citizens from 2002to 2014.7 However, limited evidence exists on MC use in orthopedic surgery and on patient perspectives of this novel therapeutic. One descriptive qualitative study of spinal cord injury patients found that patients used MC when other pain management strategies failed and when they had both initiative and connections to educate themselves on MC use.Heng et al investigated musculoskeletal trauma patients’ opinions on MC and found that most patients thought it could be effective in treating musculoskeletal pain.However, there is an overall paucity of research on hand and upper-extremity patient perspectives on MC. This patient population may differ from other orthopedic conditions in that many present electively, it includes conditions with a mix of acute and chronic pain and includes patients of a wide age range.The purpose of this study was to evaluate hand and upperextremity patient perspectives of MC and its use in treating common hand and upper-extremity musculoskeletal conditions. We further sought to identify the prevalence of patients already using MC in this patient population, perceived barriers to MC use, and opinions on the legality of cannabis. We hypothesized that most patients would consider using MC for common orthopedic conditions,and that older patients would be more reluctant to use MC compared to younger patients. Institutional review board approval was obtained prior to initiation of this anonymous cross-sectional survey study. From October 2020 to January 2021, all patients who were at least 18years old and presenting for an office visit at a metropolitan academic institution with clinic sites across New Jersey and Pennsylvania were asked to participate in this study.

All patients presented with a hand or upper-extremity complaint to 1 of 3 board certified,fellowship-trained orthopedic hand and upper-extremity surgeons.Medical cannabis is legal in both states where the survey was conducted, with New Jersey legalizing MC in 2010 and Pennsylvania in 2016. Patients completed a survey that was created by the  study investigators regarding patient opinions of MC, including opinions of its legality, safety, costs, and potential barriers for use.Medical cannabis was defined in the survey as any publicly available legal MC product, which included topical, inhalational, andoral cannabis products. All survey responses were collected and stored electronically , with no identifying patient information collected as part of the survey. During the study period, 937 clinic patients were solicited to participate in the study.Categorical data were presented as counts and percentages andanalyzed using chi-square tests. Statistical significance was set at P< .05. The present study identified numerous findings regarding hand surgery patient perspectives of MC. The majority  of patients reporting to hand and upper-extremity orthopedic surgery outpatient offices would consider using MC for chronic pain control or for pain associated with many common orthopedic conditions. As MCuse increases throughout the United States and as more MC research continues to emerge, it is important for surgeons to understand how patients perceive these substances and what factors may represent barriers to use.Most patients in our study reported that they would consider using MC for a variety of acute and chronic orthopedic pain conditions and believed it could effectively treat musculoskeletal pain.This is consistent with other orthopedic patient populations’ beliefs on the utility of MC. In a survey of orthopedic trauma patients, 81%believed cannabis can be used as a medication, and 78% believed it could be used to treat acute pain.9 In a study of elective surgery patients at a large academic center, inclusive of both orthopedic and nonorthopedic procedures, most patients believed MC could beat least somewhat effective for postoperative pain  and chronic pain , and most patients  would use MC if prescribed by a physician.The positive patient response to MC as a potential pain controloption brings into question the clinical effectiveness of MC in treating musculoskeletal pain. In multiple prior studies, cannabis users subjectively reported that cannabis provided effective pain relief.Of orthopedic trauma patients who used RC during recovery, 90% believed that it reduced their pain symptoms, and81% believed it reduced the amount of opioids they required.

Similarly, a survey of MC users, most being treated for chronicpain, revealed that 75% believed MC was effective in treating their pain and positively impacted their quality of life.5 Further, a study of orthopedic surgery patients found that preoperative RC users had lower pain scores and improved lower-extremity activity scores compared to non-cannabis users.Though most orthopedic surgery patients in the literature believe that MC is an effective treatment for pain, multiple review articles conclude that only low to moderate-quality evidence exists to support pain reduction with MC. These reviews also call for additional research on the safety, efficacy, and dosing of MC prior to making definitive conclusions on MC for pain management.To date, cannabis research has been limited by the federal classification of cannabis as a Schedule 1 substance, which has presented many barriers for researchers to perform high quality clinical trials.In our cohort, 74.7% of patients believed MC to be safe for treating orthopedic conditions and 74% of patients agreed or strongly agreed that MC was safer than prescription opioids for common pain conditions. While opioids are associated with many adverse outcomes including overdose and death, cannabis is likely perceived as safer as it is not associated with either of these critical major side effects.14 Despite this, other side effects of cannabis use must be considered. Cannabis use has been linked to negative mental health illnesses ,impaired cognition, and increased rates of cardiovascular and cerebrovascular events.There is also a reported increased risk of motor vehicle collisions, including fatal accidents, in the acute setting following cannabis use.Negative consequences of cannabis use have also been described in total joint arthroplasty,although the evidence is inconsistent. One study reported no difference in short-term outcomes in primary total kneearthroplasty with cannabis use,while another reported an increased risk of revision associated with cannabis use disorder.However, these studies are limited by the mixed inclusion of both MC and RC use.Lastly, the impact of cannabis use onanesthesia should be considered. A recent review of the perioperativec are of cannabis users highlighted increased incidence of hyperre active airway, intra operative hypothermia, and cerebrovascular ischemic events.These studies are limited by the federal classification of cannabis as a Schedule 1 substance,and further studies are needed to better inform patients on the risks and benefits of MC.Interestingly, despite our cohort’s support for MC use as an alternative to opioids, only 26% believed MC could be used as a treatment for opioid use disorder. There is limited and contradictory evidence on the effects of cannabis vertical farming on opioid use. One population level study found lower average opioid overdose mortality rates in states with legalized MC.Another study of orthopedicsurgeons prescribing opioids to Medicare Part D patients found a decrease in opioid prescriptions in states with legal MC.Most studies on the impact of cannabis on opioid use in postoperative patients focus on the effect of preoperative RC use on perioperative and postoperative opioid requirements. Increased postoperativeopioid requirements have been reported for orthopedic trauma patients. and total joint arthroplasty patients who were RCusers.In contrast, other studies reported no difference inopioid requirements for RC users among total joint arthroplasty patients and elective surgery patients, inclusive of orthopedic and nonorthopedic proceduresNone of these studies reported specifically on the effects of legal MC use on opioid requirements.

One study of total hip arthroplasty and total knee arthroplasty patients treated after surgery with dronabinol,a synthetic prescription cannabinoid, in addition to a standard multimodal painregimen found a lower mean length of stay and lower average opioid use.Further studies are required to elucidate the impact of multimodal pain regimens inclusive of MC on opioid requirements in orthopedic surgery patients.Cost was reported by nearly 50% of our patients as a potential barrier for MC use, and over 70% reported the cost as either“expensive” or “not affordable.” A previous study of MC users also revealed the most common negative aspect of MC use was the associated cost, where patients reported spending over $2,000 per year on MC.5 The cost of MC varies by state and by specific product and is challenging to study, given the heterogeneity of the required quantity. A recent study by the Minnesota Department of Health found that the average 30-day cost per patient using MC to treat pain was $314 in 2019.35 Over 90% of patients in our cohort, greater than the number of patients that endorsed a willingness to use MC,supported insurance coverage for MC. Currently, no insurance companies cover MC.Together, these findings support advocacy for policies that support patient access to MC.This study has several limitations. First, MC use remains controversial, and this may limit our patients’ willingness to report MC use and provide honest opinions on MC. We attempted to minimize this bias through collecting data anonymously, but this bias may still be present. The controversy behind MC may have impacted which patients responded to our survey, and thus, despite our favorable response rate of 72.5%, we cannot rule out non-responsebias affecting our findings. Additionally, this study is conducted with patients presenting to outpatient hand and upper extremity clinics in 2 states in which MC has been legalized for at least 4 years, therefore limiting the generalizability of study findings for patients in states where MC has been recently legalized or where it remains illegal. We defined MC as any legal MC product in our study survey , but investigating patient responses to specific MC products could be explored further in future studies. Further, our patient population consists of predominantly patients with health insurance, which limits the generalizability of study findings. Lastly, our study is limited in that we do not collect information on the patients’ current pain levels, chronicity of symptoms, or RC use status, which could affect patient willingness to use MC. These variables may act as con-founders of patient perception of MC, and these relationships should be explored further in future studies.This study found that most hand and upper-extremity orthopedic patients presenting to outpatient offices would consider using MC, and most perceive it as a safe treatment option for common orthopedic conditions. Moreover, 10% of survey participants were already using MC. One of the major barriers to MC use is the financial cost.