The Therapeutic Potential and Molecular Mechanisms Underlying the Neuroprotective Effects of Sativex® – A Cannabis-derived Spray

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“Sativex is a cannabis-based medicine that comes in the form of an oromucosal spray. It contains equal amounts of Δ9-tetrahydrocannabinol and cannabidiol, two compounds derived from cannabis plants.

Sativex has been shown to have positive effects on symptoms of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and sleep disorders. It also has analgesic, antiinflammatory, antitumoral, and neuroprotective properties, which make it a potential treatment option for other neurological disorders.

The article reviews the results of recent preclinical and clinical studies that support the therapeutic potential of Sativex and the molecular mechanisms behind its neuroprotective benefits in various neurological disorders. The article also discusses the possible advantages and disadvantages of using Sativex as a neurotherapeutic agent, such as its safety, efficacy, availability, and legal status.”

https://pubmed.ncbi.nlm.nih.gov/38318827/

https://www.eurekaselect.com/article/138318

Topical Noneuphoric Phytocannabinoid Elixir 14 Reduces Inflammation and Mitigates Burn Progression

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“Introduction: Thermal injuries are caused by exposure to a wide variety of agents including heat, electricity, radiation, chemicals, and friction. Early intervention can decrease injury severity by preventing excess inflammation and mitigating burn wound progression for improved healing outcomes.

Previous studies have demonstrated that cannabinoids can trigger anti-inflammatory responses and promote wound closure.

Therefore, the purpose of this study was to investigate whether a topical application of Noneuphoric Phytocannabinoid Elixir 14 (NEPE14) containing a full complement of phytocannabinoids (< 0.3% delta-9-tetrahydrocannabinol or cannabidiol) and other phytochemicals would mitigate burn wound progression in the treatment of deep partial-thickness burn wounds.

Methods: Deep partial-thickness burns were created on the dorsum of four anesthetized pigs and treated with NEPE14, Vehicle control, Silverlon, or gauze. The burns were assessed on postburn days 4, 7, and 14. Assessments consisted of digital photographs, Laser-Speckle imagery (blood perfusion), MolecuLight imagery (qualitative bacterial load), and biopsies for histology and immunohistochemistry (interleukin six and tumor necrosis factor-α).

Results: Topical treatment with NEPE14 significantly (P < 0.001) decreased inflammation (interleukin six and tumor necrosis factor-α) in comparison to control groups. It was also demonstrated that the reduction in inflammation led to mitigation of burn wound progression. In terms of wound healing and presence of bacteria, no statistically significant differences were observed.

Conclusions: Topical treatment of deep partial-thickness burns with NEPE14 decreased wound inflammation and mitigated burn wound progression in comparison to control treatments.”

https://pubmed.ncbi.nlm.nih.gov/38320364/

https://www.journalofsurgicalresearch.com/article/S0022-4804(24)00037-4/fulltext

Cannabidiol for Postoperative Pain Control After Arthroscopic Rotator Cuff Repair Demonstrates No Deficits in Patient-Reported Outcomes Versus Placebo: 1-Year Follow-up of a Randomized Controlled Trial

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“Background: Cannabidiol (CBD) has been shown recently to positively affect patient pain and satisfaction immediately after arthroscopic rotator cuff repair (ARCR). However, it is unclear whether the addition of CBD to a perioperative regimen could affect postoperative outcomes.

Purpose: To evaluate patient-reported outcomes among patients who underwent ARCR and received buccally absorbed CBD or an identical placebo for early postoperative pain management at 1-year follow-up.

Study design: Randomized controlled trial; Level of evidence, 2.

Methods: Eligible patients had previously participated in a multicenter, placebo-controlled, randomized, double-blinded trial that evaluated the analgesic effects of CBD in the immediate postoperative period after ARCR. The experimental group received 25 mg of CBD 3 times/day if <80 kg and 50 mg of CBD 3 times/day if >80 kg for 14 days, with the control group receiving an identical placebo. The following outcomes were assessed at minimum 1-year follow-up: visual analog scale (VAS) for pain, American Shoulder and Elbow Surgeons (ASES) score, Single Assessment Numeric Evaluation (SANE), and patient satisfaction. The rates of achievement of the Patient Acceptable Symptom State (PASS) were compared based on ASES at latest follow-up. Continuous and categorical variables were compared with the Mann-Whitney U test and Fisher exact test, respectively.

Results: Follow-up was obtained from 83 of 99 patients (83.8%) who completed the original trial. There were no significant differences between the CBD and control groups with respect to age, sex, body mass index, rate of concomitant procedures, or number of anchors used intraoperatively. At 1-year follow-up, there were no significant differences between the CBD and control groups in VAS pain (0.8 vs 1.2, P = .38), ASES (93.0 vs 91.1, P = .71), SANE (87.6 vs 90.1, P = .24), or satisfaction (97.4 vs 95.4, P = .41). A majority of patients achieved the PASS (81.0% [CBD] vs 77.5% [control]; P = .79).

Conclusion: Perioperative use of CBD for pain control among patients undergoing ARCR did not result in any significant deficits in pain, satisfaction, or patient-reported outcomes at 1-year postoperatively compared with a placebo control group. These findings suggest that CBD can be considered in a postoperative multimodal pain management regimen without detrimental effects on outcome.”

https://pubmed.ncbi.nlm.nih.gov/38322981/

“The Cannabis sativa plant is a promising alternative for augmented pain control”

https://journals.sagepub.com/doi/10.1177/23259671231222265

Integrated transcriptome and cell phenotype analysis suggest involvement of PARP1 cleavage, Hippo/Wnt, TGF-β and MAPK signaling pathways in ovarian cancer cells response to cannabis and PARP1 inhibitor treatment

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“Introduction: Cannabis sativa is utilized mainly for palliative care worldwide. Ovarian cancer (OC) is a lethal gynecologic cancer. A particular cannabis extract fraction (‘F7’) and the Poly(ADP-Ribose) Polymerase 1 (PARP1) inhibitor niraparib act synergistically to promote OC cell apoptosis. Here we identified genetic pathways that are altered by the synergistic treatment in OC cell lines Caov3 and OVCAR3. 

Materials and methods: Gene expression profiles were determined by RNA sequencing and quantitative PCR. Microscopy was used to determine actin arrangement, a scratch assay to determine cell migration and flow cytometry to determine apoptosis, cell cycle and aldehyde dehydrogenase (ALDH) activity. Western blotting was used to determine protein levels. 

Results: Gene expression results suggested variations in gene expression between the two cell lines examined. Multiple genetic pathways, including Hippo/Wnt, TGF-β/Activin and MAPK were enriched with genes differentially expressed by niraparib and/or F7 treatments in both cell lines. Niraparib + F7 treatment led to cell cycle arrest and endoplasmic reticulum (ER) stress, inhibited cell migration, reduced the % of ALDH positive cells in the population and enhanced PARP1 cleavage. 

Conclusion: The synergistic effect of the niraparib + F7 may result from the treatment affecting multiple genetic pathways involving cell death and reducing mesenchymal characteristics.”

https://pubmed.ncbi.nlm.nih.gov/38322025/

“Cannabis sativa is utilized worldwide for palliative care and to alleviate various symptoms associated with medical conditions. Several dozen compounds are biosynthesized in the female inflorescence of each C. sativa strain. In total, around 600 different molecules can be found in cannabis, among them around 150 phytocannabinoids and hundreds of flavonoids and terpenes

Multiple studies suggest that phytocannabinoids have anti-cancer properties.

They inhibit several different features associated with cancer cells and tumors, including inhibiting cell proliferation and migration, inducing cell death, reducing angiogenesis, and inhibiting cancer cells’ invasiveness. This was demonstrated in several different cancer types, including cancers of the skin, lung, breast, prostate, and brain.

The best-studied anti-cancer activity is that of the most common phytocannabinoids cannabidiol (CBD) and Δ9–tetrahydrocannabinol (THC), and related synthetic compounds (e.g., HU-210 and WIN-55 212-2).

Phytocannabinoids have been found to affect cancer cells and tumors via several different genetic pathways and molecular mechanisms. For example, several signal transduction pathways can be activated by phytocannabinoids to induce cancer cell death, including cell cycle arrest, endoplasmic reticulum (ER) stress, oxidative stress, autophagy and/or apoptosis.”

https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1333964/full


Antiviral Activities of Cannabis

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“Despite the history of scientific evidence regarding plants and their products in prophylactics and therapeutics, their applications in healthcare systems are only now gaining momentum.

Plants contain bioactive compounds that target certain viruses to cure or prevent viral diseases and infections.

They provide a rich resource of antiviral drugs. Identifying the antiviral mechanisms in plants has shed light on where they interact with the life cycle of viruses, such as viral entry, replication, assembly, and release.”

https://link.springer.com/chapter/10.1007/978-3-031-35155-6_13

Cannabis Perceptions and Patterns of Use Among Older Adult Cancer Survivors

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“Objectives: To descriptively assess cannabis perceptions and patterns of use among older adult cancer survivors in a state without a legal cannabis marketplace. 

Methods: This study used weighted prevalence estimates to cross-sectionally describe cannabis perceptions and patterns of use among older (65+) adults (N = 524) in a National Cancer Institute-designated center in a state without legal cannabis access. 

Results: Half (46%) had ever used cannabis (18% following diagnosis and 10% currently). Only 8% had discussed cannabis with their provider. For those using post-diagnosis, the most common reason was for pain (44%), followed by insomnia (43%), with smoking being the most common (40%) mode of use. Few (<3%) reported that cannabis had worsened any of their symptoms. 

Discussion: Even within a state without a legal cannabis marketplace, older cancer survivors might commonly use cannabis to alleviate health concerns but unlikely to discuss this with their providers.”

https://pubmed.ncbi.nlm.nih.gov/38311859/

https://journals.sagepub.com/doi/10.1177/08982643241231320

Terpenes and cannabidiol against human corona and influenza viruses-Anti-inflammatory and antiviral in vitro evaluation

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“The activity of the terpenes and Cannabidiol (CBD) against human coronavirus (HCoV) strain OC43 and influenza A (H1N1) was evaluated in human lung fibroblasts (MRC-5 cells). Also, we examined whether these ingredients inhibit pro-inflammatory cytokines in peripheral blood mononuclear cells (PBMC).

The tested preparations exhibited both anti-inflammatory and antiviral effects. The combination of terpenes was effective against both HCoV-OC43 and influenza A (H1N1) virus.

The addition of CBD improved the antiviral activity in some, but not all cases. This variation in activity may suggest an antiviral mechanism. In addition, there was a strong correlation between the quantitative results from a cell-viability assay and the cytopathic effect after 72 h, as observed under a microscope.

The anti-inflammatory properties of terpenes were demonstrated using a pro-inflammatory cytokine-inhibition assay, which revealed significant cytokine inhibition and enhanced by the addition of CBD.”

https://pubmed.ncbi.nlm.nih.gov/38318445/

https://www.sciencedirect.com/science/article/pii/S2215017X2400002X?via%3Dihub

Perceptions of Orthopaedic Sports Medicine Surgeons About Medical Cannabidiol Use: A Survey Study

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“Introduction: Multiple studies exist identifying cannabidiol (CBD) as an effective part of an orthopaedic patient’s pain regimen; however, there is a paucity of studies elucidating orthopaedic surgeons’ perception of the use and prescription of CBD in the medical setting. This study surveys orthopaedic sports medicine surgeons about their previous education on and current perceptions and usage of CBD in their medical practice.

Methods: Between April 2023 and July 2023, orthopaedic sports medicine surgeons from across the country were surveyed. This survey was designed in hopes of identifying physician perceptions and current use of CBD as well as their previous education and training on its use.

Results: Overall, 75 orthopaedic surgeons responded. More than three-fourths of responders had not received formal education on medical CBD use, nor did they have partners or colleagues who used CBD in their practice. More than half of all surgeons believed that there is a stigma associated with CBD use. A higher proportion of surgeons from CBD legal states recommended CBD to help patients control their pain (53.7% vs. 37.5%). Less than 15% of responders believed that CBD can adversely affect surgical outcomes. Finally, four-fifths of all responders believed that CBD is easy to legally access and affordable to buy by patients who desire it.

Discussion: The relative novelty of CBD inclusion in medicine has led to a lack of early education and overall experience with its use among orthopaedic sports medicine surgeons. Still, surgeons believe that CBD is a safe and effective option to control pain. As surgeons continue to gain more familiarity and trust with CBD’s medical uses over time, it has the potential to be a mainstay in orthopaedic multimodal pain regimens.”

https://pubmed.ncbi.nlm.nih.gov/38318555/

https://www.cureus.com/articles/205336-perceptions-of-orthopaedic-sports-medicine-surgeons-about-medical-cannabidiol-use-a-survey-study#!/

Cannabidiol Alleviates Perfluorooctanesulfonic Acid-Induced Cardiomyocyte Apoptosis by Maintaining Mitochondrial Dynamic Balance and Energy Metabolic Homeostasis

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“Perfluorooctanesulfonic acid (PFOS), a fluorine-containing organic compound, can be widely detected in the environment and living organisms. Accumulating evidence has shown that PFOS breaks through different biological barriers resulting in cardiac toxicity, but the underlying molecular mechanisms remain unclear.

Cannabidiol (CBD) is a nonpsychoactive cannabinoid without potential adverse cardiotoxicity and has antioxidant and anti-inflammatory properties that reduce multiorgan damage and dysfunction.

For these reasons, the aim of this study was to research how PFOS caused heart injury and whether CBD could attenuate PFOS-induced heart injury.

Mice were fed PFOS (5 mg/kg) and/or CBD (10 mg/kg) in vivo. In vitro, H9C2 cells were intervened with PFOS (200 μM) and/or CBD (10 μM). After PFOS exposure, oxidative stress levels and the mRNA and protein expression of apoptosis-related markers increased distinctly, accompanied by mitochondrial dynamic imbalance and energy metabolism disorders in mouse heart and H9C2 cells. Moreover, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, acridine orange/ethidium bromide staining and Hoechst 33258 staining signaled that the number of apoptotic cells increased after exposure to PFOS.

Noteworthy, CBD simultaneous treatment alleviated a series of damages caused by PFOS-mediated oxidative stress.

Our results demonstrated that CBD could alleviate PFOS-induced mitochondrial dynamics imbalance and energy metabolism disorder causing cardiomyocyte apoptosis by improving the antioxidant capacity, suggesting that CBD may represent a novel cardioprotective strategy against PFOS-induced cardiotoxicity.

Our findings facilitate the understanding of the cardiotoxic effects of PFOS and the important role of CBD in protecting cardiac health.”

https://pubmed.ncbi.nlm.nih.gov/37010249/

Multi-targeting inulin-based nanoparticles with cannabidiol for effective prevention of ulcerative colitis

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“The pathogenesis of ulcerative colitis (UC) is closely related to severe inflammation, damaged colonic mucosal barrier, increased oxidative stress and intestinal ecological imbalance. However, due to the nonspecific distribution and poor bioavailability of drugs, UC treatment is still a serious challenge. Here, a mitochondria/colon dual targeted nanoparticles based on redox response was developed to effectively alleviate UC.

Cannabidiol nanoparticles (CBD NPs) with a particle size of 143.2 ± 3.11 nm were prepared by self-assembly using polymers (TPP-IN-LA) obtained by modifying inulin with (5-carboxypentyl) triphenyl phosphonium bromide (TPP) and α-lipoic acid (α-LA). Excitingly, the constructed CBD NPs showed excellent mitochondrial targeting, with a Pearson correlation coefficient of 0.76 at 12 h.

The results of animal imaging in vivo showed that CBD NPs could be effectively accumulated in colon tissue. Not only that, CBD showed significant glutathione stimulated release in the presence of 10 mM glutathione at pH 7.4.

The results of in vivo animal experiments showed that CBD NPs significantly ameliorated DSS-induced colonic inflammation by modulating the TLR4-NF-κB signaling pathway. Moreover, CBD NPs significantly improved the histological damage of colon in UC mice, increased the expression level of tight junction protein ZO-1, and effectively restored the intestinal mucosal barrier function and intestinal mucosal permeability.

More importantly, CBD NPs significantly improved the species composition, abundance and amount of short chain fatty acids of intestinal flora in UC mice, thus effectively maintaining the balance of intestinal flora. The dual-targeted and glutathione-responsive nanoparticles prepared in this study provide a promising idea for achieving targeted delivery of CBD for effective treatment of UC.”

https://pubmed.ncbi.nlm.nih.gov/38318477/

https://linkinghub.elsevier.com/retrieve/pii/S2590006424000243