CBD-Containing Topical Formulation for Localized Pain in Fibromyalgia: A 12-Week Pilot Feasibility Study

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Fibromyalgia can be difficult to treat, particularly when pain is concentrated in specific areas and standard medications provide incomplete relief or unwanted side effects. In this 12-week pilot study, 30 women with fibromyalgia applied a CBD-containing topical formulation to a painful area three times daily. Localized pain declined significantly, with 60% of participants achieving a clinically meaningful improvement, while functional capacity also improved. No adverse events or side effects were reported. The findings support larger randomized trials to determine whether topical cannabinoid formulations can provide a useful option for localized fibromyalgia pain.

“Background: Fibromyalgia (FM) is a chronic pain condition characterized by widespread pain, fatigue, and functional impairment. Current pharmacological treatments show limited efficacy and poor tolerability. Cannabidiol (CBD) has demonstrated analgesic and anti-inflammatory properties, but evidence regarding CBD-containing topical formulations in FM remains scarce.

Objectives: To evaluate the feasibility, safety, and preliminary efficacy of a CBD-containing topical formulation for localized pain in patients with FM and to explore its potential impact on broader symptom domains.

Material and methods: This single-arm pilot study included 30 women with FM and clinically relevant localized pain due to musculoskeletal, neuropathic, or cutaneous comorbidities. Participants self-applied a commercially available CBD-containing topical formulation to a painful area every 8 h for 12 weeks. Outcomes were assessed at baseline, 4 weeks, and 12 weeks. Nonparametric repeated-measures analyses, Monte Carlo resampling, effect sizes, and minimal clinically important difference (MCID) thresholds were applied.

Results: At the 4- and 12-week follow-up visits, all participants reported full adherence to the prescribed application schedule. No adverse events or side effects were reported. Localized pain showed a significant and clinically meaningful reduction at 4 weeks, sustained at 12 weeks (60% achieving MCID). Functional capacity improved significantly, with 50% of participants exceeding the MCID at 4 weeks. Widespread Pain Index (WPI) and Symptom Severity Scale (SSS) scores decreased progressively, and a lower proportion of participants met the 2010 American College of Rheumatology (ACR) diagnostic criteria for FM at 12 weeks, while generalized pain, fatigue, anxiety, and depression did not show significant changes.

Conclusions: Topical application of a CBD-containing formulation was feasible and was associated with improvements in localized pain and functionality in this exploratory single-arm study. Changes observed in WPI and SSS, and in the proportion of participants meeting the 2010 ACR criteria at follow-up, should be interpreted cautiously and considered exploratory and hypothesis-generating, given the uncontrolled design (precluding causal inference), the symptom-based and fluctuating nature of FM, and the multicomponent composition of the product. Although limited by its uncontrolled design, this pilot study provides effect size estimates and methodological guidance to support future randomized controlled trials of topical cannabinoids in FM.”

https://pubmed.ncbi.nlm.nih.gov/42421470

https://journals.sagepub.com/doi/10.1177/25785125261468882

Evaluating the Combined Effects of Cannabinoids and Music, and Their Interactions in Mood and Emotional Regulation: An Online Survey

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Music and cannabis can each influence mood, relaxation, and emotional experience, but far less is known about how they may interact when used together. In this survey of 122 cannabis users, participants commonly reported greater relaxation, improved mood, and stronger feelings of connection when combining cannabis with music. Many also described using cannabis for pain, anxiety, or sleep, with music perceived as enhancing those effects. Because the study relied on self-reported survey responses, it cannot establish a therapeutic benefit, but the findings suggest that music may be worth studying as a supportive adjunct to cannabinoid-based approaches for emotional well-being.

“Background: While both cannabis and music have demonstrated significant independent impacts on emotional states, the synergies between these two modalities remain underexplored. This study investigates the interactions between cannabis consumption and music listening, focusing on their effects on emotional experiences, mood regulation, and sensory perceptions.

Methods: An online cross-sectional survey consisting of 176 questions was administered to 122 cannabis users. The survey captured detailed information on demographics, cannabis use patterns, music engagement behaviors, emotional responsiveness, and the interplay between cannabis and music perception.

Results: Most participants viewed the combination of cannabis and music favorably, reporting enhanced relaxation, improved mood, and increased feelings of connection. Cannabis use was also associated with altered responses to imposed music in various settings and a heightened likelihood of using music during routine activities. In addition, participants frequently reported the use of cannabis as a substitute for pharmaceutical treatments for pain, anxiety, and sleep disorders, with music further amplifying these therapeutic effects. However, no significant differences were observed in overall music reward experiences with or without cannabis, highlighting the nuanced and context-dependent nature of these interactions.

Conclusion: These findings provide novel insights into the potential for cannabis and music to act as complementary tools for emotional well-being, underscoring the need for further research to elucidate the mechanisms underlying their combined effects. This study provides a foundation for future investigations into the therapeutic integration of music as a supportive adjunct to cannabinoid-based interventions targeting emotional and psychological health.”

https://pubmed.ncbi.nlm.nih.gov/42421248

https://journals.sagepub.com/doi/10.1177/25785125261467505

Cannabidiol alleviates ferroptosis after traumatic brain injury via the miR3203p/Negr1/ERK signaling axis

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Traumatic brain injury can trigger several forms of secondary damage long after the initial impact, including ferroptosis—an iron-dependent form of cell death linked to oxidative stress and neurological deterioration. In this preclinical study, researchers found that CBD significantly reduced ferroptosis after TBI in both rat and cell models. The effect was traced to a specific molecular pathway involving miR-320-3p, Negr1, and ERK signaling, providing a clearer picture of how CBD may protect injured brain cells. The findings add to growing evidence that CBD’s potential role in traumatic brain injury may involve direct regulation of the cellular mechanisms that drive post-injury neurodegeneration.

“Traumatic brain injury (TBI) can cause severe neurological damage. Ferroptosis, a recently discovered form of iron-regulated cell death, is closely associated with TBI.

Cannabidiol (CBD) has been demonstrated to exhibit neuroprotective effects. However, the antiferroptotic role of CBD in TBI remains unclear. Investigating whether CBD inhibits ferroptosis after brain injury and its underlying mechanisms is of great significance.

We find that ferroptosis can be induced in rats after TBI, and CBD significantly inhibits ferroptosis in TBI rats both in vivo and in vitro.

MicroRNAs (miRNAs) are highly expressed in the brain. Differentially expressed miRNAs and mRNAs after TBI are detected by RNA sequencing, and miR-320-3p, Negr1, and the ERK/MEK pathway are screened out due to their strong correlations.

The results show that CBD inhibits miR-320-3p expression, increases Negr1 expression, and suppresses the ERK/MEK pathway both in vivo and in vitro. Mechanistically, transfection with miR-320-3p mimics or siNegr1 inhibits the intervention effect of CBD on ferroptosis and the ERK/MEK pathway. Additionally, Negr1 gene silencing reverses the effect of the miR-320-3p inhibitor on ferroptosis factors in PC12 cells, which suggests that miR-320-3p can target Negr1.

In conclusion, our findings indicate that CBD can inhibit TBI-induced ferroptosis through the miR-320-3p/Negr1/ERK signaling axis.”

https://pubmed.ncbi.nlm.nih.gov/42421562

https://www.sciengine.com/ABBS/doi/10.3724/abbs.2026067

Cannabis sativa phytochemicals in cancer therapy: molecular mechanisms and therapeutic potential

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Cannabis cancer research now extends far beyond THC and CBD alone. This 2026 review examines how cannabinoids, flavonoids, and other Cannabis sativa phytochemicals interact with molecular pathways involved in tumor growth, including apoptosis, oxidative stress, autophagy, angiogenesis, and metastasis. The authors highlight evidence involving THC, CBD, CBG, and several flavonoids across cancers including breast, bladder, melanoma, and pancreatic cancer, while also emphasizing that combinations are not always synergistic and that promising laboratory findings have not consistently translated into clinical success. The review concludes that cannabis-derived compounds remain important candidates for integrative oncology, but their potential will depend on better dosing strategies, rational combinations, targeted delivery, and rigorous clinical evaluation.

“Background: The therapeutic potential of Cannabis sativa has attracted growing interest in oncology. Its diverse phytochemicals, including cannabinoids, flavonoids, and terpenes, interact with oncogenic signaling pathways and the endocannabinoid system influencing tumour progression and therapeutic responses.

Objective: This review critically evaluates the molecular mechanisms by which Cannabis sativa phytochemicals modulate cancer pathways, with emphasis on apoptosis, oxidative stress regulation, autophagy, angiogenesis, and metastasis. It also explores synergistic and additive interactions among cannabinoids and flavonoids, highlighting their translational relevance.

Key findings: Cannabinoids such as Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabigerol (CBG) exhibit pathway-specific effects, including induction of apoptosis, modulation of oxidative stress, and inhibition of angiogenesis. Flavonoids such as cannflavin A, genistein, daidzein, hesperetin, and naringenin exhibit selective cytotoxicity across bladder, breast, melanoma, and pancreatic cancers, often sparing normal tissue. Importantly, phytochemical interactions are not uniformly synergistic; while combinations such as THC and CBD amplify apoptotic signaling, others act additively or antagonistically. Clinical formulations such as Nabiximols provide translational evidence of cannabinoid synergy, although outcomes remain context-dependent.

Conclusion: The disconnect between preclinical efficacy and clinical outcomes underscores critical gaps in dosing strategies, patient selection, and combination regimens. Future research should prioritize mechanistic studies, rational phytochemical combinations, and innovative drug delivery systems. Taken together, Cannabis sativa phytochemicals emerge as promising molecular entities with the potential to reshape integrative oncology, provided their therapeutic promise is matched with rigorous, evidence-based evaluation.”

https://pubmed.ncbi.nlm.nih.gov/42416829

“Taken together, these findings position Cannabis sativa phytochemicals not merely as natural products of interest, but as promising molecular entities with the potential to reshape integrative oncology.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1768210/full

Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) Diminish CD16+ Monocyte-Induced Astrocyte Inflammation, while THC Uniquely Inhibits Monocyte Chemotaxis Independent of HIV Status

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Neuroinflammation is an important contributor to HIV-associated neurocognitive disorders, in part because inflammatory monocytes can migrate into the brain and activate astrocytes. In this laboratory study, both THC and CBD reduced the production of several inflammatory mediators—including IL-6, IL-8, and MCP-1—during interactions between CD16+ monocytes and astrocytes. THC showed an additional effect not observed with CBD: it suppressed monocyte migration, including the heightened migration seen in cells from people with HIV. The findings suggest that THC, and to a lesser extent CBD, may influence multiple immune mechanisms involved in HIV-associated neuroinflammation and warrant further investigation as potential therapeutic targets.

“CD16+ monocytes are a minor subset of the total monocyte population that play a disproportionate role in contributing to neuroinflammation in human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND).

This has been evidenced by the enhanced transmigration of CD16+ monocytes into the brain compared to their CD16– counterpart. CD16+ monocytes can be activated by HIV ssRNAs through toll-like receptors (TLR) 7 and TLR8, and subsequently interact with brain-resident cells, including astrocytes. Previous studies from our laboratory identified monocyte-derived IL-1ß as an inducing cytokine for astrocyte-derived neuroinflammatory factors.

Despite cannabis use among the HIV community, the mechanisms by which immune-modulating cannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), alter human immune responses in the context of HAND-associated neuroinflammation remain elusive.

We hypothesized that THC and CBD suppress CD16+ monocyte-induced astrocyte secretion of inflammatory mediators and monocyte recruitment via chemotaxis in the context of HIV.

Results from this study show that THC and CBD impair CD16+ monocyte IL-1ß-mediated astrocyte production of IL-6, IL-8, and MCP-1 when these two cell types are cocultured in the presence of TLR7 or TLR8 stimulation. Additionally, monocytes from HIV+ subjects exhibited enhanced migration compared to monocytes from HIV- subjects, which was suppressed by THC treatment but not by CBD. The effects on migration were associated with reduced cellular expression of polymerized actin and high-affinity conformation integrin receptors.

Collectively, these findings suggest that THC, and to a lesser extent CBD, may have therapeutic potential for mitigating CD16+ monocyte-mediated neuroinflammation associated with HAND.”

https://pubmed.ncbi.nlm.nih.gov/42400870

“Taken together, this study provides evidence to support that THC, and to a lesser extent CBD, exert anti-inflammatory effects on CD16+ monocyte-mediated inflammatory and migratory responses that may be associated with HAND.”

https://link.springer.com/article/10.1007/s11481-026-10300-2


Cannabidiol Activates Integrated Stress Response Signaling and Immune Trafficking Programs in an A375 Melanoma-Jurkat T Cell Coculture Model: A Multi-Omics Analysis

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Melanoma research is increasingly focused not only on killing tumor cells, but also on understanding how cancer cells communicate with the immune system. In this multi-omics laboratory study, researchers examined CBD in a coculture model containing A375 melanoma cells and Jurkat T cells. CBD activated integrated stress-response pathways in the melanoma cells while also altering immune-trafficking and signaling programs involved in T-cell behavior. The findings suggest that CBD may influence both tumor-cell stress biology and the surrounding immune environment, adding another mechanistic layer to its potential anticancer effects. Because this was an in-vitro model, further animal and clinical research will be needed to determine whether these molecular changes translate into therapeutic benefit.

“Cannabidiol (CBD) is a nonpsychoactive cannabinoid with emerging anticancer and immunomodulatory properties; however, its systems-level mechanisms in tumor-associated immune cells remain incompletely defined.

Here, we investigated CBD in a melanoma-T cell coculture model using integrated transcriptomic and proteomic analyses.

At a subcytotoxic concentration (10 μM), CBD selectively induced apoptosis in melanoma while preserving T-cell viability and enhancing IL-2 secretion. RNA sequencing revealed coordinated activation of stress-adaptive, immune activation, and trafficking programs, including modulation of T-cell receptor signaling and cytokine networks.

Data-independent acquisition proteomics identified activation of eukaryotic initiation factor 2 (EIF2) signaling, a central node of the integrated stress response (ISR) linking redox and endoplasmic reticulum stress to translational control. Multiomics integration converged on immune cell trafficking as a consistent outcome, with upregulation of ICAM1, ITGB1, and associated adhesion-related proteins.

These findings suggest ISR-dependent translational reprogramming as a putative mechanistic axis by which CBD reshapes T-cell function in the melanoma microenvironment.

Our study provides pharmacological insight into how CBD modulates tumor-immune interactions and suggests potential utility as an adjunct immunomodulatory agent in melanoma.”

https://pubmed.ncbi.nlm.nih.gov/42396083

“Plant-derived redox-active metabolites have emerged as important modulators of these stress-adaptive pathways, acting through conserved molecular nodes that integrate oxidative stress with cellular signaling. Cannabidiol (CBD) is a nonpsychoactive phytochemical that has attracted growing attention as a redox-active compound with antioxidant, cytoprotective, and anticancer properties. Apart from its direct effects on tumor cells, CBD has been reported to modulate inflammatory signaling, oxidative stress responses, and cell death pathways, including ferroptosis.”

“In conclusion, this study provides a comprehensive multiomics characterization of CBD’s role in reshaping T-cell function within the melanoma microenvironment through redox- and stress-responsive mechanisms. Using a melanoma-T cell coculture system, we demonstrate that CBD selectively promotes melanoma cell death while inducing coordinated transcriptomic and proteomic remodeling in T cells.”

https://pubs.acs.org/doi/10.1021/acsomega.6c01965

Effect of a cannabidiol-based mouthwash on dental enamel properties and biofilm control: an In situ study

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Chlorhexidine has long been considered a standard mouthwash for controlling dental biofilm, but staining, taste changes, irritation, and other drawbacks can limit long-term use. In this in-situ study involving 14 participants, researchers tested several concentrations of CBD mouthwash against chlorhexidine while also examining effects on dental enamel. CBD at 0.05% and 0.1% produced biofilm control comparable to chlorhexidine, while the 0.05% formulation did not adversely affect enamel properties and produced less color change. The findings suggest that appropriately formulated CBD mouthwash may offer a promising plant-derived approach to biofilm control while avoiding some of the disadvantages associated with conventional chlorhexidine rinses.

“Objectives: This study evaluated the antibiofilm activity of experimental mouthwash containing different concentrations of cannabidiol (CBD) and the in situ effects on the physical and mechanical properties of dental enamel.

Methods: Bovine enamel fragments (6 × 6 × 2 mm) were mounted in intraoral appliances worn by 14 participants in a crossover design. Mouthwash containing CBD (0%, 0.01%, 0.05%, and 0.1%) and 0.12% chlorhexidine (CHX) were tested. Each experimental phase lasted 7 days, separated by washout periods. One side of the appliance was exposed to a cariogenic challenge (20% sucrose) prior to treatment. Surface roughness (Ra), microhardness (%KHN), and color change (ΔE00) were measured before and after treatments. Biofilm and yeast counts (log10 CFU) were quantified, and enamel surfaces were analyzed by scanning electron microscopy. Data were analyzed using two-way ANOVA with Bonferroni post hoc tests and Kruskal-Wallis with Dunn’s test (P < 0.05).

Results: Sucrose did not significantly affect Ra (P > 0.05), although CBD 0.1% showed higher roughness than CHX under sucrose exposure (P < 0.05). No significant differences in %KHN were observed among treatments; however, sucrose reduced microhardness in the placebo and CBD 0.01% groups (P < 0.05). CHX exhibited the highest ΔE00 values (P < 0.05). Biofilm formation was similar among CHX, CBD 0.05%, and CBD 0.1% (P > 0.05), while CHX showed lower yeast counts than CBD 0.01% and CBD 0.1% (P < 0.05).

Conclusion: CBD 0.05% demonstrated potential for biofilm control without adversely affecting enamel properties.

Clinical relevance: This study provides evidence supporting a natural compound-based mouthwash as a clinically viable alternative to chlorhexidine, showing similar efficacy and no associated adverse effects under the conditions tested.”

https://pubmed.ncbi.nlm.nih.gov/42380527

“Chlorhexidine digluconate (CHX) has been considered the gold standard mouthwash in dentistry for several decades. It is a cationic bisbiguanide with bacteriostatic activity at low concentrations and bactericidal effects at higher concentrations. However, its long-term use has been associated with several adverse effects, including taste alteration, tooth and tongue staining, oral mucosal irritation, parotid gland swelling, xerostomia, and the potential development of antimicrobial resistance.”

“Based on the findings of this study and considering its limitations, it can be concluded that cannabidiol-based mouthwashes were able to modulate dental biofilm formation in a concentration-dependent manner, with higher concentrations (0.05% and 0.1%) demonstrating performance similar to chlorhexidine in reducing biofilm accumulation, influencing its structural organization, and maintaining relative microhardness. This effect did not result in alterations to enamel surface topography. However, cannabidiol-based mouthwashes maintained color closer to acceptability thresholds.”

https://link.springer.com/article/10.1007/s00784-026-06985-7

Cannabinoids infused mouthwash products are as effective as chlorhexidine on inhibition of total-culturable bacterial content in dental plaque samples

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Dental plaque is driven by complex bacterial communities, making effective antimicrobial rinses an important part of oral-health care. In this study, researchers compared cannabinoid-infused mouthwashes with chlorhexidine by testing their ability to reduce culturable bacteria in dental plaque samples. The cannabinoid formulations performed comparably to chlorhexidine in suppressing bacterial growth, suggesting that cannabis-derived compounds may have practical potential in oral-hygiene products. Although larger clinical studies are still needed, the findings add to a growing body of research showing that cannabinoids may offer antimicrobial activity relevant to plaque control and periodontal health.

“Background: Dental plaque is a global health problem affecting people of various age groups. Cannabinoids are gaining enormous research attention due to its beneficial properties for various applications. A preliminary observation on antimicrobial property of cannabinoids against dental plaque bacteria has been reported recently. As a follow-up research, here we report the in vitro evaluation of cannabinoids infused mouthwash products against total culturable (aerobic) bacterial content from dental plaque samples.

Methods: We tested two cannabinoid-infused mouthwash products containing cannabidiol (CBD) and cannabigerol (CBG) respectively (each mouthwash containing < 1% cannabinoid by weight) in vitro against total-culturable bacteria from dental plaque samples collected from 72 adults aged between 18 and 83 years. The participants were grouped on the basis of Dutch periodontal screening index (DPSI) score. To compare the efficacy of our products, we included two most commonly available products over the counter (Product A and Product B) to represent commercially available mouthwash products and the gold standard chlorhexidine digluconate 0.2% as a positive control. The product A represents mouthwash containing essential oils and alcohol, and Product B represents alcohol-free mouthwash that contains fluoride. All the mouthwash products were evaluated directly as such without any dilution through disc diffusion and agar well diffusion approaches and the diameter of zone of inhibition was measured. The limitation in methodology was that, the samples were open-label and the person who performed the manual measurements was unblind to test and control products used.

Results: On average, the cannabinoids infused mouthwash products showed the similar bactericidal efficacy as that of chlorhexidine 0.2%. Both chlorhexidine 0.2% and cannabinoids infused mouthwash products were effective against all the samples tested. Product A did not show any significant antimicrobial activity in any of the samples tested, except that a very marginal inhibition with a zone of 7-8 mm was observed only in 9 samples. Product B did not show any detectable inhibition zone at all in any of the samples tested. The ranges of zones of inhibition (and their average) were 8-25 mm (18.1 mm) for CBD-mouthwash, 8-25 mm (17.7 mm) for CBG-mouthwash; 12-25 mm (16.8 mm) for chlorhexidine 0.2%; 0-8 mm (0.1 mm) for Product A; and 0 mm for Product B. Although the difference in performance was slightly higher than chlorhexidine in both the cases, the difference was statistically significant for CBD-mouthwash and near significant for CBG-mouthwash. No significant difference was observed between CBD- and CBG-mouthwash. No significant difference in performance was found between DPSI score groups for any of the product tested. To our knowledge this is the first report on such efficient mouthwash product with natural key ingredients including cannabinoids and without any kind of fluoride or alcohol.

Conclusions: Our in vitro results demonstrate the potential of cannabinoids in developing efficient and safer mouthwash products and next generation oral care products without fluoride and alcohol.”

https://pubmed.ncbi.nlm.nih.gov/33526124

“Cannabinoids (CBD / CBG) infused mouthwashes together with other natural key ingredients shows promising bactericidal activity in vitro against total-culturable aerobic bacterial content in dental plaque, with efficiency equivalent to or better than that of the gold standard (0.2% chlorhexidine). CannIBite mouthwash products with cannabinoids infusion offer a safer and effective alternative without any fluorides or alcohol. Based on our in vitro study, the cannabinoids infused CannIBite mouthwash products offer a much safer, efficient and natural alternative to alcohol and/or fluoride containing mouthwashes.”

https://link.springer.com/article/10.1186/s42238-020-00027-z

Tetrahydrocannabinol/cannabidiol in the treatment of restless legs syndrome

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Restless legs syndrome can severely disrupt sleep and quality of life, and some patients continue to experience symptoms despite standard treatments. This report examines the use of THC and CBD in patients with restless legs syndrome, highlighting cases in which cannabis-based treatment was associated with marked symptom relief and improved sleep. The findings suggest that cannabinoids may deserve further study as a potential option for patients whose symptoms remain difficult to control with conventional therapy.

“Background: Dopamine agonists were previously considered the first-line treatment for Restless Legs Syndrome (RLS); however, α2δ ligands are now recommended to prevent augmentation. As cannabinoids inhibit glutamate release in the striatum, they may represent an effective therapeutic option for RLS.

Objective: Evaluate the efficacy of 2.7 mg Δ9Tetrahyedrocannabinol/2.5 mg Cannabidiol (2.7mgTHC/2.5mgCBD) in RLS.

Methods: This is an exploratory, prospective, 3-month open-label trial. At baseline, patients underwent blood testing, respiratory polygraphy, and a 14-day actigraphy. Treatment was initiated at baseline, with dose titration at week 4 if required. The Expanded Disability Status Scale (EDSS), Epworth Sleepiness Scale (ESS), International Restless Legs Syndrome Rating Scale (IRLS), Modified Ashworth Scale, and EQ-5D were assessed at baseline and at weeks 4 and 12. The 14-day actigraphy was repeated at week 12. The primary endpoint was improvement in IRLS scores. Sleep parameters were evaluated as secondary endpoints. Primary end point: improvement in IRLS. Sleep parameters were secondary end points.

Results: Eighteen patients with RLS were included, of whom 16 had multiple sclerosis (MS). The cohort comprised 55.5% women, with a mean age of 51.87 years, a median EDSS score of 2, and a mean Ashworth score of 1 ± 1.19. Median iron metabolism parameters were within the normal range. At baseline, patients exhibited low daytime sleepiness (ESS: 10.63 ± 3.46) and severe RLS (IRLS: 22.44 ± 8.77). Mean sleep efficiency (SE) was 83.64 ± 6.03%, sleep latency (SL) was 26.71 ± 18.64 min, and wake after sleep onset (WASO) was 40.29 ± 10.03 min. IRLS scores improved significantly after both 1 month and 3 months of treatment (p < 0.001). WASO was significantly reduced (p = 0.015), whereas no significant changes were observed in SL or SE. After 1 year, 66.66% of patients remained on treatment and continued to show sustained improvement in IRLS scores (p = 0.000).

Conclusions: In this exploratory open-label study, treatment with 2.7 mg THC/2.5 mg CBD was effective in reducing RLS severity, as measured by the IRLS scale, in patients with MS and-associated idiopathic RLS. Improvements were observed after 1 and 3 months of treatment and were maintained after 1 year among patients who continued therapy.”

https://pubmed.ncbi.nlm.nih.gov/42387200

https://link.springer.com/article/10.1007/s00415-026-13975-y

Cannabidiol in the anterior insular cortex attenuates chronic neuropathic pain and comorbid anxiety- and depression-like behaviors: involvement of CB1 and 5-HT1A receptor signaling

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Chronic neuropathic pain often occurs alongside anxiety and depression, making treatment more difficult than addressing pain alone. In this preclinical study, researchers examined CBD activity within the anterior insular cortex, a brain region involved in pain perception and emotional processing. CBD reduced neuropathic pain while also improving anxiety- and depression-like behaviors, with the effects linked to CB1 and 5-HT1A receptor signaling. The findings suggest that CBD may influence overlapping neural pathways involved in both chronic pain and its emotional consequences, supporting further investigation of cannabinoid-based approaches for complex pain conditions.

“Background: Chronic neuropathic pain (NP) is frequently accompanied by anxiety- and depression‑like symptoms, reflecting maladaptive interactions between nociceptive and affective brain networks. The anterior insular cortex (AIC) integrates sensory and emotional dimensions of pain and represents a potential target for pharmacological modulation. Cannabidiol (CBD) exhibits analgesic and anxiolytic/antidepressant‑like properties through interactions with endocannabinoid and serotonergic systems.

Objectives: We investigated whether CBD microinjection into the AIC modulates NP and its affective comorbidities, and whether these effects depend on CB1 and 5‑HT1A receptors.

Methods: Male Wistar rats were subjected to chronic constriction injury (CCI) of the sciatic nerve. Fourteen days later, guide cannulae were implanted into the AIC. On day 21 post‑CCI, animals received intra‑AIC microinjections of CBD (15, 30, or 60 nmol/200 nL) or vehicle. Mechanical (von Frey test) and cold (acetone test) allodynia, anxiety‑like behavior (open field and elevated plus maze tests), and depression‑like behavior (forced swim and sucrose spray tests) were assessed by different psychobiological tests. The role of cannabinoid and serotonergic receptors was addressed by intra‑AIC pretreatment with either the CB1 receptor antagonist AM251 or the 5‑HT1A receptor antagonist WAY-100,635 in independent groups.

Results: AIC pretreatment with CBD dose‑dependently reduced mechanical and cold allodynia and anxiety‑ and depression‑like behaviors, with the most robust effects observed at 60 nmol. AIC Pretreatment with either AM251 or WAY-100,635 abolished the antinociceptive and affective effects of CBD.

Conclusion: CBD administration within the AIC produces integrated analgesic, anxiolytic, and antidepressant-like effects in a model of neuropathic pain. These effects are consistent with the involvement of CB1 and 5-HT1A receptor signaling. The findings identify the AIC as a relevant cortical substrate linking nociceptive and affective processes and support CBD as a promising psychopharmacological strategy for NP associated with emotional comorbidities.”

https://pubmed.ncbi.nlm.nih.gov/42390818

“In conclusion, this study demonstrates that CBD microinjection into the AIC attenuates mechanical and cold allodynia while also reducing anxiety- and depression-like behaviors in an experimental model of NP.”

“Overall, these findings highlight the AIC as a potential neural substrate involved in the interaction between chronic pain and its emotional comorbidities and identify CBD as a promising psychopharmacological approach for NP conditions associated with affective dysfunction.”

https://link.springer.com/article/10.1007/s00213-026-07116-6