Monthly Archives: January 2023

Anti-Inflammatory Effects of Cannabigerol in Rheumatoid Arthritis Synovial Fibroblasts and Peripheral Blood Mononuclear Cell Cultures Are Partly Mediated by TRPA1

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“Since its medical legalization, cannabis preparations containing the major phytocannabinoids (cannabidiol (CBD) and δ9-tetrahydrocannabinol (THC)) have been used by patients with rheumatoid arthritis (RA) to alleviate pain and inflammation. However, minor cannabinoids such as cannabigerol (CBG) also demonstrated anti-inflammatory properties, but due to the lack of studies, they are not widely used. CBG binds several cellular target proteins such as cannabinoid and α2-adrenergic receptors, but it also ligates several members of the transient potential receptor (TRP) family with TRPA1 being the main target. TRPA1 is not only involved in nnociception, but it also protects cells from apoptosis under oxidative stress conditions. Therefore, modulation of TRPA1 signaling by CBG might be used to modulate disease activity in RA as this autoimmune disease is accompanied by oxidative stress and subsequent activation of pro-inflammatory pathways. Rheumatoid synovial fibroblasts (RASF) were stimulated or not with tumor necrosis factor (TNF) for 72 h to induce TRPA1 protein. CBG increased intracellular calcium levels in TNF-stimulated RASF but not unstimulated RASF in a TRPA1-dependent manner. In addition, PoPo3 uptake, a surrogate marker for drug uptake, was enhanced by CBG. RASF cell viability, IL-6 and IL-8 production were decreased by CBG. In peripheral blood mononuclear cell cultures (PBMC) alone or together with RASF, CBG-modulated interleukin (IL)-6, IL-10, TNF and immunoglobulin M and G production which was dependent on activation stimulus (T cell-dependent or independent). However, effects on PBMCs were only partially mediated by TRPA1 as the antagonist A967079 did inhibit some but not all effects of CBG on cytokine production. In contrast, TRPA1 antagonism even enhanced the inhibitory effects of CBG on immunoglobulin production. CBG showed broad anti-inflammatory effects in isolated RASF, PBMC and PBMC/RASF co-cultures. As CBG is non-psychotropic, it might be used as add-on therapy in RA to reduce IL-6 and autoantibody levels.”

https://pubmed.ncbi.nlm.nih.gov/36614296/

“Therefore, CBG might be suited as an adjunct therapy for RA to reduce cytokine and autoantibody production.”

https://www.mdpi.com/1422-0067/24/1/855

Cannabidiol as Self-Assembly Inducer for Anticancer Drug-Based Nanoparticles

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“Cannabidiol (CBD) is a biologically active compound present in the plants of the Cannabis family, used as anticonvulsant, anti-inflammatory, anti-anxiety, and more recently, anticancer drug. In this work, its use as a new self-assembly inducer in the formation of nanoparticles is validated. The target conjugates are characterized by the presence of different anticancer drugs (namely N-desacetyl thiocolchicine, podophyllotoxin, and paclitaxel) connected to CBD through a linker able to improve drug release. These nanoparticles are formed via solvent displacement method, resulting in monodisperse and stable structures having hydrodynamic diameters ranging from 160 to 400 nm. Their biological activity is evaluated on three human tumor cell lines (MSTO-211H, HT-29, and HepG2), obtaining GI50 values in the low micromolar range. Further biological assays were carried out on MSTO-211H cells for the most effective NP 8B, confirming the involvement of paclitaxel in cytotoxicity and cell death mechanism.”

https://pubmed.ncbi.nlm.nih.gov/36615306/

https://www.mdpi.com/1420-3049/28/1/112

Medical Cannabis in Hand Surgery: A Review of the Current Evidence

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The Journal of Hand Surgery

“Acute and chronic pain management remains an ongoing challenge for hand surgeons. This has been compounded by the ongoing opioid epidemic in the United States.

With the increasing legalization of medical and recreational cannabis throughout the United States and other countries, previous societal stigmas about this substance keep evolving, and recognition of medical cannabis as an opioid-sparing pain management alternative is growing. A review of the current literature demonstrates a strong interest from patients regarding the use of medical cannabis for pain control.

Current evidence demonstrates its efficacy and safety for chronic musculoskeletal and neuropathic pain. However, definitive conclusions regarding the efficacy of cannabis for pain control in hand and upper extremity conditions require continued investigation.

The purpose of this article is to provide a general review of the mechanism of medical cannabis and a scoping review of the current evidence for its efficacy, safety, and potential applicability in hand and upper extremity conditions.”

https://pubmed.ncbi.nlm.nih.gov/36609049/

https://www.jhandsurg.org/article/S0363-5023(22)00710-9/fulltext

Preoperative Preparation and Guidelines for Cannabis-Using Patients Undergoing Elective Surgery

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“Purpose: Appropriate preoperative screening techniques are needed to safely provide anesthesia to increasing numbers of cannabis using surgical patients.

Design: This was a quasi-experimental quality improvement project.

Methods: Preoperative identification of cannabis users by registered nurses (RNs) and certified registered nurse anesthetists (CRNAs) was compared to baseline identification rates. CRNAs’ compliance with evidenced base guidelines was recorded. Perioperative medication requirements were recorded and compared between cannabis-users and non-cannabis users.

Findings: Identification of cannabis users by CRNAs conducting preanesthetic assessments increased from 4.08% to 14.36% while RN identification improved from 11.22% to 13.81%. Compliance with identification guidelines was 69.2% among CRNAs.

There were no differences in anesthetic requirements, complications, or postanesthesia care unit (PACU) length of stay between cannabis users and non-users.

Conclusion: Preoperative identification of cannabis users allows for safer, more effective perioperative care by CRNAs, registered nurses, and surgical staff.”

https://pubmed.ncbi.nlm.nih.gov/36609136/

https://www.jopan.org/article/S1089-9472(22)00544-5/fulltext

Formulation and development of novel lipid-based combinatorial advanced nanoformulation for effective treatment of non-melanoma skin cancer

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International Journal of Pharmaceutics

“Non-melanoma skin cancer is one of the most common malignancies reported with high number of morbidities, demanding an advanced treatment option with superior chemotherapeutic effects. Due to high degree of drug resistance, conventional therapy fails to meet the desired therapeutic efficacy. To break the bottleneck, nanoparticles have been used as next generation vehicles that facilitate the efficient interaction with the cancer cells.

Here, we developed combined therapy of 5-fluorouracil (5-FU) and cannabidiol (CBD)-loaded nanostructured lipid carrier gel (FU-CBD-NLCs gel). The NLCs were optimized using central composite design that showed an average particle size of 206 nm and a zeta potential of -34 mV. In addition, in vitro and ex vivo drug permeations studies demonstrated the effective delivery of both drugs in the skin layers via lipid structured nanocarriers.

Also, the prepared FU-CBD-NLCs showed promising effect in-vitro cell studies including MTT assays, wound healing and cell cycle as compared to the conventional formulation. Moreover, dermatokinetic studies shows there was superior deposition of drugs at epidermal and the dermal layer when treated with FU-CBD-NLCs.

In the end, overall study offered a novel combinatorial chemotherapy that could be an option for the treatment of non-melanoma skin cancer.”

https://pubmed.ncbi.nlm.nih.gov/36608807/

https://www.sciencedirect.com/science/article/abs/pii/S0378517322011358?via%3Dihub

[A mini-review on anti-tumor effect of cannabidiol]

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“Cannabidiol is the main non-psychoactive component of Cannabis sativa, which has multiple medicinal activities, such as antiepileptic, immunomodulation, analgesic, antioxidant, anticonvulsant, anti-anxiety and other functions.

In recent years, it has been found that cannabidiol can inhibit the proliferation of various tumor cells, induce apoptosis and autophagy of tumor cells, arrest cell cycle, interrupt invasion and metastasis of tumor cells, regulate tumor microenvironment, exert synergistic therapy with other chemotherapeutic drugs, and reduce the toxicity of chemotherapeutic drugs. However, its anti-tumor effect remains controversial and its application is limited. The study of microspheres, nano liposomes and other new drug delivery systems can improve the anti-tumor effect of cannabidiol.

In this study, the anti-tumor mechanism and application of cannabidiol were summarized and discussed in order to provide inspirations for its further investigation and application.”

https://pubmed.ncbi.nlm.nih.gov/36604902/

https://kns.cnki.net/kcms/detail/detail.aspx?doi=10.19540/j.cnki.cjcmm.20220906.601

Potential effects of cannabinoids on audiovestibular function: A narrative review

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Frontiers - Crunchbase Company Profile & Funding

“The growing interest in the development of drugs that target the endocannabinoid system has extended to conditions that affect the audiovestibular pathway. The expression of cannabinoid (CB) receptors in that pathway has been widely demonstrated, indicating a therapeutic potential for drug development at this level. These medications may be beneficial for conditions such as noise-induced hearing loss, ototoxicity, or various forms of vertigo of central or peripheral origin. The therapeutic targets of interest include natural or synthetic compounds that act as CB1/CB2 receptor agonists/antagonists, and inhibitors of the endocannabinoid-degrading enzymes FAAH and MAGL. Furthermore, genetic variations implicated in the response to treatment and the development of related disorders such as epilepsy or migraine have been identified. Direct methods of administering these medications should be examined beyond the systemic strategy.”

https://pubmed.ncbi.nlm.nih.gov/36605398/

https://www.frontiersin.org/articles/10.3389/fphar.2022.1010296/full

Evaluating the impact of cannabinoids on sleep health and pain in patients with chronic neuropathic pain: a systematic review and meta-analysis of randomized controlled trials

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“Background: Chronic neuropathic pain is often debilitating and can have a significant impact on sleep health and quality of life. There is limited information on the impact of cannabinoids on sleep health when treating neuropathic pain.

Objective: The objectives of this systematic review and meta-analysis were to determine the effect of cannabinoids on sleep quality, pain intensity, and patient impression of treatment efficacy in patients with neuropathic pain.

Evidence review: Nine available medical literature databases were searched for randomized controlled trials comparing synthetic and natural cannabinoids to placebo in patients with neuropathic pain syndromes. Data on validated tools for sleep quality, pain intensity, patients’ global impression of change (PGIC), and incidence of adverse effects of cannabinoids were extracted and synthesized.

Findings: Of the 3491 studies screened, eight randomized controlled trials satisfied the inclusion criteria for this review. Analyses were performed using R -4.1.2. using the metafor package and are interpreted using alpha=0.05 as the threshold for statistical significance. Validated measures for sleep health were not used in most studies. Meta-analysis of data from six studies showed that cannabinoids were associated with a significant improvement in sleep quality (standardized mean difference (SMD): 0.40; 95% CI: 0.19 to -0.61, 95% prediction interval (PI): -0.12 to 0.88, p-value=0.002, I2=55.26, τ2=0.05, Q-statistic=16.72, GRADE: moderate certainty). Meta-analysis of data from eight studies showed a significant reduction in daily pain scores in the cannabinoid (CB) group (SMD: -0.55, 95% CI:-0.69 to -0.19, 95% PI: -1.51 to 0.39, p=0.003, I2=82.49, τ2=0.20, Q-statistic=47.69, GRADE: moderate certainty). However, sleep health and analgesic benefits were associated with a higher likelihood of experiencing daytime somnolence, nausea, and dizziness.

Conclusions: Cannabinoids have a role in treating chronic neuropathic pain as evidenced by significant improvements in sleep quality, pain intensity, and PGIC. More research is needed to comprehensively evaluate the impact of cannabinoids on sleep health and analgesic efficacy.”

https://pubmed.ncbi.nlm.nih.gov/36598058/

https://rapm.bmj.com/content/early/2022/12/04/rapm-2021-103431

The function of the endocannabinoid system in the pancreatic islet and its implications on metabolic syndrome and diabetes

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“The following review focuses on the scientific studies related to the role of endocannabinoid system (ECS) in pancreatic islet physiology and dysfunction. Different natural or synthetic agonists and antagonists have been suggested as an alternative treatment for diabetes, obesity and metabolic syndrome. Therapeutic use of Cannabis led to the discovery and characterization of the ECS, a signaling complex involved in regulation of various physiological processes, including food intake and metabolism. After the development of different agonists and antagonists, evidence have demonstrated the presence and activity of cannabinoid receptors in several organs and tissues, including pancreatic islets. Insulin and glucagon expression, stimulated secretion, and the development of diabetes and other metabolic disorders have been associated with the activity and modulation of ECS in pancreatic islets. However, according to the animal model and experimental design, either endogenous or pharmacological ligands of cannabinoid receptors have guided to contradictory and paradoxical results that suggest a complex physiological interaction. In consensus, ECS activity modulates insulin and glucagon secretions according to glucose in media; over-stimulation of cannabinoid receptors affects islets negatively, leading to glucose intolerance, meanwhile the treatment with antagonists in diabetic models and humans suggests an improvement in islets function.”

https://pubmed.ncbi.nlm.nih.gov/36598083/

https://www.tandfonline.com/doi/full/10.1080/19382014.2022.2163826

Recreational cannabis legalization has had limited effects on a wide range of adult psychiatric and psychosocial outcomes

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Psychological Medicine

“Background: The causal impacts of recreational cannabis legalization are not well understood due to the number of potential confounds. We sought to quantify possible causal effects of recreational cannabis legalization on substance use, substance use disorder, and psychosocial functioning, and whether vulnerable individuals are more susceptible to the effects of cannabis legalization than others.

Methods: We used a longitudinal, co-twin control design in 4043 twins (N = 240 pairs discordant on residence), first assessed in adolescence and now age 24-49, currently residing in states with different cannabis policies (40% resided in a recreationally legal state). We tested the effect of legalization on outcomes of interest and whether legalization interacts with established vulnerability factors (age, sex, or externalizing psychopathology).

Results: In the co-twin control design accounting for earlier cannabis frequency and alcohol use disorder (AUD) symptoms respectively, the twin living in a recreational state used cannabis on average more often (βw = 0.11, p = 1.3 × 10-3), and had fewer AUD symptoms (βw = -0.11, p = 6.7 × 10-3) than their co-twin living in an non-recreational state. Cannabis legalization was associated with no other adverse outcome in the co-twin design, including cannabis use disorder. No risk factor significantly interacted with legalization status to predict any outcome.

Conclusions: Recreational legalization was associated with increased cannabis use and decreased AUD symptoms but was not associated with other maladaptations. These effects were maintained within twin pairs discordant for residence. Moreover, vulnerabilities to cannabis use were not exacerbated by the legal cannabis environment. Future research may investigate causal links between cannabis consumption and outcomes.”

https://pubmed.ncbi.nlm.nih.gov/36601811/

https://www.cambridge.org/core/journals/psychological-medicine/article/abs/recreational-cannabis-legalization-has-had-limited-effects-on-a-wide-range-of-adult-psychiatric-and-psychosocial-outcomes/D4AB5EB78D588473A054877E05D45F16