Discuss your use of Cannabis or CBD products with your health care provider. Dosing of CBD is variable, especially since it is not FDA regulated. Cannabis/CBD may interfere with other medications and should not be used in individuals with certain health conditions, including liver issues. CBD skin care products can be absorbed through the skin and have similar effects. Do not use Cannabis products including edibles and CBD if you are pregnant, nursing or may become pregnant. Do not use cannabis products if driving or operating difficult or dangerous machinery. Children should not be exposed to cannabis or CBD products.
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Photo by RDNE Stock project[/caption]
Ohio’s medical marijuana program offers qualifying patients safe, state-regulated access to cannabis products for symptom relief and improved quality of life. Established by House Bill 523 in 2016, the Ohio Medical Marijuana Control Program (OMMCP) began licensed sales at dispensaries on January 16, 2019, under strict rules designed to protect patients and ensure product safety. Patients receive physician-certified cards from the Ohio Board of Pharmacy, allowing them to purchase low-THC or high-CBD products in non-smoking forms—only edibles, oils, vapors, patches, tinctures, or plant matter.
Qualifying Conditions
To be eligible, patients must have at least one of the 21 state-approved conditions. The original qualifying conditions include:
Photo by RDNE Stock project[/caption]
Ohio’s medical marijuana program offers qualifying patients safe, state-regulated access to cannabis products for symptom relief and improved quality of life. Established by House Bill 523 in 2016, the Ohio Medical Marijuana Control Program (OMMCP) began licensed sales at dispensaries on January 16, 2019, under strict rules designed to protect patients and ensure product safety. Patients receive physician-certified cards from the Ohio Board of Pharmacy, allowing them to purchase low-THC or high-CBD products in non-smoking forms—only edibles, oils, vapors, patches, tinctures, or plant matter.
Qualifying Conditions
To be eligible, patients must have at least one of the 21 state-approved conditions. The original qualifying conditions include:
- Acquired immune deficiency syndrome (AIDS/HIV)
- Alzheimer’s disease
- Amyotrophic lateral sclerosis (ALS)
- Cancer
- Chronic traumatic encephalopathy (CTE)
- Crohn’s disease
- Epilepsy or other seizure disorders
- Fibromyalgia
- Glaucoma
- Hepatitis C
- Inflammatory bowel disease (including Crohn’s or ulcerative colitis)
- Multiple sclerosis
- “Chronic and severe or intractable” pain
- Parkinson’s disease
- Post-traumatic stress disorder (PTSD)
- Sickle cell anemia
- Spinal cord disease or injury
- Tourette’s syndrome
- Traumatic brain injury (TBI)
- Ulcerative colitis
- Any other condition added by the State Medical Board of Ohio
Amanda Sierra, PhD
Research Professor and Group Leader
Ramón y Cajal Fellow
Achucarro Basque Center for Neuroscience
Laida Bidea
Bizkaia Science and Technology Park
Zamudio, Bizkaia, Spain
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Sierra: Microglia phagocytosis of apoptotic cells is at the core of the brain regenerative response to recover the homeostasis of the brain parenchyma after damage because it prevents the spillover of toxic intracellular contents and is actively anti-inflammatory. However, while neuronal death is widespread in neurodegenerative diseases (Alzheimer´s, Parkinson´s, multiple sclerosis) and well as in ischemic and traumatic brain injuries, we have a complete lack of knowledge of the efficiency of microglial phagocytosis in the diseased brain.
In this paper we have discovered that microglia have a generalized response to apoptotic challenges: when confronted to a rise in the number of newborn cells, microglia display a combination of different strategies to boost their phagocytic output: increase the phagocytic capacity of each cell, recruit more cells to become phagocytic, or increase the total number of microglia (Abiega et al., PLoS Biol 2015). Thus, microglia have a very large potential for phagocytosis that could be summoned when needed.
To our surprise, however, in pathological conditions such as epilepsy (mouse and human), microglial phagocytosis was blocked. We have made use of the adult neurogenic cascade, where newborn cells undergo apoptosis naturally and are engulfed by “unchallenged microglia” (Sierra et al. Cell Stem Cell 2010), to establish the baseline of microglial phagocytosis efficiency. Whereas in physiological conditions microglia phagocytose over 90% of the apoptotic cells and remove them in under 1.5h, soon after the seizures it only engulfed 10% of the apoptotic cells and took up to 6h to digest them. This is the first quantification of microglial phagocytosis efficiency in the diseased mouse and human brain..
The block in phagocytosis was a rather complex phenomenon related to an impaired recognition (reduction of phagocytosis receptors) as well as impaired motility and targeting (reduced basal motility). We have also shown that the impairment is mediated at least partially by altered ATP microgradients: ATP is not only a neuro- and gliotransmitter widely released during seizures but is also a well-known “find-me” signal released by apoptotic cells. Thus, during seizures microglia became “blinded” by the neuronal hyperactivity and could not find the apoptotic cells.
In addition, we have shown that impairing phagocytosis releases the break on the inflammatory response. In fact, the impaired microglia were in a pro-inflammatory state and produced more cytokines such as tumor necrosis factor alfa (TNFa) or interleukin-1beta (IL-1b), which are well known neurotoxic and epileptogenic factors.
Dr. Jacqueline French[/caption]
Jacqueline French, MD
Professor, Department of Neurology
Director Translational Research& Clinical Trials Epilepsy
NYU Langone Medical Center
MedicalResearch.com: What is the background for this study?
Dr. French: Tuberous sclerosis complex (TSC) is a disease associated with abnormal cell growth, caused by dysfunction of the TSC1 or TSC2 genes and dysruption of the MTOR pathway, which leads to cortical malformations, neuronal hyperexcitability, and seizures. Seizures in patients with TSC often start within the first year of life, and tend not to respond to traditional treatments. Everolimus is a marketed drug that has been used to treat other manifestations of TSC (including giant cell tumors of the brain, renal angiomyolipomas, and angiofibromas of the skin).
This study was a placebo-controlled add-on study of everolimus for the treatment of refractory seizures in children and adults with epilepsy.Following an 8-week baseline phase, patients aged 2-65 years (stratified by age) with TSC and refractory seizures on 1-3 antiepileptic drugs were randomized to EVE LT or HT Cmin target ranges or placebo, and treated in an 18 week Core Phase (6-wk titration + 12-wk maintenance). Primary endpoints were change from baseline in average weekly frequency of TSC-seizures (seizures not previously shown to be generalized in onset by EEG), expressed as response rate (≥50% reduction [RR]), and percentage reduction.
MedicalResearch.com: What are the main findings?
Dr. French: Overall, 366 patients were randomized to EVE LT (n=117), HT (n=130), or placebo (n=119). The median percentage reduction in TSC-seizures was significantly greater with EVE LT (29.3%, P=0.003) and HT (39.6%, P<0.001) vs placebo (14.9%). RR was also significantly greater with EVE LT (28.2%, P=0.008) and HT (40%, P<0.001) vs placebo (15.1%). The most frequent ≥10% all grade adverse events (AEs) reported with EVE LT/HT vs placebo included stomatitis (28.2%/30.8% vs 3.4%), diarrhea (17.1%/21.5% vs 5%), mouth ulceration (23.9%/21.5% vs 4.2%), nasopharyngitis (13.7%/16.2% vs 16%), upper respiratory tract infection (12.8%/15.4% vs 12.6%), aphthous ulcer (4.3%/14.6% vs 1.7%), and pyrexia (19.7%/13.8% vs 5%). Discontinuations due to AEs (5.1%/3.1% vs 1.7%) were low.
