CBD (Cannabidiol)

In late 2019, COVID-19 emerged in Wuhan, China. Currently, it is an ongoing global health threat stressing the need for therapeutic compounds. Linking the virus life cycle and its interaction with cell receptors and internal cellular machinery is key to developing therapies based on the control of infectivity and inflammation. In this framework, we evaluate the combination of cannabidiol (CBD), as an anti-inflammatory molecule, and terpenes, by their anti-microbiological properties, in reducing SARS-CoV-2 infectivity. Our group settled six formulations combining CBD and terpenes purified from Cannabis sativa L, Origanum vulgare, and Thymus mastichina. The formulations were analyzed by HPLC and GC-MS and evaluated for virucide and antiviral potential by in vitro studies in alveolar basal epithelial, colon, kidney, and keratinocyte human cell lines. CONCLUSIONS AND IMPACT: We demonstrate the virucide effectiveness of CBD and terpene-based formulations. F2TC reduces the infectivity by 17%, 24%, and 99% for CaCo-2, HaCat, and A549, respectively, and F1TC by 43%, 37%, and 29% for Hek293T, HaCaT, and Caco-2, respectively. To the best of our knowledge, this is the first approach that tackles the combination of CBD with a specific group of terpenes against SARS-CoV-2 in different cell lines. The differential effectiveness of formulations according to the cell line can be relevant to understanding the pattern of virus infectivity and the host inflammation response, and lead to new therapeutic strategies.

Background: Hemp extracts are used topically as cosmetic products and may be ingested as dietary supplements. Some users report positive carboxy delta-9-tetrahydrocannabinol (COOH-THC) urinary tests following their use. This study evaluated systemic exposure to natural hemp extract-based cosmetic (NHEC) bioactive molecules following a single dose of oral or topical application and assessed urine THC positivity. Methods: Twenty healthy adults (18-50 years, males and females) of a randomized, open-label, single-dose, crossover study received the NHEC orally or topically with a 15-day washout period. Plasma samples were analyzed for cannabidiol (CBD), tetrahydrocannabinol (THC), and their metabolites using a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were calculated by non-compartmental analysis (Phoenix® WinNonlin® 8.4, Pharsight Inc., Chatham, NJ, USA). Urine samples were tested for COOH-THC using commercial test strips. Results: All analytes, except CBD and 7-hydroxy cannabidiol (7-OH-CBD), were below the limit of quantification. Oral NHEC administration resulted in a faster Tmax (3 h vs. 24 h) and a higher AUC0-24 (281 vs. 19 h·ng/mL) for CBD compared to topical administration. Urine was positive for COOH-THC in 38% of participants receiving an oral dose. Conclusions: A single oral dose resulted in detectable plasma CBD and 7-OH-CBD, whereas topical administration produced low and frequently BLQ CBD concentrations with 7-OH-CBD and THC-related analytes not quantifiable. Urine COOH-THC tests were positive only in participants after oral use of an NHEC but not with topical use. Given the absence of THC in the product and the lack of CBD-to-THC conversion in humans, the cause of urine positivity remains unclear.

BACKGROUND: With shifting perceptions about the therapeutic potential of cannabis and evolving regulatory frameworks, global prescribing of medicinal cannabis is increasing. While some emerging evidence supports its use for conditions like multiple sclerosis and epilepsy, its efficacy and safety profile for the treatment of mental health conditions remains controversial and under-explored. Previous reviews found inconclusive evidence due to heterogeneity in study design and quality. Accordingly, this review was designed as a scoping review, consistent with established methodological frameworks to map and characterise all available randomised controlled trial (RCT) evidence in this emerging and heterogeneous field. It specifically sought to synthesise the highest-quality trial evidence to date, addressing the question: How effective is medicinal cannabis in treating mental health conditions, as classified by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), and how safe and tolerable is it, as assessed through adverse events and treatment withdrawals? METHODS: A scoping review was conducted comprising RCTs investigating medicinal cannabis for mental health conditions. Eligible studies were required to meet predefined inclusion criteria based on population, intervention, comparator, outcomes, and study design (PICOS framework). PubMed, Web of Science, and PsycINFO databases were searched, supplemented by citation tracking and Google Scholar, for studies published between 1980 and 2024. RESULTS: The search identified 8061 studies, with 28 RCTs meeting inclusion criteria across 12 DSM-5 mental health conditions. Indications most frequently studied were schizophrenia (n = 5), cannabis use disorder (n = 4), cocaine use disorder (n = 4), post-traumatic stress disorder (n = 3), anxiety disorders (n = 3), and opioid use disorder (n = 2); there were two trials in autism spectrum disorder and single trials in depression, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, tobacco use disorder, and Tourette syndrome. Sample sizes ranged from 6 to 150 participants (median = 42), and follow-up durations from 1 day to 13 weeks (median = 6

BACKGROUND: Cannabidiol (CBD), a non-intoxicating phytocannabinoid, is used by athletes to enhance recovery and manage other conditions (e.g., poor sleep, anxiety). Although CBD is not prohibited by the World Anti-Doping Agency (WADA), other cannabinoids found in "broad-spectrum" CBD products (e.g., cannabigerol (CBG), cannabidivarin (CBDV)), remain prohibited. OBJECTIVES: This study aimed to determine whether 10-wk use of a broad-spectrum CBD product (150 mg·day -1 (containing trace concentrations of CBG)) could lead to detectable concentrations of prohibited cannabinoids in urine and plasma. The influence of moderate-intensity exercise was also assessed. METHODS: Thirty-six healthy individuals (47% male) self-administered either a broad-spectrum CBD product ( n = 31, CBD) or a visually identical placebo ( n = 5, PLA) for 10 wk. After 10 wk, participants completed a fasted, 90-min bout of moderate-intensity exercise (55% V̇O 2peak ). Blood and urine samples were collected at baseline (presupplementation) and pre- and postexercise. RESULTS: No cannabinoids or metabolites were detected at baseline in either the PLA or CBD group. Following 10 wk of supplementation, urinary concentrations of CBD and its metabolites (6-OH-CBD, 7-COOH-CBD, 7-OH-CBD) were present. CBG and CBDV were also detected in 42% and 68% of preexercise samples, respectively. Urinary concentrations of 6-OH-CBD ( P = 0.006), 7-OH-CBD ( P = 0.009), CBD ( P = 0.043), CBG ( P = 0.0023), and CBDV ( P = 0.033) also increased from pre- to postexercise. CBG and CBDV were detected in 74% and 84% of postexercise samples, respectively. Concentrations of ∆ 9 -THC or its metabolites (11-OH-THC, 11-COOH-THC) were not present at any timepoint. CONCLUSIONS: Daily use of a broad-spectrum CBD supplement resulted in detectable urinary concentrations of WADA-prohibited cannabinoids in urine. Exercise appeared to increase concentrations of these cannabinoids. Therefore, athletes should avoid consuming broad-spectrum CBD products, given the potential associated anti-doping risks.

OBJECTIVES: Cannabidiol (CBD) is used to alleviate fibromyalgia pain despite limited evidence for efficacy. This study assessed the efficacy and safety of CBD vs placebo in patients with fibromyalgia, hypothesising that CBD would be superior to placebo in reducing pain. METHODS: In this single-centre, double-blind, randomised, placebo-controlled trial, patients diagnosed with fibromyalgia were recruited from a specialised outpatient clinic in Denmark. Eligible participants were randomised 1:1 and stratified by sex, defined as biological sex assigned at birth based on physical anatomy. Age (<45 vs ≥45), and pain level (<7 vs ≥7) on a 0 to 10 numeric rating scale (NRS) to receive 50 mg plant-derived CBD or placebo tablets. The primary outcome was change in pain intensity at week 24, assessed on the NRS pain subitem in the revised Fibromyalgia Impact Questionnaire in the intention-to-treat population. Adverse events were monitored throughout the study in the safety population. RESULTS: Of 273 participants screened for eligibility, 200 were included and randomised to receive CBD (n = 100) or placebo (n = 100). At week 24, mean change in pain intensity was -0.4 points (95% CI: -0.82 to 0.08) in the CBD group and -1.1 points (95% CI: -1.53 to -0.63) in the placebo group, corresponding to a between-group difference of -0.7 points (95% CI: -1.2 to -0.25; P = .0028) favouring placebo. Adverse events were generally mild and evenly distributed between groups. CONCLUSIONS: The findings do not support CBD 50 mg daily as an analgesic supplement for patients with fibromyalgia. CLINICALTRIALS: gov number: NCT04729179.

Background/Objectives: Plaque-associated gingivitis is widely regarded as a local inflammatory condition initiated by the accumulation of a non-specific dental biofilm in the interaction with the host immune system. The initial symptom noticed by the patient is bleeding gums. The use of mouthwash can serve to supplement mechanotherapy. However, there is an increasing interest in mouthwashes comprising natural ingredients, including cannabidiol (CBD) and spilanthol. The objective of this study was to evaluate the effect of an oral rinse containing spilanthol and CBD oil compared to a rinse containing tea tree oil on the oral microbiota and the values of selected oral status indicators in patients with gingivitis. Methods: The study included 40 patients treated with a rinse containing tea tree oil (TTO)/TTO + spilanthol + CBD for a period of 42 days. Patients rinsed their mouth twice daily for 30 s. The patients' oral microbiome was assessed before and after treatment, and bleeding on probing (BOP) and approximal plaque index (API) were assessed. The study was double-blind. Results: API and BOP were reduced in all groups, both the test and control. The most significant decrease in baseline BOP-1 scores was observed in test groups A and D (p = 0.005062 and p = 0.005062, respectively). A significant difference in API improvement was observed between the initial and final visits in the test (A, D) and control (B, C) groups (p = 0.012516, p = 0.005062, p = 0.004028, p = 0.003172, respectively). Conclusions: Firstly, the use of a mouthwash containing cannabidiol (CBD) and spilanthol was demonstrated to be efficacious in the maintenance of oral microbiota homeostasis. Secondly, the combination of TTO with spilanthol and CBD in the rinse was shown to result in a more significant reduction in selected oral health parameters (BOP and API) and anti-inflammatory effects when compared to a rinse with TTO alone. It should be noted that this is a pilot study and will continue.

Cannabidiol (CBD) is a compound found specifically in the cannabis plant. Although a clinical trial for intractable epilepsy started in Japan in 2023, it is also available in the market as a dietary supplement. Herein, we report two cases of identical twins with developmental and epileptic encephalopathy with STXBP1 gene mutation who achieved seizure suppression through different regimens of CBD supplementation. The observation that different trace ingredients produced different effects in patients with identical genetic backgrounds is a crucial finding that has implications for the future regulation and clinical application of cannabinoid products. © 2024 The Author(s).

STUDY OBJECTIVES: Cannabidiol (CBD) is increasingly used as a health supplement, though few clinical studies have demonstrated benefits. The primary objective of this study was to evaluate the effects of an oral CBD-terpene formulation on sleep physiology in individuals with insomnia. METHODS: In this double-blind, placebo-controlled, randomized clinical trial, 125 individuals with insomnia received an oral administration of CBD (300 mg) and terpenes (1 mg each of linalool, myrcene, phytol, limonene, α-terpinene, α-terpineol, α-pinene, and β-caryophyllene) for ≥ 4 days/wk over 4 weeks using a crossover design. The study medication was devoid of Δ9-tetrahydrocannabinol. The primary outcome measure was the percentage of time participants spent in the combination of slow-wave sleep (SWS) and rapid eye movement (REM) sleep stages, as measured by a wrist-worn sleep-tracking device. RESULTS: This CBD-terpene regimen marginally increased the mean nightly percentage of time participants spent in SWS + REM sleep compared to the placebo (mean [standard error], 1.3% [0.60%]; 95% confidence interval, 0.1-2.5%; P = .03). More robust increases were observed in participants with low baseline SWS + REM sleep, as well as in day sleepers. For select participants, the increase in SWS + REM sleep averaged as much as 48 minutes/night over a 4-week treatment period. This treatment had no effect on total sleep time, resting heart rate, or heart rate variability, and no adverse events were reported. CONCLUSIONS: Select CBD-terpene ratios may increase SWS + REM sleep in some individuals with insomnia and may have the potential to provide a safe and efficacious alternative to over-the-counter sleep aids and commonly prescribed sleep medications. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Evaluation of an Oral Cannabidiol (CBD)-Terpene Formulation on Sleep Physiology in Participants With Insomnia; URL: https://clinicaltrials.gov/study/NCT05233761; Identifier: NCT05233761. CITATION: Wang M, Faust M, Abbott S, et al. Effects of a cannabidiol/terpene formulation on sleep in individuals with insomnia: a double-blind, placebo-controlled, randomized, crossover study. J Cli

Cannabidiol (CBD) is a non-intoxicating phytocannabinoid which has been proposed to possess anti-inflammatory and analgesic properties. Given the potential for perceptions of pain to limit exercise performance, the aim of the present study was to investigate if 3 weeks of daily CBD supplementation (150 mg day-1) improved performance in a 10-min performance-trial on a cycle ergometer. In a randomized, double-blind and placebo-controlled study, 22 healthy participants (n = 11 male and n = 11 female) completed two 10-min performance trials on a WattBike cycle ergometer interspersed with a 3-week supplementation period. Supplementation involved either 150 mg day-1 oral CBD or 150 mg day-1 of a visually identical placebo (PLA). During trials, ratings of perceived exertion (RPE [6-20]), heart rate (HR) and blood lactate (BLa) were collected every 2 min. Mean power (W) was also taken throughout the exercise at each time point. All data were analyzed using two-way ANOVAs. There were no significant differences (P > 0.05) between CBD or PLA groups for mean power (W) during the 10-min performance trial. There were also no significant differences (P > 0.05) in any of the physiological or perceptual parameters (HR, BLa and RPE) between conditions. Three weeks supplementation of a broad-spectrum CBD supplement did not improve performance via any change in RPE during a 10-min time trial on a cycle ergometer, and as such, this evidence does not support the claim that broad-spectrum CBD supplements could be performance-enhancing in this exercise modality. © 2024 The Authors. European Journal of Sport Science published by Wiley‐VCH GmbH on behalf of European College of Sport Science.

BACKGROUND: Rapid regeneration after intense exercise is essential for competitive athletes. Based on this assumption, supplementation strategies, focusing on food supplements, are increasing to improve the recovery processes. One such supplement is cannabidiol (CBD) which is gaining more attention in competitive sports. However, the evidence is still lacking and there are no data available about the effect of a short-term chronic application. METHODS: A three-arm double-blind cross-over study was conducted to determine the effects of two different CBD products on performance, muscle damage and inflammatory processes in well-trained athletes. In total 17 subjects took successfully part in this study. Each subject underwent the six-day, high-intensity training protocol three times. After each training session, each subject took either a placebo or a CBD product (60 mg of oil or solubilisate). Between the intervention phases, at least four weeks of washout period was conducted. Before and after the training protocols the performance capacity in countermovement jump (CMJ), back squat (BS), bench press (BP) and 1-mile run were measured and biomarkers for muscle damage (creatine kinase, myoglobin), inflammatory processes (interleukin 6 and 10) and immune cell activity (ratios of neutrophil granulocytes, lymphocytes and, platelets) were analyzed. For statistical analyses, the current version of R and a linear mixed model was used. RESULTS: It could identify different effects of the training protocol depending on performance level (advanced or highly advanced athletes) (p < .05). Regardless of the performance level, muscle damage and a reduction in performance could be induced by the training protocol. Only CBD oil was associated with a reduction in myoglobin concentration (p < .05) in advanced athletes. Concerning immune activity, a significant decrease in platelets lymphocyte ratios was observed in advanced athletes after placebo treatment (p < .05). CBD oil application showed a slight inhibitory effect (p < .10). Moreover, the reduction in performance differs between the performance levels. A significant decrease in CMJ was observed in advanced athletes and a decrea

BACKGROUND: Painful knee osteoarthritis (KOA) is common, pharmacological treatment, however, is often hampered by limited tolerability. Cannabidiol, which preclinically showed anti-inflammatory, analgesic activity, could supplement established analgesics, but robust clinical trials are lacking. The aim of our study was to investigate the effects of oral high-dose CBD administered over 8 weeks on pain, function and patient global assessment as an add-on to continued paracetamol in chronic symptomatic KOA. METHODS: Prospective, randomized, placebo-controlled, double-blind, parallel-group study. Single center, Outpatient Clinic, Department of Special Anaesthesia and Pain Therapy at Medical University of Vienna, Austria. Eligibility criteria included: age: 18-98 years; painful KOA; score ≥5 on the pain subscale of the Western Ontario and McMasters Universities Osteoarthritis (WOMAC) Index; KOA confirmed by imaging. Participants were on continued dosage of paracetamol 3 g/d and randomly assigned by web-based software 1:1 to oral cannabidiol 600 mg/d (n = 43) or placebo (n = 43). Study period: 8 weeks. Primary outcome: Change in WOMAC pain subscale scores (0 = no pain, 10 = worst possible pain) from baseline to week 8 of treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT04607603. Trial is completed. FINDINGS: The trial was conducted from October 1, 2020 to March 29, 2022. 159 patients screened, 86 randomized. Among 86 participants (mean age, 62.8 [SD 20.3] years; 60 females [69.8%]), 58 (67.4%) completed the trial. Mean baseline WOMAC pain subscale was 6.0 ± 1.1. Analysis: Intention-to-treat principal. Mean reduction in WOMAC pain subscale was 2.5 (95% CI: 1.8-3.3) in the cannabidiol group and 2.4 (95% CI: 1.7-3.2) in the placebo group with no significant group difference (p = 0.80). Adverse events were significantly more frequent with cannabidiol (cannabidiol: 135 [56%]; placebo: 105 [44%]) (p = 0.008). Rise above baseline of liver aminotransferases and gamma-glutamyltransferase was significantly more common in the cannabidiol (n = 15) than the placebo group (n = 5) (p = 0.02). INTERPRETATION: In KOA patients, oral high-dose add-on cannabidiol had no a

BACKGROUND: The endocannabinoid system is active in nervous and immune cells and involves the expression of two cannabinoid receptor genes (CB1 and CB2), along with endogenous endocannabinoid ligands, 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide (anandamide), and their synthetic enzymes. Cannabidiol (CBD) is a non-intoxicating exogenous cannabinoid agonist derived from plants that, at high doses, has received FDA approval as an anticonvulsant for epileptic seizures, and at low doses is marketed as a food-grade supplement for improved mental health, sleep quality, and immunological function. At present, the predominance of published CBD clinical research has focused on ameliorative or disease-specific intervention, with few trials investigating CBD effects in healthy populations. METHODS: This clinical study aimed to investigate the effects of 8 weeks of 50 mg oral CBD on mental health, sleep quantity and quality, and immune cell function in healthy, college-aged individuals. Twenty-eight participants (average age 25.9 ± 6.1 y) were randomized to receive either daily oral capsules of 50 mg of CBD (CB, n = 14) or a calorie-matched placebo (CN, n = 14). Participants completed pre- and post-intervention assessments, including anthropometric measurements, mental health surveys, sleep analysis, and immunological function assessments. RESULTS: After completing the 8-week intervention, there were no significant changes in body weight and BMI (CN: 1.09 ± 0.89%: CB: 1.41 ± 1.07%), or body fat percentage (CN: 9.01 ± 7.51%: CB: 8.57 ± 7.81%), respectively (values are % change pre to post, p > 0.05). There were also no significant differences between CB and CN groups with respect to mental health measures, sleep quantity, or circulating immunophenotype as a result of the intervention. However, the CB group experienced significant improvements in sleep quality measured objectively using a sleep questionnaire (p = 0.0023) and enhanced Natural Killer (NK) immune cell function assessed in situ (p = 0.0125). CONCLUSIONS: Eight weeks of daily 50 mg CBD may improve sleep quality, and NK immunosurveillance in healthy, younger adults.

HYPER-H21-4 was a randomized crossover trial that aimed to determine if cannabidiol (CBD), a non-intoxicating constituent of cannabis, has relevant effects on blood pressure and vascular health in patients with essential hypertension. In the present sub-analysis, we aimed to elucidate whether serum urotensin-II concentrations may reflect hemodynamic changes caused by oral supplementation with CBD. The sub-analysis of this randomized crossover study included 51 patients with mild to moderate hypertension that received CBD for five weeks, and placebo for five weeks. After five weeks of oral CBD supplementation, but not placebo, serum urotensin concentrations reduced significantly in comparison to baseline (3.31 ± 1.46 ng/mL vs. 2.08 ± 0.91 ng/mL, P < 0.001). Following the five weeks of CBD supplementation, the magnitude of reduction in 24 h mean arterial pressure (MAP) positively correlated with the extent of change in serum urotensin levels (r = 0.412, P = 0.003); this association was independent of age, sex, BMI and previous antihypertensive treatment (β ± standard error, 0.023 ± 0.009, P = 0.009). No correlation was present in the placebo condition (r = -0.132, P = 0.357). In summary, potent vasoconstrictor urotensin seems to be implicated in CBD-mediated reduction in blood pressure, although further research is needed to confirm these notions.

BACKGROUND: Pain is a common symptom in people with cancer; 30% to 50% of people with cancer will experience moderate-to-severe pain. This can have a major negative impact on their quality of life. Opioid (morphine-like) medications are commonly used to treat moderate or severe cancer pain, and are recommended for this purpose in the World Health Organization (WHO) pain treatment ladder. Pain is not sufficiently relieved by opioid medications in 10% to 15% of people with cancer. In people with insufficient relief of cancer pain, new analgesics are needed to effectively and safely supplement or replace opioids. OBJECTIVES: To evaluate the benefits and harms of cannabis-based medicines, including medical cannabis, for treating pain and other symptoms in adults with cancer compared to placebo or any other established analgesic for cancer pain. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 26 January 2023. SELECTION CRITERIA: We selected double-blind randomised, controlled trials (RCT) of medical cannabis, plant-derived and synthetic cannabis-based medicines against placebo or any other active treatment for cancer pain in adults, with any treatment duration and at least 10 participants per treatment arm. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. The primary outcomes were 1. proportions of participants reporting no worse than mild pain; 2. Patient Global Impression of Change (PGIC) of much improved or very much improved and 3. withdrawals due to adverse events. Secondary outcomes were 4. number of participants who reported pain relief of 30% or greater and overall opioid use reduced or stable; 5. number of participants who reported pain relief of 30% or greater, or 50% or greater; 6. pain intensity; 7. sleep problems; 8. depression and anxiety; 9. daily maintenance and breakthrough opioid dosage; 10. dropouts due to lack of efficacy; 11. all central nervous system adverse events. We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: We identified 14 studies involving 1823 participants. No study assessed the proportions of participants reporting no worse than mild pain on

Data concerning the effects of cannabidiol (CBD) on blood pressure (BP) is controversial. HYPER-H21-4 was a randomized, placebo-controlled, crossover trial which sought to elucidate if 5-week administration of CBD will reduce BP in hypertensive patients. In the substudy of this trial, we aimed to establish the mechanistic background of CBD-induced BP reduction. Specifically, we explored the dynamic of catestatin, a sympathoinhibitory peptide implicated in the pathophysiology of hypertension. In the present analysis, 54 patients with Grade 1 hypertension were included. 5-week administration of CBD but not placebo reduced serum catestatin concentration in comparison to baseline (13.50 [10.85-19.05] vs. 9.65 [6.37-12.26] ng/mL, p < 0.001). Serum catestatin levels at the start of the treatment period demonstrated a negative correlation with the extent of reduction in mean arterial pressure (r = -0.474, p < 0.001). Moreover, the extent of change in catestatin serum levels showed a strong correlation with the extent of mean arterial pressure reduction (r = 0.712, p < 0.001). Overall, the results of the present study imply that the antihypertensive effects of CBD may be explained by its interaction with the sympatho-chromaffin system, although further research is warranted.

BACKGROUND: Multimodal analgesia has become the standard of care for pain management following total knee arthroplasty (TKA). Cannabidiol (CBD) is increasingly utilized in the postoperative period. The purpose of this study was to analyze the analgesic benefits of topical CBD following primary TKA. METHODS: In this randomized double-blinded placebo-controlled trial, 80 patients undergoing primary unilateral TKA applied topical CBD (CBD; n = 19), essential oil (EO; n = 21), CBD and essential oil (CBD + EO; n = 21), or placebo (PLA; n = 19) thrice daily around the knee for two weeks postoperatively. This supplemented a standardized multimodal analgesic protocol. Outcomes included visual analog scale (VAS) pain and numeric rating scale (NRS) sleep scores (collected on postoperative day [POD] 0, 1, 2, 7, 14, 42), and cumulative postoperative opioid use (42 days). RESULTS: Demographic characteristics were similar among the four cohorts. Preoperative VAS and NRS scores were similar among groups. The CBD cohort had a higher mean VAS pain score on POD 2 compared to the EO cohort (CBD: 69.9 ± 19.3 versus. EO: 51.0 ± 18.2; P = .013). No statistically significant differences existed for VAS scores at other times, and no statistically significant differences were observed for postoperative NRS sleep scores or postoperative opioid use at any time point. CONCLUSION: Utilization of topical CBD in supplement to multimodal analgesia did not reduce pain or opioid consumption, or improve sleep scores following TKA. These results suggest that the local effects of topical CBD are not beneficial for providing additional pain relief after TKA.