“Cannabinoids are widely recognized for their potential therapeutic effects, making them significant and valuable candidates for medical research and applications across various fields.
This review aims to analyze the pharmacokinetics of Cannabidiol (CBD), Cannabigerol (CBG), and Cannabichromene (CBC), along with their corresponding acidic forms, Cannabidiolic acid (CBDA), Cannabigerolic acid (CBGA), and Cannabichromenic acid (CBCA).
Among these cannabinoids, CBD is the most extensively studied. Nevertheless, research involving all the mentioned cannabinoids has shown that their pharmacokinetic parameters are highly variable, depending significantly on factors such as dose, formulation, route of administration, and diet. Furthermore, challenges such as brain penetration and first-pass metabolism have been highlighted.
In conclusion, this review demonstrates significant progress in understanding the pharmacokinetics of non-psychotropic cannabinoids. However, it also underscores the need for further research, particularly on CBG, CBC, and their respective acidic forms, with the most significant gap being in clinical investigations. Expanding these studies is essential to facilitate their optimized use in medical treatments.”
“Background/Objectives: Current inflammatory bowel disease (IBD) treatments focus on symptomatic relief, highlighting the need for innovative approaches. Dysregulation of the cannabinoid 1 (CB1) receptor, part of the endocannabinoid system, is linked to colitis. While tetrahydrocannabinol (THC) alleviates colitis via CB1 activation, its psychotropic effects limit clinical use. ZCZ011, a CB1R allosteric modulator, and cannabidiol (CBD), a non-psychoactive cannabinoid, offer alternatives. This study investigated combining sub-therapeutic THC doses with ZCZ011 or CBD in a murine model of dextran sodium sulphate (DSS)-induced colitis.
Methods: Acute colitis was induced with 4% DSS for 7 days, followed by 3 days of water. Chronic colitis was modelled over 24 days with alternating DSS concentrations. The combination of 2.5 mg/kg THC with 20 mg/kg ZCZ011 or 10 mg/kg CBD was evaluated. Key markers were assessed to determine efficacy and safety, including disease activity index (DAI), inflammation, cytokine levels, GLP-1, and organ health.
Results: DSS-induced colitis resulted in increased DAI scores, cytokines, organ inflammation and dysregulation of GLP-1 and ammonia. THC at 10 mg/kg significantly improved colitis markers but was ineffective at 2.5 and 5 mg/kg. ZCZ011 alone showed transient effects. However, combining 2.5 mg/kg THC with either 20 mg/kg ZCZ011 or 10 mg/kg CBD significantly alleviated colitis markers, restored colon integrity and reestablished GLP-1 homeostasis. This combination also maintained favourable haematological and biochemical profiles, including a notable reduction in colitis-induced elevated ammonia levels.
Conclusions: This study demonstrates the synergistic potential of low-dose THC combined with CBD or ZCZ011 as a novel, effective and safer therapeutic strategy for ulcerative colitis.”
“This study provides compelling evidence that sub-therapeutic doses of THC combined with ZCZ011 or CBD offer a safe and effective strategy for managing both the inflammatory and metabolic components of IBD. Notably, the normalisation of GLP-1 and ammonia levels underscores the dual benefits of these treatments in alleviating colitis while addressing associated metabolic dysregulation and extraintestinal complications. This dual-action approach addresses key limitations of current therapies and emphasizes ECS modulation as a promising avenue for IBD treatment.”
“In the scenario of fighting bacterial resistance to antibiotics, natural products have been extensively investigated for their potential antibacterial activities. Among these, cannabinoids-bioactive compounds derived from cannabis-have garnered attention for their diverse biological activities, including anxiolytic, anti-inflammatory, analgesic, antioxidant, and neuroprotective properties.
Emerging evidence suggests that cannabinoids may also possess significant antimicrobial properties, with potential applications in enhancing the efficacy of conventional antimicrobial agents. Therefore, this review examines evidence from the past five years on the antimicrobial properties of cannabinoids, focusing on underlying mechanisms such as microbial membrane disruption, immune response modulation, and interference with microbial virulence factors. In addition, their synergistic potential, when used alongside standard therapies, underscores their promise as a novel strategy to address drug resistance, although further research and clinical trials are needed to validate their therapeutic use.
Overall, cannabinoids offer a promising avenue for the development of innovative treatments to combat drug-resistant infections and reduce the reliance on traditional antimicrobial agents.”
“The unique chemical properties of cannabinoids, combined with their interactions with existing therapies, contribute to their antimicrobial effects against a wide range of microorganisms, including bacteria, fungi, and viruses.The data collected support the conclusion that cannabinoids exert their effects through multiple pathways, including the disruption of microbial membranes, modulation of immune responses, and interference with microbial virulence factors.
The use of cannabinoids as alternative therapeutic options has demonstrated their potential to overcome the limitations of conventional antibiotics, offering a potential new approach to combating drug-resistant microorganisms, potentially reducing dependence on traditional antimicrobial agents that have become less effective. It also appears that the use of combinations of cannabinoids with other conventional drugs can potentially lead to a synergistic effect with improved therapeutic capabilities.”
“Introduction: Individuals living with Sickle Cell Disease (SCD) are subject to numerous chronic complications, including disabling chronic pain, often dependent on opioids and with important repercussions on quality of life. The use of Medicinal Cannabis in this scenario may be a promising strategy for mitigating this impact.
Areas covered: This work compiled current knowledge regarding the endocannabinoid system in humans and the role of this system in various organic functions. Articles were retrieved through a comprehensive search of the PubMed NCBI database, covering relevant studies up to 2024. These data bring important speculations on the potential role of the use of medicinal cannabis in modulating SCD chronic complications, and the preliminary results of clinical trials carried out in this condition are discussed.
Expert opinion: The search for understanding the role of cannabis-derived products in the management of chronic complications of sickle cell disease could add resources to the serious challenge of dealing with the multiple aspects of the disease faced by patients. They range from the management of chronic pain itself, the risks of opioid dependence, in addition to other difficult scenarios, such as leg ulcers and chronic inflammation and its consequences.”
“Human epidermal growth factor receptor 2 (HER2) is a transmembrane receptor within the ErbB family that plays a pivotal role in the progression of various aggressive cancers. HER2-positive tumors often develop resistance to standard therapies, necessitating the exploration of innovative treatment options.
Cannabinoids, bioactive compounds from Cannabis sativa such as cannabidiol (CBD), cannabigerol (CBG), and cannabinol (CBN), have gained attention for their potential anticancer properties.
This study evaluates the efficacy of CBD, CBG, and CBN in targeting HER2-positive ovarian cancer through kinase inhibition assays, surface plasmon resonance (SPR), molecular docking, and cell viability assessments.
SPR analysis revealed that cannabinoids bind strongly to HER2-tyrosine kinase (HER2-TK), with CBD showing the highest affinity (KD = 6.16 μM), significantly better than afatinib (KD = 26.30 μM), and CBG demonstrating moderate affinity (KD = 17.07 μM). In kinase inhibition assays, CBG was the most potent inhibitor (IC50 = 24.7 nM), followed by CBD (IC50 = 38 nM), suggesting their ability to disrupt HER2-mediated signaling pathways. Molecular docking studies highlighted critical interactions between cannabinoids and essential HER2 residues (Leu796, Thr862, Asp863). In cell viability assays, CBD and CBG effectively inhibited the growth of HER2-positive SKOV3 cells (IC50 = 13.8 μM and 16.6 μM, respectively), comparable to traditional tyrosine kinase inhibitors.
These findings underscore the therapeutic potential of cannabinoids, particularly CBD and CBG, as alternative or adjunct therapies for HER2-positive cancers, with the promise of mitigating resistance and adverse effects associated with existing treatments.”
“This study provides compelling evidence for the potential of cannabinoids, particularly CBD and CBG, as effective inhibitors of HER2-TK in HER2-positive ovarian cancer. The significant binding affinities and potent inhibitory effects observed in kinase assays and cell viability experiments highlight cannabinoids as promising candidates for alternative or adjunctive therapies, especially in patients facing challenges with conventional treatments.
The findings not only indicate that cannabinoids can disrupt HER2-mediated signaling pathways but also suggest that they may enhance the therapeutic efficacy of existing TKIs while potentially mitigating associated side effects. The molecular docking analysis reinforces the understanding of how cannabinoids interact with critical residues in HER2-TK, revealing a detailed mechanism of action that warrants further exploration. Given the rising concerns regarding resistance to standard HER2-targeted therapies and their adverse effects, the incorporation of cannabinoids into treatment regimens may offer a novel and beneficial strategy for managing HER2-positive ovarian cancer.”
“Background: The therapeutic use of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) to treat migraine has been understudied. Using three mouse models, we examined the impact of CBD and THC on migraine-relevant behaviors triggered by: 1) calcitonin gene-related peptide (CGRP), 2) sodium nitroprusside (SNP), and 3) cortical spreading depolarization (CSD).
Methods: Both male and female CD1 mice were treated with CBD (100 mg/kg) or THC (1 mg/kg) alone or in combinations of CBD (1, 30 or 100 mg/kg) and THC (1 mg/kg) prior to injection of CGRP or SNP. The mice were assessed for light aversion (photophobia), squint (non-evoked pain), and periorbital tactile hypersensitivity, as well as possible adverse effects. In a separate set of experiments, CSD events were optogenetically induced in familial hemiplegic migraine 1 (FHM1) mutant and wildtype littermates (WT) mice (C57BL/6 background), followed by grimace and motor assessments with and without combinations of CBD (30 or 100 mg/kg) and THC (1 mg/kg).
Results: In CD1 mice, a 100:1 CBD:THC combination mitigated light aversion induced by CGRP and SNP in males and females. Rescue of CGRP- and SNP-induced squint was observed only in male mice with 100:1 CBD:THC. None of the treatments rescued periorbital tactile hypersensitivity in either sex. In FHM1 mutant and WT mice, the 100:1 CBD:THC ratio did not affect CSD characteristics but did reduce CSD-induced grimace features (i.e., head pain mimic). No adverse effects of any of the cannabinoid treatments were observed using cognitive, emotional, or motor tests.
Conclusions: A 100:1 ratio of CBD:THC has a beneficial effect on some of the most bothersome migraine-related symptoms in three mouse models. Our findings support a potential therapeutic efficacy of combined CBD and THC treatments.”
“Our preclinical findings suggest that cannabinoids may have therapeutic potential for treating migraine symptoms without causing adverse effects. These findings are in line with previous studies that have suggested that cannabinoids may be effective in treating pain and migraine.”
“Despite extensive research on insulin resistance, which is associated with type 2 diabetes and obesity, there remains a lack of effective and safe methods to treat it. Thus, we hypothesized that cannabidiol (CBD), which influences lipid accumulation and inflammatory response, may interact with sphingolipid metabolism and insulin signaling.
To investigate the effects of CBD, male Wistar rats were fed a standard rodent chow or high-fat diet for 7 weeks to induce IR and were treated with CBD or its vehicle administered intraperitoneally for the last two weeks of the experiment. High-Performance Liquid Chromatography (HPLC) was used to assess sphingolipid concentration in the liver, while multiplex assay and western blotting were used to investigate the level or expression of proteins in the insulin signaling pathway and sphingolipid metabolism.
Our results revealed that CBD prevented ceramide deposition in the liver of high-fat-fed rats through inhibition of the ceramide de novo synthesis pathway. Moreover, the accumulation of sphingosine-1-phosphate was notably increased with impaired catabolic pathway. Observed changes in the sphingolipid pathway coincided with improved insulin signaling after CBD treatment in animals fed a high-fat diet.
Considering the presented evidence, CBD exerted a beneficial effect on insulin sensitivity in a state of lipid overload through the modification of sphingolipid deposition.
Our study reveals the importance of broadening IR treatment methods, especially with natural substances that lack serious side effects such as CBD.”
“Purpose of review: This review explores how cannabis impacts the gut microbiome, immune system, and ART outcomes in people with HIV (PWH). Given the increasing prevalence of cannabis use among PWH, we investigated its potential to reduce chronic inflammation and enhance gut health, both of which can influence HIV pathogenesis.
Recent findings: Cannabis has immunomodulatory and anti-inflammatory effects, including reducing systemic inflammatory biomarkers (such as MCP-1 and IP-10) and improving gut barrier integrity through increased short-chain fatty acid (SCFA) production.
Studies have shown that cannabis use is associated with increased gut mucosal immunity, decreased immune activation, and a unique microbiome composition. Preliminary evidence indicates that cannabis may influence HIV reservoirs, although the results remain inconclusive.
Cannabis shows promise in managing inflammation, gut dysbiosis, and immune dysfunction in PWH. However, its effects on HIV reservoirs, adherence to antiretroviral therapy, and long-term outcomes need further investigation through rigorous clinical trials using standardized formulations.”
“Across the United States, there is increased use of cannabis products and electronic delivery systems for cannabis products and nicotine, yet little is known about their impacts on lung health.
We analyzed exhaled breath condensate of 254 participants who were non-users and users who used cannabis and tobacco products. The 132 participants reported using a product (“users”) were distributed into cohorts of tobacco products and cannabis products, with some participants following into multiple cohorts.
Targeted analysis of inflammatory oxylipins found up-regulation among persons using tobacco products, while cannabis users had concentrations closer to nonusers, and often down-regulated.
Untargeted screening of 403 significant metabolites found tobacco users had similar breath profiles, and that cannabis users had a similar profile that was closer to the profile of nonusers.
Metabolites were significantly higher in breath of people using combustion products (tobacco and cannabis) relative to nonusers, and significantly lower in e-device users (nicotine and THC). Our work demonstrates the relative impact of e-delivery systems and cannabis products compared to traditional cigarette smoking on lung metabolic profiles.”
“Analysis of exhaled breath condensate was used to compare human metabolomic information of persons using tobacco and cannabis related products. Targeted measurements of oxylipin inflammatory markers found significant up-regulation among those using tobacco products relative to nonusers.
Cannabis users exhibited oxylipin levels closer to and often downregulated compared to nonusers. However, direct links to clinical outcomes such as lung disease or respiratory dysfunction were not established, limiting conclusions about the clinical impact of these biomarkers.
Untargeted screening of breath metabolites found that users of cigarettes, nicotine vapes, and any tobacco product had similar metabolite profiles, whereas cannabis smokers, vapers, and product users had a profile that was more similar to nonusers.”
“This research focused on developing a hemp protein concentrate through a potential sustainable method, with nutritional and industrial value for the emerging alternative protein industry.
By response surface methodology, the optimal processing conditions (100% ethanol, 50°C, and 10% w/v solid-to-solvents ratio) resulted in a hemp protein concentrate with 68.61% ± 1.71% protein. The process had a protein yield value of 94.11% ± 4.45%, which aligns with current sustainable food processing trends and is an excellent value compared to traditional methods for hemp seeds.
The concentrate met nutritional quality criteria for most examined parameters and showed positive results regarding essential amino acids absorption through in vitro digestion compared to nonessential amino acids. Furthermore, its techno-functional properties, particularly oil-holding capacity, emulsification properties, and gelling qualities achieved commercial standards.
This research validates the potential for producing new protein concentrates from dehulled hemp seeds through an innovative green chemistry-based method.
PRACTICAL APPLICATION: The research presents a method based on green chemistry for the obtention of hemp protein concentrate from hemp seeds. Hemp seeds are not considered a “novel food” according to the European Commission. Hemp protein concentrate had 95% protein yield and similar or better functional properties compared to commercial proteins. Thus, hemp protein is an important product for food industry applications.”
