Monthly Archives: October 2024

Treatment of Neuropsychiatric Symptoms in Alzheimer’s Disease with a Cannabis-Based Magistral Formulation: An Open-Label Prospective Cohort Study

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“Introduction: Neuropsychiatric symptoms (NPS) may be disruptive and problematic for patients with Alzheimer’s disease (AD) and for their caregivers. Cannabidiol (CBD) may be a safer alternative. The objective was to evaluate whether CBD-rich oil was effective, and safe in adults with NPS secondary to AD.

Methods: An open-label, prospective cohort, single-center study in patients with AD onset after the age of 65 with untreated NPS. A CBD-rich oil was administrated 0.1 mL sublingually every 8-12 h, up-titrated weekly. The primary outcome was to establish a reduction in the NPI-Q severity score of >30% at 12 weeks compared with the baseline. A p value of <0.05 was statistically significant.

Results: Between July 2020 and July 2023, 59 (93.5%) patients completed ≥3 months of follow-up. The patients were under treatment for a mean of 23.2 months, the median dose of CBD was 111 mg/day. The median NPI-Q severity and caregiver’s distress scores at baseline were 24 and 29, respectively. At 3 months, the median NPI-Q severity score shifted to 12 (p < 0.001) and 14 (p < 0.001), respectively. The proportion of patients who achieved a reduction in the NPI-Q severity score of >30% was 94.9%, while a reduction of >50% was achieved by 54.2%. The improvement was maintained for up to 24 months.

Conclusion: This study shows that CBD-rich oil is an effective and safe therapy for treating NPS in AD patients, while also reducing the caregivers’ distress.”

https://pubmed.ncbi.nlm.nih.gov/39474242/

“There is a need for an alternative treatment to significantly improve NPS in AD and decrease the caregiver’s stress as well as the financial burden resulting from polypharmacy and institutionalization. Any promising treatment should be safe and reduce the risk of adverse effects. This study evaluated the efficacy of a CBD-rich oil in treating NPS in a cohort of 59 patients with AD over a follow-up of more than 1 year, with a specific focus on its impact on caregiver burden. The study showed a significant reduction in the NPI-Q severity and caregiver’s distress scores after 3 months of intervention, and sustained for up to 24 months of follow-up. Notably, the effectiveness was independent of age, sex, years with AD, type of acetylcholinesterase inhibitors, and NPI-Q severity score before CBD treatment. A low CBD dose and a slow dose titration improve tolerance. These results may indicate that alleviating NPS in people with AD facilitates daily caregiving and improves caregivers’ emotional and physical distress.”

https://karger.com/mca/article/7/1/160/913137/Treatment-of-Neuropsychiatric-Symptoms-in

Controlled Inhalation of Tetrahydrocannabinol-Predominant Cannabis Flos Mitigates Severity of Post-Traumatic Stress Disorder Symptoms and Improves Quality of Sleep and General Mood in Cannabis-Experienced UK Civilians: A Real-World, Observational Study

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“Introduction: Approximately 4% of the UK population experiences PTSD. Individuals must exhibit symptoms across four clusters to receive a diagnosis: intrusion, avoidance, altered reactivity, and altered mood. Evidence suggests that cannabinoid agonists such as nabilone and tetrahydrocannabinol (THC) may alleviate PTSD symptoms. We investigated the safety and effectiveness of THC-predominant cannabis flowers for inhalation to manage PTSD symptoms in a real-world setting.

Methods: We analysed data from the UK patient registry, T21. Validated questionnaires were used to collect PROMs for health-related quality of life (HRQoL), mood/anxiety, sleep, and PTSD-specific symptoms. Inclusion criteria were (i) a confirmed diagnosis of PTSD, (ii) completed PROMs questionnaires at baseline and at the 3-month follow-up, and (iii) received a prescription for a chemotype 1 (THC-predominant) cannabis flower.

Results: Fifty-eight patients were included, 34 of which also had PROMs recorded at 6 months. Most were males (65.5%) with an average age of 39.2 years who had previously used cannabis illicitly (95.6%). At 3 months, participants reported significant improvements in overall health, mood, and sleep quality (p < 0.001) but not in the proxy for HRQoL (p = 0.052). Similarly, participants reported substantial benefits in managing intrusion symptoms (p < 0.001), mood alterations (p < 0.001), and reactivity alterations (p = 0.002), which were sustained or further improved at 6 months. Participants did not report any side effects associated with CBMPs.

Conclusions: Inhalation of THC is well tolerated and useful for managing symptoms of PTSD in cannabis-experienced individuals. However, further research is needed to evaluate the long-term safety and outcomes of controlled inhalation of CBMP in patients naïve to cannabis.”

https://pubmed.ncbi.nlm.nih.gov/39474239/

“Results from this observational study suggest an association between treatment with THC-predominant cannabis flowers and symptomatic improvement for up to 6 months in a cohort of UK civilians diagnosed with PTSD. The treatment was safe and well tolerated and characterized by marked effects on quality of sleep, general mood, and severity of PTSD-associated symptoms. Despite previous exposure to cannabis, participants continued to report benefits after initiating treatment with THC-predominant cannabis flowers.”

https://karger.com/mca/article/7/1/149/912500/Controlled-Inhalation-of-Tetrahydrocannabinol

Use of Cannabidiol-Dominant Extract as Co-Adjuvant Therapy for Type 2 Diabetes Mellitus Treatment in Feline: Case Report

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“Introduction: Diabetes mellitus (DM) is a common endocrinopathy in felines. Treatment is based on glycemic control and management of clinical signs by insulin administration coupled with a low-carbohydrate and high-protein content diet. However, achieving adequate remission or glycemia control is not always possible. Effects of cannabinoids on the regulation of glucose uptake and the incidence of diabetes have been observed in experimental models. Nevertheless, little is known about their possible relevance in controlling this condition in veterinary and human medicine.

Case presentation: This is a case study of an 18-year-old, neutered, mixed-breed female domestic longhair cat diagnosed with type 2 DM. She was treated with long-acting glargine (3-5 IU/12 h), and her diet changed to ultra-processed commercial food for diabetic cats. Three months after the start of the treatment with insulin, cannabidiol (CBD)-enriched extract in handmade olive oil, tetrahydrocannabinol: CBD ratio = 1:24, was incorporated. The route of administration was oromucosal. After 3 months, the glycemia was reduced. The patient decreased the polyuria/polydipsia, recovered sleep cycles, remained attentive to all movements, and increased her physical activity.

Conclusion: This report provides evidence that using a CBD-rich extract was effective as a co-adjuvant in alleviating clinical signs of DM and concurrent disorders, allowing for the reduction of insulin intake.”

https://pubmed.ncbi.nlm.nih.gov/39474238/

“This case report shows the beneficial effects of a CBD-enriched phytocannabinoid extract in a feline patient with type 2 DM. Added to glycemia control, indicators measured showed an improvement in the patient’s quality of life. Moreover, neurological and behavioral aspects associated with DM and aging improved. No secondary effects were observed.”

https://karger.com/mca/article/7/1/206/913300/Use-of-Cannabidiol-Dominant-Extract-as-Co-Adjuvant

A recent update on the antibacterial effects of distinct bioactive molecules derived from the Cannabis plant

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“The number of human infections with multidrug-resistant (MDR) bacteria is increasing worldwide and constitutes a serious threat to human health. Given the lack of novel antibiotic compounds worsening this dilemma, alternative antibiotic-independent treatment and prevention strategies of infectious diseases applying natural compounds appear highly appreciable.

Given the long-known health-beneficial and disease-alleviating properties of Cannabis, we performed a literature search summarizing current knowledge regarding the antibacterial effects of extracts from different parts of the Cannabis sativa plant and of defined Cannabis-derived molecules and their potential mode of action.

The included studies revealed that various extracts and essential oils of C. sativa as well as major cannabinoids exerted potent activities against a broad spectrum of Gram-positive bacteria and against some Gram-negative bacterial species including MDR strains. Particularly the disruption of the bacterial cytoplasmic membrane by some cannabinoids resulted in potent antibacterial effects against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus. Furthermore, defined cannabinoids inhibited the formation of and eradicated existing bacterial biofilms.

In conclusion, given their antibacterial properties distinct Cannabis-derived molecules expand the repertoire of antibiotics-independent treatment options in the combat of bacterial infectious diseases which should be further addressed in future studies including clinical trials.”

https://pubmed.ncbi.nlm.nih.gov/39470741/

“Collectively, results from the here reviewed studies open future perspectives for cannabis-derived molecules as alternative antibiotic-independent treatment and prevention strategies in the combat of bacterial infectious diseases which should be further addressed in future studies including clinical trials.”

https://akjournals.com/view/journals/1886/aop/article-10.1556-1886.2024.00098/article-10.1556-1886.2024.00098.xml

The molecular anti-metastatic potential of CBD and THC from Lebanese Cannabis via apoptosis induction and alterations in autophagy

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“The medicinal plant Cannabis sativa L. (C. sativa) is currently being extensively studied to determine the full extent of its therapeutic pharmacological potential. Δ9-tetrahydocannabinol (THC) and cannabidiol (CBD) are the most thoroughly investigated compounds.

We aimed to explore the anticancer activity of cannabinoids mixture isolated from the Lebanese C. sativa plant in ratios comparable to the local medicinal plant, to elucidate its mechanism of action in breast cancer cells in vitro.

Cells were subjected to cytotoxicity assay, cell cycle analysis, Annexin V/PI dual staining, cell death ELISA, immunofluorescence, in addition to western blot analysis of apoptotic and autophagy markers. We further evaluated the anti-metastatic effect of cannabinoids on MDA-MB-231 using the scratch wound-healing, trans-well migration and invasion assays.

Our results revealed the promising therapeutic benefits of CBD/THC on inhibiting the growth of breast cancer cells by promoting cellular fragmentation, phosphatidylserine translocation to the outer membrane leaflet and DNA fragmentation in both cell lines while inhibiting the motility of the triple negative breast cancer cells.

In our study, CBD/THC mixture was found to exhibit a pro-apoptotic activity via the activation of the mitochondrial apoptotic pathway, independent from ROS production while also suggesting the activation of a caspase-dependent apoptotic pathway. Even though autophagy was altered upon exposure to the cannabinoid mixture, our data suggested that it is not the mechanism responsible of inducing cell death.

In conclusion, our study demonstrates the promising therapeutic benefits of CBD and THC isolated from the Lebanese C. sativa plant on breast cancer cells in vitro.”

https://pubmed.ncbi.nlm.nih.gov/39463375/

“Our study showed that CBD and THC isolated from the Lebanese cannabis strains, in ratios comparable to the medicinal plants, exhibit promising effect on breast cancer cell lines. The anticancer activity of this mixture was revealed by its ability to promote cellular fragmentation, phosphatidylserine translocation and DNA fragmentation while inhibiting the motility of aggressive breast cancer cells. Our results showed a pro-apoptotic activity on MDA-MB-231 and MCF-7 cells via the activation of the intrinsic apoptotic pathway. Moreover, we found that even if autophagy was altered in breast cancer cell lines, it is not the major mechanism leading to cellular death. Also, we demonstrated that this mixture was effective in halting the progression of breast cancer cells via the suppression of cancer cell migration and invasion.”

https://www.nature.com/articles/s41598-024-76340-x

Harnessing Cannabis sativa Oil for Enhanced Skin Wound Healing: The Role of Reactive Oxygen Species Regulation

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“Cannabis sativa emerges as a noteworthy candidate for its medicinal potential, particularly in wound healing. This review article explores the efficacy of cannabis oil in reducing reactive oxygen species (ROS) during the healing of acute and chronic wounds, comparing it to the standard treatments.

ROS, produced from various internal and external sources, play a crucial role in wound development by causing cell and tissue damage. Understanding the role of ROS on skin wounds is essential, as they act both as signaling molecules and contributors to oxidative damage.

Cannabis oil, recognized for its antioxidant properties, may help mitigate oxidative damage by scavenging ROS and upregulating antioxidative mechanisms, potentially enhancing wound healing.

This review emphasizes ongoing research and the future potential of cannabis oil in dermatological treatments, highlighted through clinical studies and patent updates. Despite its promising benefits, optimizing cannabis oil formulations for therapeutic applications remains a challenge, underscoring the need for further research to realize its medicinal capabilities in wounds.”

https://pubmed.ncbi.nlm.nih.gov/39458608/

“Cannabis oil, especially its primary bioactive constituents, CBD and THC, demonstrates considerable potential in facilitating skin wound healing by modifying oxidative stress via the regulation of reactive oxygen species. CBD’s therapeutic effects in wound healing are largely attributed to its antioxidant, anti-inflammatory, and antimicrobial properties. Increased ROS levels can hinder wound healing by exacerbating inflammation and cellular damage; however, CBD’s antioxidant properties mitigate these effects, fostering a more conducive environment for tissue regeneration. Additionally, the antibacterial and analgesic properties of cannabis contribute to reducing the microbial load and minimizing the complications associated with chronic wounds, thereby enhancing the overall healing efficacy. Integrating cannabis oil into drug delivery systems for wound management represents a promising strategy for treating both acute and chronic wounds.”

https://www.mdpi.com/1999-4923/16/10/1277

Antidepressant-like Effects of Cannabis sativa L. Extract in an Lipopolysaccharide Model: Modulation of Mast Cell Activation in Deep Cervical Lymph Nodes and Dura Mater

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“Background: Lipopolysaccharide (LPS)-induced neuroinflammation is a well-established model for studying depression-like behavior, driven by pro-inflammatory cytokines such as TNF-α and IL-1β. Mast cells (MCs) contribute to neuroinflammation by releasing mediators that exacerbate depressive-like symptoms. This study evaluates the antidepressant-like and anti-inflammatory effects of Cannabis sativa L. inflorescence extract (CSL) in an LPS-induced neuroinflammation model.

Methods: Male C57BL/6 mice were intraperitoneally injected with CSL at doses of 10, 20, and 30 mg/kg, 30 min prior to LPS (0.83 mg/kg) administration. Depressive behaviors were assessed using the sucrose preference test (SPT), tail suspension test (TST), and forced swimming test (FST). The neutrophil-to-lymphocyte ratio (NLR) was measured to assess systemic inflammation. Cytokine levels in the prefrontal cortex (PFC) were measured, and mast cell degranulation in the lymph nodes and dura mater was analyzed histologically (approval number: WKU24-64).

Results: CSL significantly improved depressive-like behaviors and decreased the NLR, indicating reduced systemic inflammation. CSL also significantly reduced TNF-α and IL-1β levels in the PFC. Furthermore, CSL inhibited MC degranulation in the deep cervical lymph nodes and dura mater, with the strongest effects observed at 30 mg/kg.

Conclusions: CSL demonstrated antidepressant-like and anti-inflammatory effects in an LPS-induced neuroinflammation model, likely through the modulation of cytokine expression and mast cell activity. These results suggest the potential of CSL as a therapeutic option for treating inflammation-related depression.”

https://pubmed.ncbi.nlm.nih.gov/39459047/

“We demonstrated that CSL exhibits significant antidepressant-like and anti-inflammatory effects in an LPS-induced neuroinflammatory model. CSL administration effectively reduced depressive-like behaviors, as observed in the SPT, TST, and FST, and modulated the degranulation of MCs in LNs and the dura mater. Furthermore, CSL decreased the expression of pro-inflammatory cytokines TNF-α and IL-1β in the PFC in a dose-dependent manner. These findings suggest that CSL acts both through immune modulation and neuroinflammation suppression, possibly via the endocannabinoid system and pathways such as NF-κB, PPAR-γ, and VEGF-C. The synergistic interaction between cannabinoids and terpenes in CSL likely contributes to its therapeutic potential, supporting the notion of the “entourage effect”. While these results are promising, further studies are required to clarify the exact mechanisms involved and to assess the long-term safety and efficacy of CSL in chronic depression models.”

https://www.mdpi.com/1424-8247/17/10/1409

High-CBD Extract (CBD-X) in Asthma Management: Reducing Th2-Driven Cytokine Secretion and Neutrophil/Eosinophil Activity

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“Background/objectives: Asthma is a chronic inflammatory disorder of the airways affecting over 10% of the global population. It is characterized by airway inflammation, mucus hypersecretion, and bronchial hyperresponsiveness, driven predominantly by type 2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s) in a subset of patients. However, a significant portion of asthmatic individuals present with “type 2-low” asthma that is often refractory to standard inhaled corticosteroid (ICS) therapy. Therefore, developing innovative therapeutic strategies has become essential. Recent studies have highlighted cannabidiol (CBD) as a promising anti-inflammatory agent capable of modulating immune responses. This study investigates the therapeutic potential of a high-CBD extract (CBD-X) in asthma.

Methods: We evaluated the effects of CBD-X on cells involved in asthma pathogenesis using primary human Th2 cells, neutrophils, and asthma mouse model.

Results: Our findings indicate that CBD-X extract inhibits Th2 differentiation and reduces the secretion of IL-5 and IL-13, which are crucial cytokines in asthma. Additionally, CBD-X significantly reduces pro-inflammatory cytokines IL-8 and IL-6 in neutrophils and impairs their migration, a critical step in airway inflammation. In a murine asthma model, CBD-X administration led to marked downregulation of IgE and pro-asthmatic cytokines, along with reduced leukocyte, eosinophil, and neutrophil infiltration in lung tissues.

Conclusions: These results suggest that CBD-X extract could offer a novel and complementary approach to managing both type 2-high and type 2-low asthma by targeting key inflammatory pathways and modulating immune cell behavior.”

https://pubmed.ncbi.nlm.nih.gov/39459021/

“These findings indicate that CBD-X extract may provide a novel, complementary approach to managing both type 2-high and type 2-low asthma by targeting key inflammatory pathways and modulating immune responses. Further research is required to explore the molecular mechanisms underlying CBD-X’s effects. Specifically, experiments will involve treating Th2 cells and neutrophils with CBD-X to evaluate downstream inflammatory pathways. Given its therapeutic potential, CBD-X will be tested in clinical trials to assess its efficacy and safety for asthma patients.”

https://www.mdpi.com/1424-8247/17/10/1382

Cannabis Use and Cannabidiol Modulate HIV-Induced Alterations in TREM2 Expression: Implications for Age-Related Neuropathogenesis

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“Triggering receptor expressed on myeloid cells 2 (TREM2) is involved in neuroinflammation and HIV-associated neurocognitive impairment (NCI). People with HIV (PWH) using cannabis exhibit lower inflammation and neurological disorders. We hypothesized that TREM2 dysfunction mediates HIV neuropathogenesis and can be reversed by cannabinoids. EcoHIV-infected wildtype (WT) and TREM2R47H mutant mice were used to study HIV’s impact on TREM2 and behavior.

TREM2 and related gene expressions were examined in monocyte-derived macrophages (MDMs) from PWH (n = 42) and people without HIV (PWoH; n = 19) with varying cannabis use via RNA sequencing and qPCR. Differences in membrane-bound and soluble TREM2 (sTREM2) were evaluated using immunocytochemistry (ICC) and ELISA. EcoHIV increased immature and C-terminal fragment forms of TREM2 in WT mice but not in TREM2R47H mice, with increased IBA1 protein in TREM2R47H hippocampi, correlating with worse memory test performance. TREM2 mRNA levels increased with age in PWoH but not in PWH.

Cannabidiol (CBD) treatment increased TREM2 mRNA alone and with IL1β. RNA-seq showed the upregulation of TREM2-related transcripts in cannabis-using PWH compared to naïve controls. IL1β increased sTREM2 and reduced membrane-bound TREM2, effects partially reversed by CBD. These findings suggest HIV affects TREM2 expression modulated by cannabis and CBD, offering insights for therapeutic strategies.”

https://pubmed.ncbi.nlm.nih.gov/39459844/

“Altogether, results from this study underscore the potential of TREM2 as a therapeutic target for the treatment of HAND. Further research is warranted to elucidate the specific mechanisms underlying these interactions and to explore potential therapeutic strategies targeting TREM2 and cannabinoid signaling pathways in neuroinflammatory diseases.”

https://www.mdpi.com/1999-4915/16/10/1509

Comparison of Cardioprotective Potential of Cannabidiol and β-Adrenergic Stimulation Against Hypoxia/Reoxygenation Injury in Rat Atria and Ventricular Papillary Muscles

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“Background: Hypoxia is one of the most significant pathogenic factors in cardiovascular diseases. Preclinical studies suggest that nonpsychoactive cannabidiol (CBD) and β-adrenoceptor stimulation might possess cardioprotective potential against ischemia-reperfusion injury. The current study evaluates the influence of hypoxia-reoxygenation (H/R) on the function of atria and ventricular papillary muscles in the presence of CBD and the nonselective β-adrenoceptor agonist isoprenaline (ISO).

Methods: The concentration curves for ISO were constructed in the presence of CBD (1 µM) before or after H/R. In chronic experiments (CBD 10 mg/kg, 14 days), the left atria isolated from spontaneously hypertensive (SHR) and their normotensive control (WKY) rats were subjected to H/R following ISO administration.

Results: Hypoxia decreased the rate and force of contractions in all compartments. The right atria were the most resistant to hypoxia regardless of prior β-adrenergic stimulation. Previous β-adrenergic stimulation improved recovery in isolated left atria and right (but not left) papillary muscles. Acute (but not chronic) CBD administration increased the effects of ISO in left atria and right (but not left) papillary muscles. Hypertension accelerates left atrial recovery during reoxygenation.

Conclusions: H/R directly modifies the function of particular cardiac compartments in a manner dependent on cardiac region and β-adrenergic prestimulation. The moderate direct cardioprotective potential of CBD and β-adrenergic stimulation against H/R is dependent on the cardiac region, and it is less than in the whole heart with preserved coronary flow. In clinical terms, our research expands the existing knowledge about the impact of cannabidiol on cardiac ischemia, the world’s leading cause of death.”

https://pubmed.ncbi.nlm.nih.gov/39459019/

“Finally, it should be noted that in the whole heart, the beneficial effects of CBD prestimulation can be further amplified by its known anti-inflammatory and antioxidant properties as well as its ability to improve vascular function. The results of clinical trials conducted around the world suggest that cannabidiol will become more widely used in clinical practice. Our findings emphasize the necessity for further preclinical studies to investigate the cardioprotective potential of cannabidiol.”

https://www.mdpi.com/1424-8247/17/10/1379