Progressive weight loss is attenuated by THC treatment in rats with activity-based anorexia

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“Anorexia nervosa (AN) is a severe psychiatric disorder with limited effective pharmacological treatments.

Given the role of the endocannabinoid system (ECS) in regulating energy balance and its possible involvement in AN pathophysiology, cannabinoid-based interventions may hold therapeutic potential.

Using the preclinical activity-based anorexia (ABA) model, we investigated whether Δ⁹-tetrahydrocannabinol (THC) could attenuate the progression of ABA-induced weight loss.

Female rats were exposed to the ABA paradigm, which combines restricted food access (2 h/day) with unrestricted access to running wheels. After 3 days, when ABA rats had lost 10-12% of their baseline body weight, they received daily injections of either THC or vehicle. Rats were removed from the paradigm after losing 23% of their body weight or on the morning of day 8, whichever occurred first.

THC treatment significantly attenuated weight loss and prolonged survival in the paradigm.

These beneficial effects of THC were mediated by a selective suppression of excessive dark- and light-phase wheel running with no additional effects on food intake.

These findings provide the first evidence that initiating THC treatment after significant weight loss in the ABA paradigm can halt the progression of weight loss through a selective decrease in energy expenditure.

Importantly, treatment was initiated after (rather than before) the emergence of ABA-induced weight loss, thus enhancing the translational relevance of the model and our findings.

Together, these findings suggest that pharmacological activation of the ECS may represent a promising treatment for individuals with AN.”

https://pubmed.ncbi.nlm.nih.gov/42448208

“THC treatment, initiated after ∼12% body weight loss in rats with activity-based anorexia (ABA), reduced further weight loss and prolonged survival.”

“Findings support endocannabinoid-targeted therapies for anorexia nervosa.”

https://www.sciencedirect.com/science/article/abs/pii/S0031938426002313?via%3Dihub


Edible Oil-Based Extraction of Cannabis sativa L. Roots: Effect of Solvent and Temperature on Friedelin Yield and Antioxidant Activity

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“The roots of Cannabis sativa L., historically overlooked, are gaining attention as a potential source of bioactive compounds with antioxidant, antimicrobial, and anti-inflammatory properties.

While previous studies have focused on extractions using ethanol, water, or supercritical CO2, the feasibility of edible oil-based extraction remains largely unexplored.

This study evaluated the extraction of root compounds using hemp seed oil, MCT coconut oil, and grape seed oil at six temperatures (50-90 °C).

Extracts were analyzed by GC-MS for compound identification and quantification, and antioxidant activity was assessed using the DPPH assay, ABTS test and β-carotene bleaching method, with results statistically evaluated by ANOVA. Friedelin was successfully extracted with all oils, with grape seed oil yielding the highest concentration (0.810 mg/g dry roots), achieving recoveries higher than those previously reported for ethanol-based extractions.

All extracts demonstrated positive antioxidant activity, with grape seed oil, both alone and combined with extracts, showing higher values across the three methods. ANOVA revealed a significant effect of solvent type on both Friedelin concentration and antioxidant capacity.

These results demonstrate that edible oils are effective solvents for extracting bioactive compounds from C. sativa roots, supporting their potential application in cosmetic or medicinal formulations.”

https://pubmed.ncbi.nlm.nih.gov/42123839

“In conclusion, this research validates the feasibility of extracting bioactive compounds from cannabis roots using accessible edible oils, achieving Friedelin recoveries higher than those previously reported for alcoholic extractions. These findings provide an important foundation for the development of Cannabis sativa L. root-based products for cosmetic or medicinal applications.”

https://www.mdpi.com/1420-3049/31/9/1473


Cannabis sativa: A Source of Antiparasitic Compounds?

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“Cannabis sativa (hemp, marijuana, ganja) is a plant with industrial, medicinal, and recreational uses that synthesizes phytocannabinoids, a group of compounds from which tetrahydrocannabinol (THC) and cannabidiol (CBD) outstand by their known high and low psychoactive properties.

These and other cannabinoids (endocannabinoids and synthetic derivatives with modulating effects over cannabinoid receptors CB1/2) have been tested in vitro using cultured parasites and in vivo in rodent models of protozoosis affecting the central nervous system as are amoebic encephalopathy, cerebral malaria, brain toxoplasmosis as well as Chagas disease and Leishmaniasis. Helminthiasis mainly includes Nippotrongyloidosis and Schistosomiasis and even their effects on ticks as Boophilus have been reported.

The parasiticidal effect of C. sativa extracts and cannabinoids is consistently found although some points of concern arise from animal models because CB1 or CB2 inactivation/inhibition led to distinct outcomes –beneficial or deleteriousin parasite load and host survival, depending on the organism studied. Possible parasitic targets of cannabinoids include arginase, acetylcholinestherase and haemozoin, a product of hemoglobin digestion.

Collectively, these data highlight that the potential use of cannabinoids against parasitic infections should consider the effects of these compounds on their known targets at the endocannabinoid system (CB1/2) and the likely target(s) in parasites.”

“Plant-derived compounds have multiple beneficial activities for human health, including new candidates for the treatment of parasitic diseases. Among these are macrocyclic lactones terpenes and polyphenols. Unlike most plant species, C. sativa (hemp, marijuana or ganja) is a rich source of both products of industrial interest and phytomedicinal compounds as well”

“At the light of experimental evidence, the potential application of cannabinoids in parasitosis is generally promising on the basis of their parasiticidal in vitro activities”

https://biomedres.us/fulltexts/BJSTR.MS.ID.007960.php


Cannabinoids from C. sativa L.: Systematic Review on Potential Pharmacological Effects against Infectious Diseases Downstream and Multidrug-Resistant Pathogens

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“Cannabis sativa L. has garnered attention as a potential source for new antimicrobial agents, particularly due to the increased prevalence of microbial resistance to conventional antimicrobials and the emergence of multidrug-resistant pathogens.

This review, conducted according to the PRISMA 2020 statement, systematically analyzed the antimicrobial properties of C. sativa extracts and cannabinoids against various bacteria, fungi, viruses, and parasites. Data were collected from the scientific literature (102 papers) and clinical trials (5 studies) from 2014 to June 2024.

Findings revealed that cannabinoids, especially CBD, demonstrate significant antimicrobial activity against Gram-positive bacteria like MRSA, Gram-negative bacteria such as Pseudomonas aeruginosa, various Candida species, SARS-CoV-2, and HIV. Additionally, CBD showed efficacy against parasitic infections like Echinococcus granulosus and Leishmania species.

These results suggest that cannabinoids may represent a new class of antimicrobial agents with unique and diverse mechanisms of action, potentially effective in broad-spectrum therapies.

This study highlights the urgent need for further research and standardized clinical trials to validate these findings and to develop cannabinoid-based treatments.

The antimicrobial properties of C. sativa align with WHO priorities and support global health initiatives, offering promising avenues for addressing antimicrobial resistance and improving public health outcomes.”

“Cannabis sativa L., part of the natural products arsenal, has been a rich source for identifying new therapeutic agents. In recent years, there has been a growing interest in using C. sativa and understanding how its bioactive compounds—phytocannabinoids—support the prevention and treatment of various diseases and conditions. This interest is particularly relevant given the growing prevalence of microbial resistance to conventional antibiotics and the emergence of multidrug-resistant (MDR) pathogens.”

“Cannabis extracts and cannabinoids have demonstrated the capacity to inhibit the growth of certain bacterial strains at concentrations comparable to traditional antimicrobials. These findings represent a significant advancement in the battle against antimicrobial resistance, offering a perspective for future treatments.”

“The ability of Cannabis to combat antimicrobial-resistant infections, potentially in combination with traditional antimicrobials, could substantially contribute to global health by providing novel treatment avenues and reducing the burden of infectious diseases worldwide.”

https://www.mdpi.com/2673-9879/4/3/33

In vivo and in silico wound healing potential of Cannabis Sativa seed oil through inflammation mediators

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“Background: This study investigates the wound healing potential of Cannabis Sativa seed oil (CSSO), derived from the industrial hemp variety ‘NARLI’. The rich essential fatty acid profile of CSSO presents promising therapeutic opportunities; however, its specific in vivo efficacy and targeted molecular mechanisms in wound management remain underexplored. This study aimed to evaluate the in vivo tissue regeneration dynamics and the in silico anti-inflammatory mechanisms of CSSO derived from the ‘NARLI’ hemp variety in an excision wound model.

Methods: Using an excision wound model, 42 rats were divided into two groups: control (untreated) and CSSO-treated. Wound healing was assessed through clinical wound area measurement, histopathological evaluation, immunohistochemistry (IHC), and molecular docking analyses. Wound area measurements were taken on days 7, 14, and 21.

Results: On day 21, CSSO-treated animals showed a significantly higher wound closure rate (93%) compared to the control group (87.55%) (p = 0.005). Histopathological analysis revealed enhanced neovascularization, increased collagen deposition (p = 0.008), reduced inflammatory cell infiltration (p = 0.020), and increased epithelial proliferation in the CSSO group. Immunohistochemistry findings showed a marked decrease in proinflammatory cytokines TNF-α and IL-1β (p = 0.023) and TGF-β (p = 0.030), and a notable upregulation of angiogenesis and proliferation markers VEGF (p = 0.031) and Ki-67 (p = 0.001). Molecular docking analyses revealed that CSSO-derived fatty acids showed binding affinities (-5.3 to -7.5 kcal/mol) with anti-inflammatory-related proteins (COX-2 and NLRP3) and (-3.1 to -6.1 kcal/mol) binding affinities with wound healing-related proteins (SIRT1 and GSK3β), suggesting a possible mechanistic basis underlying the wound healing potential of CSSO.

Conclusions: Topical application of CSSO was associated with improved wound healing outcomes in rats, including enhanced wound closure and favourable histopathological and immunohistochemical changes. Further studies are needed to confirm these findings and clarify the mechanisms involved.”

https://pubmed.ncbi.nlm.nih.gov/42426779

https://link.springer.com/article/10.1186/s12906-026-05462-8

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

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“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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“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 (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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“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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“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