Daily Impact of Medical Cannabis on Anxiety and Sleep Quality in Older Adults

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“Objective: Older adults represent the fastest growing demographic of cannabis users, and they endorse cannabis use for a variety of reasons including modulation of chronic pain, mental health symptoms, and sleep concerns. However, current evidence leaves questions of efficacy unanswered among these groups. Goals of the present study were to examine the hypothesis that medical cannabis (MC) use will, at the daily level, predict lower pain, depression, anxiety, and improved sleep.

Method: A final sample of 106 MC users were recruited nationwide (ages 55-74, 66.67% female, 82.86% white). A fully within-subject multilevel structural equation model was conducted with use patterns and symptomology broken into four temporal epochs. MC use, operationalized as subjective intoxication (Epoch 1), averaged across the day was used to predict subsequent pain, anxiety, and depression levels (Epoch 2), which were then used to predict sleep that night (Epoch 3), then subsequent pain, anxiety, and depression the following day (Epoch 4) prior to initiation of MC use.Results: Subjective intoxication predicted lower post-use pain, anxiety, and depression. Subjective intoxication is related to lower anxiety and better sleep the following night.

Conclusions: These findings provide evidence of momentary improvements in pain, anxiety, depression, and indirect benefits for sleep quality. In combination with other findings, the results advance our understanding of the efficacy and limitations of MC among older adults. Findings are limited by MC measurement and sample homogeneity (primarily White, non-Hispanic female). Future research should seek to further measurement of use and corresponding effects and examine expectancy effects in aging clinical populations.”

https://pubmed.ncbi.nlm.nih.gov/40372396/

https://www.tandfonline.com/doi/full/10.1080/00332747.2025.2484827

Therapeutic Effect of Lebanese Cannabis Oil Extract in the Management of Sodium Orthovanadate-Induced Nephrotoxicity in Rats

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“Sodium orthovanadate is a non-selective protein tyrosine phosphatase inhibitor that can cause several types of kidney injury, including glomerulosclerosis, inflammation, and tubular damage.

Cannabis is widely known for its medicinal use, and several studies have demonstrated its anti-diabetic and anti-inflammatory properties.

The current study investigated the therapeutic effect of Lebanese cannabis oil extract (COE) against sodium orthovanadate-induced nephrotoxicity both in vitro and in vivo.

Sprague Dawley male rats were intraperitoneally injected with 10 mg/kg sodium orthovanadate for 10 days followed by 5 mg/kg; 10 mg/kg; or 20 mg/kg intraperitoneal injection of cannabis oil extract, starting on day 4 until day 10. The body weight of the rats was monitored during the study, and clinical parameters, including serum urea, creatinine, and electrolytes, as well as kidney and heart pathology, were measured. Conditionally immortalized cultured rat podocytes were exposed to either sodium orthovanadate or selective phosphatase inhibitors, including DUSPi (DUSP1/6 inhibitor) and SF1670 (PTEN inhibitor), in the presence or absence of cannabis oil extract. MTS and an in vitro scratch assay were used to assess podocyte cell viability and migration, respectively. Western blot analysis was used to evaluate the phosphorylation levels of AKT and p38 MAPK.

Rats injected with sodium orthovanadate displayed a marked reduction in body weight and an increase in serum creatinine and urea in comparison to the control non-treated group. All doses of COE caused a significant decrease in serum urea, with a significant decrease in serum creatinine observed at a dose of 20 mg/kg. Moreover, the COE treatment of rats injected with orthovanadate (20 mg/kg) showed a marked reduction in renal vascular dilatation, scattered foci of acute tubular necrosis, and numerous mitoses in tubular cells compared to the sodium orthovanadate-treated group.

The cell viability assay revealed that COE reversed cytotoxicity induced by sodium orthovanadate and specific phosphatase inhibitors (DUSPi and SF1670) in rat podocytes. The in vitro scratch assay showed that COE partially restored the migratory capacity of podocytes incubated with DUSPi and SF1670. Time-course and dose-dependent experiments showed that COE (1 μg/mL) induced a significant increase in phospho-(S473)-AKT, along with a decrease in phospho (T180 + Y182) P38 levels.

The current results demonstrated that Lebanese cannabis oil possesses important kidney protective effects against sodium orthovanadate-induced renal injury.”

https://pubmed.ncbi.nlm.nih.gov/40362381/

https://www.mdpi.com/1422-0067/26/9/4142

Targeting the Gut-Brain Axis with Plant-Derived Essential Oils: Phytocannabinoids and Beyond

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“Background: The gut-brain axis (GBA) is a complex bidirectional communication system that links the gastrointestinal tract and the central nervous system. Essential oils (EOs) have emerged as promising natural compounds capable of modulating this axis. 

Methods: A comprehensive analysis of the recent literature was conducted, focusing on studies investigating the effects of EOs on the GBA.

Particular attention was given to the endocannabinoid system, the role of cannabis-derived EOs, and other plant-based EOs with potential neuroprotective and gut microbiota-modulating effects. 

Results: Among the EOs analyzed, cannabis essential oil (CEO) gained attention for its interaction with cannabinoid receptors (CBR1 and CBR2), modulating gut motility, immune responses, and neurotransmission. While acute administration of the CEO reduces inflammation and gut permeability, chronic use has been associated with alterations in gut microbiota composition, potentially impairing cognitive function. Other EOs, such as those from rosemary, lavender, eucalyptus, and oregano, demonstrated effects on neurotransmitter modulation, gut microbiota balance, and neuroinflammation, supporting their potential therapeutic applications in GBA-related disorders. 

Conclusions: EOs demonstrate promising potential in modulating the GBA through mechanisms including neurotransmitter regulation, gut microbiota modulation, and anti-inflammatory activity. At the same time, phytocannabinoids offer therapeutic value; their long-term use warrants caution due to potential impacts on microbiota. Future research should aim to identify EO-based interventions that can synergistically restore GBA homeostasis and mitigate neurodegenerative and gastrointestinal disorders.”

https://pubmed.ncbi.nlm.nih.gov/40362887/

https://www.mdpi.com/2072-6643/17/9/1578

Exploring the Lesser-Known Bioactive Natural Products of Plant Species of the Genus Cannabis L.: Alkaloids, Phenolic Compounds, and Their Therapeutic Potential

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“Plant species of the genus Cannabis L. are predominantly recognized for their cannabinoids, which have garnered significant attention due to their bioactive properties. However, Cannabis also produces a diverse array of bioactive compounds with promising pharmacological potential that remain underexplored.

This review focuses primarily on phytochemicals derived from Cannabis sativa L. subspecies, including both its drug-type and fiber-type varieties, which are the most widely cultivated and studied within the genus.

Among these, nitrogen-containing compounds such as spermidine alkaloids exhibit neuroprotective and anti-aging properties, while hydroxycinnamic acids and hydroxycinnamic acid amides, including N-trans-caffeoyltyramine and N-trans-feruloyltyramine, have demonstrated notable antioxidant and anti-inflammatory activities.

Additionally, Cannabis species are a valuable source of unique stilbenes, such as canniprene, and flavonoids, including cannflavin A and B, which demonstrated potent anti-inflammatory and antiproliferative effects.

Despite this rich phytochemical diversity, research on these compounds remains limited, largely due to historical legal restrictions. This literature review consolidates and updates current knowledge on these lesser-studied phytochemicals of Cannabis, detailing their biosynthetic pathways, metabolic precursors, and emerging therapeutic applications.

By expanding the research focus beyond cannabinoids, this work aims to enhance our understanding of Cannabis‘s full pharmacological potential and promote further investigation into its diverse chemical constituents.”

https://pubmed.ncbi.nlm.nih.gov/40364401/

https://www.mdpi.com/2223-7747/14/9/1372

The Impact of Major and Minor Phytocannabinoids on the Maintenance and Function of INS-1 β-Cells Under High-Glucose and High-Lipid Conditions

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“Type 2 diabetes mellites (T2DM) is the most common form of diabetes and affects a significant portion of the population. Obesity-related increases in free fatty acids and glucose in the diet contribute to β-cell dysfunction and loss, ultimately leading to the onset of T2DM.

The endocannabinoid system, which is present throughout the body, plays a vital role in regulating various physiological processes, including those in the pancreas. This system has been implicated in metabolic disorders like obesity and diabetes, as it helps to regulate appetite, food intake, and fat production.

Phytocannabinoids from Cannabis sativa have the potential to influence the endocannabinoid system, offering a promising therapeutic approach for diabetes and its complications.

Using high-glucose-high-lipid (HGHL)-induced INS-1 β-cells, we investigated the protective effects of two major (THC and CBD) and three minor (THCV, CBC, and CBG) phytocannabinoids on high glucose-high lipid (HGHL)-induced apoptosis, cell cycle disruption, and impaired function of beta-cells.

Our results showed that all five phytocannabinoids reduced HGHL-induced apoptosis, likely by decreasing TXNIP protein levels. Additionally, THC and all three minor phytocannabinoids provided protective effects against functional impairments caused by HGHL exposure.”

https://pubmed.ncbi.nlm.nih.gov/40363798/

“Our findings demonstrate that all five phytocannabinoids tested effectively mitigate high-glucose–high-lipid (HGHL)-induced apoptosis in INS-1 β-cells, primarily through their mitigatory effects on thioredoxin-interacting protein (TXNIP). Among the tested compounds, THC exhibited the most pronounced impact on reducing TXNIP levels and apoptotic biomarkers, suggesting that THC may be the most promising candidate for counteracting oxidative stress and apoptosis in HGHL-induced β-cells.”

https://www.mdpi.com/1420-3049/30/9/1991

In Vitro Immunomodulatory Effects of Equine Adipose Tissue-Derived Mesenchymal Stem Cells Primed with a Cannabidiol-Rich Extract

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“Cell-based therapy using mesenchymal stem cells (MSCs) shows promise for treating several diseases due to their anti-inflammatory and immunomodulatory properties. To enhance the therapeutic potential of MSCs, in vitro priming strategies have been explored.

Cannabidiol (CBD), a non-psychoactive compound derived from cannabis, may influence MSC proliferation, differentiation, and immunomodulatory properties. This study evaluates the immunomodulatory potential of equine adipose tissue-derived MSCs (EqAT-MSCs) primed with a CBD-rich cannabis extract.

EqAT-MSCs (P3) were primed with CBD concentrations of 5 µM and 7 µM for 24 h. Morphological analysis, MTT assay, β-galactosidase activity, apoptosis assays, and gene expression of interleukins IL-1β, IL-6, IL-10, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) were conducted. Additionally, cannabinoid receptor 1 (CB1) and 2 (CB2) expression were evaluated in naïve EqAT-MSCs (P2-P5). The naïve EqAT-MSCs expressed CB1 and CB2 receptors. Priming with 5 µM significantly increased the expression of IL-10, TNF-α, and IFN-γ, while 7 µM decreased IL-1β and IL-6 expression. No significant changes were observed in other cytokines, MTT, β-galactosidase activity, or apoptosis.

These findings demonstrate that naïve EqAT-MSCs express CB1 and CB2 receptors and priming with the extract modulates the expression of pro- and anti-inflammatory cytokines, highlighting its potential immunomodulatory role in EqAT-MSC-based therapies.”

https://pubmed.ncbi.nlm.nih.gov/40362445/

https://www.mdpi.com/1422-0067/26/9/4208

Adult Neurogenesis Is Regulated by the Endocannabinoid and Kisspeptin Systems

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“Neurogenesis is considered the most robust form of plasticity in the adult brain. To better decipher this process, we evaluated the potential crosstalk of Kisspeptin and Endocannabinoid Systems (KPS and ECS, respectively) on hippocampal neurogenesis.

Male adolescent rats were exposed to kisspeptin-10 (KP10) and the endocannabinoid anandamide (AEA) administered alone or in combination with the type 1 cannabinoid receptor (CB1R) antagonist SR141716A. The expression of Kiss1 and Kisspeptin receptor (Kiss1R) has been characterized for the first time in rat hippocampus together with the expression of the CB1R and the Transient Receptor Potential Vanilloid 1 ion channel receptor (TRPV1).

Results show that both systems inhibit neurogenesis by reducing the extracellular signal-regulated kinase (ERK) signaling. Despite little differences in the expression of Kiss1R and CB1R, TRPV1 is enhanced by both KP10 and AEA treatments, suggesting TRPV1 as a common thread. KP10 administration reduces CB1R expression in the dentate gyrus, while AEA does not. KPS, unlike ECS, promotes the expression of estrogen receptor α (ER-α) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), also upregulating sirtuin 1 (SIRT1), brain-derived-neurotrophic factor (BDNF), and c-Jun.

These findings suggest that the interaction between ECS and KPS could be involved in the fine-tuning of neurogenesis, highlighting a novel role for KPS.”

https://pubmed.ncbi.nlm.nih.gov/40362219/

https://www.mdpi.com/1422-0067/26/9/3977

Cannabichromene, a key non-psychotropic phytocannabinoid in treatment of major depressive disorder: in silico and in vivo explorations

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“Cannabichromene, a non-psychotropic cannabinoid with antioxidant and neuroprotective properties, is hypothesized to possess antidepressant potential.

This study aimed to evaluate cannabichromene’s depression-alleviating effects in mice exposed to chronic unpredictable mild stress and unstressed mice using a combination of in silico and in vivo approaches.

Initially, gene targets associated with major depressive disorder were identified through GeneCards, while cannabichromene’s target genes were predicted using SwissTargetPrediction. Overlapping targets were visualized using Venny software, and protein-protein interaction networks were constructed with the STRING database.

The cannabinoid receptor two genes, encoding the cannabinoid 2 receptor, emerged as a key shared target. Molecular docking studies revealed that cannabichromene exhibited a strong binding affinity to cannabinoid 2 receptors (docking score: – 9.4) compared to cannabidiol (CBD) (- 8.8) and Δ9-tetrahydrocannabinol (- 9.1). For in vivo analysis, male Swiss albino mice were subjected to chronic unpredictable mild stress for 3 weeks to induce depression-like behavior. Cannabichromene (10 and 20 mg/kg) and imipramine (15 mg/kg) were administered for 21 days.

Cannabichromene at 20 mg/kg significantly reduced immobility in stressed mice, like imipramine, without affecting locomotor activity. Additionally, both cannabichromene and imipramine reduced elevated plasma nitrite and corticosterone levels and inhibited monoamine oxidase-A activity in the brain. Cannabichromene also reversed stress-induced catalase suppression.

In conclusion, cannabichromene revealed a relatively substantial antidepressant character with chronic unpredictable mild stress model of depression in Swiss albino male mice, likely through interaction with cannabinoid 2 receptors encoded by the cannabinoid 2 gene, as ratified via in silico modeling and in vivo findings. This highlights cannabichromene’s potential as a novel therapeutic agent for depression after further in vitro and clinical assessments in other models.”

https://pubmed.ncbi.nlm.nih.gov/40358684/

https://link.springer.com/article/10.1007/s00210-025-04236-2

Cannabidiol Pretreatment Reduces Status Epilepticus and Glutamate Uptake Induced by Kainic Acid in Adult Zebrafish

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“Background: Epilepsy is a neurological chronic disorder that affects about 70 million people worldwide. Status epilepticus (SE) are neural disturbances that cause intense glutamatergic excitatory discharges that modulate changes in normal brain physiological activity. Cannabidiol (CBD) is the main nonpsychomimetic compound present in Cannabis sativa and exhibits a wide spectrum of neuroprotective properties. The use of zebrafish (Danio rerio) is regarded as an important alternative animal model for studies on seizures, as it has neuronal mechanisms similar to humans. 

Objective: This study aims to evaluate the effects of CBD on SE induced by kainic acid (KA) in zebrafish. 

Methods: Animals received CBD (5, 10, or 40 mg·L-1 tank water) for 24 h followed by KA administration (5 mg/kg intraperitoneally). The convulsive pattern of alterations was then assessed. After 12 h, cerebral glutamate transport and oxidative stress were also verified. 

Results: CBD at 5 and 40 mg·L-1 induced a significant decrease in the seizure intensity (26.1% and 29.9%) and an increase in the latency to reach SE (from 10.71 min to 17.5 and 25 min), respectively. In addition, CBD administration (40 mg·L-1) attenuated the decrease in cerebral glutamate transport following 12 h KA-induced seizure. The KA-induced seizure was also able to alter the oxidative stress parameters 2′,7′-dichlorofluorescin, and catalase activity. However, CBD (40 mg·L-1) did not influence these markers.

The present study indicates that CBD promotes a neuroprotective response against the epileptic profile in zebrafish. These findings contribute to the understanding of the influence of CBD on the modulation of excitatory/inhibitory disruption on zebrafish seizure.”

https://pubmed.ncbi.nlm.nih.gov/40354278/

https://www.liebertpub.com/doi/10.1089/can.2024.0189

Microbial Biosynthesis of Rare Cannabinoids

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“∆9-tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD) are the most abundant natural cannabinoids isolated from the different cultivars of the Cannabis plant. Other natural ∆9-THC analogs, especially those with different alkyl chain substitutions, display different and potent bioactivity. However, these rare cannabinoids are typically isolated at minuscule amounts and are difficult to synthesize. Targeted microbial biosynthesis can therefore be an attractive route to access such molecules.

Here, we report the development of a Saccharomyces cerevisiae host to biosynthesize two rare cannabinoids from simple sugars. The yeast host is engineered to accumulate excess geranyl pyrophosphate (GPP), to overexpress a fungal pathway to 2,4-dihydroxy-6-alkyl-benzoic acids, as well as the downstream UbiA-prenyltransferase and THCA synthase. Two rare cannabinoid acids, the C1-substituted ∆9-tetrahydrocannabiorcolic acid (∆9-THCCA, ∼16 mg/L) and the C7-substituted ∆9-tetrahydrocannabiphorolic acid (∆9-THCPA, ∼5 mg/L) were obtained from this host; the latter was thermally decarboxylated to give ∆9-tetrahydrocannabiphorol (∆9-THCP).

Given the diversity of fungal biosynthetic gene clusters (BGCs) that can produce resorcylic acids, this microbial platform offers potential to produce other rare and new-to-nature cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/40359163/

https://academic.oup.com/jimb/advance-article/doi/10.1093/jimb/kuaf013/8129704?login=false