Health-related quality of life in patients receiving medicinal cannabis: systematic review and meta-analysis of primary research findings 2015-2025

Purpose: The global burden of chronic health conditions is significant. Medicinal cannabis (MC) is a legalised treatment option for patients with chronic health conditions in some countries. Health-related quality of life (HRQL) is an important patient-reported outcome across all chronic health conditions. We aimed to determine how studies of MC therapy justify, measure, and report HRQL, and assess the current evidence for HRQL following MC treatment.

Methods: Systematic review searching AMED, Medline, Web of Science, Scopus, Embase, Cinahl, and PsycINFO from Jan 2015 to Apr 2025. Studies using validated HRQL measures pre-, and post-MC treatment for any chronic health condition were included. Screening and data extraction were performed independently by two reviewers. Completeness of HRQL reporting was evaluated. Meta-analyses for short-term (2-weeks to 3-months), medium-term (> 3 to < 12-months), and long-term (≥ 12-months) HRQL outcomes were conducted, with Risk of Bias (RoB) assessed in randomised control trials (RCTs).

Results: Of 16,674 retrieved citations, 64 studies were retained for analysis:12 RCTs; 38 cohort studies; 13 case series; 1 non-randomised experimental study. Thirty-nine studies (61%) provided justification for assessing HRQL and five (8%) provided HRQL definitions. Studies used generic (n = 52, 81%) or condition-specific (n = 12, 19%) HRQL measures, with EQ-5D-5L most commonly used. Meta-analyses: RCTs showed small short-term HRQL improvements (Cohen’s d = 0.30, p = 0.03), with some concerns or low RoB. For observational studies, HRQL improved in all follow-up periods (d = 0.43 to 0.74; all p < 0.001). HRQL improvement varied between, and within, different health conditions.

Conclusion: This systematic review and meta-analyses of studies published between 2015 and 2025 found that few studies provided HRQL definitions, and a third of studies did not explain why they measured HRQL. To ensure appropriate measures are used for this important treatment outcome, future studies should define HRQL and justify the HRQL assessment in the context of research objectives.

Overall, improvements in HRQL were observed across studies of patients using MC.”

https://pubmed.ncbi.nlm.nih.gov/41621036

Plain language summary

“Medicinal cannabis (MC) is a treatment option for patients in countries where prescribing MC is legal. Health-related Quality of Life (HRQL) can mean different things to different people but remains an important treatment outcome for all patients, regardless of their specific health condition. HRQL varies depending on the context and measurement tool (questionnaire) used. We aimed to find out (1) how HRQL assessment is justified, defined and measured in MC research, and (2) if HRQL improves in patients prescribed MC. We looked at studies published over the past decade that reported HRQL in patients before and after MC treatment. Most studies (81%) used generic HRQL questionnaires (e.g., EuroQol Group: EQ-5D) and others used condition-specific questionnaires (e.g. Multiple Sclerosis Quality of Life: MSQoL-52).

Overall, HRQL improved in patients using MC.

However, only a few studies provided HRQL definitions, and a third of studies didn’t explain why they measured HRQL. This information is needed to ensure HRQL is measured and interpreted appropriately in future studies.”

https://link.springer.com/article/10.1007/s11136-026-04170-7

Cannabis sativa in the fight against drug-resistant bacteria and fungi

“Drug resistance in bacteria and fungi is a global threat to public health. The purpose of this publication is to review the latest scientific achievements, mainly from 2020-2025, concerning the use of hemp compounds from Cannabis sativa in combating drug-resistant bacterial and fungal infections.

The literature review confirms that C.sativa, a plant with a documented centuries-old therapeutic history, is a rich source of cannabinoids and terpenes that combat drug-resistant bacteria: Mycobacterium tuberculosis, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae, and fungi: Cryptococcus neoformans, as well as species from the Candida and Aspergillus.

The potential of hemp compounds is based on their activity in interacting directly with pathogens by disrupting cell membrane integrity, eradicating biofilm, having a bactericidal effect on bacterial spores, acting synergistically, affecting host inflammatory pathways, and the human endocannabinoid system.”

https://pubmed.ncbi.nlm.nih.gov/41607163

Exploring cannabinoid modulation on autophagy mechanisms in Alzheimer’s disease: a review

“Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the accumulation of toxic protein aggregates in the brain, leading to brain cell death and cognitive impairment. Central to AD pathogenesis is the autophagy pathway, a crucial cellular self-digestion process.

Cannabinoids, the fundamental phytochemical compounds derived from the Cannabis sativa plant, have been demonstrated to exhibit neuroprotective qualities when used as a treatment at microdoses.

However, the impact of multi-cannabinoid treatments on autophagy induction and subsequent cell survival in AD in vitro models remains uncertain. This review seeks to explore the potential of a multi-cannabinoid treatment strategy in enhancing neuronal cell survival through autophagy activation within an AD in vitro model.

The proposed approach involves a combination of cannabinoids in their potential to upregulate autophagy mechanisms, potentially supporting neuronal cell resilience. By unravelling the mechanistic link between autophagy, cannabinoid treatment, and neuronal viability, this review aims to elucidate how cannabinoids influence neuronal function and survival at a cellular and molecular level. By offering insights into the exploitation of the endocannabinoid system, this review contributes to the development of novel cannabinoid-based treatment avenues for AD. This pursuit aligns with the broader objective of addressing the debilitating effects of AD on the quality of life for those affected.”

https://pubmed.ncbi.nlm.nih.gov/41601969

“Emerging evidence, including a recent case report, suggests that cannabinoid microdosing may offer a potential strategy for reducing AD-related symptoms while minimizing adverse effects.”

“Pharmacokinetic data further indicate that multi-cannabinoid formulations, particularly those combining THC and CBD, add additional minor cannabinoids, may provide enhanced therapeutic efficacy and improved safety profiles compared to monotherapy.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1748368/full


Toxicological evaluation and preliminary phytochemical characterisation of a Nigerian Cannabis sativa chemovar

“Objectives: Different Cannabis sativa chemovars produce diverse pharmacological and behavioral effects. With the widespread use of cannabis in Nigeria, detailed toxicological effects of Nigerian chemovars are lacking. This study aimed to identify phytocannabinoids and investigate the toxic effects of an indigenous C. sativa.

Materials and methods: The plant samples were air-dried, powdered, extracted with ethanol, and characterized (phytochemical screening, Fourier Transformed Infrared Spectroscopy (FTIR), and Gas Chromatography-Mass Spectrometry (GC-MS)). Acute and subacute toxicity tests were done following Organisation for Economic Co-operation and Development (OECD) protocols.

Results: Screening showed appreciable levels of alkaloids, tannins, saponins, cardiac glycosides, and phenol. FTIR analysis indicated functional groups and chemical linkages like alcohols, fatty acids, alkynes, ketones, and esters, and 11 phytocannabinoids with delta-9-tetrahydrocannabinol in abundance (35.78%) reported by GC-MS. Acute toxicity test indicated an oral lethal dose (LD50) value of ˃5000 mg/kg, a no-observed-adverse-effect-level (NOAEL) dose of ≤300 mg/kg, and a significant (P<0.05) decrease in the weight of animals in the 2000 mg/kg treatment group. The sub-acute toxicity test showed significantly (P<0.05) decreased ALP and ALT levels at 25 mg/kg body weight, and significantly lower triglyceride (P<0.01) and LDL (P<0.05) levels. Urea and some haematological parameters were significantly (P<0.05) higher in the 250 mg/kg group. Also, we observed mild to moderate necrosis in the excised pancreas and liver, and mild tubular changes in the kidney.

Conclusion: This suggests that our indigenous variety of C. sativa may be considered safe following oral consumption.”

https://pubmed.ncbi.nlm.nih.gov/41586191

In Vitro Antimicrobial Effect of Tetrahydrocannabinol on Streptococcus mutans and Its Anticariogenic Potential

Introduction and aims: With the increasing use of marijuana, it is vital to understand the effect of tetrahydrocannabinol (THC) on oral microbiota, especially the primary carious pathogen Streptococcus mutans.

Methods: The minimum inhibitory concentration (MIC) of THC against S mutans was determined by antimicrobial susceptibility testing. Bacterial acid production was evaluated. The effect of THC on S mutans biofilm formation and preformed biofilms was determined by crystal violet assay. The metabolic activity and viability of the biofilm were assessed using the methylthiazolyldiphenyl tetrazolium bromide assay and live/dead assay, respectively. Extracellular polysaccharide (EPS) was examined by Cascade Blue Dextran staining. S mutans membrane potential was detected by the Baclight Bacterial Membrane Potential Kit.

Results: The MIC of THC against S mutans was 2 µg/mL (P < .0001). A total of ≥2 µg/mL THC reduced bacterial acidogenicity and inhibited over 90% of biofilm formation (P < .0001). Additionally, ≥1 µg/mL THC reduced biofilm viability and EPS production (P < .0001), as assessed by fluorescence measurements and microscopy. While 1 to 64 µg/mL THC did not degrade preformed biofilm, metabolic activity was reduced by 16 to 64 µg/mL THC (P < .01), and 8 to 32 µg/mL THC reduced biofilm viability in a time- and dose-dependent manner (P < .001). Moreover, 2 to 8 µg/mL THC promoted membrane hyperpolarization after a 5-minute treatment (P < .01).

Conclusion: THC inhibits S mutans growth and biofilm formation while also reducing bacterial viability, EPS production, and acid production. Although it does not degrade preformed biofilm biomass, THC diminishes its metabolic activity and viability. These effects may be linked to THC-induced membrane hyperpolarization. This in vitro study suggests that THC may reduce the cariogenic capacity of S mutans.

Clinical relevance: This study shows that THC inhibits S mutans growth, biofilm formation, properties of preformed biofilms, and acid production. It provides preliminary scientific evidence on the impact of THC on oral health, specifically cannabinoid consumption on cariogenesis, and a potential new avenue for developing a new anticariogenic agent.”

https://pubmed.ncbi.nlm.nih.gov/41576726

“Among the cannabinoids, THC is the most abundant and exhibits a range of therapeutic effects, including analgesic, antiemetic, anti-inflammatory, anticancer, and antiseizure properties, as well as offering neuroprotective benefits in cases of neurodegeneration.”

Taken together, we herein provide evidence of the efficacy of THC in antibacterial and antibiofilm activity against S mutans by reducing planktonic growth of S mutans, inhibiting biofilm formation, and interfering with preexisting biofilm activity and function.

In addition, it may be a potential new avenue for developing new anticariogenic agents by suppressing the growth of S mutans and decelerating the acidification process that leads to enamel demineralization.”

https://www.sciencedirect.com/science/article/pii/S0020653925086678?via%3Dihub

Anticariogenic (meaning “anti-cavity”) describes substances or practices that prevent or arrest the development of dental caries (tooth decay).”

Plant Growth-Promoting Rhizobacteria Colonize Δ9-Tetrahydrocannabinolic Acid Drug-Type Cannabis sativa L. Roots and Modulate Cannabinoid Metabolism

“Plant growth-promoting rhizobacteria (PGPR) establish beneficial associations with plants, enhancing nutrient uptake, growth, and stress tolerance.

Cannabis sativa L., a medicinal plant producing over 300 specialized metabolites with relevant medicinal properties, remains underexplored for PGPR influence on its metabolism. This study assessed the ability of four PGPR taxa: Bacillus, Pseudomonas, Flavobacterium, and Burkholderia to colonize roots and modulate cannabinoid metabolism.

Two Δ9-tetrahydrocannabinolic acid (THCA) drug-type C. sativa cultivars, Amnesia Haze and Gorilla Glue, were tested. Plants grown hydroponically were inoculated under controlled conditions. Root colonization was confirmed via endophyte-specific assays.

Phenotypic analyses revealed no effects on plant phenotype, while chemical analyses revealed a response shared across taxa and cultivars. Bacterial inoculation increased the precursor cannabinoid Cannabigerolic acid (CBGA) concentration significantly by +27.37% while reducing Δ9-tetrahydrocannabinol (Δ9-THC) by -15.76%. The CBGA/THCA and THCA/CBDA ratios shifted significantly, indicating a favored CBGA accumulation and CBDA production, respectively.

PGPR treatments reduced in vivo and post-harvest decarboxylation of THCA into Δ9-THC, preserving the acidic cannabinoid profile. Under a standardized, soilless hydroponic regimen with a single shared reservoir and identical fertigation across groups, PGPR colonization was associated with shifts in cannabinoid metabolism and reduced decarboxylation.

This study demonstrates that PGPR can influence the specialized metabolism of high-THCA C. sativa, offering insights into sustainable cultivation and pharmaceutical exploitation of this relevant medicinal plant species.”

https://pubmed.ncbi.nlm.nih.gov/41578722

“Plants and bacteria share a long history that spans over a 100 million years. Since then, they have co-evolved to form complex relationships that facilitate the survival of both.”

“PGPRs can promote growth in several ways.”

“The findings and methodology of this research lay the groundwork for further evaluating and exploiting the potential beneficial relationship between PGPRs and C. sativa and implementing their sustainable applications in the agricultural, biotechnological, and pharmaceutical sectors.”

https://onlinelibrary.wiley.com/doi/10.1111/ppl.70756

Ewing sarcoma-related pain: potential role of medical cannabis monotherapy in symptom management – a case report

“Persistent, multimodal cancer pain remains a challenge, particularly in long-term survivors facing treatment-related complications. The management of high-dose opioid dependence concurrent with chronic, multi-drug resistant (MDR) periprosthetic infection presents a critical unmet need. This case reports the potential use and sustained efficacy of medical cannabis monotherapy, highlighting an unexpected temporal association with the resolution of inflammatory and infectious symptoms in a highly complex oncologic setting.

Case presentation

A 27-year-old male, a long-term survivor of high-risk Ewing Sarcoma of the proximal tibia, presented with intractable mixed pain (VAS 9–10) secondary to chronic, recurrent MDR periprosthetic osteomyelitis and multiple surgical revisions (2013–2024). Despite continuous use of high-dose opioids (up to 120 mg/day morphine equivalents), pain levels remained moderate-to-severe (VAS 6–7) and functional status was poor. The patient had previously found temporary relief with self-administered cannabis. In January 2025, after refusing limb amputation, supervised medical cannabis therapy (Bedrocan®, 22% THC, 1% CBD, 1 g/day) was initiated. Pain levels gradually stabilized at VAS 2–3, coinciding with complete opioid discontinuation within four weeks. Over nine months of follow-up, the patient maintained full autonomy and an active lifestyle. Notably, sustained cannabis monotherapy was associated with the complete closure of the chronic draining fistula and a reduction in systemic inflammatory markers (CRP from 9.6 to 2.3 mg/dL). No significant adverse effects were reported.

Conclusions

This case suggests that THC-rich medical cannabis may represent a feasible strategy for achieving opioid-free analgesia in selected patients with refractory oncologic pain. While causality cannot be established from a single observation, the correlation between cannabis initiation and the resolution of severe chronic inflammatory and infectious symptoms is intriguing and suggests a potential pleiotropic role extending beyond traditional pain management. While these findings align with emerging evidence highlighting the potent immunomodulatory and anti-inflammatory properties of cannabinoids, they contrast with some recent neutral meta-analyses in broader populations, an this would justify warrant urgent controlled investigation into the potential mechanisms of cannabinoids in complex inflammatory pain states and their role as a possible adjunct in managing long-term oncological complications.”

https://pubmed.ncbi.nlm.nih.gov/41572388

https://link.springer.com/article/10.1186/s42238-026-00388-x

The psychoactive cannabinoid THC inhibits peripheral nociceptors by targeting NaV1.7 and NaV1.8 nociceptive sodium channels

“Δ⁹-Tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, is widely recognized for its central effects mediated by cannabinoid receptors. Here, we uncover a distinct peripheral mechanism by which THC inhibits the excitability of nociceptive neurons.

We show that THC directly targets the nociceptive voltage-gated sodium channels NaV1.7 and NaV1.8 through the conserved local anesthetic binding site. This interaction reduces sodium currents and suppresses action potential generation in peripheral sensory neurons.

Our findings demonstrate that, beyond its central psychoactivity, THC exerts direct peripheral nociceptor inhibition via modulation of NaV1.7 and NaV1.8, offering new insight into cannabinoid-based analgesia independent of cannabinoid receptor signaling.”

https://pubmed.ncbi.nlm.nih.gov/41565997

“Cannabis has been used for centuries for its analgesic properties, and its clinical relevance in pain management continues to grow.”

 “These findings reveal a previously unrecognized mechanism for THC-mediated peripheral analgesia and establish a non-canonical molecular pathway through which the psychoactive cannabinoid can inhibit nociceptor excitability and thereby pain.”

https://www.nature.com/articles/s41386-026-02355-9

Exploring the neuroprotective effects and underlying mechanisms of medical cannabinoids in ischemic stroke: a systematic meta-analysis with bibliometric mapping of cerebral ischemia research

Background: Ischemic stroke is an acute neurological disorder with limited treatment options. Medical cannabinoids (MCs), primary bioactive compounds extracted from cannabis plants, have shown therapeutic prospects for ischemic stroke. This study integrates bibliometrics and meta-analysis to comprehensively summarize the research landscape of MCs in cerebral ischemia and thoroughly investigate their role and potential mechanisms in ischemic stroke.

Methods: Bibliometric analysis was performed based on literature retrieved from Web of Science Core Collection (WoSCC), PubMed, and Scopus. For meta-analysis, a comprehensive search was conducted across four databases (WoSCC, PubMed, Embase, and Cochrane Library) and grey literature repositories. Studies were screened according to predefined criteria. Pooled standardized mean differences with 95% confidence interval were calculated, followed by subgroup analysis.

Results: A total of 241 publications were identified for bibliometric analysis. From 2000 to June 2025, the annual publication output on MCs in cerebral ischemia displayed a fluctuating yet overall upward trend. Keyword co-occurrence analysis revealed three major research topics: neuroprotective mechanisms of MCs, pathological models of cerebral ischemia, and bioactive components of MCs. Meta-analysis of 26 studies demonstrated that MCs provided significant neuroprotection in animal models of ischemic stroke, including cerebral infarct volume, neurological function score (NFS), cerebral blood flow (CBF), blood-brain barrier (BBB) permeability, brain water content, apoptosis (TUNEL-positive cells), oxidative stress markers, inflammation (TNF-α, IL-1β), and excitotoxicity (Glu/NAA, Lac/NAA ratio). Subgroup analysis revealed that intraperitoneal administration and a full-course of cannabidiol (CBD) treatment were associated with reduced heterogeneity and enhanced therapeutic benefit. Isoflurane was identified as a potentially suitable anesthetic.

Conclusion: MCs exert multi-target neuroprotection in ischemic stroke by improving CBF, reducing brain edema and BBB permeability, and inhibiting oxidative stress, neuroinflammation, apoptosis, and excitotoxicity. Future research should focus on high-quality clinical trials to validate these findings and translate MCs into clinical practice.”

https://pubmed.ncbi.nlm.nih.gov/41551042

“THC produces anti-inflammatory effects, reduces neuronal damage, and promotes hippocampal neurogenesis.”

“CBD acts as a negative allosteric modulator of cannabinoid receptors (CBR) and exerts brain-protective effects through multi-target regulatory properties “

 “Moreover, the results of meta-analysis consolidate preclinical evidence, demonstrating that MCs confer neuroprotection by mitigating multiple pathological processes, including cerebral tissue perfusion, BBB permeability and cerebral edema, oxidative stress, excitotoxicity, inflammatory responses, and apoptosis.”

https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2025.1731738/full

The Evidence for Medical Cannabis in Chronic Musculoskeletal Pain Management

“Chronic musculoskeletal pain (CMP) is a pervasive condition that can impair daily functioning and quality of life. Traditional pharmaceutical therapies, including non-steroidal anti-inflammatory drugs, gabapentinoids, and opioids, often yield suboptimal results and carry notable risks, such as adverse side effects and dependence.

Increasing interest has turned toward medical cannabis, particularly combined formulations of cannabidiol (CBD) and tetrahydrocannabinol (THC), as a potential alternative or complement to current pain management strategies.

Evidence suggests that cannabinoids interact with the endocannabinoid system to modulate nociception and inflammation, offering meaningful pain relief and possibly reducing opioid requirements.

However, heterogeneity in study designs, product formulations, and regulatory frameworks presents challenges in drawing definitive conclusions. Additionally, while most adverse effects, such as fatigue, dizziness, and mild cognitive changes, are generally reported as tolerable, concerns remain about long-term safety and standardization of dosing.

Taken together, the existing literature points to a promising role for medical cannabis in CMP management, underscoring the need for further high-quality research to establish best practices, clarify patient selection, and guide clinicians in safe and effective cannabinoid therapy.”

“This scoping review highlights the potential role of medical cannabis in managing musculoskeletal pain. Evidence suggests it may reduce pain, enhance well-being, and improve quality of life, particularly as an alternative or adjunct to opioids. Adverse effects are typically mild, supporting its use as a safer long-term option. However, data on long-term efficacy, especially for CBD, remain limited.

Given the risks of opioid dependence, cannabis offers a promising therapeutic alternative.”

https://surgicoll.scholasticahq.com/article/138573-the-evidence-for-medical-cannabis-in-chronic-musculoskeletal-pain-management