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

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

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

Phytocannabinoids and gingival inflammation: Preclinical findings and a placebo-controlled double-blind randomized clinical trial with cannabidiol

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“Objective: The aim of this study was to: (1) evaluate the anti-inflammatory effects of cannabidiol (CBD) on primary cultures of human gingival fibroblasts (HGFs) and (2) to clinically monitor the effect of CBD in subjects with periodontitis.

Background: The use of phytocannabinoids is a new approach in the treatment of widely prevalent periodontal disease.

Materials and methods: Cannabinoid receptors were analyzed by western blot and interleukin production detected using enzyme immunoassay. Activation of the Nrf2 pathway was studied via monitoring the mRNA level of heme oxygenase-1. Antimicrobial effects were determined by standard microdilution and 16S rRNA screening. In the clinical part, a placebo-control double-blind randomized study was conducted (56 days) in three groups (n = 90) using dental gel without CBD (group A) and with 1% (w/w) CBD (group B) and corresponding toothpaste (group A – no CBD, group B – with CBD) for home use to maintain oral health. Group C used dental gel containing 1% chlorhexidine digluconate (active comparator) and toothpaste without CBD.

Results: Human gingival fibroblasts were confirmed to express the cannabinoid receptor CB2. Lipopolysaccharide-induced cells exhibited increased production of pro-inflammatory IL-6 and IL-8, with deceasing levels upon exposure to CBD. CBD also exhibited antimicrobial activities against Porphyromonas gingivalis, with an MIC of 1.5 μg/mL. Activation of the Nrf2 pathway was also demonstrated. In the clinical part, statistically significant improvement was found for the gingival, gingival bleeding, and modified gingival indices between placebo group A and CBD group B after 56 days.

Conclusions: Cannabidiol reduced inflammation and the growth of selected periodontal pathogenic bacteria. The clinical trial demonstrated a statistically significant improvement after CBD application. No adverse effects of CBD were reported by patients or observed upon clinical examination during the study. The results are a promising basis for a more comprehensive investigation of the application of non-psychotropic cannabinoids in dentistry.”

https://pubmed.ncbi.nlm.nih.gov/38311974/

Health-Promoting Opportunities of Hemp Hull: The Potential of Bioactive Compounds

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“Hemp hull is the outer coat of the hemp seed, derived from the plant Cannabis sativa L., Cannabaceae. While much attention has been paid to hemp seed for its oil, protein and micronutrient content, far less attention has been given to hemp hull, a side stream of hemp processing.

Hemp hull is a source of bioactive compounds, dietary fiber, minerals as well as protein, lipids and carbohydrates.

Of note, two bioactive compounds, n-trans-caffeoyltyramine and n-trans-feruloyltyramine have been identified in hemp hull as key bioactive compounds that support gut health, liver function and other physiological processes. Both of these compounds were identified as agonists of the transcription factor, hepatic nuclear factor-4 alpha which has been implicated in gene expression that governs gut permeability, factors associated with inflammatory bowel diseases, and hepatic lipid homeostasis.

Additionally, the dietary fibers in hemp hull have been demonstrated to be novel prebiotics, which may further amplify hemp hull’s effect on gut health and metabolic health. This review article summarizes the nutritional content of hemp hull, explores the physiological effects of bioactive compounds found in hemp hull, and identifies opportunities for further research on hemp hull for human health benefit.”

https://pubmed.ncbi.nlm.nih.gov/38303514/

https://www.tandfonline.com/doi/full/10.1080/19390211.2024.2308264

Cannabidiol reduces intraventricular hemorrhage brain damage, preserving myelination and preventing blood brain barrier dysfunction in immature rats

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“Intraventricular hemorrhage (IVH) is an important cause of long-term disability in extremely preterm infants, with no current treatment.

This study assessed the potential neuroprotective effects of cannabidiol (CBD) in an IVH model using immature rats.

CBD prevented the long-lasting motor and cognitive consequences of IVH, reduced brain damage in the short- and long-term, protected oligodendroglial cells preserving adequate myelination and maintained BBB integrity.

The protective effects of CBD were associated with the modulation of inflammation, excitotoxicity and oxidative stress.

In conclusion, in immature rats, CBD reduced IVH-induced brain damage and its short- and long-term consequences, showing robust and pleiotropic neuroprotective effects.

CBD is a potential candidate to ameliorate IVH-induced immature brain damage.”

https://pubmed.ncbi.nlm.nih.gov/38301326/

“Cannabidiol (CBD), the main non-euphoric component of Cannabis sativa, has demonstrated neuroprotective effects in different models of acute diffuse or mild to moderate focal hypoxic-ischemic brain damage in newborn animals with a brain developmental stage similar to that of term human newborns.”

https://www.sciencedirect.com/science/article/pii/S1878747924000126?via%3Dihub

Development and preliminary validation of the positive consequences of cannabis (PCOC) scale

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“Introduction: While extensive research exists on the negative consequences of cannabis use, there is a noticeable gap in the literature regarding positive consequences on patterns of cannabis use. The goal of the present study was to develop and test the psychometric properties of a novel scale, the Positive Consequences of Cannabis scale (PCOC) to assess positive outcomes of cannabis use among current adult cannabis users.

Methods: Participants (n = 768) were recruited through online platforms. The sample was predominantly non-Hispanic (92.3 %) male (62.92 %) with an average age of 29.08 years (SD = 6.10). A split half validation method was used to assess the factor structure of the PCOC scale. Data analysis also included Exploratory factor analysis (EFA) to identify underlying factor structures of the PCOC, confirmatory factor analysis (CFA) to validate the factor structure, and the assessments of internal consistency and validity.

Results: The EFA identified a two-factor solution for the PCOC: Social and Psychological Consequences and Cognitive and Motivational Consequences. The CFA confirmed the validity of this factor structure with good model fit (χ2 = 321.33, p < 0.001; CFI = 0.95; TLI = 0.95; RMSEA = 0.038; SRMR = 0.048). Internal consistency coefficients for the PCOC subscales and total scale exceeded acceptable thresholds. A hierarchical regression model showed that both PCOC subscales were significantly associated with cannabis use frequency and quantity.

Discussion: The development and validation of the PCOC represent a significant advancement in assessing positive consequences in understanding cannabis use patterns, indicating that individuals who experience a range of positive effects are more likely to engage in more frequent and intense cannabis use.”

https://pubmed.ncbi.nlm.nih.gov/38295608/

https://www.sciencedirect.com/science/article/abs/pii/S0306460324000261?via%3Dihub

Unravelling the landscape of Cannabis craving pharmacological treatments: a PRISMA-guided review of evidence

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“Currently, few treatments are available for craving in general, and none of them have received approval for cannabis craving.

The objective of this review is to evaluate existing studies analysing treatments for cannabis craving and explore novel treatment possibilities for these patients.

The current pharmacological treatments largely involve off-label drug use and the utilisation of cannabinoid-based medications, such as combinations of THC and lofexidine, oxytocin, progesterone, and N-acetylcysteine.

These emerging treatments show promise and have the potential to revolutionise current clinical practices, but further investigation is needed to establish their efficacy.”

https://pubmed.ncbi.nlm.nih.gov/38299652/

https://www.tandfonline.com/doi/full/10.1080/09540261.2023.2231540

Cannabis sativa: origin and history, glandular trichome development, and cannabinoid biosynthesis

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“Is Cannabis a boon or bane? Cannabis sativa has long been a versatile crop for fiber extraction (industrial hemp), traditional Chinese medicine (hemp seeds), and recreational drugs (marijuana). 

Cannabis faced global prohibition in the twentieth century because of the psychoactive properties of ∆9-tetrahydrocannabinol; however, recently, the perspective has changed with the recognition of additional therapeutic values, particularly the pharmacological potential of cannabidiol.

A comprehensive understanding of the underlying mechanism of cannabinoid biosynthesis is necessary to cultivate and promote globally the medicinal application of Cannabis resources. Here, we comprehensively review the historical usage of Cannabis, biosynthesis of trichome-specific cannabinoids, regulatory network of trichome development, and synthetic biology of cannabinoids.

This review provides valuable insights into the efficient biosynthesis and green production of cannabinoids, and the development and utilization of novel Cannabis varieties.”

“Historically, Cannabis use has encompassed various productive and religious purposes, playing a crucial role in diverse aspects of people’s lives.”

“Remarkable advancements in the cultivation of Cannabis plants with high-yielding cannabinoids and the reconstruction of cannabinoid production in microorganisms via metabolic engineering have been achieved.”

“In conclusion, Cannabis, an ancient medicinal plant with a longstanding history of global usage over millennia, can make a substantial transformative effect on human health in the future.”

https://academic.oup.com/hr/article/10/9/uhad150/7231120?login=false

“Cannabis sativa: Historical significance, genetic insights, and future potential in medicine and horticulture”

https://phys.org/news/2024-01-cannabis-sativa-historical-significance-genetic.html