“Soluble epoxide hydrolase (sEH) is a therapeutic target for inflammation. In the present study, we isolated one new (1) and four known (2–5) compounds from the ethyl acetate fraction of hemp seed hulls. Their structures were elucidated as lignanamides via nuclear magnetic resonance and mass spectral analyses. All five compounds inhibited sEH activity, with half-maximal inhibitory concentrations of 2.7 ± 0.3 to 18.3 ± 1.0 μM. These lignanamides showed a competitive mechanism of inhibition via binding to sEH, with ki values below 10 μmol. Molecular simulations revealed that compounds 1–5 fit stably into the active site of sEH, and the key amino acid residues participating in their bonds were identified. It was confirmed that the potential inhibitors 4 and 5 continuously maintained a distance of 3.5 Å from one (Tyr383) and four amino (Asp335, Tyr383, Asn472, tyr516) residues, respectively. These findings provide a framework for the development of naturally derived sEH inhibitors.”
“Postnatal neurogenesis has been shown to rely on the endocannabinoid system. Here we aimed at unravelling the role of Cannabidivarin (CBDV), a non-psychoactive cannabinoid, with high affinity for the non-classical cannabinoid receptor TRPV1, on subventricular zone (SVZ) postnatal neurogenesis.
Using the neurosphere assay, SVZ-derived neural stem/progenitor cells (NSPCs) were incubated with CBDV and/or 5′-Iodoresinferotoxin (TRPV1 antagonist), and their role on cell viability, proliferation, and differentiation were dissected. CBDV was able to promote, through a TRPV1-dependent mechanism, cell survival, cell proliferation and neuronal differentiation. Furthermore, pulse-chase experiments revealed that CBDV-induced neuronal differentiation was a result of cell cycle exit of NSPCs. Regarding oligodendrocyte differentiation, CBDV inhibited oligodendrocyte differentiation and maturation. Since our data suggested that the CBDV-induced modulation of NSPCs acted via TRPV1, a sodium-calcium channel, and that intracellular calcium levels are known regulators of NSPCs fate and neuronal maturation, single cell calcium imaging was performed to evaluate the functional response of SVZ-derived cells. We observed that CBDV-responsive cells displayed a two-phase calcium influx profile, being the initial phase dependent on TRPV1 activation.
Taken together, this work unveiled a novel and untapped neurogenic potential of CBDV via TRPV1 modulation. These findings pave the way to future neural stem cell biological studies and repair strategies by repurposing this non-psychoactive cannabinoid as a valuable therapeutic target.”
“Introduction: The effects of cannabidiol (CBD) on cognition has been investigated in recent years to determine the therapeutic potential of this cannabinoid for a broad gamut of medical conditions, including neuropsychiatric disorders. The aim of the present study was to perform a systematic review of studies that analyzed the effects of the acute and chronic administration of CBD on cognition in humans and animals both to assess the cognitive safety of CBD and to determine a beneficial potential of CBD on cognition.
Methods: The PubMed, Web of Science, PsycINFO, and Scopus databases were searched in December of 2022 for relevant articles using the following combinations of keywords: (“cannabidiol” OR “CBD”) AND (“cognition” OR “processing cognitive” OR “memory” OR “language” OR “attention” OR “executive function” OR “social cognition” OR “perceptual motor ability” OR “processing speed”).
Results: Fifty-nine articles were included in the present review (36 preclinical and 23 clinical trials). CBD seems not to have any negative effect on cognitive processing in rats. The clinical trials confirmed these findings in humans. One study found that repeated dosing with CBD may improve cognitive in people who use cannabis heavily but not individuals with neuropsychiatric disorders. Considering the context of neuropsychiatric disorders in animal models, CBD seems to reverse the harm caused by the experimental paradigms, such that the performance of these animals becomes similar to that of control animals.
Conclusions: The results demonstrate that the chronic and acute administration of CBD seems not to impair cognition in humans without neuropsychiatric disorders. In addition, preclinical studies report promising results regarding the effects of CBD on the cognitive processing of animals. Future double-blind, placebo-controlled, randomized clinical trials with larger, less selective samples, with standardized tests, and using different doses of CBD in outpatients are of particular interest to elucidate the cognitive effects of CBD.”
“Cannabis-based biomaterials have the potential to deliver anti-inflammatory therapeutics specifically to desired cells, tissues, and organs, enhancing drug delivery and the effectiveness of anti-inflammatory treatment while minimizing toxicity. As a major component of Cannabis, Cannabidiol (CBD) has gained major attention in recent years because of its potential therapeutic properties, e.g., for restoring a disturbed barrier resulting from inflammatory conditions. The aim of this study was to test the hypothesis that CBD has beneficial effects under normal and inflammatory conditions in the established non-transformed intestinal epithelial cell model IPEC-J2. CBD induced a significant increase in transepithelial electrical resistance (TER) values and a decrease in the paracellular permeability of [³H]-D-Mannitol, indicating a strengthening effect on the barrier. Under inflammatory conditions induced by tumor necrosis factor alpha (TNFα), CBD stabilized the TER and mitigated the increase in paracellular permeability. Additionally, CBD prevented the barrier-disrupting effects of TNFα on the distribution and localization of sealing TJ proteins. CBD also affected the expression of TNF receptors. These findings demonstrate the potential of CBD as a component of Cannabis-based biomaterials used in the development of novel therapeutic approaches against inflammatory pathogenesis.”
“Overall, these findings suggest that CBD will be a promising component in biomaterial-based therapeutic approaches for the treatment of inflammatory pathomechanisms.”
“Recently, there has been a renewed interest in Cannabis sativa and its uses. The recreational use of inflorescences as a source of THC has led to the legal restriction of C. sativa cultivation to limit the detrimental effects of psychotropic substance abuse on health. However, this has also limited the cultivation of textile/industrial varieties with a low content of THC used for textile and nutritional purposes. While previously the bans had significantly penalized the cultivation of C. sativa, today many countries discriminate between recreational use (marijuana) and industrial and food use (hemp). The stalks of industrial hemp (low in psychotropic substances) have been used extensively for textile purposes while the seeds are nutritionally versatile. From hemp seeds, it is possible to obtain flours applicable in the bakery sector, oils rich in essential fatty acids, proteins with a high biological value and derivatives for fortification, supplementation and nutraceutical purposes. Hemp seed properties seem relevant for vegetarian diets, due to their high nutritional value and underestimated employment in the food sector. Hemp seed and their derivatives are a valuable source of protein, essential fatty acids and minerals that could provide additional benefit to vegetarian nutrition. This document aims to explore the information available in the literature about hemp seeds from a nutritional point of view, highlighting possible beneficial effects for humans with particular attention to vegetarian nutrition as a supplemental option for a well-planned diet.”
“Inflammation is a natural response of the body to signals of tissue damage or infection caused by pathogens. However, when it becomes imbalanced, it can lead to various disorders such as cancer, obesity, cardiovascular problems, neurological conditions, and diabetes. The endocannabinoid system, which is present throughout the body, plays a regulatory role in different organs and influences functions such as food intake, pain perception, stress response, glucose tolerance, inflammation, cell growth and specialization, and metabolism. Phytocannabinoids derived from Cannabis sativa can interact with this system and affect its functioning. In this study, we investigate the mechanisms underlying the anti-inflammatory effects of three minor phytocannabinoids including tetrahydrocannabivarin (THCV), cannabichromene (CBC), and cannabinol (CBN) using an in vitro system. We pre-treated THP-1 macrophages with different doses of phytocannabinoids or vehicle for one hour, followed by treating the cells with 500 ng/mL of LPS or leaving them untreated for three hours. To induce the second phase of NLRP3 inflammasome activation, LPS-treated cells were further treated with 5 mM ATP for 30 min. Our findings suggest that the mitigation of the PANX1/P2X7 axis plays a significant role in the anti-inflammatory effects of THCV and CBC on NLRP3 inflammasome activation. Additionally, we observed that CBC and THCV could also downregulate the IL-6/TYK-2/STAT-3 pathway. Furthermore, we discovered that CBN may exert its inhibitory impact on the assembly of the NLRP3 inflammasome by reducing PANX1 cleavage. Interestingly, we also found that the elevated ADAR1 transcript responded negatively to THCV and CBC in LPS-macrophages, indicating a potential involvement of ADAR1 in the anti-inflammatory effects of these two phytocannabinoids. THCV and CBN inhibit P-NF-κB, downregulating proinflammatory gene transcription. In summary, THCV, CBC, and CBN exert anti-inflammatory effects by influencing different stages of gene expression: transcription, post-transcriptional regulation, translation, and post-translational regulation.”
“Cannabis sativa L. contains more than 80 cannabinoids, among which cannabidiol (CBD) is the main neuroactive component. We aimed to investigate the anti-inflammatory efficacy of CBD in vitro and in vivo isolated from “Pink pepper”, a novel hemp cultivar, by repeating the method of selecting and cultivating individuals with the highest CBD content. We investigated the effects of CBD on inflammatory markers elevated by lipopolysaccharide (LPS) treatment in RAW 264.7 mouse macrophage cells through Western blot and RT-PCR. In addition, we confirmed these effects through the ELISA of inflamed paw tissue of a λ-carrageenan-induced mouse edema model that received an oral administration of CBD. CBD inhibited the LPS-induced phosphorylation of NF-κB and MAPK in RAW 264.7 and exhibited anti-inflammatory effects by participating in these pathways. In our in vivo study, we confirmed that CBD also inhibited the inflammatory mediators of proteins extracted from edematous mouse paw tissue. These results show that CBD isolated from “Pink pepper” exhibits potent anti-inflammatory effects. These anti-inflammatory effects of CBD have pharmacological and physiological significance, highlighting the industrial value of this novel cultivar.”
“Aims: Patients with chronic health conditions not responding to conventional treatment can access medicinal cannabis (MC) prescriptions from clinicians in Australia. We aimed to assess overall health-related quality of life (HRQL), pain, fatigue, sleep, anxiety, and depression in a large real-world sample of patients accessing prescribed medicinal cannabis. We hypothesized that all patient-reported outcomes (PROs) would improve from baseline to 3-months.
Methods: The QUEST Initiative is a large prospective multicenter study of patients with any chronic health condition newly prescribed medicinal cannabis between November 2020 and December 2021. Eligible patients were identified by 120 clinicians at medical centers across six Australian states. Consenting participants completed the EuroQol Group EQ-5D-5L health status questionnaire; European Organization for Research & Treatment of Cancer Quality of Life questionnaire (QLQ-C30); Patient-Reported Outcomes Measurement Information System (PROMIS) Short Forms in Fatigue and Sleep Disturbance, and the Depression Anxiety Stress Scale (DASS-21) before starting therapy, at 2-weeks titration, then monthly for 3-months.
Results: Of the 2762 consenting participants, 2327 completed baseline and at least one follow-up questionnaire. Ages ranged between 18-97 years (mean 51y; SD = 15.4), 62.8% were female. The most commonly treated conditions were chronic pain (n = 1598/2327; 68.7%), insomnia (n = 534/2327; 22.9%), generalized anxiety (n = 508/2327; 21.5%), and mixed anxiety and depression (n = 259/2327; 11%). Across the whole cohort both EQ-5D-5L utility scores and QLQ-C30 summary scores showed clinically meaningful improvement in HRQL from baseline to mean follow-up with d = 0.54 (95%CI:0.47 to 0.59) and d = 0.64 (95%CI:0.58 to 0.70) respectively; and clinically meaningful improvement in fatigue (d = 0.54; 95%CI:0.48 to 0.59). There was clinically meaningful reduction of pain for those with chronic pain (d = 0.65; 95%CI:0.57 to 0.72); significant improvements for those with moderate to extremely severe anxiety (X2 = 383; df = 4; p<0.001) and depression (X2 = 395; df = 4; p<0.001); and no changes in sleep disturbance.
Conclusions: We observed statistically significant, clinically meaningful improvements in overall HRQL and fatigue over the first 3-months in patients with chronic health conditions accessing prescribed medical cannabis. Anxiety, depression, and pain also improved over time, particularly for those with corresponding health conditions. The study continues to follow-up patients until 12-months to determine whether improvements in PROs are maintained long-term.”
“Short-term findings over 3-months indicate that patients prescribed MC in practice have improved HRQL and reduced fatigue. Patients experiencing anxiety, depression, or chronic pain also improved in those outcomes over 3-months, but no changes in sleep disturbance were observed in patients with sleep disorders.”
“Cannabinoids are phytochemicals from cannabis with anti-inflammatory actions in immune cells. Lipid mediators (LM), produced from polyunsaturated fatty acids (PUFA), are potent regulators of the immune response and impact all stages of inflammation. How cannabinoids influence LM biosynthetic networks is unknown. Here, we reveal cannabidiol (CBD) as a potent LM class-switching agent that stimulates the production of specialized pro-resolving mediators (SPMs) but suppresses pro-inflammatory eicosanoid biosynthesis. Detailed metabololipidomics analysis in human monocyte-derived macrophages showed that CBD (i) upregulates exotoxin-stimulated generation of SPMs, (ii) suppresses 5-lipoxygenase (LOX)-mediated leukotriene production, and (iii) strongly induces SPM and 12/15-LOX product formation in resting cells by stimulation of phospholipase A2-dependent PUFA release and through Ca2+-independent, allosteric 15-LOX-1 activation. Finally, in zymosan-induced murine peritonitis, CBD increased SPM and 12/15-LOX products and suppressed pro-inflammatory eicosanoid levels in vivo. Switching eicosanoid to SPM production is a plausible mode of action of CBD and a promising inflammation-resolving strategy.”
“Many patients with ulcerative colitis after ileoanal pouch anastomosis report improvement of pouchitis with the use of cannabis. Nine patients with chronic pouchitis used 1 g/d of cannabis: 7 patients were male with average age 51 ± 16 years. Average partial pouchitis disease activity index were 11 (range 8-17), 6 (range 5-8), and 5 (range 4-8); endoscopic subscores were 7 .3 ± 2.3, 6 ± 1.1, and 4.4 ± 0.9; average bowel movements per day were 14 (range 8-20), 8 (range 2-13), and 10 (range 13-8); and quality of life increased from 72 ± 1 to 90 ± 16 and 97 ± 10 (P = 0.001) before cannabis treatment and after 8-12 and 52 weeks, respectively. No adverse events were reported.”
“In conclusion, cannabis use led to significant symptomatic improvement and better quality of life in this group of patients with refractory pouchitis.”
