“Pancreatic cancer is one of the most aggressive and lethal malignancies, with limited therapeutic options and low survival rates, primarily due to late-stage diagnosis and resistance to conventional therapies. Recently, cannabinoids have gained attention for their analgesic and antiemetic properties in cancer symptom management, as well as for their potential anticancer effects. This review explores the mechanisms by which cannabinoids may impact pancreatic cancer progression, focusing on their molecular interactions and therapeutic potential.”
“Preclinical studies revealed that cannabinoids, primarily Δ9- tetrahydrocannabinol (THC) and cannabidiol (CBD), exert anti-tumor effects through mechanisms such as apoptosis induction, cell cycle arrest, inhibition of angiogenesis, immune modulation, and reduction of oxidative stress.”
“THC, the principal psychoactive cannabinoid, and CBD, a non-psychoactive counterpart, have both demonstrated pro-apoptotic properties in pancreatic cancer cells by inducing apoptosis”
“Studies have shown that THC and CBD can induce cell cycle arrest at the G0/G1 phase, limiting cancer cell division and tumor growth.”
“Taken together, these studies suggest that cannabinoids play anticancer roles in pancreatic cancer, and should be further studied for use as therapeutic agents in the treatment of pancreatic cancer.”
“Introduction: Cannabis is widely used and becoming legal in many countries. While some acute ocular effects of cannabis are well-known (e.g., reduced intraocular pressure, vasodilation), little is known about the consequences of long-term cannabis use for ocular health. The aim of this study was to examine the association between persistent cannabis use across adulthood and measures of ocular health in midlife.
Methods: Participants were members of the Dunedin Study (n=1037), a longitudinal cohort followed since birth. Cannabis use has been measured by self-report at every assessment from age 18 to 45. Ocular health data were collected as part of a larger assessment at age 45 (2017-2019). Statistical analysis was performed in 2022.
Results: Cannabis use and ocular health data were obtained from 887 Study members. Generalised estimating equation analysis showed higher cannabis use was associated with poorer visual acuity, wider retinal arterioles and venules, and a thicker inferior hemifield of the ganglion cell-inner plexiform layer (GC-IPL). However, when controlling for tobacco smoking and socioeconomic status (known to be associated with these ocular health domains), the associations with visual acuity, arterioles, and venules were no longer significant. The association with GC-IPL remained significant in this adjusted model.
Conclusions: Persistent cannabis use appears to be neither harmful nor beneficial to the eye at age 45, although the thicker inferior GC-IPL hemifield in users of cannabis suggests biologically plausible neuroprotection. Further assessments as this cohort ages will illuminate the relationship between persistent cannabis use and ocular neuroprotection.”
“Adolescent binge drinking has lasting behavioral consequences by disrupting the endocannabinoid system (ECS) and depleting brain omega-3.
The natural accumulation of omega-3 fatty acids in cell membranes is crucial for maintaining the membrane structure, supporting interactions with the ECS, and restoring synaptic plasticity and cognition impaired by prenatal ethanol (EtOH) exposure. However, it remains unclear whether omega-3 supplementation can mitigate the long-term effects on the ECS, endocannabinoid-dependent synaptic plasticity, and cognition following adolescent binge drinking.
Here, we demonstrated that omega-3 supplementation during EtOH withdrawal increases CB1 receptors in hippocampal presynaptic terminals of male mice, along with the recovery of receptor-stimulated [35S]GTPγS binding to Gαi/o proteins. These changes are associated with long-term potentiation (LTP) at excitatory medial perforant path (MPP) synapses in the dentate gyrus (DG), which depends on anandamide (AEA), transient receptor potential vanilloid 1 (TRPV1), and N-methyl-D-aspartate (NMDA) receptors. Finally, omega-3 intake following binge drinking reduced the time and number of errors required to locate the escape box in the Barnes maze test.
Collectively, these findings suggest that omega-3 supplementation restores Barnes maze performance to levels comparable to those of control mice after adolescent binge drinking. This recovery is likely mediated by modulation of the hippocampal ECS, enhancing endocannabinoid-dependent excitatory synaptic plasticity.”
“Cannabis sativa L. is known for its high-value compounds, like Cannabidiol (CBD) and Cannabidiolic Acid (CBDA). It is widely used in the pharmaceutical and food industries.
Different extraction methods, like Soxhlet and maceration, are commonly employed to obtain its extracts. High temperature and long extraction time can influence the yield and the purity of the extracts, affecting the quality of the final product.
This study focused on optimizing CBD oil extraction from hemp inflorescences and its incorporation into a gluten-free bakery product for functionalization.
Dynamic maceration (DME), assisted by ultrasound and microwave irradiation, was used. Our study explored the impact of varying sonication times (three distinct durations) and microwave powers (three levels, applied for two different irradiation times) on the resulting extracts. HPLC analysis was performed on these extracts. Subsequently, we used hemp flour and hemp oil to bake gluten-free cupcakes, which were fortified with the extracted CBD oil. Rheological characterization was used to investigate the cupcake properties, along with stereoscopic, color and puncture analysis performed on the baked samples.
The most effective extraction parameters identified were 30 s of microwave irradiation at 700 W, yielding 45.2 ± 2.0 g of CBD extract, and 15 min of sonication, which resulted in 53.2 ± 2.5 g. Subsequent rheological characterization indicated that the product exhibited mechanical properties and a temperature profile comparable to a benchmark, evidenced by a height of 4.1 ± 0.2 cm and a hardness of 1.9 ± 0.2 N.
These promising values demonstrate that hemp oil and hemp flour are viable ingredients for traditional cakes and desserts, notably contributing increased nutritional value through the CBD-enriched hemp oil and the beneficial profile of hemp flour.”
“In conclusion, our findings demonstrate that dynamic maceration assisted by ultrasound and microwave irradiation is an efficient method for extracting CBD-rich oil. Furthermore, hemp oil presents a viable alternative to traditional oils and fats for creating functional foods.”
“Objectives: To explore the effects of cannabidiol on endoplasmic reticulum stress and neuronal apoptosis in rats with multiple concussions (MCC).
Methods: SD rats were randomized into sham group, MCC group, 1% tween20 (TW) treatment group, and low-dose (10 mg/kg) and high-dose (40 mg/kg) cannabidiol treatment groups. In all but the sham group, MCC models were established using a metal pendulum percussion device, after which the rats received daily intraperitoneal injections of the corresponding agents for 2 weeks. The expressions of PERK, eIF2α, ATF4, CHOP, TRIB3, p-Akt and pro-caspase-3 in the brain tissue of the rats were detected with qRT-PCR, Western blotting and immunofluorescence staining. The core targets of cannabidiol in treatment of traumatic brain injury (TBI) were identified by network pharmacology analysis, and molecular docking was carried out to simulate the interaction of cannabidiol with the factors related to endoplasmic reticulum stress and apoptosis.
Results: Compared with the sham-operated rats, the rat models of MCC showed significantly increased mRNA expressions of PERK, eIF2α and CHOP and protein expressions of PERK, eIF2α, ATF4, CHOP, TRIB3, p-AKT and pro-caspase-3 in the cerebral cortex. CBD treatment, especially at the high dose, obviously increased the expression of p-Akt and lowered the expression levels of the other factors tested in the rat models. Network pharmacology analysis indicated interactions of the core targets of CBD with the factors related to endoplasmic reticulum stress and TBI, and molecular docking study showed a high binding energy of CBD with multiple factors pertaining to endoplasmic reticulum stress and apoptosis.
Conclusions: MCC induce endoplasmic reticulum stress and apoptosis in rat brain tissues, for which CBD, especially at a high dose, provides neuroprotective effects by inhibiting endoplasmic reticulum stress and cell apoptosis.”
“Cannabidiol (CBD), a non-psychoactive cannabinoid, has shown therapeutic potential for treating inflammatory respiratory diseases such as chronic obstructive pulmonary disease and asthma.
However, the therapeutic efficacy of CBD is limited by extensive hepatic metabolism and low oral bioavailability (approximately 20 %). These problems can be overcome by choosing an appropriate targeted drug delivery system. Delivering CBD to the lungs via a dry powder formulation could be an effective method to achieve adequate concentration and therapeutic efficacy.
This study aims to develop a dry powder formulation of CBD with Inulin (INU) and L-leucine (LEC) using spray drying and to characterize its physicochemical and aerodynamic properties.
A design of experiments (DOE) approach was used to optimize the formulation by varying feed concentration (0.2 % w/v to 0.8 % w/v), LEC concentration (5 % w/w to 20 % w/w), and CBD concentration (5 % w/w to 20 % w/w).
The resulting CBD dry powder formulations exhibited a wrinkled morphology with particle sizes ranging from 1 to 5 µm and displayed a crystalline structure, as determined by powder X-ray diffraction. The response surface method (RSM) showed that increasing the feed concentration correlated with higher yields of the CBD formulations. Specifically, the formulation with a feed concentration of 0.8 % w/v achieved a yield of 61 %.
The aerosolization data demonstrated a direct relationship between the Fine Particle Fraction (FPF) and LEC concentration, indicating that FPF increases as the LEC concentration increases. The highest FPF of 62 % was achieved with a 20 % w/w LEC concentration and a feed concentration of 0.2 % w/v. Based on this, LEC plays a crucial role in enhancing aerosolization efficiency. While feed concentration negatively affects FPF, lower feed concentrations lead to an increase in FPF.
The Fine Particle Dose (FPD) varied with the concentration of CBD, with higher concentrations resulting in a higher FPD. A 28 days stability study under different humidity conditions (<15 % and 53 %) confirmed the stability of the CBD formulations. INU and LEC exhibited minimal cytotoxicity on A549 cells, while the raw CBD and CBD formulations showed comparable levels of cytotoxicity, pIC50 4.5 ± 0.3 and 4.2 ± 0.2.
Interestingly, the CBD dry powder formulations significantly reduced inflammation (pEC50 = 4.9) induced by lipopolysaccharide (LPS).
These findings suggest that an inhalable formulation of CBD, incorporating LEC and INU, has been successfully developed. The formulations demonstrated improved aerosolization properties, stability, and promising anti-inflammatory effects, potentially making them a viable therapeutic option for inflammatory lung diseases.”
“This study successfully developed a stable and effective dry powder formulation of CBD for inhalation, which could have the potential to treat COPD and other inflammatory respiratory diseases.”
“The present study investigates the effects of cannabidiol (CBD), the major non-psychoactive compound of Cannabis sativa L. extracts, on ferroptotic cell death in human articular chondrocytes.
Exposure to known ferroptosis inducers RSL3, erastin and its analogue IKE, FINO2 and FIN56 led to a varying extent of reduced cell viability in two chondrocyte cell lines (in C-28/I2, T/C-28/A2) and primary chondrocytes, suggesting different sensitivity and defence mechanisms towards the respective substances. The cytotoxic effects were aggravated by additional exposure to iron and inhibited by the specific ferroptosis inhibitor ferrostatin-1 (Fer-1), proving the occurrence of ferroptosis.
Strikingly, co-treatment of ferroptosis inducers with CBD clearly restored cell viability in a dose-dependent manner (10 nM to 1 μM CBD) in both cell lines and primary chondrocytes. Moreover, CBD restored the activity of GPX4, a major anti-oxidative enzyme, to varying degrees when combined with IKE or RSL3. Increasing evidence has emerged for an important role of iron dyshomeostasis and ferroptosis in the onset and progression of various orthopaedic diseases, including osteoarthritis.
Therefore, the here demonstrated and previously unreported cytoprotective and anti-oxidative effects of CBD in the context of ferroptosis have highly promising therapeutic implications.”
“The endocannabinoid system (ECS) is a vital biological network essential for maintaining homeostasis and supporting various physiological functions. It comprises cannabinoid receptors, endogenous lipid-based ligands, known as endocannabinoids, as well as metabolic enzymes and associated proteins responsible for regulating their levels within tissues. The ECS plays a central role in modulating processes involving the central nervous system (CNS). Recent studies have highlighted its antioxidant, anti-inflammatory, and neuroprotective properties.
The therapeutic potential of cannabinoids, particularly phytocannabinoids derived from plants, has attracted significant attention in medical and pharmaceutical research. This interest has grown in parallel with the increasing availability of cannabinoid-based food supplements on the pharmaceutical market. Given the complexity of the ECS and its broad range of interactions, the discovery of this system has spurred extensive investigations into the use of cannabinoids for various health conditions.
In this review, we examine recent preclinical evidence supporting the use of phytocannabinoids in the context of neurodegenerative diseases, particularly in Alzheimer’s disease and Parkinson’s disease. Targeting the ECS through phytocannabinoid-based pharmacological modulation offers a promising therapeutic strategy for these neurological disorders. Among these compounds, cannabidiol has emerged as a key focus of research due to its multifaceted effects and favorable safety profile. Nonetheless, continued investigation is necessary to clarify its mechanisms of action, and to develop effective, evidence-based clinical applications.”
“Recent advances in cannabinoid research have shed light on the considerable therapeutic potential of phytocannabinoids, particularly CBD, in the treatment of neurodegenerative diseases.
The preclinical studies presented in this review demonstrate consistent neuroprotective, anti-inflammatory, antioxidant, and neuromodulator effects in models of AD, PD, or HD.
These effects are largely mediated through the complex interplay of phytocannabinoids with the ECS, as well as their interactions with non-cannabinoid targets, such as TRPV1, 5-HT1A receptors, and PPARs.The ECS emerges as a crucial modulator of CNS homeostasis, and its dysregulation appears to be closely linked with the pathophysiology of major neurodegenerative diseases.
Phytocannabinoid-mediated modulation of ECS activity has shown promising outcomes in various animal models, including reductions in neuroinflammation, attenuation of excitotoxicity, and preservation of cognitive and motor function.The evidence suggests that phytocannabinoids may contribute to neuronal preservation, attenuation of neuroinflammatory cascades, and improvement in motor and cognitive performance in disease models. Moreover, their favorable safety profile and ability to act on multiple molecular pathways position them as promising candidates for disease-modifying interventions.
As interest in cannabinoid pharmacotherapy continues to grow, phytocannabinoids represent a promising, multifaceted class of compounds with the potential to address unmet therapeutic needs in the field of neurodegeneration.”
“Background/Objectives: The main biologically active molecules of Cannabis sativa L. are cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). Both exert anticonvulsant effects when evaluated as single drugs, but their possible interaction as components of C. sativa extracts has been scarcely studied. For this reason, we evaluated CBD and THC, combined or not, in two seizure models in mice, using an improved vehicle formula.
Methods: Firstly, acute seizures were induced by intraperitoneal (i.p.) pentylenetetrazole (PTZ, 80 mg/kg), and mice received CBD or THC at 1, 3, 6, and 10 mg/kg, or a CBD/THC 1:1 combination at 1.5, 3, and 6 mg/kg, per os (p.o.), one hour before PTZ administration. Secondly, mice received p.o. CBD (10 mg/kg), CBD/THC (1.5, 3, and 6 mg/kg), valproic acid (50 mg/kg), or vehicle (nanoemulsions without CBD or THC), one hour before PTZ (30 mg/kg, i.p.) every other day for 21 days. Behavioral, biochemical, and immunohistochemical analyses were performed to assess the response to PTZ, oxidative stress, and astroglial activation.
Results: In the acute model, CBD and THC at 3-10 mg/kg, and their combinations, significantly increased latency to generalized seizures and death, and improved survival rates. In the chronic model, similarly to valproic acid, CBD 10 mg/kg and CBD/THC at 1.5 and 3 mg/kg delayed kindling acquisition, while CBD/THC 6 mg/kg had no effect. CBD and CBD/THC treatments reduced oxidative and nitrosative stress and attenuated astrogliosis, as indicated by decreased glial fibrillary acidic protein and GABA transporter 1 expression and increased inwardly rectifying potassium channel 4.1 expression in hippocampal regions. However, no cannabinoid treatment prevented the impairment in novel object recognition and Y maze tests.
Conclusions: These findings support the potential role of cannabinoids in counteracting seizures, possibly by reducing oxidative stress and astrogliosis. The study also highlights the importance of nanoemulsions as a delivery vehicle to enhance cannabinoid effectiveness while considering the risks associated with direct cannabinoid receptor activation.”
“This study underscores the potential of CBD and THC nanoemulsions in seizure models, highlighting their capacity to reduce convulsions and brain damage. These formulations significantly decreased markers of oxidative and nitrosative stress, enhancing our grasp of their antiseizure mechanisms.”
“Aim: The aim of this Phase I/II open-label study was to assess the safety and efficacy of NTI164, a novel full-spectrum medicinal cannabis plant extract 0.08% Δ-9-tetrahydrocannabinol (THC), in Rett syndrome (RTT).
Methods: Eleven female participants (5-16 years) with a pathogenic variant in the MECP2 gene were recruited to this study, receiving NTI164 twice daily for 12 weeks. The primary outcome measure was the Clinical Global Impression-Improvement (CGI-I) Scale, with secondary outcomes measured using the CGI-Severity (CGI-S), RTT Behaviour Questionnaire (RSBQ), RTT-Symptom Index Score (RTT-SIS), RTT-Domain-Specific Concerns-Visual-Analog Scale (RTT-DSC-VAS), Impact of Childhood Neurological Disability/Quality of Life (ICND+QoL), and RTT-Caregiver Burden Inventory (RTT-CBI). Paired-samples t-test was used to assess significance between baseline and Week 12.
Results: Improvements were seen in the total CGI-I score (p = 0.028), with improvements in communication skills (p = 0.003), mental alertness (p = 0.033), socialisation/eye contact (p = 0.0004), attentiveness (p = 0.001), and anxiety (p = 0.004). CGI-S also demonstrated better outcomes after NTI164 administration (p = 0.008). RSBQ showed improvements in total score (p = 0.0005), general mood (p = 0.0003), breathing problems (p = 0.041), repetitive face movements (p = 0.004), and fear/anxiety (p = 0.006). RTT-DSC-VAS showed positive developments in abilities to communicate choices (p = 0.041). ICND total score was improved (p = 0.003), as well as cognition (p = 0.027) and Quality of Life (p = 0.0002). Total score on the RTT-CBI was improved (p = 0.006).
Conclusion: NTI164 demonstrated safety and improved some clinical and functional outcomes in RTT. These improvements justify ongoing research into NTI164, which may be a potential adjunct therapy in RTT.”
“This paper demonstrates efficacy of this novel medical cannabis compound in reducing complex symptoms of Rett syndrome and improving quality of life in these patients.”
