Adolescent cannabidiol treatment produces antidepressant-like effects without compromising long-term cognition in rats

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“Background: Recent preclinical studies have shown sex-dependent antidepressant-like responses of cannabidiol in adolescence, which were dependent on biological sex, early-life stress, and dose. In particular, cannabidiol (10 mg/kg) induced acute and sustained antidepressant-like responses in adolescent male rats, while it lacked efficacy in females. This follow-up study aimed at further characterizing cannabidiol’s effects in adolescence, in an attempt to overcome female unresponsiveness, while also evaluating its long-term safety profile in adulthood.

Methods: Groups of adolescent rats of both sexes were treated (ip) with cannabidiol (10, 30, 60 mg/kg) or vehicle (1 ml/kg) for 7 days. Acute (30 min post-injection) and repeated (24 h post-treatment) antidepressant-like responses were measured in the forced-swim test. Brains were collected to evaluate several neurochemical correlates in the hippocampus (CBR1, CBR2, BDNF, and cell proliferation) after adolescent cannabidiol exposure (acute and repeated). Some rats were left undisturbed until adulthood, when long-term effects on cognition were measured in the Barnes maze (short- and long-term memory) or affective-like responses in the forced-swim test. Data was analyzed with two-way ANOVAs (independent variables: sex and treatment).

Results: While the dose of 10 mg/kg of cannabidiol induced antidepressant-like effects in adolescent rats, higher doses had no effect in adolescent rats of both sexes. No changes were observed in any of the hippocampal neuroplasticity markers evaluated. Adolescent cannabidiol exposure did not induce long-term changes in cognitive performance or affective-like behavior.

Conclusions: Overall, our data suggest that adolescent cannabidiol treatment produces dose-dependent antidepressant-like effects of moderate magnitude without compromising long-term cognition in rats.”

https://pubmed.ncbi.nlm.nih.gov/40522606/

“To conclude, our data suggest that adolescent cannabidiol treatment produces dose-dependent antidepressant-like effects without compromising long-term cognition in rats. In particular, it reinforces prior studies by including more doses of cannabidiol tested during adolescence, while demonstrating efficacy mainly in male rats. Based on the literature, the combination of another antidepressant with cannabidiol might be a good strategy for attempting to induce efficacy in adolescent female rats, and should be further explored. Since no molecular print could be found to parallel the antidepressant-like potential of cannabidiol in adolescence, future studies should explore other avenues while searching for the specific role of sex hormones in the lack of response in females. Finally, and in line with the results that demonstrate that cannabidiol improves cognitive performance, this study adds to this existing literature by providing long-term results on this topic following adolescent cannabidiol exposure in rats of both sexes.”

https://link.springer.com/article/10.1007/s43440-025-00750-5

Patterns, Efficacy, and Cognitive Effects of Medical Cannabis Use in Chronic Musculoskeletal Pain Patients

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“Background: Medical cannabis (MC) is being used with greater frequency in the management of chronic pain. While its efficacy in pain relief is promising, questions about patterns of use and efficacy warrant further investigation. This study aimed to evaluate long-term MC use patterns, perceived efficacy, and its impact on cognition among patients with chronic musculoskeletal noncancer pain.

Methods: This prospective study included patients who were certified for MC between October 2022 and December 2024. Patients who were certified for MC under Pennsylvania state guidelines for a minimum of one year were tracked, yielding 129 patients for analysis. The patients completed an Inventory of Medical Cannabis Use (IMCU) questionnaire assessing usage patterns, dosage knowledge, efficacy, cognitive effects, and tolerance changes. The responses were collected in a password-protected database.

Results: A total of 77.5% of patients reported using MC daily or near daily. Topical formulations were most frequently used (63.6%). Approximately half of the respondents were uncertain of their exact tetrahydrocannabinol/cannabidiol (THC/CBD) dosage, with a median oral dose of 10 mg recorded among those who provided estimates. High levels of perceived efficacy were reported, with over 93% of respondents agreeing or strongly agreeing that MC improved their primary symptoms. Cognitive and motor effects were minimal for most users, with 72.1% reporting no impact. Furthermore, 79.8% of respondents indicated stable usage patterns over the prior three months, and very few reported a need or external suggestion to reduce MC intake.

Conclusions: Long-term MC use is a stable and well-tolerated option for managing chronic musculoskeletal pain, with high patient-reported efficacy and minimal cognitive impact. These findings support its role in pain management while highlighting the need for further research on optimal dosing and long-term safety.”

https://pubmed.ncbi.nlm.nih.gov/40519367/

https://www.cureus.com/articles/365077-patterns-efficacy-and-cognitive-effects-of-medical-cannabis-use-in-chronic-musculoskeletal-pain-patients#!/

New cannabidiol structure-related terpene N-acyl-hydrazones with potent antinociceptive and anti-inflammatory activity

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“Inflammation is the organism’s protective mechanism to restore cellular and tissue homeostasis. Cannabidiol has been reported for its ability to bind to diverse receptors related to or not related to the endocannabinoid system, with good safety being one of the most promising phytocannabinoids for therapeutical purposes. CBD has shown in vitro and in vivo ability to significantly reduce the production of cytokines and other inflammatory mediators, with an unclear mechanism of action.

Herein, we report the design and synthesis of a novel series of eight terpene N-acylaryl hydrazone analogues and their pharmacological evaluation for potential antioxidant, antinociceptive, and anti-inflammatory properties.

Our results led to the identification of compounds 5a (PQM-242), with significant peripheral and central antinociceptive effects, 5b (PQM-243), and 5g (PQM-248) with antinociceptive activities probably related to the ability of modulation of TRPV1 receptors, and 5c (PQM-244) that seems to have the most promising peripheral antinociceptive profile, showing significant effects on both neurogenic and inflammatory phases of formalin-induced licking test, coupled to potential antioxidant activity.

Overall, our experimental data suggest that the new CBD-based architecture is capable of ensuring peripheral and central antinociceptive effects by different modes of action, with no in vivo toxicity and adequate predicted ADME properties.”

https://pubmed.ncbi.nlm.nih.gov/40521634/

“Several compounds showed similar antinociceptive and anti-inflammatory effects to those described for CBD.”

https://www.tandfonline.com/doi/full/10.1080/17568919.2025.2515821

In vitro antibacterial activity of hemp (Cannabis sativa L.) extract seed oil against multidrug resistant bacterial pathogens in small animal veterinary dermatology

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“There is an urgent need for alternative antimicrobial therapies in veterinary small animal dermatology due to the limited therapeutic options available for treatment of infections caused by multidrug-resistant bacteria.

This study aimed to evaluate the potential of hemp (Cannabis sativa L.) seed oil for topical treatment of localized infections of the skin, such as otitis externa.

Antimicrobial activity was determined by broth microdilution using a strain collection of bacterial pathogens associated with skin infections, including Staphylococcus pseudintermedius (n=120), Staphylococcus aureus (n=48), and Pseudomonas aeruginosa (n=26). Checkerboard dilution tests were used to assess the interaction of hemp seed oil with two antimicrobials used for management of otitis externa, gentamicin and enrofloxacin, while in vitro cytotoxicity was evaluated by the cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay on mouse fibroblast cell line L929. Minimum inhibitory concentrations (MICs) in staphylococci (0.025-0.2% v/v) were markedly lower than in P. aeruginosa (>0.4% v/v). Within S. pseudintermedius, methicillin-resistant strains displayed lower susceptibility compared to susceptible strains.

Hemp seed oil showed synergy with gentamicin (Fractional Inhibitory Concentration Index < 0.5), reducing the MIC of gentamicin-resistant S. pseudintermedius strains (≥16µg/ml) below the clinical susceptibility breakpoint (≤4µg/ml). No changes in cell viability were observed at concentrations below 2% v/v.

These findings suggest that hemp seed oil could be an effective and safe alternative or adjuvant to conventional antimicrobials for managing otitis externa and other skin focal infections caused by staphylococci, including methicillin-resistant strains.”

https://pubmed.ncbi.nlm.nih.gov/40513980/

“The findings suggest that hemp seed oil could serve as an effective and safe alternative or adjunct to conventional antimicrobial treatments for localized skin infections, including otitis externa caused by staphylococci, even those resistant to methicillin;”

https://www.sciencedirect.com/science/article/pii/S1090023325000966?via%3Dihub

Nutrients and Bioactive Compounds from Cannabis sativa Seeds: A Review Focused on Omics-Based Investigations

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“Hemp (Cannabis sativa L.) is a versatile crop that can be processed to obtain different products with multiple applications. Its seeds are a well-documented ancient source of proteins, fibers and fats, all of which possess high nutritional value. Additionally, metabolites such as flavones and phenols are present in the seeds, contributing to their antioxidant properties.

Due to hemp seeds’ distinctive nutritional profile, the interest in exploring the potential use in food and nutraceuticals is growing, and they can be considered an interesting and promising alternative resource for human and animal feeding. Omics studies on hemp seeds and their by-products are also being developed, and they contribute to improving our knowledge about the genome, transcriptome, proteome, metabolome/lipidome, and ionome of these sustainable food resources.

This review illustrates the main nutrients and bioactive compounds of hemp seeds and explores the most relevant omics techniques and investigations related to them. It also addresses the various products derived from processing the whole seed, such as oil, dehulled seeds, hulls, flour, cakes, meals, and proteins. Moreover, this work discusses research aimed at elucidating the molecular mechanisms underlying their protein, lipid, fiber, and metabolic profile. The advantages of using omics and multi-omics approaches to highlight the nutritional values of hemp seed by-products are also discussed.

In our opinion, this work represents an excellent starting point for researchers interested in studying hemp seeds as source of nutrients and bioactive compounds from a multi-level molecular perspective.”

https://pubmed.ncbi.nlm.nih.gov/40508032/

“By advancing the understanding and utilization of hemp seeds and their by-products in food, feed, and medical applications, we hope to contribute to positioning hemp as a sustainable and valuable resource for the future.”

https://www.mdpi.com/1422-0067/26/11/5219

Physiological Muscle Function Is Controlled by the Skeletal Endocannabinoid System in Murine Skeletal Muscles

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“The endocannabinoid system (ECS) is known to regulate crucial bodily functions, including healthy muscle activity. However, its precise roles in normal skeletal muscle function and the development of muscle disorders remain unclear. Previously, we developed a tamoxifen-inducible, skeletal muscle-specific CB1 receptor knockdown (skmCB1-KD) mouse model using the Cre/LoxP system.

In this study, we aimed to clarify the mechanisms behind the observed reduction in muscle force generation in these mice. To investigate this, we analyzed calcium dynamics following electrical stimulation-induced muscle fatigue, assessed store-operated calcium entry (SOCE), and performed functional analysis of mitochondrial respiration.

Our findings suggest that the reduced muscle performance observed in vivo likely arises from interconnected alterations in ATP production by mitochondria. Moreover, in skmCB1-KD mice, we detected a significant decrease in a component of the respiratory chain (complex IV) and a slowed dissipation of mitochondrial membrane potential upon the addition of an un-coupler (FCCP).”

https://pubmed.ncbi.nlm.nih.gov/40508098/

“To develop effective therapies for conditions with defective endocannabinoid system (ECS) activity, it is essential to understand the skeletal ECS’s function in health and disease. Here, we present a detailed functional and molecular characterization of a transgenic mouse model with skeletal muscle-specific Cnr1 genetic ablation.

Our in vivo results demonstrate that CB1R knockdown impairs motor coordination and grip strength in mice. Furthermore, at the cellular level, we observed modestly altered calcium homeostasis and significantly decreased mitochondrial function (decreased complex IV activity). Therefore, we propose that the ECS (particularly CB1R) plays a key role in physiological muscle force generation and in maintaining cellular and mitochondrial homeostasis and function.”

https://www.mdpi.com/1422-0067/26/11/5291

Cannabidiol as Modulator of Spontaneous Adipogenesis in Human Adipose-Derived Stem Cells

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“Mesenchymal stem cells isolated from human adipose tissue (hASCs) are a promising tool for tissue repair due to their ability to differentiate into specific cell lineages. The possibility of modulating the adipogenic differentiation of hASCs is crucial in improving their therapeutic potential.

This study aimed to investigate the effects of cannabidiol (CBD), a phytocannabinoid isolated from Cannabis sativa L., on hASCs. Few studies have evaluated its role in stem cell (SC) properties and their differentiation potential.

hASCs were first treated with different concentrations of CBD (ranging from 0.1 to 10 μM) to assess its effects on viability, demonstrating that this molecule is non-toxic, except at the concentration of 10 μM. Subsequently, the role of CBD in the proliferation, metabolism and adipogenic potential of hASCs was analyzed.

CBD promoted adipogenesis in a dose-dependent manner, even in the absence of differentiation medium. This result was evidenced by the presence of lipid vacuoles, the expression of adipogenic markers, cytoskeletal actin rearrangement and modulation in the expression of osteogenic genes.

Although the results indicated a role of CBD in promoting hASC adipogenesis, further research will be needed to explore the mechanism of action of CBD in SC differentiation and to deepen its utility in SC-based approaches.”

https://pubmed.ncbi.nlm.nih.gov/40509260/

“Therefore, as the field of regenerative medicine continues to evolve, the integration of CBD’s properties into therapeutic strategies could hold significant promise in terms of enhancing tissue repair and recovery, offering novel strategies for optimizing healing outcomes and improving patient well-being.”

https://www.mdpi.com/1420-3049/30/11/2367

Single cell multiomic analysis of the impact of Delta-9-tetrahydrocannabinol on HIV infected CD4 T cells

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“Cannabis use is prevalent among individuals living with HIV in the United States, but the impact of cannabis exposure on the reservoir of latently infected cells that persists during antiretroviral therapy (ART) remains unclear. To address this gap, we analyzed the effect of Δ-9-tetrahydrocannabinol (THC) on primary CD4 T cells that were latently infected with HIV.

We found that THC had no detectable effect on baseline or latency reversing agent (LRA) stimulated HIV expression, or on expression of an activation marker (CD38). However, using an integrated multiomic single-cell analysis of genome-wide chromatin accessibility and gene expression, we observed altered expression of several hundred genes in HIV infected CD4 T cells after THC exposure, including transcriptional downregulation of genes involved in protein translation and antiviral pathways, indicating that THC suppresses innate immune activation in infected cells. Additionally, chromatin accessibility analysis demonstrated upregulated chromatin binding activity for the transcriptional regulator CTCF, and reduced activity for members of the ETS transcription factor family in infected cells after THC exposure.

These findings provide insights into the mechanisms by which cannabis use could influence the persistence of HIV within cellular reservoirs and the molecular phenotype of latently infected cells. Further elucidation of the underlying mechanisms involved in THC-mediated changes to HIV infected cells, will lead to an improved understanding of the impact of cannabis use on the HIV reservoir.

Importance: Cannabis use is common among individuals living with HIV, but the long-term effects of cannabis use on the HIV reservoir are not yet studied completely. We employed advanced single-cell technologies to reveal how cannabis components, specifically THC, influence HIV-infected immune cells and their pattern of gene expression. We found that, while THC doesn’t reactivate virus in latently infected cells, it alters the molecular characteristics of these infected immune cells. These findings are important because they underscore how cannabis could regulate persistent infection in people living with HIV. Understanding these cellular changes in response to THC could be helpful for successful treatment for people living with HIV.”

https://pubmed.ncbi.nlm.nih.gov/40502036/

https://www.biorxiv.org/content/10.1101/2025.06.02.657468v1

“Yes, there is growing evidence that cannabis could play a role in regulating persistent HIV infection. Studies suggest that cannabinoids, particularly THC, can alter the molecular characteristics of HIV-infected immune cells without reactivating the virus. These changes might be beneficial in reducing inflammation and improving treatment outcomes for people living with HIV.”

Cannabidiol reverses microglia activation and loss of parvalbumin interneurons and perineuronal nets in a mouse model of schizophrenia

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“Cannabidiol (CBD) has shown potential for treating schizophrenia (SCZ) by targeting its positive and negative cognitive symptoms. In this study, we investigated if CBD could reverse the memory impairment observed after chronic administration of the NMDA receptor antagonist MK-801.

Chronic treatment with MK-801 (0.5 mg/kg i.p., twice a day, for 14 days) resulted in short- and long-term memory deficits and decreased relative power of γ oscillations in freely moving animals. CBD administration (30 mg/kg i.p. daily for seven days after the MK-801 treatment period) reversed these changes. The cognitive effects of CBD were prevented by blocking 5-HT1A but not CB2 receptors.

At the cellular level, the depletion of parvalbumin-positive neurons and their associated perineuronal nets in the prelimbic medial prefrontal cortex (mPFC) and ventral hippocampus (vHip) induced by MK-801 was reversed by CBD. This neuroprotective effect was mediated by 5-HT1A and CB2 receptors in the vHip but was independent of these receptors in the mPFC. Additionally, CBD reversed MK-801-induced microglial activation in both mPFC and vHip, again through 5-HT1A and CB2 receptors.

These findings suggest that CBD modulates multiple pathways affected in SCZ-like conditions, offering a promising therapeutic avenue for SCZ treatment.”

https://pubmed.ncbi.nlm.nih.gov/40484109/

https://www.sciencedirect.com/science/article/abs/pii/S0006899325003336?via%3Dihub

Activation of CB1R alleviates autism spectrum disorder-like behavior and synaptic impairments

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“We previously found that enhancing the levels of 2-arachidonoylglycerol (2-AG) and anandamide (AEA) could improve autism spectrum disorder (ASD) symptoms. This study investigated the effect of cannabinoid type 1 receptor (CB1R) in ASD with pharmacological, genetic and brain-targeted intervention and the underlying mechanisms.

Results showed that blocking CB1R counteracted the beneficial effects of boosting 2-AG or AEA on ASD-like behaviors in valproic acid (VPA)-exposed mice. Besides, CB1R knockout mice exhibited ASD-like behaviors and synaptic deficits.

In CB1R-specific brain-targeted regulation, activating CB1R ameliorated synaptic dysfunction, including neuronal complexity, spine density, dendritic integrity, synaptic protein expression, and neuronal damage. Moreover, activating CB1R enhanced the expression and current density of Kir4.1, indicating that CB1R may influence synaptic activity by modulating Kir4.1.

Collectively, our findings indicated a critical role for CB1R in the improvement of ASD-like behavior and synaptic dysfunction, which may offer promising avenues for developing effective treatments for ASD.”

https://pubmed.ncbi.nlm.nih.gov/40484367/

“Brain-specific activation of CB1R improves synaptic impairments in ASD model mice.”

https://www.sciencedirect.com/science/article/abs/pii/S0024320525004321?via%3Dihub