Cannabidiol Alleviates Chronic Prostatitis and Chronic Pelvic Pain Syndrome via CB2 Receptor Activation and TRPV1 Desensitization

Abstract

Purpose

This study elucidates the mechanism of the physiological effect of cannabidiol (CBD) by assessing its impact on lipopolysaccharide (LPS)-induced inflammation in RWPE-1 cells and prostatitis-induced by 17β-estradiol and dihydrotestosterone in a rat model, focusing on its therapeutic potential for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Materials and Methods

RWPE-1 cells were stratified in vitro into three groups: (1) controls, (2) cells with LPS-induced inflammation, and (3) cells with LPS-induced inflammation and treated with CBD. Enzyme-linked immunosorbent assays and western blots were performed on cellular components and supernatants after administration of CBD. Five groups of six Sprague–Dawley male rats were assigned: (1) control, (2) CP/CPPS, (3) CP/CPPS and treated with 50 mg/kg CBD, (4) CP/CPPS and treated with 100 mg/kg CBD, and (5) CP/CPPS and treated with 150 mg/kg CBD. Prostatitis was induced through administration of 17β-estradiol and dihydrotestosterone. After four weeks of CBD treatment, a pain index was evaluated, and prostate tissue was collected for subsequent histologic examination and western blot analysis.

Results

CBD demonstrated efficacy in vivo for CP/CPPS and in vitro for inflammation. It inhibited the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway by activating the CB2 receptor, reducing expression of interleukin-6, tumor necrosis factor-alpha, and cyclooxygenase-2 (COX2) (p<0.01). CBD exhibited analgesic effects by activating and desensitizing the TRPV1 receptor.

Conclusions

CBD inhibits the TLR4/NF-κB pathway by activating the CB2 receptor, desensitizes the TRPV1 receptor, and decreases the release of COX2. This results in relief of inflammation and pain in patients with CP/CPPS, indicating CBD as a potential treatment for CP/CPPS.

INTRODUCTION

Chronic prostatitis remains an enigma for many physicians and patients. Approximately 4.5% to 9.0% of men receive a diagnosis of prostatitis, with recurrence rates up to 50% in older patients. Chronic prostatitis can be categorized into two types: bacterial and non-bacterial. The former is caused by a bacterial infection, while non-bacterial chronic prostatitis may be associated with inflammation, neurological abnormalities, or other causes [1]. Clinical observations suggest that individuals with a history of benign prostatic hyperplasia and CP/CPPS are at increased risk of prostate cancer [2]. CP/CPPS is characterized by persistent pelvic pain without a discernible underlying pathology. Symptoms include lower urinary tract symptoms, genital discomfort, painful ejaculation, abdominal pain, and sexual dysfunction including erectile dysfunction, posing substantial challenges for patients and healthcare providers [3]. Despite the availability of treatment modalities such as antibiotics, anti-inflammatory drugs (including bioflavonoids), neuromodulators, and alpha-blockers, few antimicrobial agents can effectively penetrate prostate tissue to achieve sufficient concentrations at the infection site [4].

In recent years, interest in the main phytocannabinoid cannabidiol (CBD) has increased dramatically. From 2008 to the present, a search on PubMed using the keyword “cannabidiol” yielded 1,205 publications. In comparison, only 275 reports were published between 1999 and 2007. CBD was first isolated from cannabis in 1940 [5], and subsequent research on cannabis led to identification of tetrahydrocannabinol (THC) as the “active” principle. Research since has focused largely on THC, almost to the exclusion of CBD, likely due to the perception that “active” means psychoactive. This is unfortunate, as some of the potentially therapeutic behavior associated with the use of CBD has been overlooked [6]. Although CBD is widely used to treat inflammation, cancer, pain, and other areas and has been shown to be effective, its specific role in CP/CPPS and its mechanisms have not been reported.

This paper examines the main effects of CBD on the response to inflammation in patients with CP/CPPS and explores the underlying mechanisms. The research establishes a vital theoretical foundation for the utilization of CBD in treating CP/CPPS.

MATERIALS AND METHODS

1. Cell culture

RWPE-1 cells (ATCC) were cultured in Dulbecco’s modified Eagle medium (Gibco) containing low glucose, with 20% fetal bovine serum (Gibco) and 5 ng/mL of human epidermal growth factor (CST). A humidified environment of 5% CO₂ was used to incubate the cells at 37 ℃. Removal of non-adherent cells occurred after 2 days, followed by the addition of fresh medium. The medium was refreshed every two days thereafter and was passaged when the cells reached approximately 90% confluence.

2. Cytotoxicity assay

To assess the cytotoxicity of CBD (KCA Labs) in RWPE-1 cells, cell viability was determined by measuring mitochondrial succinate dehydrogenase activity. After treating the cells with CBD for 6 or 24 hours, the medium in each well was suctioned and 200 µL of 3,4,5-dimethylthiazol-2-yl-2-5-diphenyltetrazolium bromide was added for 30 to 40 minutes. After a purplish-red color appeared, 200 µL of a solution of isopropanol and dimethyl sulfoxide (ratio 90:10) was added to the cells. The absorbance at 570 nm was quantified with an Envision spectrophotometer (PerkinElmer).

CBD exhibited no significant cytotoxicity in RWPE-1 cells after 6 hours of treatment at concentrations below 0.5 µg/mL. No significant cytotoxicity was observed after 24 hours of CBD treatment at concentrations below 0.1 µg/mL (Fig. 1). Consequently, in our in vitro experiments, we selected a CBD concentration of 0.1 µg/mL for a 24-hour treatment.

Fig. 1. Cannabidiol (CBD)-induced cytotoxicity in RWPE-1 cells. Cell viability was determined utilizing 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide. RWPE-1 cells have been treated with varying concentrations of CBD (up to 100 µg/mL) for distinct durations of 6 or 24 hours, administered once daily. Measurements were plotted in triplicate expressed as mean±standard deviation. ^*p<0.05 indicates significant difference between treatment and vehicle groups.

3. CBD administration of RWPE-1 cells

CBD was dissolved in 0.5% dimethyl sulfoxide (DMSO; Sigma-Aldrich). RWPE-1 cells were randomly allocated to 1 of 3 groups: (1) control cells, (2) a lipopolysaccharide (LPS) group, and (3) a CBD group. Cells in the CBD group were subjected to CBD treatment, whereas the normal and LPS groups underwent sham treatment involving an equivalent quantity of CBD dilution (in DMSO) without an active CBD component.

After cell attachment, a chronic non-bacterial prostatitis model was induced with LPS (10 µg/mL) for 24 hours, then treated with CBD and placebo. Each generation was treated only once. Cells and supernatant samples were collected 24 hours later and stored at −80 ℃ for western blot analysis and enzyme-linked immunosorbent assay (ELISA) detection.

4. Design of in vivo studies

Thirty six Sprague–Dawley male rats (Orient Bio Co.), 8 weeks of age, and weighing between 280 and 310 g each was included in the study. The rats (n=30) were randomly divided into five groups: group 1 was the control group, group 2 was the prostatitis group, group 3 received CBD treatment at 50 mg/kg, group 4 received CBD treatment at 100 mg/kg, and group 5 received CBD treatment at 150 mg/kg (six rats per group). Animal models of prostatitis were referenced from similar previous studies, and rats in the prostatitis and CBD-treated groups were injected with 17β-estradiol and dihydrotestosterone for 4 weeks [7]. Rats in the CBD treatment group received CBD administration following establishment of the model, while rats in the control or prostatitis groups received only placebo. CBD was also administered to normal rats in the CBD group (n=6) to further investigate the anti-inflammatory mechanism of CBD in prostatitis. A pilot study involving 10 rats achieved a 100% success rate in effectively inducing prostatitis.

5. CBD administration to rats

During the experiment, rats assigned to the CBD group were treated with CBD for 4 weeks. Briefly, CBD was dissolved in sesame oil (Sigma-Aldrich) and administered orally to rats in groups 3, 4, and 5 at 50, 100, and 150 mg per kg of body weight, respectively, based on previous study that used oral gavage [8]. Sesame oil without CBD was administered orally to the control and prostatitis groups at 5 mL/kg once daily [9].

6. Pain index assessment

All rats were measured for pain before and after treatment with Von Frey (VF) filaments and dynamic plantar aesthesiometer (DPA) systems [10,11,12]. Rats were placed individually in wire-mesh cages for testing. Mechanical anisocoria was tested using a VF filament, and stimulus increments and scrotal retractions were considered positive responses. The procedure was repeated 10 times at short intervals for each rat.

A 2 g/s ramp and a 30 g threshold were used in the DPA test. After recording the value of scrotal contraction, the probe automatically returns to its original position. A mean value was recorded as the threshold after 3 DPA tests were conducted in each rat. At the end of pain index assessment, sodium pentobarbital (50 mg/kg) was injected intraperitoneally, followed by bilateral thoracotomy. The prostate was collected and analyzed histologically and assayed by western blot.

7. Western blot analysis

An ice-cold RIPA buffer (CST) supplemented with a protease inhibitor cocktail (ethylenediaminetetraacetic acid–free) and a phosphatase inhibitor cocktail (Roche Diagnostics Ltd.) was used for homogenization of RWPE-1 cells and rat prostate tissue. After homogenization, samples were cooled to 4 ℃ and centrifuged at 15,000 g for 15 minutes to separate the supernatant, and the proteins were transferred to a nitrocellulose membrane. After membrane transfer, the membrane was blocked for 1 hour at room temperature and incubated with primary antibodies to help minimize potential for content overlap. The primary antibodies used were cannabinoid receptor 2 (CB2) (dilution 1:500; Abcam), transient receptor potential vanilloid 1 (TRPV1) (dilution 1:1000; Abcam), tumor necrosis factor-alpha (TNF-α) (dilution 1:1000; Santa Cruz), nuclear factor-kappa B (NF-κB) (dilution 1:500; CST), cyclooxygenase-2 (COX2) (dilution 1:500; CST), interleukin-6 (IL-6) (dilution 1:1000; CST), toll-like receptor 4 (TLR4) (dilution 1:1000; CST), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) (dilution 1:5,000; Abcam) followed by membrane-binding to horseradish peroxidase–bound secondary antibodies and incubation for 1 hour at room temperature. Enhanced chemiluminescence (Amersham) was used to detect proteins. Images were analyzed using ImageJ (NIH) to quantify the individual protein bands.

8. ELISA

Cells were stimulated with LPS in RWPE-1 cells for 24 hours. Cells in the treatment group underwent additional treatment with CBD (0.1 µg/mL) for another 24 hours. The levels of NF-κB, IL-8, and COX2 in the collected supernatants were assayed quantitatively with ELISA kits (Abcam).

9. H&E staining

The collected prostate was fixed in 4% paraformaldehyde at 4 ℃ for 24 hours and then embedded in paraffin. Paraffin sections of the prostate were subjected to H&E staining, following the manufacturer’s instructions (Sigma).

10. Statistical analysis

Results were analyzed in SPSS (version 20.0; SPSS Inc.) and recorded as mean±standard deviations. Triple comparisons by analysis of variance followed by post hoc comparisons using the Tukey–Kramer tests. Data were expressed as proportions with chi-square tests. The statistical significance threshold was p<0.05.

11. Ethics statement

The animal studies were performed after receiving approval of the Institutional Animal Care and Use Committee (IACUC) in The Catholic University of Korea (IACUC approval No. CUMC-2021-0353-02).

RESULTS

1. CBD improved prostatitis by attenuating inflammation

We measured the levels of inflammatory factors IL-8, COX2, and NF-κB by ELISA in vitro (Fig. 2). When assessing inflammation after CBD treatment, we observed a reduction in tissue edema, hemorrhage, and inflammatory cells compared with prostatitis (Fig. 3). We also detected both in vitro and in vivo inflammatory factors, through western blotting, such as IL-6, TNF-α, and COX2 (Fig. 4). CBD treatment, both in vitro and in vivo, resulted in a decrease in the concentration of COX2, IL-8, IL-6, TNF-α, and NF-κB, (p<0.01). In the ELISA, CBD inhibited the release of IL-8, COX2, and NF-κB in RWPE-1 cells by more than 90%. These results suggest that CBD treatment reduces the inflammatory response. However, the mechanism by which CBD ameliorates prostatitis remained unclear, prompting us to conduct further mechanistic studies.

Fig. 2. LPS-induced quantitative changes in levels of IL-8, COX2, and p-NF-κB in RWPE-1 cells. The levels of IL-8 (A), COX2 (B), and NF-κB (C) were determined by enzyme-linked immunosorbent assays. Measurements were plotted in triplicate and expressed as mean±standard deviation. LPS: lipopolysaccharide, CBD: cannabidiol, IL-8: interleukin-8, COX2: cyclooxygenase-2, NF-κB: nuclear factor-kappa B. ^*p<0.01 compared with the LPS group.

Fig. 3. H&E staining of prostate tissues from different groups of rats (magnification ×100): (A) Staining of healthy controls showed no inflamed cell infiltration or proliferation of fibrous tissue. The prostatic glandular epithelial cells and glandular epithelial tissue of pseudo hyperplasia remained regularly arranged. No glandular hyperplasia was observed in the ductal lumen. (B) In the chronic prostatitis/chronic pelvic pain syndrome group, proliferation of fibrous tissue can be seen in the intercellular structure, along with infiltration of inflammatory cells, disorganization of the epithelial cell layer of the prostate, and a large number of tumor-like epithelial hyperplasia protruding into the lumen of the ducts. (C–E) In cannabidiol treatment groups at doses of 50, 100, and 150 mg/kg, respectively, tumor-like epithelial hyperplasia in the ductal lumen was significantly reduced and prostate glandular epithelia were regularly aligned; this effect was more pronounced at higher doses.

Fig. 4. (A) Results of western blot analysis of IL-6, TNF-α, and COX2 in vivo in each group. Quantitative western blot analysis of IL-6/GAPDH, TNF-α/GAPDH, and COX2/GAPDH in vivo. (B) Results of western blot analysis of IL-6, TNF-α, and COX2 in each group in vitro; quantitative western blot analysis of IL-6/GAPDH, TNF-α/GAPDH, and COX2/GAPDH in vitro. CP/CPPS: chronic prostatitis/chronic pelvic pain syndrome, CBD: cannabidiol, LPS: lipopolysaccharide, IL-6: interleukin-6, TNF-α: tumor necrosis factor-alpha, COX2: cyclooxygenase-2, GAPDH: glyceraldehyde 3-phosphate dehydrogenase. ^ap<0.01 compared with the CP/CPPS group. ^bp<0.01 compared with the LPS group.

2. CBD inhibited TLR4/NF-κB signaling through activation of the CB2 receptor

Down-regulation of inflammatory factors by CBD was observed both in vivo and in vitro, as some of the research suggests that CBD has an agonistic effect on CB2 receptors. To explore the relationship between CB2 receptors and the TLR4/NF-κB pathway, we administered CBD to normal rats and analyzed the response. TLR4 and NF-κB expression were significantly reduced in both the normal and CP/CPPS rat receiving CBD treated (p<0.01) relative to the CP/CPPS group. CBD appeared to inhibit the TLR4/NF-κB pathway. CB2 exhibited a significant enhancement in both the normal rats treated with CBD and the CP/CPPS group. The results suggest CBD can reduce prostate inflammation by inhibiting the TLR4/NF-κB pathway through activation of the CB2 receptor (Fig. 5).

Fig. 5. (A) Results of western blot of TLR4, NF-κB, and CB2 in vivo in each group. (B) Quantitative western blot of TLR4/GAPDH, NF-κB/GAPDH, and CB2/GAPDH in vivo. TLR4: toll-like receptor 4, NF-κB: nuclear factor-kappa B, CB2: cannabinoid receptor 2, GAPDH: glyceraldehyde 3-phosphate dehydrogenase, CBD: cannabidiol, CP/CPPS: chronic prostatitis/chronic pelvic pain syndrome. ^*p<0.01 compared with control rates.

3. Assessment of pain indices in rats with prostatitis after CBD treatment

To assess the effect of CBD treatment on prostatitisinduced pain in rats, we administered VF filaments and DPA to each group of rats (Fig. 6A, 6C). Control rats and rats with CP/CPPS received CBD at doses of 50, 100, and 150 mg/kg. Fig. 6B shows that the response frequency of VF filaments improved after CBD treatment compared with CP/CPPS rats (p<0.05). Fig. 6D shows that the DPA threshold also increased after CBD treatment (p<0.01). These results suggest that CBD can significantly mitigate the pain caused by prostatitis, and the improvement was more pronounced with higher doses of CBD.

Fig. 6. (A) Representative image of the Von Frey (VF) filament test. (B) Quantitative results of VF filament for each group. (C) Representative image of dynamic plantar anesthesia. (D) Quantification of DPA in each group. DPA: dynamic plantar aesthesiometer, CP/CPPS: chronic prostatitis/chronic pelvic pain syndrome. ^*p<0.01 compared with the CP/CPPS group.

4. CBD relieved pain by desensitizing TRPV1 receptors

CBD paroxysms are thought to be one of the mechanisms of desensitization after TRPV1 activation [13]. We used western blots to test for TRPV1 expression under CBD treatment and to explore the desensitizing action induced by CBD. The results showed that the TRPV1 level was significantly higher in the CP/CPPS group compared with the control group and was lower in the CBD group compared with the CP/CPPS group (p<0.01) (Fig. 7). These data suggest that CBD relieves pain by activating TRPV1 and then desensitizing it.

Fig. 7. (A) Results of western blot analysis of TRPV1 in the prostate in each group. (B) Quantitative western blot analysis of TRPV/GAPDH in the prostate. TRPV1: transient receptor potential vanilloid 1, GAPDH: glyceraldehyde 3-phosphate dehydrogenase, CP/CPPS: chronic prostatitis/chronic pelvic pain syndrome, CBD: cannabidiol. ^*p<0.01 compared with CP/CPPS.

DISCUSSION

The primary discoveries of this investigation can be summarized as follows. First, CBD reduces inflammatory responses in a rat model of CP/CPPS and in RWPE-1 cells. Second, CB2 receptor activation and suppression of the TLR-4/NF-κB signaling are crucial for CBD regulation of the inflammatory response in a CP/CPPS rat model. Third, in terms of pain relief in CP/CPPS, CBD produces a desensitization response to TRPV1 receptors in the prostate and is associated with a reduction of COX2 in the microenvironment. In summary, CBD can be used to treat CP/CPPS.

Current treatments for CP/CPPS include anti-inflammatory medications, antibiotics, alpha-adrenergic blockers, and neuromodulatory medications, but the results are often less than optimal, creating ongoing challenges for patients [14]. The mechanism of action is poorly understood, and the search for an effective approach continues [7]. In a pilot study, we compared CBD and antibiotic therapy in non-bacterial prostatitis, finding that CBD was more than 50% more effective in inhibiting inflammation compared with antibiotic therapeutics. To investigate CP/CPPS treatment, Yuan et al [14] collected prostate fluid and scored pain and discomfort for 172 patients with chronic prostatitis and 151 healthy men. Their findings suggest that activation of the COX2 pathway led to elevated concentrations of PGE2, potentially contributing to pain or discomfort in individuals with chronic non-bacterial prostatitis. However, the underlying cause of prostatitis-induced pain in the prostate region remains unknown, posing challenges for effective treatment.

Recent studies have indicated that antioxidants and anti-inflammatory drugs and treatments have significant efficacy in alleviating oxidative stress and inflammation in patients with CP/CPPS [15]. This finding offers hope for exploring new avenues for the treatment of this medical condition, particularly in the complex interplay of regulating oxidative stress and inflammatory responses. In a study involving the biochemical effects of natural and synthetic CBD derivatives, Atalay et al [10] detailed the antioxidant and anti-inflammatory properties of CBD. The study delved into the molecular mechanisms by which CBD exerts its therapeutic effects, revealing its potential to modulate oxidative stress and inflammation. Oxidative modifications have a critical effect in the regulation of transcription factors responsive to redox, such as Nrf2 and NF-κB.The remarkable antioxidant effects of CBD include protecting lipids and proteins against oxidative damage through the reduction of lipid and protein modifications, as well as the modulation of oxidative stress levels in cellular signaling pathways. This process not only contributes to the maintenance of cellular structural integrity but may also have wide-ranging effects on cell signaling. CBD’s antioxidant effects go beyond simply reducing oxidative stress levels; they involve targeted protection of lipids and proteins, crucial for normal cellular function. Through modulating oxidative stress levels in cell signaling pathways, CBD may provide a promising therapeutic option for CP/CPPS patients.

Fitzpatrick and Downer [16] reported that cannabinoids can regulate TLR signaling mechanisms. Specifically, phytocannabinoids (THC and CBD) can suppress TLR4-induced signaling across diverse cell types, such as endothelial cells, astrocytes, and microglia [17,18,19]. Fitzpatrick et al [20] found that MyD88-dependent and non-dependent signaling is also activated by TLR4 receptor agonists. TLR-4 and NF-κB pathways are chronically active in several inflammatory diseases, and cannabinoids inhibit the TLR-4 and NF-κB signaling pathways, exerting anti-inflammatory and antioxidant effects [21,22]. CB1 and CB2 are the sites where endogenous cannabinoids and cannabinoids function, CB1 is primarily located in the central nervous system and CB2 is found primarily in peripheral cells. When there is an imbalance in the body, endocannabinoids may bind to CB2 receptors in immune cells, signaling that it is time to reduce inflammation. Instead of binding directly to CB2 receptors, CBD takes a more indirect approach by preventing the breakdown of endogenous cannabinoids, thus enhancing their effects. To explore whether CB2 receptors are involved in TLR-4/NF-κB signal-pathway inhibition, we refer to Dos Santos et al [23]. In animal experiments, CBD treatment increased CB2 receptor expression and decreased TLR4 expression in the spine of animals [23]. To confirm this result by treating normal rats with CBD and examining the expression of CB2 receptors in the prostate, the present study showed that CBD-treated rats had greater expression of CB2 receptors in prostate tissue compared with normal rats not treated with CBD. However, compared with the normal group, CB2 expression was significantly higher in the CP/CPPS group. CBD treatment of rats in the CP/CPPS group also led to a reduction in CB2 expression, aligning with results reported by Turcotte et al [24] that CB2 receptors are involved in the inhibition of inflammation.

More extensive research findings have found that CBD binds to TRPV1 receptors and directly interacts with them to exert anti-inflammatory and analgesic effects.TRPV1 is an ion-channel protein belonging to the transient receptor potential family. TRPV1 channels are expressed primarily in sensory neurons, particularly in the terminals of major sensory neurons, where it plays a pivotal role in sensing and transmitting nociception, temperature, and other physiological stimuli. TRPV1 channels are regulated primarily by stimulatory substances, most notably capsaicin. In addition, TRPV1 is sensitive to high temperatures, low pH (acidic environments), and endogenous substances (e.g., capsaicin and lipid metabolites). It is important for the detection of thermal stimuli and inflammatory substances, as well as for transmitting signals related to nociception to the brain. TRPV1 is activated during inflammation, leading to an increase in pain perception. In addition, alterations in TRPV1 activity may be associated with the release of neurotransmitters such as neuropeptide substance P, which affects nociceptive transmission. Prolonged or repeated exposure to TRPV1 activators such as capsaicin may lead to desensitization of TRPV1, undermining adaptation to stimuli. The analgesic effect of CBD is similar to the desensitization mechanism of capsaicin on TRPV1. Following the experimental methodology outlined in a previous study of the desensitization mechanism of capsaicin on the TRPV1 receptor [25], we conducted a test on TRPV1 expression in rat prostate tissue. The results indicated a significant elevation in TRPV1 expression in CP/CPPS rats. However, with CBD treatment, TRPV1 expression was reduced. This suggests that CBD desensitizes the response to TRPV1 and has an effect on pain relief. Another study proposed that pain in CP/CPPS may be alleviated by reducing COX2 levels in the microenvironment [7], and our results align with this observation.

CONCLUSIONS

The present results show that CBD can inhibit the release of inflammation-associated factors in RWPE-1 cells, and that CBD alleviates inflammation in a CP/CPPS rat model by activating CB2 receptors. This inhibits the TLR-4/NF-κB pathway and reduces pain by desensitizing TRPV1 receptors and decreasing the release of COX2 (Fig. 8).

Fig. 8. A proposed mechanism for CBD treatment of prostatitis. CBD treatment can downregulate the expression of TLR4 and impede the NF-κB signaling pathway, while partially activating CB2 and inhibiting the signaling pathway of TLR4/NF-κB. With the decrease of the expression of NF-κB in the nucleus, the lack of regulation of the target cells reduces the expression of the inflammatory cytokines, such as IL-6, TNF-α, and COX2. CBD improves the prostatitis through its effect on TRPV1 activation, a desensitizing effect, and the combined effect of decreased COX2 expression to relieve pain. CBD: cannabidiol, TRPV1: transient receptor potential vanilloid 1, CB2: cannabinoid receptor 2, TLR4: toll-like receptor 4, NF-κB: nuclear factor-kappa B, IL-6: interleukin-6, TNF-α: tumor necrosis factor-alpha, COX2: cyclooxygenase-2.

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.