Updated clinical recommendations for the management of tuberous sclerosis complex associated epilepsy

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Children with tuberous sclerosis complex (TSC), may experience a variety of seizure types in the first year of life, most often focal seizure sand epileptic spasms. Drug resistance is seen early in many patients, and the management of TSC associated epilepsy remain a major challenge for clinicians. In 2018 clinical recommendations for the management of TSC associated epilepsy were published by a panel of European experts. In the last five years considerable progress has been made in understanding the neurobiology of epileptogenesis and three interventional randomized controlled trials have changed the therapeutic approach for the management of TSC associated epilepsy. Pre-symptomatic treatment with vigabatrin may delay seizure onset, may reduce seizure severity and reduce the risk of epileptic encephalopathy.

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Emerging Therapeutic Potential of Cannabidiol (CBD) in Neurological Disorders: A Comprehensive Review

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Δ9-Tetrahydrocannabinol (Δ9-THC) is a principal psychoactive extract of Cannabis sativa and has been traditionally used as palliative medicine for neuropathic pain. Cannabidiol (CBD), an extract of hemp species, has recently attracted increased attention as a cancer treatment, but Δ9-THC is also requiring explored pharmacological application. This study evaluated the pharmacological effects of Δ9-THC in two human colorectal cancer cell lines. We inves-tigated whether Δ9-THC treatment induces cell death in human colorectal cancer cells.

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Real-World evidence on the use of cannabidiol for the treatment of drug resistant epilepsy not related to Lennox-Gastaut syndrome, Dravet syndrome or Tuberous Sclerosis Complex

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Highly purified cannabidiol (CBD) has a broad spectrum of action and could be useful for the treatment of drug resistant epilepsy regardless of etiology or syndrome. Multicenter retrospective study that evaluated the efficacy and safety of CBD for the treatment of drug resistant epilepsy of different etiologies in patients >2 years of age.

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A comparison of advertised versus actual cannabidiol (CBD) content of oils, aqueous tinctures, e-liquids and drinks purchased in the UK

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To evaluate the efficacy and safety of cannabidiol (CBD) for the treatment of epilepsy in a real-world setting.
In this retrospective observational study, we included PwE with epilepsy who received a prescription for CBD between 01.03.2019 and 30.11.2022 and had a follow-up period ≥ 3 months. Participants were evaluated at baseline and after 3, 6, and 12 months. “Responders” were defined as individuals experiencing a reduction in seizure frequency > 30% but < 80% compared to baseline, while "super responders" were those with a reduction ≥ 80%. Adverse events were recorded to assess safety.

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Real-world experience with cannabidiol as add-on treatment in drug-resistant epilepsy

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To evaluate the efficacy and safety of cannabidiol (CBD) for the treatment of epilepsy in a real-world setting.
In this retrospective observational study, we included PwE with epilepsy who received a prescription for CBD between 01.03.2019 and 30.11.2022 and had a follow-up period ≥ 3 months. Participants were evaluated at baseline and after 3, 6, and 12 months. “Responders” were defined as individuals experiencing a reduction in seizure frequency > 30% but < 80% compared to baseline, while "super responders" were those with a reduction ≥ 80%. Adverse events were recorded to assess safety.

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Cannabidiol in the acute phase of Febrile Infection-Related Epilepsy Syndrome (FIRES)

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Febrile infection-related epilepsy syndrome (FIRES) is a prolonged refractory status epilepticus (SE) that develops among healthy individuals after a febrile infection.

FIRES treatment is challenging due to its poor response to anti-seizure medications (ASMs) and anesthetic drugs. The use of cannabidiol (CBD) as an adjunctive treatment has been suggested, albeit data about its role in the acute phase is lacking. This report describes the use of purified CBD in the acute phase of two pediatric cases of FIRES and their long-term outcome.

Both children were treated with several ASMs, immunomodulators, anesthetics, and non-pharmacological treatment (ketogenic diet). CBD was administered, as an adjunctive treatment, through nasogastric tube about 30 days after onset. SE resolved within three days of reaching the target dose and both were seizure-free for one year after.

Although it is difficult to define the extent to which each previous therapy contributed to recovery, in both cases CBD therapy was a turning point, reinforcing its potential role as add-on treatment in the acute phase of FIRES.

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Cannabidiol Negatively Regulates Androgenic Signal in Prostate Cancer Cells and Fine-Tunes the Tumorigenesis by Modulating Endoplasmic Reticulum-Associated Degradation, Unfolded Protein Response, and Autophagy

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Cannabis sativa L., Cannabaceae, has been used as a herbal medicine for several thousand years in many cultures and it has more than 540 metabolites that provide therapeutic effects. Cannabinoids are the major compounds derived from the Cannabis species. There are over 120 isolated and identified cannabinoids from C. sativa and (−)-cannabidiol is one of the most well-researched among them. Recent studies have focused on the expanding usage of cannabidiol in many therapeutic areas as well as cancer. Studies demonstrated a negative correlation between cannabidiol administration and the growth of various cancer types, including prostate cancer. However, the detailed mode of action of cannabidiol on prostate cancer remains unclear. In the present study, we investigated the molecular mechanism of cannabidiol prostate cancer cells. For this aim, we examined the effect of cannabidiol on autophagy, endoplasmic reticulum-associated degradation, endoplasmic reticulum stress, unfolded protein response, epithelial-mesenchymal transition, angiogenesis, and androgenic signaling in vitro. We found that cannabidiol remarkably inhibited autophagy. Also, it strongly induced unfolded protein response and endoplasmic reticulum-associated degradation mechanisms. Moreover, it exerted anti-cancer activity by reducing epithelial-mesenchymal transition and causing cell cycle arrest. Additionally, cannabidiol importantly disrupted androgenic signaling by affecting basal androgen receptor levels and inhibiting nuclear translocation of this receptor.

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Cannabidiol modulates excitatory-inhibitory ratio to counter hippocampal hyperactivity

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Rosenberg et al. reveal a potential mechanism by which cannabidiol (CBD) reduces seizures. They discover that CBD restores the hippocampal excitatory-to- inhibitory ratio by preventing the actions of the lipid LPI at the receptor GPR55. Seizures acutely potentiate the GPR55- LPI axis, providing a target for CBD’s anti- seizure action.

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Cannabidiol goes nuclear: The role of PPARγ

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Cannabidiol (CBD) is one of the main phytocannabinoids found in Cannabis sativa. In contrast to Δ9-tetrahydrocannabinol, it has a low affinity for cannabinoid receptors CB1 and CB2, thereby it does not induce significant psychoactive effects. However, CBD may interact with other receptors, including peroxisome proliferator-activated receptor gamma (PPARγ). CBD is a PPARγ agonist and changes its expression. There is considerable evidence that CBD’s effects are mediated by its interaction with PPARγ. So, we reviewed studies related to the interaction of CBD and PPARγ.

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Effects of Cannabidiol on Innate Immunity Experimental Evidence and Clinical Evidence

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Cannabidiol (CBD) is the main non-psychotropic cannabinoid derived from cannabis (Cannabis sativa L., fam. Cannabaceae). CBD has received approval by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of seizures associated with Lennox–Gastaut syndrome or Dravet syndrome. However, CBD also has prominent anti-inflammatory and immunomodulatory effects; evidence exists that it could be beneficial in chronic inflammation, and even in acute inflammatory conditions, such as those due to SARS-CoV-2 infection. In this work, we review available evidence concerning CBD’s effects on the modulation of innate immunity. Despite the lack so far of clinical studies, extensive preclinical evidence in different models, including mice, rats, guinea pigs, and even ex vivo experiments on cells from human healthy subjects, shows that CBD exerts a wide range of inhibitory effects by decreasing cytokine production and tissue infiltration, and acting on a variety of other inflammation-related functions in several innate immune cells. Clinical studies are now warranted to establish the therapeutic role of CBD in diseases with a strong inflammatory component, such as multiple sclerosis and other autoimmune diseases, cancer, asthma, and cardiovascular diseases

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Use of cannabinol in the treatment of epilepsy: Lennox-Gastaut Syndrome , Dravet, and Tuberous Sclerosis Complex

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Purpose: The objective of this systematic review with meta-analysis was to evaluate the efficiency, safety and short and long term tolerability of Cannabidiol CBD, as an adjunct treatment , in children and adults with Dravet Syndrome (SD) and Lennox Gastaut Syndrome(LGS) or Tuberous Sclerosis Complex with inadequate control of seizures.

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Long-term efficacy and safety of cannabidiol in patients with treatment-resistant epilepsies: 4-year results from the expanded access program

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Cannabidiol (CBD) expanded access program (EAP), initiated in 2014, provided add-on CBD to patients with treatment-resistant epilepsy (TRE) at 35 US epilepsy centers. Prior publications reported results through December 2016; herein, we present efficacy and safety results through January 2019.

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