CBD for prostate inflammation

What is prostatitis and how is it classified?

Prostatitis is an inflammatory disease of the prostate – a gland about the size of a chestnut, located directly below the bladder and surrounding the urethra. It is part of the male reproductive system and is responsible, among other things, for producing a portion of the seminal fluid. Due to its anatomical proximity to the bladder, perineum, and rectum, inflammation of the prostate can cause a variety of complaints – including pain, urinary problems, and sexual dysfunction.

Prostatitis is one of the most common urological diseases in men, especially in middle age. Depending on the cause and course, it is divided into different clinical subtypes that differ significantly in terms of symptoms, diagnostics, and therapeutic approach.

Classifications

The medical classification is divided into four main categories:

Acute bacterial prostatitis: This form arises from an acute infection of the prostate with bacteria. It usually occurs suddenly and is accompanied by fever, chills, pain during urination, and a pronounced feeling of illness.

Chronic bacterial prostatitis: This involves a recurring bacterial infection that can persist for months or occur in episodes. The symptoms are often less intense than in the acute form but are long-lasting. Common complaints include a feeling of pressure in the perineal area, pain during urination, and sexual dysfunction.

Chronic non-bacterial prostatitis / Chronic pelvic pain syndrome (CP/CPPS): This form is the most commonly diagnosed. It is not caused by a bacterial infection but is based on complex inflammatory, neurological, and immunological processes. Typical symptoms include persistent or recurring pain in the pelvic area, urinary problems, pain during ejaculation, and loss of libido – often without any identifiable organic cause. Despite numerous therapeutic approaches, treatment remains difficult and individually variable in effectiveness.

Asymptomatic prostatitis: This occurs without clinical symptoms and is often only detected incidentally through the analysis of prostate tissue or semen samples.

Pathophysiology

Especially in the chronic form (CP/CPPS), there is a combination of inflammatory reactions, immunological dysregulation, and neurological hypersensitivity. Inflammatory mediators such as interleukin-6, TNF-alpha, or COX-2 play a central role. At the same time, the so-called TRPV1 receptor, which transmits pain signals, is often overactivated in affected individuals. This overreaction can lead to increased pain sensitivity in the pelvic area – even with minimal stimuli.

The endocrine system also appears to be involved, as hormonal influences by estrogens and androgens have been observed. Chronic stress, impaired microcirculation, and pelvic floor dysfunctions are considered additional influencing factors.

Importance for therapy

The classification of prostatitis is essential for selecting treatment: while acute bacterial forms are usually treated with antibiotics, chronic non-bacterial forms require a multimodal approach consisting of anti-inflammatory substances, pain therapy, physical measures, and psychological support. Especially in CP/CPPS, there is a great need for new, well-tolerated treatment options—such as non-hormonal, locally acting substances like cannabidiol, which has been studied for symptom relief.

What role does cannabidiol (CBD) play in the anti-inflammatory context?

Cannabidiol (CBD) has versatile biological properties, including strong anti-inflammatory effects. These are based on the targeted modulation of the body's own signaling pathways, which play a central role in chronic inflammatory processes—such as those occurring in prostatitis and especially in chronic pelvic pain syndrome (CP/CPPS).

Inhibition of inflammatory signaling pathways

CBD inhibits the Toll-like receptor 4 (TLR4) and the associated NF-κB signaling pathway, which is considered a central hub in inflammation regulation. When this pathway is blocked, the release of key inflammatory mediators such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2) decreases. These substances not only promote inflammation but are also associated with pain, swelling, and tissue changes. CBD interrupts this cascade at the cellular level.

Activation of immunomodulatory receptors

Another central mode of action involves the cannabinoid receptor type 2 (CB2). This receptor is mainly found on immune system cells. When activated by CBD, it leads to a suppression of overactive immune responses—without the psychotropic effects seen with CB1 receptors. Activation of CB2 helps calm inflamed tissue without affecting the central nervous system.

Influence on pain receptors

CBD binds to the TRPV1 receptor, also known as the "capsaicin receptor." This receptor plays a key role in transmitting pain signals. By desensitizing TRPV1, CBD reduces sensitivity to painful stimuli. This mechanism is particularly therapeutically relevant in CP/CPPS, where chronic pain in the pelvic area is prominent.

Regulation of oxidative balance

Inflammatory processes are often accompanied by increased production of reactive oxygen species (ROS) and disruption of cellular redox balance. CBD acts as an antioxidant by reducing ROS formation while supporting antioxidant defense mechanisms such as glutathione. This effect protects cells from oxidative stress, which can exacerbate inflammation and tissue damage.

What preclinical findings are there regarding the effect of CBD on prostate inflammation?

Preclinical studies provide valuable insights into how cannabidiol (CBD) can act against prostate inflammation at the cellular and molecular levels. Both in vitro experiments with human prostate cells and animal models of chronic prostatitis show clear anti-inflammatory and pain-relieving effects.

In vitro results on human prostate cells

In experiments with RWPE-1 cells (a non-malignant human prostate cell line), an inflammatory response was specifically induced by lipopolysaccharide (LPS). The addition of CBD led to:

• Reduction of proinflammatory cytokines such as IL-6, TNF-α, and COX-2
• Inhibition of TLR4/NF-κB activation, which is crucial for inflammatory gene regulation
• Maintenance of cell viability, i.e., CBD showed no cytotoxic effects at therapeutic concentrations

These results demonstrate that CBD can specifically interrupt inflammatory processes without damaging healthy prostate cells.

Animal model for chronic prostatitis (CP/CPPS)

In a rat model, prostatitis was induced by combined administration of 17β-estradiol and dihydrotestosterone – an established method to replicate chronic inflammatory processes of the prostate.

The animals were treated with different doses of CBD (50 mg/kg, 100 mg/kg, 150 mg/kg) over four weeks. The evaluations showed:

• Significant reduction in pain behavior (per Behavioural Pain Index)
• Histologically detectable regression of prostatitis
• Reduced expression of IL-6, TNF-α, and COX-2 in prostate tissue
• Activation of the CB2 receptor, associated with anti-inflammatory effects
• Desensitization of the TRPV1 receptor, which is responsible for pain signals
  
  

Significance of the results

The preclinical data show that CBD acts against prostate inflammation on multiple levels: it inhibits central signaling pathways, reduces pain perception, and protects tissue from chronic remodeling. These effects occur both at the cellular level and in whole organisms – a strong argument for further clinical studies.

How does CBD work for chronic prostatitis or CP/CPPS?

Chronic prostatitis or chronic pelvic pain syndrome (CP/CPPS) is one of the most common urological complaints in men and is characterized by persistent pain and inflammation without detectable bacterial cause. A modern preclinical model was used to investigate how cannabidiol (CBD) acts on exactly these disease mechanisms.

Study design overview

The focus is on an established animal model to replicate CP/CPPS. In male rats, inflammatory and painful changes of the prostate were induced by administering 17β-estradiol and dihydrotestosterone over a period of four weeks – comparable to the clinical manifestations of human CP/CPPS. Subsequently, the animals were treated with different doses of CBD (50, 100, 150 mg/kg). The effects were examined both functionally (behavioral tests for pain sensitivity) and at the molecular biological and histological levels.

Pain modulation through TRPV1 desensitization

A central finding was the desensitization of the TRPV1 receptor, which is considered a key factor for pain perception. CBD significantly reduced the excitability of this receptor. As a result, there was:

• reduced pain response in behavioral test
• increased pain tolerance during palpation examination

This pain-relieving effect is of high clinical relevance, as CP/CPPS is typically associated with persistent, therapy-resistant pelvic pain.

Anti-inflammatory effect through CB2 activation

CBD showed targeted activation of the CB2 receptor, which is present in immune cells and inflammatory tissues. This led to:

• Significant reduction of proinflammatory markers, including IL-6, TNF-α, and COX-2
• Attenuation of TLR4/NF-κB activation, a central inflammatory signaling pathway
• Improved histological findings with regression of inflammatory prostate tissue changes

Dose effect and tolerability

All tested doses of CBD were well tolerated. With increasing dosage, the anti-inflammatory and pain-relieving effects increased – without signs of toxicity or adverse side effects.

Summary of mechanisms of action in CP/CPPS

CBD exerts a dual effect in chronic prostatitis / CP/CPPS: It relieves pain by modulating neuronal receptors and combats inflammation via immunological signaling pathways. Thus, it represents a promising therapeutic approach for patients with therapy-resistant symptoms – especially as a locally applied, non-hormonal preparation.

Are there indications of a tumor-inhibiting effect of CBD in prostate cancer?

In addition to its anti-inflammatory effect, cannabidiol (CBD) is increasingly coming into focus as a potential tumor-inhibiting substance. Several preclinical studies have investigated how CBD affects the growth, spread, and survival of prostate cancer cells – with remarkable results.

Inhibition of cell proliferation

CBD showed a pronounced growth-inhibiting effect on prostate carcinoma cells in various experimental models, especially on the aggressive cell lines PC-3, DU145, and LNCaP. The observed effects include:

• Reduction of cell viability by up to 60% in a concentration-dependent manner
• Cell cycle blockade by downregulation of key cell cycle proteins such as Cyclin D3, CDK2, CDK4, and CDK1
• Inhibition of AKT phosphorylation, which is central to cancer cell survival and growth

These antiproliferative effects occurred independently of classical cannabinoid receptors (CB1, CB2), indicating receptor-independent mechanisms.

Induction of apoptosis

CBD specifically triggered programmed cell self-destruction (apoptosis) in prostate carcinoma cells. The mechanistic findings:

• Activation of the caspase-3/7 cascade leading to cell death
• DNA fragmentation as a sign of irreversible apoptosis
• Increase of proapoptotic proteins such as Bax and CHOP
• Reduction of intracellular ATP levels by disrupting mitochondrial function

These processes were accompanied by an increase in reactive oxygen species (ROS) and a shift in the redox balance, which additionally contributed to cell damage.

Inhibition of invasion and metastasis

A particularly relevant finding concerns the anti-invasive effect of CBD:

• In particularly aggressive cell lines (e.g., PC-3), cellular invasiveness was significantly reduced
• At the same time, the expression of E-Cadherin was increased, a marker for stabilization of cell-cell contacts and inhibition of metastasis

In vivo results

In a mouse model, CBD combined with the silencing of the tumor-promoting gene RBBP6 showed significant tumor growth inhibition. The combination of CBD with cisplatin was also effective, with CBD alone already showing antiproliferative effects.

Summary of antitumor mechanisms of action

CBD shows a broad spectrum of antitumor effects in preclinical models of prostate carcinoma – from inhibition of cell growth through induction of apoptosis to inhibition of metastasis. These promising results support the hypothesis that CBD could play a therapeutic role as an adjunct substance in oncology in the future – especially in aggressive or therapy-resistant tumor forms.

What do clinical studies say about the use of CBD for prostatitis?

While preclinical studies convincingly demonstrate the effect of cannabidiol (CBD) in prostate inflammations, the question arises whether these effects can also be confirmed in humans. Two clinical studies provide initial indications: A phase I study with oral CBD (Epidiolex) in prostate cancer and a pilot study with rectal CBD suppositories (CANNEFF® SUP) in patients with CP/CPPS.

Epidiolex – Oral CBD for biochemical recurrence after prostate cancer

This phase I study investigated the safety and tolerability of orally administered CBD (Epidiolex) in men with biochemical recurrence after prostate cancer, i.e., with rising PSA levels without visible tumor manifestation.

The goal was not the treatment of acute prostatitis but the assessment of possible anti-inflammatory or antiproliferative effects in the oncological context.

Results:

• Good tolerability of Epidiolex at doses up to 800 mg daily
• No serious side effects
• First indications of stable PSA levels in individual patients over the study period

These results show that oral CBD in high doses is safe to use but do not provide direct statements on efficacy in inflammatory prostatitis.

CANNEFF® SUP – Rectal CBD for CP/CPPS

In a single-arm open pilot study, 16 men with chronic, non-bacterial prostatitis / CP/CPPS were treated for 30 days with CANNEFF® SUP – a suppository with CBD and hyaluronic acid for rectal use.

Measurement parameters:

• NIH-CPSI total score (symptom index for CP/CPPS)
• IPSS (urination symptoms)
• IIEF-5 (erectile function)

Results after 30 days of use:

• Significant decrease in the total symptom score (−7.2 points; p = 0.001)
• Significant pain reduction (−3.75 points; p = 0.005)
• Improvement of urination complaints (IPSS from 13.5 to 10; p = 0.002)
• No relevant side effects
• Clinical improvement in 81% of patients

Compared to known therapies such as quercetin, alpha-blockers, or COX-2 inhibitors, CANNEFF® showed comparable or better symptom reduction – but with a purely local, non-systemic mode of action.

Summary of the clinical studies

How safe and well-tolerated is CBD in the treatment of prostatitis? 

The safety and tolerability of cannabidiol (CBD) is a central criterion for therapeutic use in chronic prostatitis or CP/CPPS. Previous preclinical and clinical studies show a very favorable side effect profile – both with systemic and local application.

Tolerability in preclinical models

In animal studies with chronic prostatitis, different CBD doses (50, 100, 150 mg/kg) were administered over several weeks. The following were observed:

• No signs of toxicity, even at higher doses
• No negative effects on organ functions or behavior
• The anti-inflammatory and analgesic effects were dose-dependently positively correlated

These results support a high therapeutic index and a good controllability of the effect.

Clinical safety: CANNEFF® SUP (rectal)

In the pilot study with CANNEFF® SUP in men with CP/CPPS:

• Was not a single adverse effect reported
• Daily use over 30 days was easily possible
• There were neither local irritations nor systemic complaints on
• The Application was well accepted by the patients

The good safety profile is particularly due to local application and the physiologically balanced formulation attributed to CBD and hyaluronic acid.

Systemic application: Epidiolex (oral)

In the Phase I study with Epidiolex in patients with PSA recurrence after prostate cancer:

• Daily doses up to 800 mg were well tolerated over several weeks
• No serious side effects occurred
• Only mild gastrointestinal symptoms were occasionally reported

These data confirm that also systemically highly applicable CBD in men with prostate diseases safe can be used.

Comparison to standard therapies

How do pure CBD formulations differ from full-spectrum extracts? 

Cannabidiol (CBD) can be administered in different pharmaceutical qualities and compositions. Two basic types are pure CBD formulations (isolates) and so-called full spectrum extracts, which contain besides CBD also other cannabinoids, terpenes, and flavonoids. Both forms differ significantly in their active ingredient composition, mode of action, bioavailability, and regulatory assessment.

Composition

Pure CBD (Isolate):  Contains exclusively the isolated active ingredient cannabidiol in high purity (usually >99%). Other cannabinoids such as THC, CBG, or CBN are not included. This form allows for precise dosing and is free from psychoactive effects.

Full spectrum extract: Contains, besides CBD, small amounts of other phytocannabinoids (e.g., THC < 0.2%), flavonoids, and terpenes. These plant constituents can synergistically produce the so-called Entourage effect trigger, which potentially enhances the overall effect.

Mode of action and clinical relevance

CBD isolate: The pharmacological effect is directly on CBD itself attributable. The signaling pathways (e.g., CB2, TRPV1, NF-κB) are specifically targeted without other substances having an influence. This form is especially suitable for scientifically standardized studies as well as for patients who THC-free medication are needed.

Full spectrum: The effect is more complex and not exclusively attributable to CBD. Other cannabinoids and terpenes additionally act, for example, anti-inflammatory, muscle-relaxing, or pain-relieving. However, this complicates the exact assignment of effects to individual ingredients. This aspect is relevant for medical practice, if a broad mode of action is desired is.

Bioavailability

The Bioavailability of pure CBD can – depending on the formulation – be limited, especially with oral intake. Modern carrier systems (emulsions, liposomes, microcapsules) improve absorption.

Full spectrum extracts contain natural carrier substances that can improve solubility and absorption, especially due to lipophilic components. This can lead to a faster or prolonged effect lead to – but is less standardized.

Regulatory aspects

Pure CBD (Isolate): Is classified in the EU as Novel Food or classified as medicinal products, depending on the intended use. Products like Epidiolex are approved as medicinal products but are subject to strict regulatory requirements (purity, GMP, dossier obligation).

Full spectrum extracts: Subject to stricter control due to possible THC content. Even small amounts of THC (<0.2%) can be regulatorily relevant – especially in doping controls, driving license law, or use in risk groups. In medical use (e.g. as a prescription drug), national cannabis laws apply.

Pure CBD formulations offer standardization, purity and safety – ideal for medically controlled applications such as with CANNEFF® SUP. Full spectrum extracts can, through the entourage effect, provide a broader, natural effect unfold, but are regulatorily more demanding. The choice of the appropriate form depends on the therapy goal, patient profile, and legal framework.

What role could CANNEFF® SUP with CBD and hyaluronic acid play in the treatment of prostatitis?

The treatment of chronic, non-bacterial prostatitis (CP/CPPS) presents a therapeutic challenge due to its multifactorial causes. With CANNEFF® SUP, a novel suppository is available that combines cannabidiol (CBD) and hyaluronic acid. It offers a locally effective approach with anti-inflammatory, pain-relieving, and tissue-supporting properties – without systemic burden.

Pharmaceutical peculiarity: emulsion matrix

CANNEFF® SUP uses a patented emulsion matrix, which distinguishes itself from traditional lipophilic suppositories. Advantages:

• Rapid release of the active ingredients: almost complete release within 45 minutes
• Optimized distribution in the rectal area with good mucosal adhesion
• Uniform drug exposure, even with variable mucosal conditions

This pharmaceutical-technical innovation supports the targeted, locally limited effect, minimizes systemic side effects and increases patient acceptance.

Results of the pilot study in CP/CPPS

In an open clinical pilot study with 16 men with CP/CPPS, the use of CANNEFF® SUP over 30 days showed:

• Significant symptom reduction in the NIH-CPSI total score (−7.2 points; p = 0.001)
• Significant improvement in the pain component (−3.75 points; p = 0.005)
• Reduction of urinary symptoms (IPSS from 13.5 to 10; p = 0.002)
• No undesirable side effects, very good tolerability
• 81% clinical improvement rate within one month

These results are comparable to standard therapies such as quercetin, α-blockers, or COX-2 inhibitors – but without their typical side effects and with a local rather than systemic mode of action.

Summary of therapeutic benefits

CANNEFF® SUP combines modern cannabinoid research with innovative pharmaceutical technology. The combination of CBD and Hyaluronic Acid in a formulation-optimized, locally acting application form offers an effective and safe option for the treatment of chronic prostatitis. It is particularly suitable for patients who respond poorly to systemic therapies or are seeking a well-tolerated long-term solution.

What are open questions and next steps in research on CBD for prostatitis?

The existing preclinical and clinical results suggest that Cannabidiol (CBD) can be effective and safe in the treatment of prostatitis – especially the chronic, non-bacterial form (CP/CPPS). Nevertheless, numerous open questions remain that must be answered through further research to establish CBD as a fixed component of urological therapy.

Confirmation by larger, controlled studies

The clinical data available so far, especially on the rectal application of CANNEFF® SUP, come from small, open pilot studies. To ensure clinical relevance and statistical robustness, the following are necessary:

• Placebo-controlled, randomized double-blind studies
• Long-term observations over several months
• Comparisons with established therapy forms (e.g. alpha blockers, COX-2 inhibitors, phytotherapeutics)

The goal is the Validation of efficacythat Determination of optimal dosages and the Identification of responder profiles.

Precise definition of target groups

Research should clarify which patient groups particularly benefit from CBD. Open questions include, among others:

• Is CBD effective in inflammatory-dominated CP/CPPS forms particularly effective?
• What role do comorbidities (e.g., stress, pelvic floor dysfunction) play?
• Are there differences in response with Initial diagnosis vs. chronic-recurrent?
  

Standardization of active ingredients and application forms

CBD preparations differ significantly in:

• Purity (isolate vs. full spectrum)
• Pharmaceutical form (oil, capsule, suppository, emulsion)
• Bioavailability

Clear definitions are required for reliable clinical use regarding:

• Dosage and potency
• Uniform pharmaceutical quality
• Stability and release profile the formulation

Regulatory and legal issues

Despite positive study results, the approval of CBD-containing medicinal products is still highly regulated:

• CBD as Novel Food or active ingredient requires clear distinction
• For full-spectrum extracts with traces of THC, the following apply Narcotics laws
• Clinical application must be accompanied by national drug law and medical device law are coordinated

Future-proof solutions lie in clearly defined, THC-free, locally acting pharmaceutical forms with proven efficacy – like CANNEFF® SUP.

Long-term effects and safety data

Knowledge is still lacking on:

• Long-term use over several months or years
• Interactions with other drugs
• Long-term tissue changes or sensitizations

Such data are essential, especially when used in chronically recurring courses.

Conclusion and Outlook

The existing data on CBD for prostatitis – especially for CP/CPPS – are promising but not yet sufficient for a widespread recommendation. The next step is:

• multicenter, controlled studies,
• a standardization of formulations,
• the integration into clinical guidelines,
• as well as a regulatory clear classification.

With further research steps, CBD – especially in the form of CANNEFF® SUP – could become an established, well-tolerated, and effective treatment option for chronic prostatitis.

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