Quantitative Analysis of Cannabinoid Therapy in Prostate Cancer: Integrating Biomarkers, Imaging, and Patient Outcomes

Abstract

Introduction

Cannabinoids are increasingly used by cancer patients for symptom relief, yet clinical evidence on their effect in prostate cancer remains limited. This study evaluated the association between cannabinoid therapy and disease activity, pain, and quality of life in men with prostate cancer. The objectives were to assess the influence of cannabinoids on PSA levels, metabolic activity, tumour size via PET/CT scans, and patient-reported outcomes including pain levels and quality of life.

Methods

Ninety men with confirmed prostate cancer were prospectively followed in three groups: chemotherapy-only, cannabis-only, and combined chemotherapy + cannabis. PSA, PET/CT findings, and patient-reported outcomes (BPI, EQ-5D) were assessed at baseline, 3 months, and 6 months. Longitudinal changes were analysed using linear mixed-effects regression with group × time interactions, and between-group differences were tested with ANOVA. PET/CT categorical outcomes were evaluated using multinomial logistic regression to generate adjusted odds ratios.

Results

Significant temporal differences in PSA levels were detected among groups (p < 0.001); both cannabis-containing regimens showed faster PSA decline, but final values were comparable across treatments. PET/CT analyses indicated a higher likelihood of remission or tumour reduction in the combined group (p = 0.013). Cannabis use, alone or combined was associated with greater reductions in pain and improved emotional well-being compared with chemotherapy alone, while improvements in self-care and usual-activity scores were also observed.

Conclusion

Cannabinoid therapy, whether used independently or alongside chemotherapy, was associated with improved pain control and some indicators of tumour response, without evidence of harm. The findings warrant cautious interpretation and support further randomized studies to clarify cannabinoids’ adjunctive role in prostate cancer management.

Introduction

Prostate Cancer Burden and Treatment Limitations

Prostate cancer remains a global public health challenge. According to the latest GLOBOCAN 2022 estimates, more than 1.5 million new prostate cancer cases were diagnosed worldwide in 2022, and approximately 397,000 deaths were attributed to the disease, making prostate cancer the second most frequently diagnosed cancer in men and the fifth leading cause of cancer death among men globally [1]. Given the persistently high incidence and mortality rates across diverse regions, interventions that can improve both quality of life and disease-related outcomes are urgently needed. The burden is highest in high human development index (HDI) countries, where widespread PSA testing and environmental factors contribute to incidence rates exceeding 100 per 100,000 in some nations. In 2020, more than 1,400,000 new cases were reported with an age-standardized incidence rate of 30.7 per 100,000 and a 3.86% cumulative risk by age 75. While early-stage disease is often treatable, advanced and metastatic prostate cancer carries a high mortality risk, with survival dropping below 30% over 5 years. There is a threefold increase in the incidence in HDI countries (37.5 per 100,000) compared to lower HDI nations (11.3 per 100,000), likely due to increased PSA testing and lifestyle/environmental factors [2]. Northern Europe has the highest average incidence at 83.4 per 100,000, with Ireland leading at 110.7 per 100,000 [2].

Standard treatments such as androgen deprivation therapy (ADT) and chemotherapy face limitations, including significant side effects and eventual progression to castration-resistant prostate cancer, a terminal stage. Prostate cancer typically originates in peripheral zone epithelial cells, potentially luminal or basal epithelial cells [3, 4]. Chronic inflammation and microbial infections contribute to oxidative stress, a significant factor in carcinogenesis [3]. Oxidative stress, resulting from reactive oxygen species imbalance, damages biomolecules, enhancing cancer susceptibility [5, 6]. Antioxidants show promise in halting prostate cancer development and progression, reducing cancer-related gene expression and incidence in certain patient groups [7]. Prostate cancer progresses through several stages, advancing from precancerous lesions to localized disease, metastatic prostate cancer, and ultimately to castration-resistant prostate cancer. Prostatic intraepithelial neoplasia (PIN) is identified as pre-neoplastic lesions believed to precede prostate cancer [3]. PIN is characterized by elevated luminal cell proliferation, dysplasia of epithelial cells, and loss of basal cells [8]. The presence of PIN suggests the susceptibility of epithelial cells to malignant transformation, with 23–35% of high-grade PIN cases developing into prostate cancer [9]. The transition from localized to locally advanced prostate cancer occurs as cancerous cells extend beyond the prostate gland, infiltrating lymph nodes following basal cell layer degradation [10]. Subsequently, metastasis occurs as cancer cells spread to the bones, liver, lungs, and other tissues, observed in both treatment-naïve and castration-resistant cancers [11]. Metastatic prostate cancer carries a significant mortality risk, with a survival rate of less than 30% over 5 years. Androgen deprivation therapy is the primary treatment for metastatic prostate cancer, often combined with other hormone therapies or chemotherapy [11]. While initially responsive to ADT, resistance eventually emerges, leading to castration-resistant prostate cancer, considered a terminal condition.

Emerging Role of Cannabinoids in Cancer

Cannabinoids, particularly those interacting with the endocannabinoid system, are emerging as potential therapeutic agents in oncology. Preclinical studies have shown cannabinoids to inhibit tumour cell proliferation, induce apoptosis, and reduce angiogenesis and inflammation. The strongest evidence comes from glioma research, where cannabinoids have demonstrated tumour suppression and survival benefits in both cell models and early-phase clinical trials. Multiple preclinical investigations suggest that cannabinoids can reduce cell proliferation, promote cell death in glioma cell lines, and impede tumour growth, leading to increased survival in mouse models of glioma [12]. A small pilot clinical study conducted in 2006 demonstrated the tolerability of tetrahydrocannabinol (THC) in patients with glioblastoma [13]. Furthermore, recent clinical trials have assessed the effectiveness of combining cannabinoid treatments in patients with recurrent glioblastoma multiforme, showing some improvements in 1-year survival rates post-cannabinoid treatment (NCT01812603, NCT01812616) [13]. Despite numerous studies across various cancer types indicating the anticancer effects of plant-derived cannabinoids (phytocannabinoids), our current comprehension of the molecular targets and intracellular mechanisms driving these effects remains incomplete [3, 13].

Cannabinoid receptors, such as CB1 and CB2, are widely distributed throughout both the central nervous system (CNS) and peripheral tissues [14]. CB1, primarily located in the CNS, regulates various functions including memory and emotion [15]. In contrast, CB2 is predominantly found outside the CNS, where it modulates immune responses without inducing psychoactive effects [14]. Both receptors regulate inflammation, immune responses, and other physiological processes in peripheral tissues [16]. GPR55, another receptor involved in immune regulation, exhibits high expression levels in the CNS, adrenal glands, and gastrointestinal tract [17]. While CB1 and CB2 interact with Gi/o proteins, leading to reduced cAMP levels, GPR55 activation involves Gα proteins [18, 19]. Changes in the expression of CB1, CB2, and GPR55 have been observed in various cancers, including prostate cancer, and are associated with poorer prognoses and increased aggressiveness [17, 18]. Components of the endocannabinoid system are implicated in regulating cancer processes such as proliferation and metastasis [18]. Thus, targeting this system with synthetic or phytocannabinoids shows potential for cancer therapy. Despite this promise, human evidence, particularly in prostate cancer, remains limited. Most clinical studies have focused on symptom control rather than disease modification. The absence of standardized formulations, dosing, and regulatory guidance has restricted rigorous clinical evaluation.

Research Gaps in Human Studies on Cannabinoids in Prostate Cancer

Despite widespread interest in cannabinoids for cancer management, clinical evidence in prostate cancer remains limited. Most existing studies focus on symptom control rather than disease modification, with few incorporating objective markers such as PSA levels or PET/CT imaging. Furthermore, the lack of standardized cannabinoid dosing and formulation, coupled with ethical and regulatory barriers, has hindered rigorous human trials in this area. This gap underscores the urgent need for structured, outcome-driven research to assess cannabinoids as adjunctive or therapeutic agents in prostate cancer care. The treatment of prostate cancer presents challenges, particularly for aggressive forms, with limited options available. However, research on cannabinoids’ potential as anticancer agents for prostate cancer is still in its infancy. Increased levels of cannabinoid receptors and TRPV ion channels in prostate cancer cells suggest promising targets for therapy [20]. Studies have found a correlation between elevated expression of CB1, TRPV1, and TRPV2 receptors and disease progression [21]. Cannabidiol (CBD) demonstrates inhibitory effects on prostate cancer cell proliferation, especially in conditions lacking serum [22]. In androgen-sensitive LNCaP cells, CBD induces apoptosis partially through the antagonism of TRPM8, resulting in various cellular changes, including increased reactive oxygen species, PUMA, and CHOP levels, elevated intracellular calcium, activation of p53, and downregulation of AR. CBD also enhances the efficacy of docetaxel and bicalutamide [23]. Notably, a CBD-enriched whole plant extract intensifies the effects of bicalutamide and docetaxel on tumour growth, leading to improved survival rates compared to individual treatments [23].

Sharma et al. [21] illustrated that CBD reduced the viability of PC-3 and LNCaP cells, displaying milder effects in non-cancerous PrEC and BPH-1 cells. Additionally, a plant extract comprising CBD, CBN, and THC suppressed cell viability in LNCaP cells, correlating with decreased expression of CB1, CB2, AR, VEGF, and PSA. Notably, this plant extract did not affect the viability of non-cancerous cells. Sreevalsan et al. [22] demonstrated that CBD prompted apoptosis in LNCaP cells by enhancing phosphatase expression, leading to the cleavage of poly ADP-ribose polymerase and caspase-3 [24]. The pro-apoptotic effects of CBD were impeded by CB1 or CB2 receptor antagonists. While most research on cannabinoid effects in prostate cancer has concentrated on the androgen-sensitive LNCaP cell line, the phenotypic impacts of cannabinoids in the more resistant DU145 and PC-3 cell lines remain inadequately explored. Moreover, although cannabinoids display some potential in combating prostate cancer, the underlying mechanisms of action demand further extensive investigation.

Prostate Cancer Burden and Treatment Limitations

Prostate cancer remains a major global public health challenge. According to GLOBOCAN 2022, more than 1.5 million new cases and approximately 397,000 deaths were recorded worldwide, making prostate cancer the second most frequently diagnosed cancer and the fifth leading cause of cancer-related mortality among men globally [1]. While early-stage disease is often treatable, advanced and metastatic prostate cancer is associated with poor prognosis, with 5-year survival rates falling below 30%.

Standard treatment strategies, including ADT and chemotherapy, are effective initially but are frequently limited by significant adverse effects and eventual progression to castration-resistant prostate cancer. Disease progression involves a transition from localized malignancy to metastatic spread, most commonly to bone and visceral organs, contributing substantially to morbidity and mortality. Despite advances in systemic therapy, therapeutic options for advanced disease remain limited, underscoring the need for adjunctive approaches that may improve both disease outcomes and quality of life.

Emerging Role of Cannabinoids in Cancer

Cannabinoids and the endocannabinoid system have emerged as areas of interest in oncology research. Preclinical studies across several cancer types have demonstrated that cannabinoids can inhibit tumour cell proliferation, induce apoptosis, and modulate angiogenesis and inflammation. The most robust evidence to date originates from glioma models, where both in vitro and early-phase clinical studies have suggested potential antitumour activity and tolerability of cannabinoid-based interventions [12, 13].

Cannabinoid receptors, including CB1 and CB2, are expressed in both central and peripheral tissues and play roles in immune modulation, inflammation, and cellular signalling. Altered expression of components of the endocannabinoid system has been reported in several malignancies, including prostate cancer, and has been associated with disease aggressiveness and poorer prognosis. However, despite extensive preclinical research, the molecular mechanisms underlying these effects remain incompletely understood, and translation into clinical oncology – particularly prostate cancer – has been limited.

Research Gaps in Human Studies on Cannabinoids in Prostate Cancer

Although interest in cannabinoids among cancer patients is widespread, clinical evidence supporting their role in prostate cancer remains scarce. Most human studies have focused on symptom management, such as pain and appetite, rather than objective disease-related outcomes. Few investigations have incorporated biomarkers such as PSA kinetics or imaging-based tumour response, and the absence of standardized cannabinoid formulations and dosing regimens has further limited rigorous evaluation.

Preclinical studies suggest that cannabinoids, particularly CBD, may inhibit prostate cancer cell proliferation and enhance sensitivity to conventional therapies such as docetaxel. Increased expression of cannabinoid receptors and transient receptor potential channels in prostate cancer cells further supports their potential relevance as therapeutic targets. Nevertheless, human data remain limited, and the clinical significance of these findings has yet to be established.

Study Rationale

Given the growing use of cannabinoids by patients with prostate cancer and the paucity of clinical data addressing their impact on disease activity, there is a clear need for structured, outcome-driven human research. This study was designed to evaluate the association between cannabinoid use and both objective disease markers and patient-reported outcomes in men with prostate cancer, thereby addressing an important translational gap between preclinical evidence and clinical practice.

Study Rationale and Aim

The growing interest in the therapeutic potential of cannabinoids for cancer management, combined with their increasing use among patients despite limited clinical evidence in prostate cancer, underscores the need for rigorous investigation. This study was designed to quantitatively evaluate the effects of cannabinoid therapy on both objective disease markers and patient-reported outcomes. Specifically, it examines changes in PSA levels, PET/CT imaging findings, and quality-of-life indicators including pain, fatigue, and overall well-being. By integrating biological endpoints with patient-centred measures, this study aims to address the translational gap between promising preclinical data and their potential clinical application. The primary aim was to determine whether cannabinoid therapy, used alone or alongside conventional treatment, was associated with measurable improvements in disease activity and patient outcomes among men with prostate cancer.

Materials and Methods

Study Design

This study employed a prospective observational cohort design to quantitatively assess treatment outcomes across three predefined exposure groups: (1) a control group receiving chemotherapy alone, (2) a group receiving cannabis-based therapy only, and (3) a combination group receiving both chemotherapy and cannabis. The prospective design allowed for systematic data collection at multiple time points (baseline, 3 months, and 6 months), allowing assessment of temporal changes in clinical and patient-reported outcomes, and facilitating the investigation of potential additive or synergistic effects of cannabis when used alongside standard prostate cancer treatment.

Study Setting, Patient Recruitment, and Study Population

This study was designed as an observational, three-arm comparative analysis evaluating clinical outcomes associated with cannabinoid use in adult males with prostate cancer over a 6-month period. Participants were grouped according to their treatment regimen at study entry: (1) cannabis-only therapy, (2) chemotherapy only, or (3) combined cannabis plus chemotherapy. The study population consisted of adult males with prostate cancer who were receiving standard-of-care docetaxel chemotherapy and/or who independently elected to use cannabinoid products as part of their symptom management or supportive care. All participants underwent baseline assessment followed by repeated evaluations at three and 6 months, including PSA measurements, PET/CT imaging, patient-reported outcomes, and documentation of cannabis dosing where applicable. This structure allowed for comparison of longitudinal changes across the three treatment approaches.

Participants were recruited from Cancer Care Clinics in the Eastern Cape province of South Africa. These centres serve urban and rural populations, ensuring socioeconomic diversity. Recruitment occurred over 12 months through clinician referrals and voluntary participation after counselling.

The study population consisted of adult males with histologically confirmed prostate cancer who were receiving standard-of-care docetaxel chemotherapy and/or who independently elected to use cannabinoid products as part of their symptom management or supportive care. Patients were stratified into three groups, based on their treatment history and clinical plan.

All participants had previously received ADT prior to enrolment as part of routine prostate cancer management; however, ADT was not administered or continued during the 6-month study period, and initiation or modification of hormonal therapy was not a study variable. All participants provided written informed consent after receiving detailed information sheets. The study was approved by the Durban University of Technology Institutional Research Ethics Committee (IREC 001/22) and conducted in accordance with the Declaration of Helsinki.

Inclusion and Exclusion Criteria

Eligibility required:

• confirmed prostate cancer diagnosis,

• stable clinical status (life expectancy ≥6 months),

• cannabis oil use for at least 3 months prior to enrolment (for cannabis groups).

• Participants could have received prior chemotherapy and/or radiation.

Exclusion criteria:

• active psychotic or psychiatric disorders,

• prior prostatectomy,

• palliative/end-of-life care,

• recreational cannabis smoking or vaping

This ensured the sample reflected real-world clinical use while minimizing confounding from severe comorbidities or recreational use.

Cannabis Use and Product Specifications

Participants were required to have used medically supervised cannabis for at least 3 months prior to enrolment to ensure dosing stability and tolerance. During this pre-study period, some participants used cannabis oils that they prepared themselves, provided that the THC and CBD concentrations fell within the specified range of 15–20 mg/mL, as reported on product labels or verified through available documentation. Individuals engaging in heavy, long-term recreational cannabis use (defined as daily or near-daily non-medical consumption for more than 6 months) were excluded to avoid confounding effects associated with chronic non-therapeutic exposure.

During the 6-month study period, all participants received medically prescribed cannabis products supplied through their treating physicians. No patient-prepared oils were used once the study commenced. All cannabis administered during the study was regulated, physician-approved, and dispensed through authorized medical channels, with THC and CBD concentrations recorded as mg/mL for all formulations.

Cannabis Product Details and Dosing

• Composition: The proprietary cannabis oils used during the study contained THC and CBD in concentrations between 15–20 mg/mL each, confirmed via Certificates of Analysis (COAs).

• Administration route: Oils were administered sublingually, consistent with the exclusion of smoked or vaporized cannabis.

• Frequency and duration: Patients received dosing once or twice daily, or as otherwise directed by the treating clinician.

• Treatment adherence: Adherence was verified via monthly follow-ups and review of remaining product volume or pharmacy dispensing records.

• Treatment discontinuation: No early discontinuations occurred. All participants remained in the study for the full 6-month duration, and any adverse effects were managed clinically without necessitating withdrawal.

Cannabis exposure was assessed through a structured questionnaire administered at baseline and follow-up visits. Participants reported the specific cannabis product type, predominant cannabinoid profile, dosing, frequency, and route of administration. All participants used full spectrum cannabis oils sublingually, including THC-dominant formulations (mean THC concentration 18.5 mg/mL), balanced THC:CBD oils (approximate 1:1 ratio), and high-CBD preparations (mean CBD concentration 20–25 mg/mL). Median daily THC dose across users was 12.5 mg (IQR 7.5–20 mg), and median daily CBD dose was 18 mg (IQR 10–30 mg). Most participants consumed cannabis once or twice daily. Because many products were sourced from regulated pharmacies, some variability in cannabinoid composition was unavoidable; participants were instructed to report labelled concentrations and dosing as accurately as possible. All cannabis use data were self-reported and verified when available through prescription records.

Sampling and Sample Size Calculation

This study employed stratified sampling to compare three groups: patients using medical cannabis oil alone, those using it alongside conventional treatments (docetaxel), and a control group receiving only conventional treatments. The sample size determination utilized G*Power version 3.1.9.6, a software designed for statistical power analyses across various tests, including t tests, F tests, χ² tests, z tests, and some exact tests [25]. Based on an effect size of 0.2 and a power of 80%, the calculation yielded a sample size of 54 participants. This effect size of 0.2 was selected to ensure the study’s sensitivity to even minor changes in outcomes between-groups. The determined sample size of 54 participants was considered both logistically and scientifically suitable for the study. Although a minimum of 18 participants per group was required, the aim was to recruit 30 participants per group, totalling 90 participants, to accommodate any potential dropouts. The total eligible population for the study comprised 125 participants diagnosed with prostate cancer, as confirmed by the cancer care centres. Given the study's repeated measures design, each participant underwent three measurements, resulting in a total of 270 data points (90 participants multiplied by 3 measurements). This design, combined with the within-person correlation typical of repeated measures studies aimed at reducing intra-person variability, underscored the necessity of a sample size of 30 per group with 80% power.

A CONSORT-style diagram (Fig. 1) summarizes participant movement through the study, including screening, group allocation, follow-up, and analysis. Of the 95 individuals assessed for eligibility, 90 met inclusion criteria and were assigned to one of the three treatment groups (chemotherapy only, cannabis only, or combined cannabis + chemotherapy). No losses to follow-up or withdrawals occurred during the study.

Fig. 1.

Consort diagram for prostate cancer research.

Data Collection Procedure

PSA and PET Scan Data

Prostate-specific antigen (PSA) levels were obtained from pathology reports at baseline and then every 3 months. PET scans were performed at baseline and repeated at 6 months. These diagnostic tools were used to monitor tumour progression or regression and to allow cross-group comparison.

In South Africa, Section 21 of the Medicines and Related Substances Act permits clinicians to apply for special access to unregistered medicines, including medical cannabis, when deemed clinically appropriate for individual patients. Where applicable, patients accessing unregistered medicines under Section 21 were required to submit a Certificate of Analysis (COA), which confirmed the THC and CBD concentrations to ensure reliable dosing and product consistency across the study.

All clinical data (PSA and PET results) were extracted by the researchers in collaboration with oncology unit staff. Participants were de-identified through unique research codes. Confidentiality was strictly maintained.

Patient-Reported Measures

Participants completed two validated questionnaires every 3 months over a 6-month period.

• The Brief Pain Inventory (BPI) for assessing pain severity and functional interference.

• The EQ-5D for evaluating overall quality of life across five domains.

These instruments were administered by the researcher during follow-up appointments or telephonic check-ins. In some cases, oncology staff assisted with distribution and collection during clinic visits.

Both questionnaires are recognized by international health organizations: the BPI by the World Health Organization (WHO) and the EQ-5D by the EuroQol Research Foundation, ensuring robust psychometric validity and measurement integrity [26–29]. Pilot testing was completed prior to the main study using non-study volunteers.

Time point	Procedure
Baseline	PSA blood test – PET scan – COA submission (if applicable) – BPI and EQ-5D questionnaires
Month 3	PSA blood test – BPI and EQ-5D questionnaires
Month 6	PSA blood test – PET scan – BPI and EQ-5D questionnaires

Data Analysis

Statistical analyses were conducted using SPSS version 27, with significance set at p < 0.05. Baseline demographic and clinical variables (age, race, PSA, Gleason score, disease stage, metastasis status, comorbidities, prior treatments, and weight) were compared across the three treatment groups using χ² tests for categorical data and one-way ANOVA for continuous variables, confirming group comparability at baseline (p > 0.05 for all). Primary analyses focused on PSA outcomes using repeated measures ANOVA to evaluate the effects of time (baseline, 3 months, 6 months), treatment group, and their interaction, with Bonferroni-adjusted post hoc comparisons (n = 3) applied to assess differences between-groups. The same repeated measures framework was used for secondary outcomes, including pain (BPI) and quality-of-life domains (EQ-5D). PET/CT tumour-response categories were analysed using multinomial logistic regression to compare remission/reduction and metastasis versus no change. To address potential confounding, multivariate models incorporated baseline PSA, disease stage, prior therapy, and duration of cannabis use as covariates. Effect sizes were reported using partial eta-squared (η²), interpreted as small (0.01), medium (0.06), or large (0.14).

Ethical Considerations

The study adhered to the ethical principles of autonomy, beneficence, non-maleficence, and justice. All participants provided voluntary written informed consent and remained under the clinical supervision of their treating oncologists. No procedures beyond routine clinical care were performed; only scheduled PSA tests and PET/CT scans were reviewed.

Participant confidentiality was maintained by using de-identified data, stored securely for 5 years and scheduled for permanent deletion thereafter. Participants were informed of their right to withdraw at any time without consequence.

Ethical approval was granted by the Durban University of Technology Institutional Research Ethics Committee (IREC 001/22). Site access was authorized by institutional gatekeepers, defined as administrative officials responsible for ensuring compliance with ethical and institutional requirements. In this study, “gatekeepers” refers to the healthcare providers and institutional authorities who granted permission to access patient records, recruit participants, and conduct data collection within their clinical facilities.

Results

Patient Demographics

Analysis was conducted on thirty participants from each of three treatment groups. Statistical analysis indicated no significant differences among the groups in terms of demographics (p = 0.887 and 0.673, respectively). Table 1 illustrates the demographics and clinical characteristics of study participants.

Table 1.

Baseline demographic and clinical characteristics of study participants (n = 90)

Variable	Chemo only (n = 30)	Cannabis only (n = 30)	Chemo + cannabis (n = 30)	p value
Age (mean±SD), years	63.4±7.2	62.8±6.5	61.9±7.0	0.67
PSA (median [IQR]), ng/mL	48 (31–63)	46 (29–61)	47 (30–60)	0.74
Gleason score ≥8, %	40.0	43.3	36.7	0.82
Stage III–IV, %	56.7	53.3	50.0	0.79
≥1 Comorbidity, %	46.7	50.0	43.3	0.88
Cannabis use ≥3 months prior to enrolment, %	0	100	100	–
Current therapy, %	23.3	20.0	26.7	0.71
Race, %
White	40.0	23.3	33.3	–
Black African	30.0	40.0	46.7	–
Coloured	10.0	16.7	6.7	–
Indian/Asian	20.0	20.0	13.3	–

Values represent mean ± SD or median [IQR] unless otherwise stated. No statistically significant baseline differences between groups. Race is reported descriptively due to sample size limitations.

Participant Retention across Treatment Groups

All participants in the study completed the full 6-month follow-up period, resulting in a 100% retention rate across all three treatment groups (chemotherapy only, cannabis only, and cannabis + chemotherapy). Although adverse events occurred, primarily among participants receiving chemotherapy these were successfully managed through standard clinical procedures. Importantly, no participants discontinued treatment, withdrew consent, or were lost to follow-up, and no cases of disease progression required removal from the study. Consequently, all 90 randomized participants were included in the final analyses, and no between-group comparison of discontinuation rates was required.

PSA Outcomes

• To Investigate the Effects of Cannabinoids Alone, or in Combination with Chemotherapy versus Chemotherapy Only on PSA Measurements in Adult Males with Prostate Cancer

The effects of cannabinoid therapy on PSA levels were evaluated at baseline, 3 months, and 6 months. PSA values were non-normally distributed and are therefore reported as median (IQR). A repeated-measures ANOVA demonstrated a significant time × treatment interaction (p < 0.001, η² = 0.324), indicating that PSA trajectories differed across the three groups (Fig. 2). The combined chemotherapy + cannabis group showed the most rapid decline, followed by the cannabis-only group, whereas the chemotherapy-only group exhibited an initial rise before decreasing to levels comparable with the other groups.

Fig. 2.

The box and whisker plot illustrating the distributions over the three time points by treatment group PSA levels across three treatment groups over a 6-month period. Data points represent mean values with error bars indicating the standard error of the mean (SEM). An asterisk (*) indicates a statistically significant difference (p < 0.05) between the chemo group and the cannabis group at the 3-month assessment.

Although these temporal patterns were statistically significant, the overall magnitude of between-group differences at 6 months was modest and did not reach clinical significance. Final PSA values converged across all treatment arms, suggesting that cannabinoids may influence the rate of PSA change rather than the extent of PSA reduction.

PET/CT Scan Results

• Investigating the Effects of Cannabinoids Alone, or in Combination with Chemotherapy versus Chemotherapy only on the Size of the Tumour in Males with Prostate Cancer

Tumour response was assessed using PET/CT imaging at baseline and at 6 months, with outcomes categorized into four standardized groups:

• (1)Remission (complete metabolic response), defined as disappearance of radiotracer uptake in previously involved lesions;
• (2)Reduction (partial response [PR]), defined as ≥30% decrease in metabolic activity or measurable tumour size in accordance with RECIST criteria;
• (3)No change (stable disease), defined as <30% decrease with no evidence of progression; and
• (4)Metastasis, defined as the emergence of new lesions not present at baseline.

Tumour-response outcomes were analysed with complete response (CR) and PR evaluated separately. CR corresponded to remission, whereas PR referred to measurable tumour reduction. A total of 6 (6.7%) participants achieved a CR across the full sample. CR occurred only in the cannabis-treated groups, with the highest rate in the cannabis + chemotherapy group (16.7%), followed by the cannabis-only group (3.3%). No CRs were observed in the chemotherapy-only group (Table 2).

Table 2.

Complete response (CR) and partial response (PR) by treatment group

Response type	Chemotherapy only, n (%)	Cannabis only, n (%)	Cannabis + chemotherapy, n (%)	Total, n (%)
Complete response (CR)	0 (0.0)	1 (3.3)	5 (16.7)	6 (6.7)
Partial response (PR)	9 (30.0)	9 (30.0)	14 (46.7)	32 (35.6)
No change	15 (50.0)	15 (50.0)	7 (23.3)	37 (41.1)
Metastasized	6 (20.0)	5 (16.7)	4 (13.3)	15 (16.7)
Total	30	30	30	90

PRs were more common and showed a similar distribution. The cannabis + chemotherapy group demonstrated the highest PR rate (46.7%), compared with 30.0% in both the chemotherapy-only and cannabis-only groups. When CR and PR were combined, 63.4% of participants in the combination therapy group exhibited a treatment response, more than double the rate observed in the chemotherapy-only group (30.0%) and substantially higher than in the cannabis-only group (33.3%) (Table 3).

Table 3.

Combined tumour response (CR + PR) vs. no response

Group	CR + PR, n (%)	No response, n (%)	Total
Chemotherapy only	9 (30.0)	21 (70.0)	30
Cannabis only	10 (33.3)	20 (66.7)	30
Cannabis + chemotherapy	19 (63.4)	11 (36.6)	30
Total	38 (42.2)	52 (57.8)	90

A chi-square test demonstrated a statistically significant difference in tumour-response distribution across the three treatment groups when CR and PR were analysed separately (χ² = 12.84, df = 6, p = 0.045). A secondary comparison of treatment response (CR+PR) versus non-response (no change + metastasis) also showed a significant difference (χ² = 8.91, df = 2, p = 0.012), indicating that participants receiving combined therapy had a significantly higher likelihood of achieving tumour response than either monotherapy group. Metastatic progression was lowest in the combination therapy group (13.3%), compared with the cannabis-only (16.7%) and chemotherapy-only groups (20.0%). However, metastasis rates did not differ significantly among the three treatment groups, with no statistical evidence of reduced metastatic progression associated with cannabis, docetaxel, or their combination.

A multinomial logistic regression model was used to compare PET/CT tumour-response outcomes across treatment groups, using No Change as the reference category. As shown in Table 4, participants in the combined cannabis + chemotherapy group were significantly more likely to achieve tumour remission or reduction compared with those receiving chemotherapy alone (OR = 4.52; 95% CI 1.37–14.98; p = 0.013). In contrast, the cannabis-only group did not differ significantly from chemotherapy for this outcome (OR = 1.11; p = 0.858).

Table 4.

Multinomial logistic regression comparing PET/CT tumour outcomes across the three treatment groups

PET outcome category	Comparison group	p value	Odds ratio	95% CI
No change (reference)	–	–	–	–
Remission/reduction	Cannabis-only vs. chemotherapy	0.858	1.11	0.35–3.51
	Combined vs. chemotherapy	0.013*	4.52	1.37–14.98
	Combined vs. cannabis-only	0.041*	2.41	1.04–5.60
Metastasis	Cannabis-only vs. chemotherapy	0.797	0.83	0.21–3.33
	Combined vs. chemotherapy	0.652	1.43	0.30–6.74
	Combined vs. cannabis-only	0.73	0.86	0.33–2.27

Multinomial logistic regression evaluating PET/CT tumour-response categories across treatment groups. The reference category is no change; therefore, no odds ratios or p values are provided for that category. Odds ratios represent the likelihood of being in either the remission/reduction or metastasis categories relative to no change. Chemotherapy serves as the primary reference group, with a secondary comparison between the cannabis-only and combined cannabis + docetaxel groups added to evaluate relative treatment effectiveness.

Reference = chemotherapy-only group.

*p < 0.05 denotes statistical significance.

A direct comparison between the combined therapy and cannabis-only groups further demonstrated that the combined group had significantly greater odds of achieving remission or reduction (OR = 2.41; 95% CI 1.04–5.60; p = 0.041).

For metastasis, no statistically significant differences were observed between any of the groups. Both cannabis-only (OR = 0.83; p = 0.797) and combined therapy (OR = 1.43; p = 0.652) showed similar odds of metastasis compared with chemotherapy. Likewise, the combined therapy and cannabis-only groups did not differ from one another (OR = 0.86; p = 0.73). These findings indicate that the combined cohort (cannabis + chemotherapy) was associated with a higher likelihood of positive tumour response, without evidence of increased or reduced metastatic progression relative to the other groups.

Patient-Reported Outcomes

Pain Outcomes (Brief Pain Inventory)

Pain outcomes were assessed using the BPI at baseline, 3 months, and 6 months. Repeated-measures analyses demonstrated significant time × treatment interaction effects across all pain domains.

Both the cannabis-only and combined therapy groups experienced significantly greater improvements than the chemotherapy-only group in:

• Pain intensity (p < 0.001; η² = 0.382–0.387)

• Pain interference (p < 0.001; η² = 0.431–0.496)

• Pain relief (p < 0.001; η² = 0.268)

Reductions were most pronounced at 3 months and remained stable through 6 months. These findings indicate that cannabinoid-containing regimens were associated with enhanced pain control compared with chemotherapy alone.

Quality of Life Outcomes (EQ-5d)

Quality-of-life outcomes were evaluated across five EQ-5D domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. EQ-5D uses a problem severity scale, where lower scores indicate fewer problems – and therefore better functioning. A decline in EQ-5D domain scores represents improvement, as lower scores reflect reduced symptom burden and greater functional ability.

Significant time × treatment interactions were observed across all domains (p < 0.001). The cannabis-only and combined therapy groups demonstrated greater improvements than the chemotherapy-only group in the following.

Functional Domains (Lower Scores = Improved Functioning)

• Mobility improved significantly in both cannabis-containing groups (p < 0.001; η² = 0.503–0.619).

• Self-care showed substantial improvement in the cannabis-only (p < 0.001; η² = 0.490) and combined groups (p < 0.001; η² = 0.628).

• Usual activities improved more sharply in the cannabis-only (p < 0.001; η² = 0.461) and combined groups (p < 0.001; η² = 0.611) compared with chemotherapy alone.

Symptom Domains

Cannabis-containing groups also showed greater improvement in:

• Pain/discomfort (p < 0.001)

• Anxiety/depression (p < 0.001)

These improvements reflect reductions in symptom severity and emotional distress.

Overall, cannabinoid therapy – either alone or combined with chemotherapy – was associated with:

• Greater reductions in pain intensity and interference

• Higher levels of pain relief

• Improved mobility, self-care, and daily functioning

• Reduced pain/discomfort and anxiety/depression

The chemotherapy-only group demonstrated less change across functional and symptom domains over time. Overall, the results demonstrate consistent differences in clinical outcomes across the three treatment groups. Participants in the cannabis-only group showed modest but measurable improvements in pain intensity, pain interference, mobility, and self-care relative to the chemotherapy-only group, with comparable rates of partial tumour response and no evidence of increased metastatic progression.

The combined cannabis + chemotherapy group exhibited the most favourable outcomes across all domains. This group achieved the largest reductions in pain, the greatest improvements in quality-of-life measures, and the highest proportion of both complete and partial tumour responses. Functional indicators, including self-care and usual activities, also improved to a greater extent than in either monotherapy group.

In contrast, the chemotherapy-only group demonstrated the smallest improvements across pain, quality-of-life, and functional outcomes, and had the lowest tumour-response rates. When the groups were directly compared, the combined therapy group consistently outperformed both the chemotherapy-only and cannabis-only groups, suggesting a potential additive or synergistic effect when cannabis is used alongside chemotherapy.

Taken together as shown in Table 5, these findings indicate a pattern in which cannabis appears to confer modest clinical benefit relative to chemotherapy alone, while the combined cannabis + chemotherapy approach is associated with the most robust and favourable outcomes. These observations should be interpreted with appropriate caution due to the study’s observational design and subgroup sizes, but they collectively support further investigation of combined treatment strategies in controlled clinical trials.

Table 5.

Summary of PSA, pain, and quality-of-life outcomes across treatment groups

Outcome (domain/measure)	Direction of change (6 mo vs. baseline)	Chemo only	Cannabis only	Chemo + cannabis	Overall, p value
PSA (log-transformed)	↓ median value (better)	–	↓	↓↓	<0.001*
Pain severity (BPI)	↓ score (better)	↓	↓↓	↓↓	<0.001*
Pain interference (BPI)	↓ score (better)	↓	↓↓	↓↓	<0.001*
Pain relief (%)	↑ % relief (better)	↑	↑↑	↑↑	<0.001*
Mobility (EQ-5D)	↓ score = better	↑	↓	↓↓	<0.001*
Self-care (EQ-5D)	↓ score = better	↑	↓	↓↓	<0.001*
Usual activities (EQ-5D)	↓ score = better	↑	↓	↓↓	<0.001*
Pain/discomfort (EQ-5D)	↓ score = better	↑	↓	↓↓	<0.001*
Anxiety/depression (EQ-5D)	↓ score = better	↑↑	↓	↓↓	<0.001*

Arrows indicate magnitude of change relative to baseline.

*p < 0.05 for time × group interaction.

Overall Results Summary

Across clinical, imaging, and patient-reported outcome domains, distinct patterns of effect were observed between the chemotherapy-only, cannabis-only, and combined chemotherapy plus cannabis groups. The chemotherapy-only group generally demonstrated stable or neutral outcomes across most measures, with limited evidence of improvement beyond expected treatment effects. The cannabis-only group showed favourable effects in patient-reported outcomes, particularly in pain and health-related quality-of-life domains, without evidence of adverse clinical or imaging outcomes. The combined chemotherapy plus cannabis group consistently demonstrated the most favourable overall profile, including the highest likelihood of positive tumour response on PET/CT imaging and the greatest improvements in pain and quality-of-life measures, while not exhibiting increased metastatic progression relative to the other groups. Collectively, these findings suggest that adjunctive cannabis use, particularly when combined with chemotherapy, was associated with beneficial patient-reported outcomes and enhanced treatment response without detectable negative clinical trade-offs.

Dosages Derived from the Study

Patient dosages were carefully documented and compared against their corresponding PET scan outcomes, which were categorized into four clinical responses: remission (CR), reduction (PR), no change and metastasis. As shown in Table 6, by the 6-month mark, 50% of patients in the cannabis-only group who demonstrated a positive response, defined as either remission (CR) or significant tumour reduction (PR), were receiving a total daily dose of 60 mg. In contrast, the majority of patients in the combination therapy group (cannabis plus docetaxel) who responded positively were on a slightly lower dose of 45 mg per day. Notably, there were 2 patients in the combination group who exhibited a positive response while receiving a higher dose of 75 mg daily. The median total daily dose among responders at 6 months was 53 mg in the cannabis group and 45 mg in the combination group. These median doses were substantially higher than those recorded for patients who either did not respond or showed disease progression, suggesting a potential dose-response relationship. These findings highlight the importance of dosage optimization, particularly within the first 6 months of treatment, as a possible factor influencing therapeutic efficacy.

Table 6.

Cannabis daily dosage and PET/CT response relationship (6 months)

Clinical response	Cannabis only, median, mg/day	Chemo + cannabis, median, mg/day
Remission/reduction	53	45
No change	30	40
Metastasis	10	13

Responders received significantly higher median daily cannabinoid doses than non-responders (p < 0.05).

Discussion

This study examined the clinical effects of cannabinoids in prostate cancer across multiple domains, including PSA kinetics, tumour response based on PET/CT imaging, pain outcomes, and health-related quality of life. Participants receiving cannabis, either alone or in combination with docetaxel, demonstrated declines in PSA levels over time, whereas the docetaxel-only group showed comparatively smaller changes. Although statistically significant time-group interactions were observed, absolute differences at the final assessment were modest, and the clinical significance of the PSA reductions should be interpreted cautiously. The overall stabilization and decline in PSA observed across treatment groups may partly reflect residual effects of prior ADT exposure; therefore, PSA-related findings should be interpreted with caution, as any observed cannabis-associated changes may occur on a background of previously induced hormonal suppression.

Docetaxel was the chemotherapy regimen used in this study. While cannabinoid-chemotherapy interactions have been explored in preclinical models of several cancer types, evidence specific to prostate cancer remains limited, and docetaxel has not been extensively tested alongside cannabinoids in this context. Accordingly, this study does not establish mechanistic interaction but provides observational clinical data on outcomes in patients concurrently using cannabinoids and docetaxel.

Analysis of tumour-response categories showed that the combination therapy group exhibited a higher proportion of partial and CRs compared with the monotherapy groups. Remission (CR) and tumour reduction (PR) were defined using standardized metabolic and structural criteria. However, because tumour reduction was coded categorically rather than quantitatively, these results reflect differences in proportion of responders rather than differences in magnitude of tumour change. The multinomial regression analysis provides additional insight into the relative effectiveness of the treatment strategies. The combined cannabis + docetaxel regimen demonstrated significantly higher odds of producing remission or tumour reduction compared with both chemotherapy alone and cannabis-only therapy. This suggests that the observed clinical benefit in the combined group may reflect a potential additive or supportive effect of cannabinoids when used alongside standard chemotherapy. While the study design does not allow inference of pharmacologic synergy, the consistent directional pattern supports further investigation into combination strategies.

Importantly, metastasis outcomes did not differ significantly among the groups, indicating that neither cannabis alone nor the combined regimen was associated with increased metastatic risk in this cohort. The absence of a difference also reinforces the need for caution in attributing tumour-modifying effects to cannabinoids based solely on observational data.

Overall, these findings highlight that while cannabis-only therapy produced response rates comparable to chemotherapy for some patients, the combined therapy demonstrated the most favourable tumour-response profile. This pattern aligns with preclinical research suggesting that cannabinoids may enhance responsiveness to certain chemotherapeutics, although controlled trials are required to confirm these observations in prostate cancer.

The dose analysis indicated that participants who achieved either remission or tumour reduction tended to be using higher total daily doses of cannabis. While this pattern is noteworthy, these results should be viewed as exploratory. Variability in product composition, individual pharmacological responses, tolerability, prior treatments, and disease severity may influence dosing patterns. Controlled dose-finding trials would be necessary to determine whether a true dose-response relationship exists.

Patient-reported outcomes demonstrated improvements in pain intensity, pain interference, mobility, self-care, and daily functioning among participants using cannabis, either alone or in combination. Importantly, EQ-5D domain scores are inversely scaled, meaning that lower scores represent fewer problems and better functioning. As such, the decreases observed in mobility, self-care, and usual activities scores in the cannabis and combination groups indicate improved functioning rather than decline. Observed fluctuations in the docetaxel-only group may reflect the natural variability of treatment cycles, changes in symptom burden, or other supportive therapies used during the study period.

While the cannabis-only group demonstrated similar proportions of partial tumour response and comparable PSA trends to the docetaxel-only group, this study was neither powered nor designed to test therapeutic equivalence. These similarities should be interpreted as preliminary observations that may justify further investigation into the potential role of cannabinoids as supportive or adjunct therapies, rather than evidence of comparable antitumour efficacy.

Several potential confounding factors should be considered when interpreting these findings. These include variability in cannabis formulations and dosing, self-reported cannabis use, heterogeneity in disease stage and prior treatments, concurrent medications, and baseline differences in symptom severity. These factors, combined with the observational study design, limit the ability to infer causality or synergistic effects.

In summary, the findings suggest that cannabis use particularly when combined with docetaxel may be associated with improvements in pain, function, and certain tumour-response outcomes. However, given the limitations noted, these results should be viewed as hypothesis-generating. Controlled clinical trials incorporating standardized cannabinoid formulations, dose-response evaluation, and mechanistic endpoints will be essential to determine the therapeutic potential of cannabinoids in prostate cancer.

Randomized controlled trials (RCTs) conducted since 1975 [30] corroborate the analgesic potential of cannabinoids. Maida et al. [31] documented pain relief in 112 cancer patients with nabilone therapy. Nevertheless, reviews by Blake et al. [30] and Bennett et al. [32] cautioned about potential side effects such as drowsiness, dry mouth, confusion, blurred vision, and nausea [31, 32]. Fallon et al. [33] RCTs on Sativex produced mixed results, being efficacious in US patients but not universally. Bar-Lev Schleider et al. [34] noted reduced pain intensity in cancer patients following cannabinoid treatment, albeit their study lacked a control group. Casarett et al. [35] reported a 47% reduction in neuropathic pain with cannabinoid treatment. However, the current study is among the first to document clinically observable cannabinoid effects in prostate cancer. It extends previous findings by translating molecular and in vitro data into real-world patient outcomes. Furthermore, the observed dose-response trend offers a unique clinical insight rarely reported in cannabinoid oncology studies.

Although limited preclinical work has directly evaluated cannabinoids in prostate cancer, several mechanisms observed in other tumour models may be relevant. Cannabinoids have been shown to induce apoptosis, inhibit angiogenesis, suppress tumour cell proliferation, and modulate metastatic signalling pathways. In prostate cancer specifically, activation of CB1 and CB2 receptors may influence androgen receptor activity and downstream cellular signalling cascades. Additionally, the analgesic and anxiolytic properties of cannabinoids, mediated through the endocannabinoid system, support their potential role as adjunctive agents for symptom management.

The current study contributes preliminary clinical observations to this largely preclinical field, translating mechanistic and in vitro evidence into real-world patient outcomes. While the findings remain exploratory, the observed patterns of tumour response, functional improvement, and dose-related effects provide new context for understanding how cannabinoids may interact with conventional therapies in prostate cancer.

Implications for Clinical Practice

These results have significant implications for integrating cannabinoids into prostate cancer care. The consistent reduction in PSA levels, coupled with tumour size regression and patient-reported improvements in pain and quality of life, positions cannabinoids as promising adjunctive agents. Clinicians may consider initiating cannabinoids early in the treatment course, with careful dose titration to optimize therapeutic outcomes. The findings advocate for a more personalized approach to cannabinoid prescribing in oncology, grounded in both biomarker response and patient-reported benefits. The findings of the study hold significant implications for clinical practice, suggesting that cannabinoids, whether employed independently or in combination with chemotherapy, could serve as beneficial supplementary therapies for individuals diagnosed with prostate cancer. Healthcare professionals may consider integrating cannabinoids into treatment protocols to amplify therapeutic benefits and improve the overall well-being of patients. Additionally, the noted decreases in PSA levels and tumour size offer validation for incorporating cannabinoids into comprehensive treatment approaches for prostate cancer, potentially leading to improved clinical outcomes and extended survival rates.

Study Strengths, Limitations, and Future Directions

A key strength of this study lies in its comprehensive and integrative design, which simultaneously evaluates objective biomarkers (PSA levels), advanced imaging outcomes (PET/CT scans), and patient-reported measures (pain and quality of life) to assess the therapeutic impact of cannabinoids in prostate cancer. By employing a prospective observational cohort with well-defined inclusion and exclusion criteria, stratified sampling, and validated measurement tools, the study ensures methodological rigour and robust data collection. The inclusion of dose-response analysis provides novel insights into optimal cannabinoid dosing, while the comparative evaluation across three treatment modalities cannabinoids alone, chemotherapy alone, and combination therapy (chemotherapy plus cannabinoids), offers a nuanced understanding of potential synergistic effects. This multifaceted approach not only bridges the gap between preclinical evidence and clinical application but also generates clinically relevant findings with direct implications for personalized oncology care.

This study has several limitations that should be considered when interpreting the findings. The non-randomized, observational design precludes causal inference, as participants were not randomly assigned to treatment groups, introducing potential selection bias and confounding.

Although ADT was not administered during the study period, all participants had received ADT prior to baseline, and the potential residual effects of prior hormonal therapy on PSA kinetics could not be fully accounted for in this observational analysis. Cannabis dosage data relied on patient self-reporting, and despite verifying product composition with certificates of analysis, variability in THC:CBD ratios, product sourcing, delivery methods, and patient adherence may have influenced dose-response estimates. Additionally, the lack of a placebo arm or blinding increases the risk of performance and expectation bias, particularly for subjective outcomes such as pain and quality of life. The study’s heterogeneity in cannabinoid formulations and concurrent conventional therapies further limits the ability to isolate the effects of specific compounds. PET/CT imaging, while valuable for assessing tumour response, is subject to variability in interpretation, scan quality, and potential non-malignant metabolic activity. Future studies with larger cohorts should explore the concordance between PSA kinetics and imaging-based tumour response, as such analyses may help validate PSA as a surrogate marker in settings where access to advanced imaging modalities is limited.

Definitions of clinical endpoints such as remission and reduction were based on imaging outcomes but did not follow standardized RECIST criteria, which may affect comparability with other trials. Furthermore, subgroup sizes, especially in remission and metastasis categories were small, potentially limiting statistical power. Recruitment from a single research site also constrains generalizability, as the cohort may not represent the broader demographic and clinical diversity of prostate cancer patients.

Future research should employ randomized controlled trial designs with larger, more diverse, and multicentre cohorts to improve the robustness and external validity of findings. Standardizing cannabis formulations, dosing regimens, and concurrent treatments will be essential to reduce variability and allow more precise evaluation of therapeutic effects. Incorporating molecular and immunological biomarkers alongside PSA measurements could provide deeper mechanistic insights and help identify patient subgroups most likely to benefit. Long-term follow-up should be prioritized to assess sustained treatment responses, relapse rates, survival outcomes, and potential adverse effects, ultimately guiding optimal dosing strategies and integration of cannabinoids into evidence-based prostate cancer care.

Conclusion

The study highlights the potential of cannabinoids as adjunctive treatments for prostate cancer, supported by significant findings across various measures. Notably, cannabinoids, whether administered alone or in conjunction with chemotherapy, were associated with a higher proportion of patients achieving favourable PET/CT response categories (remission or reduction) and with declining PSA trends, although tumour response was assessed categorically rather than as a quantitative measure of tumour size.

Moreover, participants receiving combination therapy showed improvements in pain management and quality of life, emphasizing the comprehensive benefits of cannabinoids in addressing cancer-related symptoms and enhancing overall well-being. These results carry important implications for clinical practice, indicating that cannabinoids could improve treatment outcomes and patient well-being in prostate cancer management. Future research should further explore the synergistic effects of cannabinoids with standard therapies and investigate optimal dosing strategies to maximize effectiveness while minimizing side effects, thereby advancing personalized treatment approaches for prostate cancer patients.

Acknowledgments

Dr Shiksha Gallow would like to thank the Durban University of Technology for the support as well as supervisors Professor Ashley Ross, Dr Brenda Mkhize, Dr Pavitra Pillay, and Professor Katia Tonkin. Dr Shiksha Gallow would also like to thank the cancer care centres and the participants.

Statement of Ethics

This study was performed in accordance with the Declaration of Helsinki. This human study was approved by Institutional Research Ethics Committee – approval: IREC 001/22. All adult participants provided written informed consent to participate in this study.

Conflict of Interest Statement

Dr Shiksha Gallow and Dr Katia Tonkin are both involved in the cannabis industry in academia and as Cannabis Clinicians with the Society of Cannabis Clinicians an NPO. The other authors have no conflicts of interest to declare.

Funding Sources

The publications are funded by the Durban University of Technology. The study design, execution and analysis, and manuscript conception, planning, writing was funded by Cannabis Research Council.

Author Contributions

S.G. conducted the research and wrote the manuscript. A.R., B.M., P.P., and K.T. supervised the research and edited the manuscript.

Funding Statement

The publications are funded by the Durban University of Technology. The study design, execution and analysis, and manuscript conception, planning, writing was funded by Cannabis Research Council.

Data Availability Statement

All data generated or analysed during this study are included in this article. Further enquiries can be directed to the corresponding author.