Cannabidiol Treatment for Adult Patients with Drug-Resistant Epilepsies: A Real-World Study in a Tertiary Center

Posted on by
Reply
pubmed logo

“Background and purpose: Around 30% of patients with epilepsy show drug-resistant epilepsy (DRE). While cannabidiol has demonstrated efficacy as an adjunctive treatment in Dravet syndrome (DS), Lennox-Gastaut Syndrome (LGS), and epilepsy related to tuberous sclerosis complex (TSC), its more global effectiveness in adult patients with DRE apart from these three specific contexts needs to be clarified.

Methods: We conducted a retrospective study at the epilepsy unit of Pitié Salpêtrière Hospital. Patients initiating pharmaceutical cannabidiol treatment and followed for at least 1 year were included. Patients were categorized into “authorized” (LGS, DS, or TSC) and “off-label” groups. Cannabidiol effectiveness and tolerance were compared between groups, and characteristics of responders (patients with >50% reduction in seizure frequency) in the off-label group were examined.

Results: Ninety-one patients, followed by a median duration of 24 months, were included. A total of 35.2% of the patients were in the authorized group. No significant differences were observed in responder rates between groups (31.3% vs. 35.6%, p = 0.85) and retention rates at 1 year (75.0% vs. 74.6%, p = 0.97). Sleepiness was more commonly reported in the authorized group (50.0% vs. 22.0%, p = 0.01), with no other significant differences. Among off-label patients (n = 59), clobazam co-prescription was more prevalent in responders (71.4% vs. 28.9%, p = 0.002).

Conclusion: Our findings suggest that cannabidiol may benefit all adult patients with DRE, particularly those already receiving clobazam. Randomized controlled trials are warranted in off-label patients to validate these observational findings.”

https://pubmed.ncbi.nlm.nih.gov/39501537/

https://onlinelibrary.wiley.com/doi/10.1002/brb3.70122

Effects of cannabidiol on AMPKα2 /HIF-1α/BNIP3/NIX signaling pathway in skeletal muscle injury

Posted on by
Reply
pubmed logo

“Cannabidiol: (CBD) is a non-psychoactive natural active ingredient from cannabis plant, which has many pharmacological effects, including neuroprotection, antiemetic, anti-inflammatory and anti-skeletal muscle injury. However, the mechanism of its effect on skeletal muscle injury still needs further research.

In order to seek a scientifically effective way to combat skeletal muscle injury during exercise, we used healthy SD rats to establish an exercise-induced skeletal muscle injury model by treadmill training, and systematically investigated the effects and mechanisms of CBD, a natural compound in the traditional Chinese medicine Cannabis sativa L., on combating skeletal muscle injury during exercise.

CBD effectively improved the fracture of skeletal muscle tissue and reduced the degree of inflammatory cell infiltration. Biochemical indexes such as CK, T, Cor, LDH, SOD, MDA, and GSH-Px in serum of rats returned to normal. Combining transcriptome and network analysis results, CBD may play a protective role in exercise-induced skeletal muscle injury through HIF-1 signaling pathway. The experimental results implied that CBD could down-regulate the expression of IL-6, NF-κB, TNF-α, Keap1, AMPKα2, HIF-1α, BNIP3 and NIX, and raised the protein expression of IL-10, Nrf2 and HO-1.

These results indicate that the protective effect of CBD on exercise-induced skeletal muscle injury may be related to the inhibition of oxidative stress and inflammation, thus inhibiting skeletal muscle injury through AMPKα2/HIF-1α/BNIP3/NIX signal pathways.”

https://pubmed.ncbi.nlm.nih.gov/39502531/

“This study preliminarily explored the protective effect of CBD on skeletal muscle in the rat model of acute exercise-induced skeletal muscle injury. The CBD intervention can reduce CK and LDH levels and increase T/COR ratio. The MDA content in the low-dose and high-dose groups of CBD was declined, while the SOD and GSH-Px content were raised. The intervention of CBD can reduce the level of oxidative stress and inflammatory response, and then reduce the expressions of AMPKα2, HIF-1α, BNIP3 and NIX, thus protecting skeletal muscle from injury. This study could provide a new potential target for the treatment of exercise-induced skeletal muscle injury. It can provide new ideas for the basic research and clinical treatment of CBD repairing skeletal muscle injury in the future.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1450513/full

Effectiveness and safety of cannabis-based products for medical use in patients with fibromyalgia syndrome: A systematic review

Posted on by
Reply
pubmed logo

“Background: There is a need to explore pharmacological options for syndrome (FMS), such as medical cannabis. The aim of this systematic review was to synthesize and analyze the available information about the effectiveness/efficacy and safety of cannabis-based products for medical use (CBPMs) and cannabis-based medicines (CBMs), in patients with FMS.

Methods: Interventional or observational studies, systematic reviews and meta-analysis regarding the effectiveness/efficacy and safety of CBPMs and CBMs in patients with FMS were retrieved from the PubMed/Medline database until April 2024. Then, the information was summarized in tables, with the type of CBPM and CBM, the method used in the study and the effective-ness/efficacy and safety outcomes.

Results: 19 publications were selected from the search or form the relevant references. Different CBPM and CBM were used across the studies. Also, different instruments for measuring the effectiveness were used. In general, the use of CBPMs and CBM showed an important improvement in pain, quality of life, and sleep habits. There were no serious adverse events.

Conclusions: The results show that CBMPs and CBMs could be effective and safe in patients with FMS; however, the evidence is limited and there is a need for high-quality clinical studies conducted with improved methodological design.”

https://pubmed.ncbi.nlm.nih.gov/39498228/

“Cannabis-based products for medicinal use (CBPMs) and cannabis-based medicines (CBMs) improve the fibromyalgia symptoms.”

https://www.sciencedirect.com/science/article/pii/S2667276624001215?via%3Dihub

Investigation in the cannabigerol derivative VCE-003.2 as a disease-modifying agent in a mouse model of experimental synucleinopathy

Posted on by
Reply
pubmed logo

“Background: The cannabigerol derivative VCE-003.2, which has activity at the peroxisome proliferator-activated receptor-γ has afforded neuroprotection in experimental models of Parkinson’s disease (PD) based on mitochondrial dysfunction (6-hydroxydopamine-lesioned mice) and neuroinflammation (LPS-lesioned mice). Now, we aim to explore VCE-003.2 neuroprotective properties in a PD model that also involves protein dysregulation, other key event in PD pathogenesis.

Methods: To this end, an adeno-associated viral vector serotype 9 coding for a mutated form of the α-synuclein gene (AAV9-SynA53T) was unilaterally delivered in the substantia nigra pars compacta (SNpc) of mice. This model leads to motor impairment and progressive loss of tyrosine hydroxylase-labelled neurons in the SNpc.

Results: Oral administration of VCE-003.2 at 20 mg/kg for 14 days improved the performance of mice injected with AAV9-SynA53T in various motor tests, correlating with the preservation of tyrosine hydroxylase-labelled neurons in the SNpc. VCE-003.2 also reduced reactive microgliosis and astrogliosis in the SNpc. Furthermore, we conducted a transcriptomic analysis in the striatum of mice injected with AAV9-SynA53T and treated with either VCE-003.2 or vehicle, as well as control animals. This analysis aimed to identify gene families specifically altered by the pathology and/or VCE-003.2 treatment. Our data revealed pathology-induced changes in genes related to mitochondrial function, lysosomal cell pathways, immune responses, and lipid metabolism. In contrast, VCE-003.2 treatment predominantly affected the immune response through interferon signaling.

Conclusion: Our study broadens the neuroprotective potential of VCE-003.2, previously described against mitochondrial dysfunction, oxidative stress, glial reactivity and neuroinflammation in PD. We now demonstrate its efficacy against another key pathogenic event in PD as α-synuclein dysregulation. Furthermore, our investigation sheds light on the molecular mechanisms underlying VCE-003.2 revealing its role in regulating interferon signaling. These findings, together with a favorable ADMET profile, enhance the preclinical interest of VCE-003.2 towards its future clinical development in PD.”

https://pubmed.ncbi.nlm.nih.gov/39487447/

“Cannabinoids have emerged as promising neuroprotective agents given their ability to work as pleiotropic compounds against the multiple events that affect neural cell homeostasis, integrity and survival in conditions of brain damage and neurodegeneration.”

https://behavioralandbrainfunctions.biomedcentral.com/articles/10.1186/s12993-024-00256-9

Therapeutic potentials of cannabidiol: Focus on the Nrf2 signaling pathway

Posted on by
Reply
pubmed logo

“Cannabidiol (CBD), a cannabinoid that does not create psychoactive activities, has been identified as having a multitude of therapeutic benefits.

This study delves into the chemical properties, pharmacokinetics, safety and toxicity, pharmacological effects, and most importantly, the association between the therapeutic potential of CBD and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway.

The relationship between Nrf2 and CBD is closely linked to certain proteins that are associated with cardiovascular dysfunctions, cancers, and neurodegenerative conditions. Specifically, Nrf2 is connected to the initiation and progression of diverse health issues, including nephrotoxicity, bladder-related diseases, oral mucositis, cancers, obesity, myocardial injury and angiogenesis, skin-related inflammations, psychotic disorders, neuropathic pain, Huntington’s disease, Alzheimer’s disease, Parkinson’s disease, neuroinflammation, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis.

The association between CBD and Nrf2 is a zone of great interest in the medical field, as it has the potential to significantly impact the treatment and prevention of wide-ranging health conditions. Additional investigation is necessary to entirely apprehend the mechanisms underlying this crucial interplay and to develop effective therapeutic interventions.”

https://pubmed.ncbi.nlm.nih.gov/39491419/

“CBD plays a protective role in cardiovascular dysfunctions, cancers, and neurodegenerative conditions by targeting the Nrf2 signaling pathway.”

https://www.sciencedirect.com/science/article/pii/S0753332223016037?via%3Dihub

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

Posted on by
Reply
pubmed logo

“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

Posted on by
Reply
pubmed logo

“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

Posted on by
Reply
pubmed logo

“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

Posted on by
Reply
pubmed logo

“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

Posted on by
Reply
pubmed logo

“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