Long-Term Inhaled Cannabis Therapy for Chronic Low Back Pain: A Five-Year Retrospective Analysis of Prospectively Collected Patient-Reported Outcomes in 241 Treatment-Refractory Patients

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“Background/Objectives: Chronic low back pain (CLBP) affects approximately 20% of the global population and is a leading cause of years lived with disability. Long-term, real-world evidence for inhaled cannabis in patients refractory to conventional multimodal therapy remains scarce. We assessed the five-year efficacy and safety of inhaled cannabis in CLBP patients who had documented failure of ≥1 year of opioid analgesics, anticonvulsants, antidepressants, NSAIDs, and physiotherapy, with each patient serving as their own historical control. 

Methods: We analyzed prospectively collected clinical data from 241 consecutive adults with treatment-refractory CLBP (mean age 49.3 ± 14.9 years; 37.8% female; mean pain duration 15.1 years) initiated on inhaled medical cannabis (predominantly smoking, THC 4-22%, CBD 2-22%) in a single-center tertiary orthopedic clinic between 2020 and 2025 (Hasharon Hospital, Rabin Medical Center, Israel; IRB protocols 0807-21-RMC and 0634-25-RMC). Year-0 outcomes during conventional therapy were compared with outcomes at Years 1-5 on cannabis. Primary outcomes were the Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), and Brief Pain Inventory severity/interference (BPI-S/BPI-I). Concomitant-medication trajectories were a secondary outcome. The primary analysis was a mixed model for repeated measures (MMRM) with random intercept and slope, REML estimation, and time as a categorical fixed effect. Multiple imputation (MAR, m = 20, Rubin’s rules) was the primary missing-data approach; complete-case and tipping-point pattern-mixture sensitivity analyses were used. A multivariate Hotelling T2 provided a joint test across the four correlated PROMs. Concomitant-medication discontinuation was modeled with GEE logistic regression and exact McNemar tests. Time to discontinuation was estimated by Kaplan-Meier and Cox regression. The Bonferroni-adjusted significance threshold for the four primary outcomes was α = 0.0125. BioWell gas-discharge-visualization (GDV) parameters were exploratory only. 

Results: Of 241 patients, 238 (98.8%) provided Year-5 data and 224 (92.9%) remained on cannabis at Year 5; only five patients (2.1%) discontinued for adverse events or inefficacy. All four primary PROMs improved markedly and durably. MMRM-estimated Year-5 minus Year-0 changes were: NRS -5.36 (95% CI -5.65, -5.07), ODI -17.68 (95% CI -19.73, -15.63), BPI-S -6.73 (95% CI -6.99, -6.47), and BPI-I -3.41 (95% CI -3.65, -3.16); all four contrasts had |z| ≥ 16.9 and p < 10-20. MI-pooled estimates were within 0.05 of MMRM (FMI < 0.03 for all outcomes). Hotelling T2 was F(4, 232) = 872.8, p < 10-20. At Year 5, 89.2% achieved ≥30% NRS reduction, 77.2% ≥ 50%, and 93.4% met the NRS minimum clinically important difference (MCID); ODI MCID 65.6%, BPI-S MCID (≥1 pt) 98.3%, BPI-I MCID (≥1 pt) 91.3%. Concomitant opioid use fell from 100% at baseline to 4.6% at Year 5 (within-patient absolute risk reduction 95.4%, McNemar exact p = 1.16 × 10-69), NSAID from 100% to 7.1%, SSRI/SNRI from 80.5% to 5.4%, and gabapentinoid from 38.6% to 2.5%. The ARR-derived NNT for opioid discontinuation was 1.05; this NNT is referenced to each patient’s own documented maximal-conventional-therapy state and is not equivalent to a between-arm randomized-trial NNT. Cannabis dose × time interaction was consistent with no pharmacological tolerance (β = -0.0044 per gram-month per year, p = 0.074). Across 1205 patient-years of cannabis exposure (calculated as 241 patients × 5 follow-up years from Year 1 through Year 5; baseline Year 0 represents pre-cannabis state and is not included in person-time on cannabis), 1338 organ-system AE events were recorded at 1.110/patient-year (Poisson 95% CI 1.05-1.17); 99.8% of graded events were mild (grade 1), with ocular (476 events, 0.40/PY), cognitive (460, 0.38/PY), and gastrointestinal (368, 0.31/PY) reactions predominating. The Year-3 retention dip reflected a documented telemedicine-clinic phenomenon during 2022-2024, with patients returning to in-person follow-up by Year 4-5. BioWell GDV discriminated NRS ≥ 4 only at chance level (BWS AUC 0.574, 95% CI 0.54-0.60; BWV AUC 0.51). 

Conclusions: In a treatment-refractory CLBP cohort with five-year longitudinal follow-up, inhaled cannabis was associated with large, sustained, and statistically robust improvements in pain, disability, and pain interference, accompanied by near-total displacement of opioids, NSAIDs, antidepressants, and gabapentinoids. These observational associations, although mechanically less susceptible to bias for the binary medication-discontinuation outcomes than for self-reported PROMs, cannot be interpreted causally in the absence of a concurrent randomized control arm and may reflect a combination of pharmacological effect, regression to the mean from a high pre-treatment baseline, expectancy and self-selection effects intrinsic to an actively chosen open-label therapy, and secular trends in pain reporting. The within-patient benefit-risk profile-ARR-derived NNT ≈ 1 for opioid sparing against a predominantly mild adverse-event burden-supports consideration of cannabis as a potentially clinically meaningful, opioid-sparing option in patients who have failed multimodal conventional therapy, pending confirmation in randomized comparative trials.”

https://pubmed.ncbi.nlm.nih.gov/42351683

“Inhaled medical cannabis has emerged as a candidate analgesic for refractory chronic-pain syndromes.

Mechanistically, exogenous Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) modulate the endocannabinoid system through CB1- and CB2-receptor signaling, with downstream effects on descending pain modulation, peripheral nociceptor sensitization, and affective dimensions of suffering.”

 “These data support consideration of inhaled cannabis as a potentially clinically meaningful, opioid-sparing option for patients who have failed conventional multimodal therapy.”

https://www.mdpi.com/2227-9059/14/6/1255

Metabolic Responses of Melanocytes and Melanoma Cells to UVA Radiation and Phytocannabinoids Exposure

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“Ultraviolet A (UVA) radiation disrupts the redox balance of melanocytes and may lead to the development of melanoma, highlighting the need for new skin protection strategies.

This study assessed the effect of phytocannabinoids [cannabigerol (CBG), cannabidiol (CBD), and CBG + CBD] on redox homeostasis in control and UVA-exposed melanocytes and in melanoma cells (SK-Mel-5).

UVA radiation increased the activity of prooxidant enzymes in both melanocytes and SK-Mel-5 cells and, consequently, the level of reactive oxygen species (ROS) (approx. 2-fold). It also activated nuclear factor erythroid 2 (Nrf2), as reflected by increased expression of heme oxygenase 1 (HO-1) (melanocytes approx. 2-fold; SK-Mel-5 approx. 7-fold). Concomitantly, antioxidant mechanisms were impaired, as demonstrated by reduced superoxide dismutase (SOD1/SOD2) activity and impaired glutathione and thioredoxin function. These changes were accompanied by increased levels of oxidative damage markers (isoprostanes, 4-hydroxynonenal-4-HNE, and 4-HNE-protein adducts) (43-100%) and increased inflammatory signaling, including increased expression of nuclear factor kappa B (NF-κB) subunits (melanocytes: p52 ~2-fold, p65 ~75%; SK-Mel-5: ~4-4.5-fold) and tumor necrosis factor alpha (TNF-α; ~30%).

Phytocannabinoid treatment modulated these UVA-induced changes.

In SK-Mel-5 cells, phytocannabinoids normalized the activity of prooxidant enzymes and consequently reduced ROS levels (~30%). They also reduced Nrf2 activation and HO-1 expression; however, CBG increased HO-1 level in melanocytes (~25-40%). Furthermore, phytocannabinoids enhanced antioxidant defense by increasing SOD activity, particularly in melanocytes (~10-40%), and restoring the glutathione and thioredoxin systems. Markers of oxidative damage were reduced by approximately 23-37% after treatment. Furthermore, phytocannabinoids attenuated NF-κB activation (p52 ~18-28%, p65 ~25-29% in melanocytes; ~20% in SK-Mel-5), while TNF-α levels remained unchanged. The effects in non-irradiated cells were modest (<15%).

These results suggest that phytocannabinoid-mediated modulation of redox balance may stabilize melanocytes exposed to UVA radiation and potentially reduce the risk of neoplastic transformation. However, the observed protective effects in SK-Mel-5 cells require further investigation and detailed molecular analysis.”

https://pubmed.ncbi.nlm.nih.gov/42351996

“The observed stabilizing effect of phytocannabinoids on the redox homeostasis of UVA-irradiated melanocytes is particularly relevant, as it may reduce conditions that favor neoplastic transformation.”

https://www.mdpi.com/2076-3921/15/6/690

Cannabigerol and Cannabichromene Induce Lung Cancer Cell Death and Apoptosis-Contribution of PPARα to Cannabigerol Effects

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“Cannabinoids are potential anticancer agents for the add-on treatment of malignant tumors.

Here, the effects of the previously less-explored non-psychoactive phytocannabinoids cannabigerol (CBG) and cannabichromene (CBC) on survival, apoptosis, and mitochondrial function were assessed in A549 and H460 lung cancer cells.

CBG and CBC triggered concentration-dependent cell death, autophagy, and mitochondrial apoptosis in both cell lines, with apoptosis indicated by Annexin V staining, activation of caspase-8, -9, and -3/7, loss of mitochondrial membrane potential, and elevated cytosolic levels of mitochondrial cytochrome c. CBG also upregulated ATF4, a stress-responsive transcription factor involved in autophagy and apoptotic signaling, and enhanced PARP cleavage. Both cannabinoids increased mitochondrial superoxide formation and reduced the mitochondrial oxygen consumption rate, with CBG additionally decreasing NDUFB8, a subunit of respiratory chain complex I.

Pharmacological receptor modulation showed that CBG- and CBC-induced cell death occurred independently of CB1, CB2, TRPV1, TRPM8, and PPARγ, whereas CBG-mediated cell death relied on PPARα, which also contributed to its apoptotic effects.

In summary, CBG and CBC induce apoptosis and cell death in A549 and H460 cells, with PPARα mediating the effects of CBG, highlighting its potential as a therapeutic target.”

https://pubmed.ncbi.nlm.nih.gov/42352060

“There is now substantial preclinical evidence supporting an anticancer action of various cannabinoids in different tumor entities.”

“This study investigates the effects of CBG and CBC on lung cancer cell survival, apoptosis, and mitochondrial function and bioenergetics, with particular emphasis on the role of PPARα in this process.

Here, we show convincing cytotoxic, pro-apoptotic and mitochondrial toxic effects of both cannabinoids.

More importantly, this study demonstrates for the first time a mediating role of PPARα in the induction of tumor cell death and apoptosis by CBG, which makes this non-psychoactive phytocannabinoid an interesting compound in the search for new targeted therapies for the treatment of malignant tumors.”

“The non-psychoactive phytocannabinoids CBG and CBC, which remain comparatively underexplored, were shown to induce pronounced pro-apoptotic effects and mitochondrial dysfunction in the human lung cancer cell lines A549 and H460, with CBG acting via the transcription factor PPARα to promote apoptotic cell death.”

https://www.mdpi.com/2076-3921/15/6/754

CBD-Containing Hemp Extracts and Isolated CBD for Acne: A Systematic Review of Anti-Inflammatory Mechanisms, Clinical Signals and Sustainability

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“Industrial hemp (Cannabis sativa L.) has emerged as a sustainable source of bioactive compounds, with increasing interest in cosmeceutical applications for acne management.

This systematic review synthesises evidence on cannabinoid-containing hemp extracts, particularly cannabidiol (CBD), with emphasis on anti-inflammatory and sebostatic mechanisms, alongside formulation considerations and supply-chain sustainability.

Reporting followed PRISMA 2020 guidelines and encompassed preclinical and clinical evidence relevant to acne-associated outcomes. The review protocol was registered prospectively with PROSPERO (CRD420251272093).

Across cell-based, ex vivo and early clinical studies, CBD modulated key inflammatory mediators, including TNF-α, IL-1β, IL-6 and IL-8; normalised sebocyte activity and attenuated Cutibacterium acnes (Propionibacterium acnes)-induced inflammatory signalling.

Preliminary clinical observations indicate reductions in lesion counts and erythema, with generally favourable short-term tolerability; however, interpretation is limited by small sample sizes, predominantly non-randomised designs, heterogeneous formulations and frequent co-formulation with additional active ingredients. Evidence supporting direct antimicrobial efficacy and durable clinical benefit remains limited.

Lipid-rich hemp seed-derived products were considered only in a contextual capacity for barrier-supportive and nutritional properties and were excluded from efficacy synthesis unless cannabinoid content was verified. Sustainability analyses highlight hemp’s low water requirements, carbon sequestration potential and relevance to Sustainable Development Goal 3 (SDG 3: Good Health and Well-Being) and Sustainable Development Goal 12 (SDG 12: Responsible Consumption and Production), supporting its role in environmentally responsible cosmeceutical development.

Overall, CBD-containing hemp extracts show biologically plausible and clinically promising adjunctive potential for mild-to-moderate inflammatory acne, but current evidence remains preliminary. This review highlights the need for methodologically rigorous and transparent clinical studies, standardised formulations, validated outcome measures and the integration of sustainability metrics to strengthen evidence synthesis, clarify clinical relevance and guide responsible cosmeceutical development.”

https://pubmed.ncbi.nlm.nih.gov/42357416

“This systematic review focuses on CBD-containing hemp extracts and isolated CBD as cosmeceutical interventions for acne, explicitly distinguishing these from hemp seed oil, which is a cold-pressed nutritional oil with negligible cannabinoids.”

“Mechanistic evidence demonstrates that CBD exerts sebostatic and anti-inflammatory effects in human sebocytes and modulates keratinocyte responses to Cutibacterium acnes vesicles, providing biologically plausible pathways for clinical benefit.”

“Collectively, the available evidence supports the biological plausibility and emerging clinical relevance of CBD-containing hemp extracts in acne management”

https://www.mdpi.com/1420-3049/31/12/2017

Sedative and anesthetic-sparing effects of perioperative full-spectrum cannabis oil in female dogs undergoing unilateral mastectomy and ovariohysterectomy

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“The anesthetic management of female dogs with mammary neoplasia, usually classified as ASA II and undergoing invasive procedures such as mastectomy and ovariohysterectomy, requires effective sedation and anesthetic stability due to the increased anesthetic risk associated with advanced age and underlying disease.

In this context, this study aimed to evaluate the sedative effects and reduction in anesthetic requirements of a full-spectrum cannabis oil (FSCO) containing cannabidiol (CBD) and tetrahydrocannabinol (THC) in female dogs undergoing mastectomy and ovariohysterectomy.

Twenty dogs were randomly assigned to two groups: group A (n = 10), treated with FSCO (0.02 mL/kg PO; 0.2 mg/kg CBD and 0.12 mg/kg THC) twice daily for seven days, plus 0.2 mL/kg (2 mg/kg CBD; 1.2 mg/kg THC) one hour before premedication; and group B (n = 10), treated with placebo. Groups A and B had similar ages (9.6; 10.2 years) and weights (7.4; 6.8 kg). Anesthesia was induced with propofol and maintained with sevoflurane. Outcomes included sedation scores, anesthetic requirements, rescue analgesia, responses to instrumentation, and adverse effects. The treated group required less propofol (2.33 vs. 5.98 mg/kg; p = 0.001) and lower sevoflurane concentrations from T0 to T4 (p < 0.05). Sedation scores were higher at 40 and 60 min (median of 4 vs. 0, and 6.5 vs. 0.5; p = 0.015 and p = 0.002, respectively). Fewer treated dogs required rescue analgesia (3/10 vs. 6/10; p = 0.178). No differences were observed in catheterization, intubation, or adverse effects.

Preoperative CBD/THC oil produced sedative effects and reduced anesthetic requirements without clinical complications.

These findings support the potential of cannabinoids as safe adjuvants in multimodal anesthesia in veterinary medicine.”

https://pubmed.ncbi.nlm.nih.gov/42348039

“The findings of this study indicate that preoperative administration of full-spectrum Cannabis sativa oil containing CBD and THC exerts significant sedative and anesthetic-sparing effects in female dogs with mammary neoplasia undergoing mastectomy and ovariohysterectomy.

The use of this phytocannabinoid extract significantly reduced the required doses of both propofol for induction and sevoflurane for maintenance, supporting its potential as an adjuvant in multimodal anesthetic protocols. Furthermore, the therapy was not associated with clinical adverse effects or compromised anesthetic safety, suggesting a favorable safety profile for perioperative use in oncological patients.”

https://link.springer.com/article/10.1007/s11259-026-11367-1

Preparation of new natural hemp fiber-based antibacterial hydrogel dressing and its performance in promoting wound healing of bacterial infection

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“Bacterial infections can lead to wound inflammation and delay wound healing due to the cytotoxicity of the chemicals used in conventional wound dressings. Therefore, developing a new natural and non-toxic form of antibacterial hydrogel dressing is very important.

In this study, natural hemp fibers were used as the internal skeleton of hydrogels, combined with N-halamine antimicrobial nanosystems, and chitosan reaction was used to prepare Schiff base-type N-halamine hemp fiber-based hydrogels (N-hemp-gel).

This is mainly due to the unique polygonal cavity structure and phenolics of the hemp fibre itself, as well as the release of oxidized halide ions by N-halamine through electrostatic action, and the oxidation of bacterial enzymes and other intracellular compounds, which synergistically and significantly enhance the antimicrobial properties of the wound dressing.

Antimicrobial experiments showed that N-hemp-gel had significant bactericidal effects against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In a mouse model of infected wounds, N-hemp-gel showed a 100 % wound healing rate on day 7 with no visible scarring. Storage stability confirmed that the chlorine content of N-hemp-gel decreased by only 25.5 % after 30 days at room temperature. Renewability demonstrated that the chlorine content of N-hemp-gel decreased by only 0.54 % after ten cycles.

This natural hemp fibre hydrogel with excellent antimicrobial properties, good storage stability and renewability, and green environmental protection has a broad prospect in the field of wound dressing and biomedicine.”

“Hemp fibre belongs to the bast natural fibre, is extracted from the stem of the hemp plant, is the highest toughness of natural fibres, can be naturally decomposed green fibre, through photosynthesis can be renewable, and more than 60 kinds of unique phenolic substances in the hemp hemp fibre makes hemp fibre has excellent anti-bacterial and anti-inflammatory function.”

“In this study, N-halamine Schiff base type cannabinoid cellulose based hydrogels were successfully prepared.

Antibacterial assays demonstrated that the material exhibits significant antibacterial activity against E. coli and S. aureus, effectively addressing the innate lack of antibacterial properties in cellulose materials, while also offering good storage stability and renewability.”

https://www.sciencedirect.com/science/article/abs/pii/S0927775725009112

A cannabidiol-containing alginate based hydrogel as novel multifunctional wound dressing for promoting wound healing

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“In addition to preventing infection and promoting angiogenesis, novel hydrogel dressings are highly expected to possess the potential to scavenge reactive oxygen species (ROS) and reduce inflammatory responses during the wound healing process.

In this study, we designed and fabricated a hydrogel dressing (CBD/Alg@Zn) containing cannabidiol (CBD) based on the ion crosslinked interaction between Zn2+ ions and the alginate polymer (Alg).

The as-fabricated hydrogel exhibited a suitable swelling ratio, sufficient thermal stability, and stable rheological property. In vitro biological activity experiments indicated that the hydrogel has good biocompatibility, antibacterial activity, and angiogenesis properties. Moreover, it could significantly scavenge DPPH (2,2-diphenyl-1-picrylhydrazyl) free radicals and reduce the inflammatory response.

In vivo studies revealed that the CBD/Alg@Zn hydrogel significantly facilitated the wound healing process by controlling the inflammatory infiltration, promoting collagen deposition and the granulation tissue, and benefiting the formation of blood vessels.

We, therefore, suggested that CBD/Alg@Zn hydrogel should be a potential candidate material for wound dressing and skin tissue engineering.”

https://pubmed.ncbi.nlm.nih.gov/35523648/

“A cannabidiol-containing alginate based hydrogel (CBD/Alg@Zn) was developed as novel multifunctional wound dressing.•

The Alg@Zn hydrogel not only acts as a drug carrier but also shows significantly anti-bacterial and angiogenic activities.•

The introduction of cannabidiol (CBD) endowed the hydrogels with antioxidant and anti-inflammatory effects.•

The CBD/Alg@Zn hydrogel showed accelerated wound healing effect in vivo.”

https://www.sciencedirect.com/science/article/abs/pii/S0928493121007001?via%3Dihub

Chitosan-based films with cannabis oil as a base material for wound dressing application

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“This study focuses on obtaining and characterizing novel chitosan-based biomaterials containing cannabis oil to potentially promote wound healing.

The primary active substance in cannabis oil is the non-psychoactive cannabidiol, which has many beneficial properties.

In this study, three chitosan-based films containing different concentrations of cannabis oil were prepared. As the amount of oil increased, the obtained biomaterials became rougher as tested by atomic force microscopy. Such rough surfaces promote protein adsorption, confirmed by experiments assessing the interaction between human albumin with the obtained materials. Increased oil concentration also improved the films’ mechanical parameters, swelling capacity, and hydrophilic properties, which were checked by the wetting angle measurement. On the other hand, higher oil content resulted in decreased water vapour permeability, which is essential in wound dressing. Furthermore, the prepared films were subjected to an acute toxicity test using a Microtox.

Significantly, the film’s increased cannabis oil content enhanced the antimicrobial effect against A. fischeri for films in direct contact with bacteria. More importantly, cell culture studies revealed that the obtained materials are biocompatible and, therefore, they might be potential candidates for application in wound dressing materials.”

https://pubmed.ncbi.nlm.nih.gov/36333591/

“In this study, novel chitosan-based biomaterials containing cannabidiol were obtained, with cannabis oil being used as a source of cannabidiol.”

“The results suggest that the cannabidiol-containing chitosan-based films (CBD-CS) possess the most prerequisites for a good dressing for wound healing applications.”

“Therefore, chitosan-based films incorporating cannabis oil might be an excellent candidate for wound treatment and dressing.”

https://www.nature.com/articles/s41598-022-23506-0

Self-reported cannabis use to manage opioid withdrawal symptoms and reductions in opioid use among people who use unregulated opioids: a cross-sectional analysis

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Background: Opioid withdrawal is a significant challenge for people seeking to reduce or eliminate opioid use, and unmanaged withdrawal increases the risk of relapse and overdose. Using cannabis to manage opioid withdrawal has been reported by people who use opioids, yet it is not clear whether this leads to reductions in opioid use. Moreover, because pain is prevalent among people who use unregulated opioids (PWUO) and may contribute to ongoing opioid use, the effects of cannabis use to manage withdrawal symptoms may differ among individuals experiencing moderate to severe pain. We investigated the relationship between cannabis use to manage unregulated opioid withdrawal and self-reported reductions in opioid use among PWUO.

Methods: Data were derived from a cross-sectional questionnaire administered to cannabis-using PWUO in Vancouver, Canada, between December 2019 and November 2021. Multivariable logistic regression estimated the associations between cannabis use for opioid withdrawal and self-reported reductions in opioid use. A sub-analysis explored if these associations varied among participants living with and without moderate to severe pain.

Results: Among 197 participants, 89 (45.2%) reported cannabis use to manage symptoms of opioid withdrawal in the past six months. In multivariable analysis, cannabis use for opioid withdrawal was significantly associated with self-reported reductions in opioid use (adjusted Odds Ratio [AOR] = 2.16, 95% Confidence Interval [CI]: 1.13-4.19) in the same time period. In a sub-analysis, this association was only significant among participants with moderate to severe pain (AOR = 6.55; 95% CI: 2.44-19.63).

Conclusions: We observed a significant association between self-reported use of cannabis to manage unregulated opioid withdrawal and reductions in opioid use among cannabis-using PWUO living with pain. Aligned with other studies, these findings support conducting experimental trials of cannabinoids to support individuals experiencing opioid withdrawal and living with pain.”

https://pubmed.ncbi.nlm.nih.gov/42343486

https://link.springer.com/article/10.1186/s42238-026-00458-0

Signaling pathways of inflammation in CIA model of rheumatoid arthritis regulated by cannabichromene

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“Background: Rheumatoid arthritis is a chronic autoimmune disease characterized by synovial inflammation, cytokine imbalance, and progressive joint destruction. The endocannabinoid system has emerged as a potential therapeutic target; however, the anti-inflammatory mechanisms of non-psychoactive cannabinoids such as cannabichromene (CBC) remain insufficiently defined. This study aimed to evaluate the anti-inflammatory effects of CBC in vitro and in a collagen-induced arthritis (CIA) rat model, with a focus on key inflammatory signaling pathways.

Methods: CBC effects were assessed in LPS-stimulated HUVEC cells by qPCR analysis of inflammatory markers. In vivo, female Wistar rats were assigned to four groups: CIA + saline (placebo), CIA + CBC, CIA + methylprednisolone, and non-immunized controls receiving saline. Disease progression was evaluated using clinical scoring, paw thickness, and body weight. Synovial tissues and serum were analyzed by qPCR, Western blotting, and ELISA to assess cytokines, inflammasome components, and signaling pathways, including NF-κB and JAK/STAT.

Results: CBC reduced TNF-α expression in vitro at low micromolar concentrations. In vivo, CBC significantly decreased arthritis scores compared to placebo and attenuated weight loss, although it did not significantly reduce paw swelling. Molecular analyses revealed downregulation of IL-6, STAT3, and IL-17 A, indicating suppression of the TNF-NF-κB-IL-6-STAT3-Th17 axis. CBC also significantly inhibited inflammasome components (NLRP3, NLRP1A, caspase-11). However, MMP-3 and MMP-9 levels were not significantly affected.

Conclusions: CBC exhibits significant anti-inflammatory activity in vitro and in vivo by modulating key cytokine and inflammasome pathways. While its effects on structural joint damage markers were limited, CBC represents a promising candidate for inflammatory arthritis therapy, warranting further investigation.”

https://pubmed.ncbi.nlm.nih.gov/42343451

https://link.springer.com/article/10.1186/s42238-026-00464-2