“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.”
“Overview: Cannabinoids have gained increasing attention for their therapeutic potential in treating several neurological conditions, including neurodegenerative diseases, chronic pain, and epilepsy. This review aims to assess the current clinical trials investigating cannabinoids, primarily Tetrahydrocannabinol and Cannabidiol, for neurological disorders. This review will aim to highlight the efficacy, safety, and outcome measures used in these trials.
Methods: Clinical trials were identified using ClinicalTrials.gov, focusing on studies that examined the effects of cannabinoids in treating neurological conditions. All trials that fulfilled the following criteria were included: Phase 1-4, focused on cannabinoids as primary intervention, and measured relevant outcomes such as pain relief, cognitive function, or spasticity reduction. Data on conditions, interventions, primary and secondary outcomes, and trial phases were extracted and analysed.
Results: A total of 47 clinical trials were identified, including different neurological conditions. The most frequently studied conditions were Multiple Sclerosis, Fibromyalgia, and Parkinson’s Disease. Most trials were in Phase 2, with the primary outcome measures focused on pain management, spasticity, and cognitive function. Secondary outcomes included safety and tolerability measures.
Conclusion: The review highlights the broad therapeutic potential of cannabinoids in neurology, with promising results in symptom management for conditions like Multiple Sclerosis and Fibromyalgia. However, the lack of standardized study protocols, dosing, and outcome measures presents challenges for broader clinical implementation.”
“The results of this analysis showed that both CBD and THC have significant potential as therapeutic agents for neurological disorders, particularly in managing pain, motor dysfunction, and behavioural disturbances. However, their different pharmacological profiles and side effect risks mean that each cannabinoid may be better suited to different patient populations and conditions. While THC’s broader range of applications in cognitive and motor symptoms positions it as a more multipurpose treatment option, the psychoactive risks associated with its use should not be ignored. On the other hand, CBD’s safety and non-psychoactive nature make it more preferred option for managing chronic pain, but its therapeutic benefits may be more limited. Future research should focus on addressing the gaps in long-term safety and efficacy data, as well as exploring the full potential of lesser-known cannabinoids and combination therapies to further enhance the treatment of neurological disorders.”
“Background and aims: Conduct a pilot randomized double-blind placebo-controlled crossover trial for adults with subthreshold insomnia symptoms to examine the effectiveness of a cannabinoids supplement on sleep quality and health outcomes.
Methods: Adults with subthreshold insomnia symptoms (N = 20, Mage = 47.40) were randomized to either the Cannabinoids Supplement (CS) or Placebo Condition (PC) for 10 days. The CS was an oral soft gel that contained 3 mg Δ9-tetrahydrocannabinol, 6 mg cannabinol, 10 mg cannabidiol, and 90 mg of a proprietary food-grade terpene blend. Following a 2-week washout, they completed the alternate condition. The following validated questionnaires were collected at baseline and following each condition: Insomnia Severity Index, Pittsburgh Sleep Quality Index, Bergen Insomnia Scale, Profile of Mood States (POMS), Perceived Stress Scale, Pain and Sleep Questionnaire. Trait Anxiety Inventory, Flinders Daytime Fatigue, and Health-related Quality of Life Scale. Clinical trial registry number = ISRCTN 15022302.
Results: When compared to PC, the CS Condition had significantly improved sleep quality/efficiency, insomnia symptoms, and health-related quality of life, p < 0.05. Nonsignificant improvements for the CS compared to the PC were found for the POMS mood subscales of tension, anger, fatigue, depression, and vigor, as well as anxiety. The Esteem subscale improved significantly from Baseline to Post for the PC. Both the CS and PC Vigor improved significantly from baseline. Anxiety improved significantly from Baseline to Post for the CS. No adverse events reported.
Conclusion: This cannabinoid-based formulation was a well-tolerated oral supplement that may improve adults’ sleep quality/efficiency and health-related quality of life. Larger controlled trials are encouraged to examine the longer-term effects of this supplement in a variety of populations and environments.”
“Cannabidiol (CBD), the primary non-psychoactive cannabinoid isolated from cannabis, exhibits promising antibacterial effects. However, the antibacterial mechanism of CBD remains poorly understood.
In this study, the mechanism was investigated using bacterial inhibition assays, label-free proteomics, and untargeted metabolomics, with Bacillus licheniformis (B. licheniformis), Staphylococcus aureus (S. aureus), and Enterococcus faecium (E. faecium) selected as representative Gram-positive bacteria.
The results revealed that CBD caused significant damage to bacterial cell walls and membranes, leading to notable changes in proteomic and metabolic profiles. Specifically, 437, 120, and 195 proteins, as well as 52, 153, and 94 metabolites, were differentially expressed in B. licheniformis, S. aureus, and E. faecium, respectively.
The antimicrobial mechanism of CBD shares similarities with previously known antibacterial agents, such as penicillin and cephalosporins, particularly in affecting the bacterial cell wall, but differs in its detailed mode of action. CBD disrupted the biosynthesis of primary and secondary metabolites and altered bacterial metabolism, contributing to its antibacterial activity.
This study provides valuable insights into the antibacterial mechanism of CBD, supporting its potential development as an antibiotic alternative and its application in food safety.
SIGNIFICANCE: It is crucial to find alternatives to antibiotics to mitigate the impact of pathogenic bacteria on food safety and reduce the use of antibiotics. CBD is the primary non-psychoactive cannabinoid derived from cannabis, and it has shown promising antibacterial effects. However, the antimicrobial mechanisms of CBD have not been well elucidated. This study provides a deep understanding of the antibacterial mechanism from the cellular to molecular level, which will contribute to the development of CBD as a novel antibacterial agent.”
