Author Archives: David

∆9-Tetrahydrocannabinol Increases Growth Factor Release by Cultured Adipose Stem Cells and Adipose Tissue in vivo

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“Background: Because of its biocompatibility and its soft and dynamic nature, the grafting of adipose tissue is regarded an ideal technique for soft-tissue repair. The adipose stem cells (ASCs) contribute significantly to the regenerative potential of adipose tissue, because they can differentiate into adipocytes and release growth factors for tissue repair and neovascularization to facilitate tissue survival. The present study tested the effect of administering a chronic low dose of ∆9-tetrahydrocannabinol (THC) on these regenerative properties, in vitro and in vivo.

Methods: Human ASCs were exposed to increasing concentrations of THC. Resazurin conversion was applied to investigate the effect on metabolic activity, cell number was assessed by crystal violet staining, tri-linear differentiation was evaluated by specific colorimetric approaches, and the release of growth factors was analyzed by ELISA. Two groups of mice were treated daily either with a low dose of THC (3 mg/kg) or a vehicle solution. After 3 weeks, adipose tissue was obtained from excised fat deposits, homogenized and tested for growth factor contents.

Results: THC decreased ASC proliferation but increased metabolic activity as well as adipogenic and chondrogenic differentiation. A low concentration of THC (1 µM) enhanced the growth factor release by ASCs. The concentration of these cytokines was also increased in adipose tissue of mice treated with THC.

Conlusion: Our results indicate that chronic activation of the endocannabinoid system promoted differentiation and growth factor release of ASCs, which could be of specific value for enhancing the regenerative potential of adipose tissue.”

https://pubmed.ncbi.nlm.nih.gov/39825991/

“Our findings may offer a new approach for improved application of adipose tissue in regenerative medicine.”

https://link.springer.com/article/10.1007/s13770-024-00692-8

Unveiling cellular changes in leukaemia cell lines after cannabidiol treatment through lipidomics

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“The present study was aimed at revealing the metabolic changes that occurred in the cellular lipid pattern of acute and chronic myeloid leukaemia cells following treatment with cannabidiol (CBD).

CBD is a non-psychoactive compound present in Cannabis sativa L., which has shown an antiproliferative action in these type of cancer cells.

CBD treatment reduced cell viability and initiated apoptotic and necrotic processes in both cancer cell lines in a time and dose-dependent manner, showing acute myeloid leukaemia (HL-60) cells greater sensitivity than chronic myeloid leukaemia ones (K-562), without differences in the activation of caspases 3/7. Then, control and treated cells of HL-60 and K-562 cell lines were studied through an untargeted lipidomic approach.

The treatment was carried out with CBD at a concentration of 10 μM for HL-60 cells and 23 µM CBD for K-562 cells for 48 h. After the extraction of the lipid content from cell lysates, the samples were analysed by UHPLC-QTOF-MS/MS both in the positive and the negative ionization modes. The comprehensive characterization of cellular lipids unveiled several classes significantly affected by CBD treatment. Most of the differences correspond to phospholipids, including cardiolipins (CL), phosphatidylcholines (PC) and phosphosphingolipids (SM), and also triacylglycerols (TG), being many TG species increased after CBD treatment in the acute and chronic models, whereas phospholipids were found to be decreased.

The results highlight some important lipid alterations related to CBD treatment, plausibly connected with different metabolic mechanisms involved in the process of cell death by apoptosis in cancer cell lines.”

https://pubmed.ncbi.nlm.nih.gov/39824876/

“Cannabinoids have shown to be effective both as a single agent and in combination with antineoplastic drugs.”

https://www.nature.com/articles/s41598-025-86044-5

[Impact of dronabinol shortage on a population of chronic pain patients: A retrospective observational study]

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“Objective: A supply shortage of dronabinol occurred between December 2023 and February 2024, forcing chronic pain patients to discontinue this treatment. We assessed the impact of this shortage on patients in our hospital.

Method: A retrospective observational study of patients treated with dronabinol was conducted. Collected data included socio-demographic, pharmacological and clinical data. Pain intensity and its interference, the intensity of other pain dimensions (mood, relationship with others, etc.) and quality of sleep were collected before discontinuation (dronabinol dosage balanced, M0) and at the end of discontinuation (dronabinol stopped for several weeks, M3). The patient’s perception of his state of health evolution was collected at the end of the shortage.

Results: Health deterioration was reported by 86% of patients after 3 months of rupture. Pain intensity and its interference with patients’ daily lives increased significantly. Patients’ sleep deteriorated significantly. The number of patients with permanent pain increased 5-fold (n=2 at M0 and n=10 at M3). The number of patients with more than 20 painful attacks per 24hours increased 2-fold (n=2 at M0 and n=4 at M3).

Conclusion: Although data on the efficiency of dronabinol are currently limited, this supply disruption has had negative clinical consequences for our patients. With drug shortages multiplying in recent years, the marketing of new specialties and therefore the availability of therapeutic alternatives could help reduce the clinical impact of a possible new dronabinol shortage in these refractory chronic pain patients.”

https://pubmed.ncbi.nlm.nih.gov/39824703/

https://www.sciencedirect.com/science/article/abs/pii/S0040595724002191?via%3Dihub

“Dronabinol has preferential antileukemic activity in acute lymphoblastic and myeloid leukemia with lymphoid differentiation patterns”

https://pubmed.ncbi.nlm.nih.gov/26775260/

Characterization of phenolic compounds and evaluation of anti-diabetic potential in Cannabis sativa L. seeds: In vivo, in vitro, and in silico studies

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“Moroccan Cannabis sativa L. seeds were investigated for their phenolic profile and antidiabetic potential.

Ultra-high-performance liquid chromatography with diode array detection and electrospray ionization mass spectrometry analysis revealed a rich phenolic composition, including benzoic acid, cannabisin B, genistein, and epicatechin. 

In vitro, the seed extract exhibited potent α-amylase inhibitory activity (half-maximal inhibitory concentration = 25.02 ± 4.03 μg/mL). In vivo studies in diabetic rats demonstrated significant hypoglycemic, hypolipidemic, hepatoprotective, and nephroprotective effects. Molecular docking studies further supported these findings, revealing strong interactions between identified phenolic and the α-amylase enzyme.

These results highlight the potential of C. sativa seeds as a natural source of bioactive compounds for diabetes management.”

https://pubmed.ncbi.nlm.nih.gov/39822379/

“Our findings demonstrate that C. sativa L. seed extract (CSSE) holds significant promise as a novel therapeutic approach for managing diabetes and its associated complications.”

https://www.degruyter.com/document/doi/10.1515/biol-2022-1024/html

Cannabis use in Crohn’s disease: a systematic review and meta-analysis of randomized controlled trials (RCTs)

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“Objective: This meta-analysis aims to systematically evaluate the efficacy and safety of cannabis in the management of Crohn’s disease (CD) by synthesizing evidence from randomized controlled trials (RCTs). By adhering to the 2020 PRISMA guidelines and registering the study protocol with PROSPERO, this research intends to offer robust, evidence-based recommendations for healthcare practitioners on the therapeutic potential and clinical implications of cannabis use in CD management.

Methods: A literature search encompassing PubMed, Google Scholar, and the Cochrane Library was conducted to identify relevant RCTs comparing cannabis to placebo or standard therapy in CD patients. Inclusion criteria focused on outcomes such as remission rates, C-reactive protein (CRP) levels, quality of life (QoL), and adverse events (AEs). Statistical analysis using RevMan 5.3 involved weighted mean differences (MD) and 95% confidence intervals to compare outcomes between the cannabis and control groups.

Results: The meta-analysis revealed significant findings regarding the impact of cannabis on CD management. The cannabis group exhibited significantly higher clinical remission rates at 8 weeks compared to the control group, with low heterogeneity [MD = – 67.98; 95% CI: (- 100.68, – 35.29)]. However, a statistically significant improvement in QoL was observed in the placebo group compared to the cannabis-treated group [MD = 19.62; 95% CI (14.24 to 25.00)]. There was a non-significant lowering in serum CRP levels compared to the placebo group [MD: – 0.51; 95% CI: (- 1.05, 0.02)].

Conclusion: The study concludes that cannabis shows promise as a therapeutic option for CD, demonstrating higher remission rates and potential benefits for disease management. However, it also highlights the need for larger, standardized research studies to solidify conclusions regarding efficacy, safety, and biomarker responses in CD patients.”

https://pubmed.ncbi.nlm.nih.gov/39821383/

https://link.springer.com/article/10.1007/s11845-024-03844-w

Evaluation of the Antibacterial Potential of Ethanolic Cannabis sativa L. (Hang Kra Rog Phu Phan ST1) Extracts Against Human Pathogenic Bacteria

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“Background and Objective: Amid the escalating challenge of antibiotic resistance, the exploration of new sources has become essential, with plants serving as a promising reservoir of bioactive compounds.

Cannabis sativa has attracted significant research interest for its antimicrobial properties and broad applications in medicine, industry and nutrition.

This study aimed to investigate the antibacterial activity of ethanolic extracts from the stems and leaves of the Hang Kra Rog Phu Phan ST1 strain against twelve human pathogenic bacteria.

Materials and Methods: Stems and leaves from the Hang Kra Rog Phu Phan ST1 strain were subjected to ethanol extraction. The primary antibacterial activity of ethanolic extracts from Tanao Si Kan Dang RD1 was assessed using the disc diffusion method, while the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined via the broth microdilution method. The inhibition zone diameter (mm) was analyzed using Duncan’s Multiple Range Test (DMRT) with the SAS software.

Results: The findings revealed that the ethanolic extract from the leaves of Hang Kra Rog Phu Phan ST1 produced the largest inhibition zone diameter of 10.00 mm against <i>Bacillus subtilis</i> TISTR 008. The MIC and MBC of the leaf extract showed the lowest values of 0.09 and 0.19 mg/mL, respectively, recorded against <i>Staphylococcus aureus</i> TISTR 1466.

Conclusion: This is the first report on the antibacterial activity of the ethanolic extracts from the leaves and stems of Hang Kra Rog Phu Phan ST1, which offers potential benefits for developing natural antibiotic drugs to combat infections caused by the tested pathogenic bacteria.”

https://pubmed.ncbi.nlm.nih.gov/39820562/

https://scialert.net/abstract/?doi=pjbs.2025.1.7

Lebanese Cannabis sativa L. extract protects from cisplatin-induced nephrotoxicity in mice by inhibiting podocytes apoptosis

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“Background: Cisplatin is an anti-cancer drug used to treat a plethora of solid tumors. However, it is associated with dose dependent nephrotoxicity limiting its use as anticancer agent.

Objective: The current study aimed to investigate the nephroprotective effect of native Lebanese Cannabis sativa in both in vitro and in vivo mice model of cisplatin-induced nephrotoxicity.

Methods: Podocytes cell viability was assessed using MTS assay with cisplatin (30µM) in presence or absence of Cannabis oil extract (COE) at 0.5, 1 and 2µg/ml for 24h. Acute renal injury was established in adult female C57BL/6 mice with 20mg/kg, i.p. single dose cisplatin. Mice were divided into control group (vehicle), COE group, cisplatin group and cisplatin plus COE (2.5, 5 and 20mg/kg, i.p.). Animal body weight, serum creatinine, blood urea nitrogen (BUN), and proteinuria were measured.

Results: Cell viability assay and western blot analysis revealed that COE prevented apoptosis induced by cisplatin in cultured immortalized rat podocytes. In addition, in vitro scratch assay demonstrated the ability of COE to promote and restore the migratory capacity of podocytes in cisplatin-treated cells. Interestingly, COE treatment improved urinary and serum parameters characterized by a significant decrease in serum creatinine, urea, and proteinuria at various COE doses. Western blot analysis showed that COE inhibited COX-2 protein induction as well as apoptosis marker production (Bax/Bcl2 ratio) in cisplatin-treated mice when compared to mice treated with cisplatin alone.

Conclusion: Collectively, the aforementioned findings indicate that COE could be a promising approach to protect against cisplatin-induced nephrotoxicity.”

https://pubmed.ncbi.nlm.nih.gov/39819647/

“In conclusion, our results corroborated previous findings but on kidney podocytes. We strongly suggest that the Lebanese Cannabis oil extract may be of significant therapeutic benefits against the renal complications of cisplatin. Thus, Lebanese COE produces its renoprotective effects partly through activating antiinflammatory and antiapoptoric mechanisms in podocytes.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00260-4

Emerging trends in cannabis administration for women with chronic pain

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“Cannabis use among women who experience chronic pain is on the rise in the United States. However, little is known about women’s motives and preferences for cannabis administration. The purpose of this study was to characterize cannabis use among women with chronic pain.

This study examined self-reported forms of cannabis administration and preferred source of cannabis, frequency and quantity of use, and self-reported side effects, and type, level, and intensity of chronic pain among adult women in the United States. This study also compared women who use cannabis for chronic pain and those who do not across the level of chronic pain, length of chronic pain, and the number of types of chronic pain experienced.

Participants showed a significant preference (60%) for using recreational cannabis to treat chronic pain but reported that medical cannabis was more effective. For participants who preferred medical cannabis 24.3% reported daily use, as compared to only 7.8% of recreational cannabis users. Smoking was the most common form of administration (62.1%), followed by edibles (25.3%), vaporizing in any form (7.4%), tinctures and concentrates (3.2%), and topicals (2.1%). Participants reported using 1-6 different forms of cannabis administration. Those who preferred smoking were significantly likely to use all other forms of administration. However, those who preferred alternatives to smoking were significantly likely to use all forms of administration except for smoking. Medical cannabis users preferred to obtain cannabis from a dispensary, while recreational users preferred to obtain cannabis from unlicensed sources.

Additionally, participants who used cannabis for chronic pain reported a 74% reduction in past 30-day opioid use.

Future research is needed to investigate the health effects associated with single and combined forms of cannabis administration for women with chronic pain. Results can inform educational and intervention programs, treatment development, content regulation of products, policy formation, women’s health research, and public health guidelines.”

https://pubmed.ncbi.nlm.nih.gov/39816373/

https://onlinelibrary.wiley.com/doi/10.1002/mhs2.88

Cannabidiol abrogates cue-induced anxiety associated with normalization of mitochondria-specific transcripts and linoleic acid in the nucleus accumbens shell

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“Anxiety disorders are one of the top contributors to psychiatric burden worldwide. Recent years have seen a dramatic rise in the potential anxiolytic properties ascribed to cannabidiol (CBD), a non-intoxicating constituent of the Cannabis Sativa plant.

This has led to several clinical trials underway to examine the therapeutic potential of CBD for anxiety disorders. Yet, CBD’s anxiolytic effects are mixed with some studies reporting little to no impact on trait anxiety but significant reductions in pathological anxiety with suggestions that CBD’s effect may relate to triggered or cue-induced behavior.

Here, we studied the effects of CBD on cued and non-cued behaviors and related neurobiological underpinnings. To investigate the effect of CBD on cue-induced anxiety, male rats underwent a fear conditioning protocol (odor associated with shock) followed by assessments of avoidance behavior. CBD (10 mg/kg) was administered 1 h prior to anxiety assessments. To understand molecular mechanisms associated with behavior, we investigated the transcriptome and lipid profile of the nucleus accumbens shell (NAcSh), a structure implicated in cue-mediated behaviors and aversion.

Administration of CBD significantly reduced avoidance behavior, but only in animals repeatedly exposed to a shock-paired cue. CBD did not affect behavior in animals exposed to neutral cue or encoding of the cue behavioral response. RNA sequencing revealed substantial impact of the shock-paired cue in control animals, recruiting mechanisms ranging from cytoskeletal dynamics to mitochondria dysfunction. The shock-paired cue also resulted in elevated linoleic acid in vehicle animals which correlated with anxiety-like behavior. CBD either reversed or normalized these cue-induced molecular phenotypes. CBD also recruited lipid networks which correlated with transcripts involved in synaptic plasticity, signaling, and epigenetic mechanisms.

These results suggest that CBD may specifically alleviate salient, conditioned anxiety and normalize related biological mechanisms in the NAcSh which may guide therapeutic interventions for anxiety disorders.”

https://pubmed.ncbi.nlm.nih.gov/39815058/

https://www.nature.com/articles/s41380-024-02881-2

Cannabinoid-based Pharmacology for the Management of Substance Use Disorders

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“In the last two decades, the endocannabinoid system has emerged as a crucial modulator of motivation and emotional processing. Due to its widespread neuroanatomical distribution and characteristic retrograde signaling nature, cannabinoid type I receptors and their endogenous ligands finely orchestrate somatic and axon terminal activity of dopamine neurons.

Owing to these unique features, this signaling system is a promising pharmacological target to ameliorate dopamine-mediated drug-seeking behaviors while circumventing the adverse side effects of, for instance, dopaminergic antagonists.

Despite considerable preclinical efforts, an agreement on the efficacy of endocannabinoid-targeting compounds for treating drug substance use disorders in humans has not been reached. In the following chapter, we will summarize preclinical and clinical evidence addressing the therapeutic potential of cannabinoids and endocannabinoid-targeting compounds in substance use disorders.

To bridge the gap between animal and clinical research, we capitalize on studies evaluating the impact of endocannabinoid-targeting compounds in relevant settings, such as the management of drug relapse.

Finally, we discuss the therapeutic potential of novel cannabinoid compounds that hold promise for treating substance use disorders.”

https://pubmed.ncbi.nlm.nih.gov/39813001/

https://link.springer.com/chapter/10.1007/7854_2024_551