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Stability of Cannabinoids in Cannabis: Plant Material, Extracts, Oil Formulations, and Isolates (CBD and Δ9-THC) Under Different Storage Conditions

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“Background: The chemical stability of cannabinoids in Cannabis sativa plant material and formulated products is a critical factor for quality control, therapeutic efficacy, and regulatory compliance. Cannabinoids such as THC are prone to degradation over time, which is heavily influenced by storage conditions and the product matrix. Despite its importance, comprehensive long-term stability data comparing different plant chemovars (high THC, high cannabidiol [CBD], and intermediate) alongside processed products like extracts and isolates remains limited. This study aims to evaluate the stability of cannabinoids in plant material, extracts, oil formulations, and isolates (CBD and Δ9-THC) under distinct environmental temperatures to optimize storage guidelines.

Methods: Cannabis plant material representing three distinct chemovars-high THC, high CBD, and intermediate (balanced THC/CBD), extracts, pure isolates (THC and CBD) and CBD extract as oil formulation were subjected to extended stability testing over a prolonged period under three controlled temperature environments: room temperature, refrigeration, and freezing. Quantitative analysis of cannabinoid content was performed at regular intervals using gas chromatography (GC/FID) to track degradation and potency over time.

Results: The stability profiles varied depending on the cannabinoid profile, temperature, and matrix type. For the majority of cannabis-derived products, exposure to room temperature accelerated the degradation of THC into cannabinol (CBN), whereas storage at -20°C preserved cannabinoid integrity over the extended timeline. Notably, a distinct divergence was observed between the compounds: CBD-only products demonstrated robust long-term stability even when maintained at room temperature. Conversely, THC-rich matrices were highly susceptible to ambient degradation but exhibited the highest stability when formulated as ethanolic solutions and stored in the freezer (-20°C).

Conclusion: To maximize cannabinoid shelf-life and prevent degradation, storage temperatures must match product composition. While CBD-dominant products can tolerate room-temperature storage, THC-rich products require cold chain management, ideally stored in a freezer at -20°C for optimal long-term potency.”

https://pubmed.ncbi.nlm.nih.gov/42576671

https://journals.sagepub.com/doi/10.1177/25785125261478275

Priming Canine Adipose Tissue-Derived Mesenchymal Stem Cells with CBD-Rich Cannabis Extract Modulates Neurotrophic Factors Expression Profile

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“The endocannabinoid system regulates key biological functions such as neuroprotection, pain modulation, inflammation, and immunomodulation.

Cannabis-based therapies have gained attention due to the therapeutic potential of their bioactive compounds, particularly phytocannabinoids like cannabidiol (CBD), which exhibit anti-inflammatory, neuroprotective, and immunomodulatory properties.

Mesenchymal stem cells (MSCs) are widely studied for their regenerative and immunomodulatory potential.

This study evaluated the effects of priming canine adipose tissue-derived MSCs (cAT-MSCs) with a CBD-rich cannabis extract on cell morphology, viability, neurotrophic factor gene expression, and cytokine gene and protein expression.

cAT-MSCs (n = 5) were primed for 24 h and divided into three groups: Control (C, unprimed), D1 (2.25 µM CBD), and D2 (225 nM CBD). No morphological or viability changes were observed. Gene expression analysis showed that groups D1 and D2 exhibited increased HGF expression. D1 also showed increased IDO and decreased BDNF expression. In contrast, no significant changes were observed in GDNF, IL-10, TNF-α, IFN-γ, or PTGES2. Regarding the cytokine profile, GM-CSF, IL-2, and IL-10 were undetectable. Notably, IL-8 and MCP-1 levels were significantly reduced in D1 compared to the control.

These findings suggest that CBD priming modulates key regenerative and inflammatory mediators in cAT-MSCs, supporting its potential application in enhancing the efficacy of cell-based therapies.”

https://pubmed.ncbi.nlm.nih.gov/41150065

“Mesenchymal stem cells (MSCs) are used in veterinary medicine for their regenerative, immunomodulatory, and anti-inflammatory properties. Compounds from cannabis, especially cannabidiol (CBD), have shown promising anti-inflammatory and healing effects.

This study evaluated whether a CBD-rich cannabis extract modulates important regenerative and inflammatory factors in MSCs derived from canine adipose tissue. After priming canine adipose tissue-derived MSCs for 24 h, we found no changes in their morphology or viability. However, the priming with CBD-rich cannabis extract has increased the activity of certain genes linked to tissue repair and reduced the levels of inflammatory cytokines.

These results suggest that CBD can influence key factors that help stem cells repair tissue and control inflammation, potentially improving their use in future veterinary therapies.”

https://www.mdpi.com/2306-7381/12/10/926

Delta-9-Tetrahydrocannabinol (∆9-THC) Induce Neurogenesis and Improve Cognitive Performances of Male Sprague Dawley Rats

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“Neurogenesis is influenced by various external factors such as enriched environments. Some researchers had postulated that neurogenesis has contributed to the hippocampal learning and memory.

This project was designed to observe the effect of Delta-9-tetrahydrocannabinol (∆9-THC) in cognitive performance that influenced by the neurogenesis.

Different doses of ∆9-THC were used for observing the neurogenesis mechanism occurs in the hippocampus of rats. The brains were stained with antibodies, namely BrdU, glial fibrillary acidic protein (GFAP), nestin, doublecortin (DCX) and class III β-tubulin (TuJ-1). The cognitive test was used novel-object discrimination test (NOD) while the proteins involved, DCX and brain-derived neurotrophic factor (BDNF), were measured.

Throughout this study, ∆9-THC enhanced the markers involved in all stages of neurogenesis mechanism. Simultaneously, the cognitive behaviour of rat also showed improvement in learning and memory functions observed in behavioural test and molecular perspective.

Administration of ∆9-THC was observed to enhance the neurogenesis in the brain, especially in hippocampus thus improved the cognitive function of rats.”

https://pubmed.ncbi.nlm.nih.gov/28933048

“The treatment of 1.5 mg/kg of ∆9-THC has increase all the markers for neurogenesis and cognition function while improve the cognitive performance.”

https://link.springer.com/article/10.1007/s12640-017-9806-x

“Neurogenesis is the scientific term for the birth and growth of new brain cells.”


Cannabis sativa chemotypes modulate TLR-associated innate immune gene expression and reduce BoAHV-1 replication in bovine cells

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“Cannabis sativa L. produces a wide range of bioactive metabolites, including phytocannabinoids such as tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabigerol (CBG), which exhibit antiviral activity and modulate innate immune responses through Toll-like receptors (TLRs), particularly TLR4 and TLR7. The cross-regulation between cannabinoids and TLRs can influence the production of cytokines and antimicrobial peptides.

Given their key role in orchestrating innate immunity, particularly inflammatory responses and antiviral activity, understanding these processes in bovine immune cells is essential.

This study evaluated the immunomodulatory and antiviral effects of extracts from C. sativa chemotypes – THC-dominant (I), intermediate THC:CBD (II), CBD-dominant (III) and CBG-dominant (IV) – in bovine cells.

In peripheral blood mononuclear cells, chemotype I induced an enhanced inflammatory response, increasing TLR4 and BMAP28 transcription and pro-inflammatory cytokine expression at both transcriptional and protein levels. Similarly, chemotype IV promoted a pro-inflammatory profile characterised by increased TLR4, BMAP28 and IFNβ expression, as well as elevated TNFα protein levels.

In contrast, chemotypes II and III elicited anti-inflammatory effects. Chemotype III decreased TLR4, TLR7, BMAP28, TNFα and IFNβ transcription, although IFNγ protein levels increased. Chemotype II produced a comparable, although less pronounced, anti-inflammatory pattern, reducing TLR4, TLR7, TNFα and IFNβ while increasing BMAP28. Additionally, chemotypes II, III, and IV exhibited antiviral activity in BoAHV-1-infected MDBK cells, significantly reducing viral titres at 48 h post-infection.

Overall, these findings demonstrate that C. sativa chemotypes differentially modulate bovine innate immune gene expression and may also exert antiviral effects, highlighting their potential as dual immunomodulatory and antiviral agents in bovine infectious contexts.”

https://pubmed.ncbi.nlm.nih.gov/42561569

“Cannabis sativa L. (Cannabaceae) produces diverse chemically active compounds, with cannabinoids being the most studied class due to their biological and therapeutic potential.”

https://www.sciencedirect.com/science/article/abs/pii/S0161589026001768?via%3Dihub


Real-world quality of life and sleep outcomes in patients treated with THC- and CBD-rich Cannabis oil: a cross-sectional study

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“The endocannabinoid system plays an important role in the modulation of pain, mood, sleep, and subjective wellbeing. Despite the growing clinical use of medicinal Cannabis, real-world data simultaneously evaluating quality of life and sleep-related outcomes in heterogeneous clinical populations remain limited.

This study aimed to assess quality of life and sleep satisfaction in patients using medical Cannabis oil under supervised clinical follow-up. This cross-sectional observational study included patients treated with full-spectrum medical Cannabis oil rich in tetrahydrocannabinol (THC) and cannabidiol (CBD) in a real-world clinical setting.

Quality of life was assessed using the World Health Organization Quality of Life-BREF (WHOQOL-BREF), and sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). Sociodemographic, clinical, and treatment-related data were collected via an electronic questionnaire. Nonparametric analyses, Spearman correlation, and ordinal logistic regression models were performed. Seventy-one participants were included, predominantly female, with diverse clinical conditions.

Participants reported generally favorable perceptions regarding quality of life and sleep satisfaction, with median scores concentrated in the higher response categories. Positive correlations were observed between the psychological domains of quality of life and sleep satisfaction.

Higher Cannabis oil concentrations and longer treatment duration were associated with higher odds of better outcomes.

In a real-world clinical context, supervised use of full-spectrum medical Cannabis oil was associated with favorable patient-reported perceptions of quality of life and sleep, consistent with perceived effectiveness.

These findings highlight the need for longitudinal studies with pre-treatment baseline assessment.”

https://pubmed.ncbi.nlm.nih.gov/42558508

“Cannabis sativa L. [Cannabaceae] has a documented history of medicinal use spanning thousands of years across diverse cultural and geographic contexts, with traditional applications encompassing pain relief, mood modulation, sleep induction, and the management of inflammatory and neurological conditions.”

“The growing integration of Cannabis into contemporary clinical practice reflects both the long-standing ethnopharmacological tradition associated with this species and the expanding body of evidence supporting the pharmacological activity of its principal phytocannabinoid metabolites, tetrahydrocannabinol (THC) and cannabidiol (CBD).”

“In summary, the results suggest that, in supervised clinical practice, patients using full-spectrum THC and CBD rich oil reported favorable perceived quality of life and sleep satisfaction.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1862725/full


Cannabidiol selectively attenuates lipotoxic immunometabolic inflammation in human macrophages

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“The role of saturated fatty acid-induced immunometabolic stress in macrophage dysfunction during metabolic disease remains incompletely understood, particularly the interplay between inflammatory signaling and intracellular lipid handling.

We employed a tightly controlled palmitic acid (PA)-based lipotoxicity model in PMA-differentiated U937-derived human macrophage-like cells to investigate how lipid excess reshapes inflammatory responses and to evaluate the modulatory effects of cannabidiol (CBD).

PA exposure induced a metabolically stressed yet viable macrophage phenotype, characterized by a broad cytokine remodeling profile. This included induction of classical proinflammatory cytokines such as interleukin (IL)-6, together with activation of inflammasome-associated cytokines IL-1β and IL-18 and additional immunoregulatory mediators, while tumor necrosis factor alpha (TNF-α) contributed to the overall inflammatory profile in a multivariate analysis. These changes were accompanied by a significant, time-dependent storage of intracellular triglycerides (TG) consistent with lipid overload and altered lipid handling.

CBD co-treatment did not compromise cell viability but selectively attenuated PA-induced inflammatory response in a cytokine-dependent manner, with the most significant reduction observed at higher concentrations. In parallel, CBD significantly reduced intracellular TG accumulation under lipotoxic conditions.

Collectively, these findings define a lipotoxicity-associated macrophage phenotype driven by saturated fatty acids and identify CBD as a context-dependent modulator of immunometabolic inflammation.

This work provides a controlled experimental framework to study lipid-driven inflammatory dysfunction and supports the potential of CBD as a targeted strategy to modulate metabolic inflammation without broadly suppressing immune function.”

https://pubmed.ncbi.nlm.nih.gov/42534637

“Cannabidiol (CBD), a non-psychoactive phytocannabinoid, has emerged as a potential regulator of inflammatory and metabolic processes. Unlike traditional anti-inflammatory drugs, CBD exerts context-dependent immunomodulatory effects across multiple experimental systems, encompassing both immune and metabolic cells.”

“Overall, this work supports CBD as a context-dependent modulator of immunometabolism response in PMA-differentiated U937-derived macrophages and provides a controlled experimental framework for studying lipid-driven inflammatory dysfunction in U937-derived macrophages.”

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1873494/full

Cannabidiol-Dominant Cannabis sativa L. Inflorescence Extract Ameliorates Atopic Dermatitis by Modulating NLRP3 Inflammasome and JAK1/STAT6 Signaling in DNCB-Induced Mice

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“Background/objectives: Atopic dermatitis (AD) is a chronic inflammatory skin disorder requiring sustainable therapeutic alternatives. Cannabis sativa L. is a valuable industrial crop rich in bioactive secondary metabolites; its potential as a standardized functional ingredient for promoting skin health has not yet been fully investigated. This study aimed to evaluate the therapeutic effects of a chemically characterized C. sativa inflorescence ethanol extract (CSE) on AD.

Methods: To evaluate the efficacy of CSE, phytochemical profiling was performed using UPLC, and its underlying molecular mechanisms were investigated in a DNCB-induced mouse model.

Results: UPLC analysis was employed to establish the phytochemical profile, identifying 15 cannabinoids and quantifying 8 major components. CBDA was the most abundant component, with a content of 261.79 mg/g in the extract. In a DNCB-induced mouse model, CSE significantly reduced mast cell infiltration and serum IgE levels while downregulating Th2-associated cytokines. At the molecular level, CSE inhibited the activation of the MAPK, NLRP3 inflammasome, and JAK1/STAT6 signaling pathways. Crucially, CSE treatment substantially increased the expression of skin barrier proteins, such as filaggrin and involucrin, thereby enhancing skin hydration.

Conclusions: These findings suggest CSE as a high-value functional ingredient capable of ameliorating AD by modulating multi-target immune responses. This study provides a robust scientific basis for utilizing standardized C. sativa inflorescence as a potent functional ingredient or a nutraceutical agent for the management of chronic skin inflammatory conditions.”

https://pubmed.ncbi.nlm.nih.gov/42514451

“In conclusion, this study provides a comprehensive scientific basis for the use of CSE by demonstrating its multi-target modulation of inflammatory pathways, specifically the MAPK/NLRP3 and JAK1/STAT6 pathways. These results indicate that CSE is a promising candidate for the management of AD. Despite the recognized limitations, such as the need for comparative studies with isolated compounds, our findings suggest that CSE possesses substantial potential as a valuable nutraceutical and cosmeceutical resource. Ultimately, CSE represents a high-value material with significant prospects for both therapeutic and industrial applications.”

https://www.mdpi.com/2072-6643/18/14/2382

Phytochemistry, bioactivity, and medicinal use of Cannabis sativa roots: a comprehensive review

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“Background: Cannabis sativa is among the earliest domesticated plants and has been widely utilized for nutritional, industrial, and medicinal purposes. While its aerial parts, particularly the leaves and inflorescences, have been extensively studied due to their recreational and therapeutic applications, the roots remain comparatively neglected, despite their long-standing use in traditional medicine for treating wounds, burns, and inflammation.

Aim: This review aims to summarize the current knowledge on the phytochemical composition and biological activities of C. sativa roots, with emphasis on their pharmacological potential. RESULTS: The roots of C. sativa contain a diverse spectrum of secondary metabolites, including phytosterols, alkaloids, terpenes, and phenolic compounds. These bioactive constituents have been reported to exert antioxidant, anti-inflammatory, and antimicrobial activities. In vivo studies further demonstrate nociceptive and antispasmodic effects, with no evidence of cytotoxicity.

Conclusion: C. sativa roots represent an underexplored pharmacognostic resource with significant potential for the discovery of novel bioactive compounds. Their chemical diversity and biological activities provide a strong rationale for renewed scientific attention, supporting future research into this underestimated part of a species of growing medical and economic relevance.”

https://pubmed.ncbi.nlm.nih.gov/42477783

https://link.springer.com/article/10.1186/s42238-026-00470-4

Effects of cannabidiol in comparison to hormonal therapy on estrogen decline-induced memory impairments and endocannabinoid system in rats

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“The aim of this study was to investigate the effects of cannabidiol (CBD) on memory deficits induced by ovariectomy and to directly compare its effects with those of hormone therapy, in order to better understand potential shared mechanisms related to menopause-associated cognitive decline, with a particular focus on the endocannabinoid system.

Three-month-old female Wistar rats were randomly assigned to four experimental groups: SHAM-Veh (Vehicle), OVX-Veh, OVX-E2 (estradiol), and OVX-CBD. Animals underwent either bilateral ovariectomy or sham surgery. Following a three-week recovery period, rats received daily subcutaneous injections of CBD (10 mg/kg), estradiol (10 μg/kg), or vehicle for 21 consecutive days. Behavioral assessments included object recognition and fear-motivated memory tests. Twenty-four hours after the final treatment, animals were euthanized for neurochemical and molecular analyses. Levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were measured using high-performance liquid chromatography. Gene expression of cannabinoid receptors CB1 and CB2, as well as enzymes involved in the synthesis and degradation of endocannabinoids (NAPE-PLD, DAGL-A, FAAH, and MGLL), was evaluated in the hippocampus by RT-qPCR.

The results demonstrated that CBD treatment produced memory improvements in the object recognition task comparable to those observed with estradiol. Ovariectomy-induced impairments in fear-motivated memory were completely reversed by both CBD and estradiol treatments. Additionally, CBD reduced the expression of FAAH and MGLL, resulting in increased hippocampal levels of AEA and 2-AG, effects similar to those observed with hormone therapy. Estradiol also increased NAPE-PLD expression, contributing to elevated AEA levels.

Overall, the findings suggest that CBD exerts a protective effect on memory comparable to standard estrogen therapy, supporting its therapeutic potential for menopause-related cognitive impairments.”

https://pubmed.ncbi.nlm.nih.gov/42476954

https://onlinelibrary.wiley.com/doi/10.1111/jne.70234


Endocannabinoid system modulation in bruxism: a neurobiological hypothesis and translational model of ECS-targeted intervention

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“Bruxism is a multifactorial motor behavior of predominantly central origin, characterized by repetitive masticatory muscle activity and associated with dysregulation of dopaminergic, serotonergic, GABAergic, and glutamatergic pathways involved in motor control, emotional regulation, and stress responsivity.

The endocannabinoid system (ECS) has emerged as a key homeostatic neuromodulator capable of integrating these neurotransmitter systems, thereby influencing pain processing, sleep-wake dynamics, and motor output.

This article develops a neurobiological hypothesis based on a narrative integrative synthesis of clinical, experimental, and translational evidence regarding ECS involvement in the pathophysiology of bruxism.

Findings from randomized clinical trials suggest that topical cannabidiol (CBD) may modulate motor neuron excitability and reduce pain-related outcomes, while case-based and experimental evidence supports the interaction between cannabinoid signaling and neural circuits implicated in motor control and behavioral regulation.

Building on this evidence, we propose a hypothesis-driven translational model in which ECS-mediated neuromodulation may influence central mechanisms underlying bruxism, including motor pattern generation, stress responsivity, and nociceptive processing.

Rather than providing prescriptive therapeutic recommendations, this model is intended as a hypothesis-generating construct that integrates current knowledge on ECS signaling within the broader neurobiology of motor control. Although heterogeneity in study design and outcome measures limits definitive conclusions, the available evidence supports the ECS as a plausible modulatory system in bruxism, with potential implications for future mechanistic and clinical research in centrally mediated motor disorders.”

https://pubmed.ncbi.nlm.nih.gov/42459362

“In summary, the integration of neurobiological knowledge about bruxism with advances in understanding the endocannabinoid system supports the development of a hypothesis-driven translational model in which ECS-mediated neuromodulation may represent a relevant pathway for influencing centrally mediated motor behaviors.”

https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2026.1854001/full