“Cannabidiol (CBD) has been used as a pharmacological treatment for psychiatric disorders in many studies, but few of good quality at the moment. Our objective was to assess the effect of CBD in mono/add-on therapy on symptom severity in psychiatric disorders. We performed a systematic review of clinical trials and randomized controlled trials that used CBD as treatment for psychiatric disorders. PRISMA criteria have been used for methodological purposes. Two assessors individually examined the results based on title and abstract, and decided which papers warranted full read. We included studies in English that measured disease severity as primary outcome. Out of 226 studies returned from the search, 9 warranted full read. There were 4 studies using CBD in schizophrenia, 3 studies of substance use disorder and 2 studies of social anxiety. CBD has a good safety profile even in higher doses, but results are inconclusive regarding improvements in disease severity.”
“Background Opioids, commonly used to control pain associated with surgery, are known to prolong the duration of mechanical ventilation and length of hospital stay. A wide range of adjunctive strategies are currently utilized to reduce postoperative pain, such as local and regional nerve blocks, nerve cryoablation, and adjunctive medications. We hypothesized that dronabinol (a synthetic cannabinoid) in conjunction with standard opioid pain management will reduce opioid requirements to manage postoperative pain. Methods Sixty-eight patients who underwent isolated first-time coronary artery bypass graft surgery were randomized to either the control group, who received only standard opioid-based analgesia, or the dronabinol group, who received dronabinol (a synthetic cannabinoid) in addition to standard opioid-based analgesia. Dronabinol was given in the preoperative unit, before extubation in the ICU, and after extubation on the first postoperative day. Preoperative, intraoperative, and postoperative parameters were compared under an IRB-approved protocol. The primary endpoints were the postoperative opioid requirement, duration of mechanical ventilation, and ICU length of stay, and the secondary endpoints were the duration of inotropic support needed, left ventricular ejection fraction (LVEF), and the change in LVEF. This study was undertaken at Northwest Medical Center, Tucson, AZ, USA. Results Sixty-eight patients were randomized to either the control group (n = 37) or the dronabinol group (n = 31). Groups were similar in terms of demographic features and comorbidities. The total postoperative opioid requirement was significantly lower in the dronabinol group [39.62 vs 23.68 morphine milligram equivalents (MMEs), p = 0.0037], representing a 40% reduction. Duration of mechanical ventilation (7.03 vs 6.03h, p = 0.5004), ICU length of stay (71.43 vs 63.77h, p = 0.4227), and inotropic support requirement (0.6757 vs 0.6129 days, p = 0.7333) were similar in the control and the dronabinol groups. However, there was a trend towards lower durations in each endpoint in the dronabinol group. Interestingly, a significantly better preoperative to postoperative LVEF change was observed in the dronabinol group (3.51% vs 6.45%, p = 0.0451). Conclusions Our study found a 40% reduction in opioid use and a significantly greater improvement in LVEF in patients treated with adjunctive dronabinol. Mechanical ventilation duration, ICU length of stay, and inotropic support requirement tended to be lower in the dronabinol group, though did not reach statistical significance. The results of this study, although limited by sample size, are very encouraging and validate our ongoing investigation.”
“Neuroinflammation stands as a critical player in the pathogenesis of diverse neurological disorders, with microglial cells playing a central role in orchestrating the inflammatory landscape within the central nervous system.
Cannabidiol (CBD) has gained attention for its potential to elicit anti-inflammatory responses in microglia, offering promising perspectives for conditions associated with neuroinflammation.
Here we investigated whether the NLRP3 inflammasome and inducible nitric oxide synthase (iNOS) are involved in the protective effects of CBD, and if their modulation is dependent on cannabinoid receptor 2 (CB2) and PPARγ signalling pathways.
We found that treatment with CBD attenuated pro-inflammatory markers in lipopolysaccharide (LPS)-challenged BV2 microglia in a CB2- and PPARγ-dependent manner. At a molecular level, CBD inhibited the LPS-induced pro-inflammatory responses by suppressing iNOS and NLRP3/Caspase-1-dependent signalling cascades, resulting in reduced nitric oxide (NO), interleukin-1β (IL-1β), and tumour necrosis factor-alpha (TNF-α) concentrations.
Notably, the protective effects of CBD on NLRP3 expression, Caspase-1 activity, and IL-1β concentration were partially hindered by the antagonism of both CB2 receptors and PPARγ, while iNOS expression and NO secretion were dependent exclusively on PPARγ activation, with no CB2 involvement. Interestingly, CBD exhibited a protective effect against TNF-α increase, regardless of CB2 or PPARγ activation.
Altogether, these findings indicate that CB2 receptors and PPARγ mediate the anti-inflammatory effects of CBD on the NLRP3 inflammasome complex, iNOS activity and, ultimately, on microglial phenotype. Our results highlight the specific components responsible for the potential therapeutic applications of CBD on neuroinflammatory conditions.”
“This study aimed to investigate the chemical components and potential health benefits of the fruits of Cannabis sativa L.
Fourteen new phenylpropanamides designated as cannabisin I-XIV (1–14) and 40 known analogs were isolated and characterized via nuclear magnetic resonance spectroscopy, high-resolution electrospray ionization mass spectrometry, and electronic circular dichroism.
In vitro bioassay using H2O2-induced PC12 cell damage models demonstrated that hempseeds extract and compounds 1, 3, 15, 26, 30, 36, 41, and 48 exhibited neuroprotective properties. 3,3′-Demethylgrossamide (30) displayed encouraging protection activity, which was further investigated to relieve the oxidative stress and apoptosis of PC12 cells treated with H2O2.
The isolation and characterization of these neuroprotective phenylpropanamides from the fruits of C. sativa provide insights into its health-promoting properties as a healthy food and herbal medicine for preventing and treating neurodegenerative diseases, especially Alzheimer’s disease.”
“Policosanols (PCs) are bioactive compounds extracted from different natural waxes.
In this work, the purification, characterization and assessment of the antioxidant and anti-inflammatory activity was carried out on PCs from an innovative source, i.e. a waxy material from supercritical-fluid extraction (SFE) of non-psychoactive Cannabis sativa L. (hemp) inflorescences.
Starting from this material, PCs were obtained by microwave-assisted trans-esterification and hydrolysis, followed by preparative liquid chromatography under normal phase conditions. The purified product was characterized using high-performance liquid chromatography (HPLC) with an evaporative light scattering detector (ELSD). In vitro cell-free and cell-based antioxidant and anti-inflammatory assays were then performed to assess their bioactivity. HPLC-ELSED analysis of the purified mixture from hemp wax revealed C26OH and C28OH as the main compounds.
In vitro assays indicated an inhibition of intracellular reactive oxygen species (ROS) production, a reduction of nuclear factor kappa B (NF-κB) activation and of the activity of the neutrophil elastase. Immunoblotting assays allowed us to hypothesize the mechanism of action of the compounds of interest, given the higher levels of MAPK-activated protein kinase 2 (MK2) and heme oxygenase-1 (HO-1) protein expression in the PC pretreated HaCaT cells.
In conclusion, even if more research is needed to unveil other molecular mechanisms involved in hemp PC activity, the results of this work suggest that these compounds may have potential for use in oxinflammation processes.”
“Hemp (Cannabis sativa L.) has experienced a significant resurgence in popularity, and global interest in diversifying its use in various industries, including the food industry, is growing. Therefore, due to their exceptional nutritional value, hemp seeds have recently gained increasing interest as a valuable ingredient for obtaining high-quality foods and dietary supplements.
Hemp seeds stand out for their remarkable content of quality proteins, including edestin and albumin, two distinct types of proteins that contribute to exceptional nutritional value. Hemp seeds are also rich in healthy lipids with a high content of polyunsaturated fatty acids, such as linoleic acid (omega-6), alpha-linolenic acid (omega-3), and some vitamins (vitamins E, D, and A). Polyphenols and terpenoids, in particular, present in hemp seeds, provide antimicrobial, antioxidant, and anti-inflammatory properties.
This review examines the scientific literature regarding hemp seeds’ physicochemical and nutritional characteristics. The focus is on those characteristics that allow for their use in the food industry, aiming to transform ordinary food products into functional foods, offering additional benefits for the body’s health. Innovating opportunities to develop healthy, nutritionally superior food products are explored by integrating hemp seeds into food processes, promoting a balanced and sustainable diet.”
“Cannabidiol (CBD) is a non-psychoactive compound derived from Cannabis sativa. It has demonstrated promising effects in combating inflammation and holds potential as a treatment for the progression of chronic inflammation. However, the clinical application of CBD is limited due to its poor solubility and bioavailability.
This study introduces an effective method for preparing CBD-loaded solid lipid nanoparticles (CBD-SLNs) using a combination of low-energy hot homogenization and ultrasonication. We enhanced this process by employing statistical optimization with response surface methodology (RSM). The optimized CBD-SLN formulation utilizes glyceryl monostearate as the primary lipid component of the nanocarrier. The CBD-SLN formulation is screened as a potential tool for managing chronic inflammation. Stable, uniformly dispersed spherical nanoparticles with a size of 123 nm, a surface charge of -32.1 mV, an encapsulation efficiency of 95.16%, and a drug loading of 2.36% were obtained.
The CBD-SLNs exhibited sustained release properties, ensuring prolonged and controlled CBD delivery, which could potentially amplify its therapeutic effects. Additionally, we observed that CBD-SLNs significantly reduced both reactive oxygen and nitrogen species and proinflammatory cytokines in chondrocyte and macrophage cell lines, with these inhibitory effects being more pronounced than those of free CBD.
In conclusion, CBD-SLNs demonstrated superiority over free CBD, highlighting its potential as an effective delivery system for CBD.”
“Introduction: Cannabidiol (CBD) is the primary non-psychoactive chemical derived from Cannabis Sativa, and its growing popularity is due to its potential therapeutic properties while avoiding the psychotropic effects of other phytocannabinoids, such as tetrahydrocannabinol (THC). Numerous pre-clinical studies in cellular and animal models and human clinical trials have demonstrated a positive impact of CBD on physiological and pathological processes. Recently, the FDA approved its use for the treatment of seizures, and clinical trials to test the efficacy of CBD in myocarditis and pericarditis are ongoing.
Areas covered: We herein reviewed the current literature on the reported effects of CBD in the cardiovascular system, highlighting the physiological effects and the outcomes of using CBD as a therapeutic tool in pathological conditions to address this significant global health concern.
Expert opinion: The comprehensive examination of the literature emphasizes the potential of CBD as a therapeutic option for treating cardiovascular diseases through its anti-inflammatory, vasodilatory, anti-fibrotic, and antioxidant properties in different conditions such as diabetic cardiomyopathy, myocarditis, doxorubicin-induced cardiotoxicity, and ischemia-reperfusion injury.”
“Background context: The opioid epidemic is a public health crisis affecting spine care and pain management. Medical marijuana is a potential non-opioid analgesic yet to be studied in the surgical setting since its effects on bone healing are not fully understood. Studies have demonstrated analgesic and potentially osteoinductive properties of cannabinoids with endocannabinoid receptor expression in bone tissue.
Purpose: We hypothesize that tetrahydrocannabinol (THC) and cannabidiol (CBD) will not decrease bone healing in spinal fusion.
Study design: Seventy-eight adult Sprague-Dawley rats were used for this study. Utilizing allogenic bone grafts (6 donor rats), posterolateral inter-transverse lumbar fusion at the L4-L5 level was performed. The animals were equally divided into four treatment groups, each receiving 0.1ml intraperitoneal injections weekly as follows: placebo (saline), 5mg/kg THC, 5mg/kg CBD, and a combination of 5mg/kg THC and 5mg/kg CBD (Combo).
Methods: Callus tissue was harvested 2- and 8-weeks post-surgery for qPCR assessment to quantify changes in the expression of osteogenic genes. Manual palpation was done to assess the strength of the L4-L5 arthrodesis on all rats. μCT image-based callus analysis and histology were performed. One-way ANOVA followed by post hoc comparisons was performed.
Results: μCT demonstrated no significant differences. Treatment groups had slightly increased bone volume and density compared to control. qPCR at two weeks indicated downregulated RANKL/OPG ratios skewing towards osteogenesis in the CBD group, with the THC and CBD+THC groups demonstrating a downward trend (P>0.05). ALPL, BMP4, and SOST were significantly higher in the CBD group, with CTNNB1 and RUNX2 also showing an upregulating trend. The CBD group showed elevation in Col1A1 and MMP13. Data at eight weeks showed ALPL, RUNX2, BMP4, and SOST were downregulated for all treatment groups. In the CBD+THC group, RANK, RANKL, and OPG were downregulated. OPG downregulation reached significance for the THC and CBD+THC group compared to saline. Interestingly, the RANKL/OPG ratio showed upregulation in the CBD and CBD+THC groups. RANKL showed upregulation in the CBD group. At 2 and 8 weeks, the CBD treatment group showed superior histological progression, increasing between time points.
Conclusion: This study demonstrates that CBD and THC have no adverse effect on bone healing and the rate of spinal fusion in rats. Osteogenic factors were upregulated in the CBD-treated groups at two weeks, which indicates a potential for bone regeneration. In this group, compared to control, the RANKL/OPG ratio at the early healing phase demonstrates the inhibition of osteoclast differentiation, enhancing bone formation. Interestingly, it shows promoted osteoclast differentiation at the later healing phase, enhancing bone remodeling. This aligns with the physiological expectation of a lower ratio in the early phases and a higher ratio in the later remodeling phases.
Clinical significance: CBD and THC showed no inhibitory effects on bone healing in a spinal fusion model. Moreover, histologic and gene expression analysis demonstrated that CBD may, in fact, enhance bone healing. Further research is needed to confirm the safe usage of THC and CBD in the post-operative setting following spinal fusions.”
“There is a significant global upsurge in the number and proportion of older persons in the population. With this comes an increasing prevalence of age-related conditions which pose a major challenge to healthcare systems. The development of anti-ageing treatments may help meet this challenge by targeting the ageing process which is a common denominator to many health problems.
Cannabis-like compounds (cannabinoids) are reported to improve quality of life and general well-being in human trials, and there is increasing preclinical research highlighting that they have anti-ageing activity. Moreover, preclinical evidence suggests that endogenous cannabinoids regulate ageing processes.
Here, we review the anti-ageing effects of the cannabinoids in various model systems, including the most extensively studied nematode model, Caenorhabditis elegans.
These studies highlight that the cannabinoids lengthen healthspan and lifespan, with emerging evidence that they may also hinder the development of cellular senescence. The non-psychoactive cannabinoid cannabidiol (CBD) shows particular promise, with mechanistic studies demonstrating it may work through autophagy induction and activation of antioxidative systems. Furthermore, CBD improves healthspan parameters such as diminishing age-related behavioural dysfunction in models of both healthy and accelerated ageing. Translation into mammalian systems provides an important next step. Moreover, looking beyond CBD, future studies could probe the multitude of other cannabis constituents for their anti-ageing activity.”
“Ageing is a complex and multifactorial process that occurs as a gradual accumulation of cellular damage in various tissues of the body, leading to a decline in physiological functions across all systems. One main aim of ageing research is to identify compounds that can postpone deteriorative changes linked to ageing. Finding interventions that promote healthy ageing may provide a paradigm shift in medicine, by targeting the common denominator of many diseases, that is, the ageing process. With the ongoing trend of cannabis legalisation globally, there is a demand for research that explores the impact of cannabis and cannabinoids on healthy ageing and diseases of ageing.
The current review highlights that cannabinoids, whether endogenous or exogenous, extend lifespan and healthspan in model systems.
However, more research is needed to observe whether these results translate in mammalian systems and ultimately in the clinic. The anti-ageing effects of cannabinoids have a number of different mechanisms, including the reduction of oxidative stress and the triggering of autophagy. More research is needed to further explore the anti-ageing mechanisms of the cannabinoids and to more comprehensively examine their impact on the hallmarks of ageing including cellular senescence. The development of anti-ageing agents that tone up endocannabinoid transmission could also be examined. Moreover, plant cannabinoids beyond CBD could be explored, as well as other cannabis constituents, alone and in combination. In addition, given the robust findings with CBD, chemical analogues of CBD might be developed. The current review underscores that there is much promise for the further development of cannabinoids as anti-ageing agents, to improve healthy ageing and general well-being.”
