Kathryn Nichol

Background and objectives: As cannabis products become increasingly accessible across the United States, understanding how patients obtain medical information on cannabis and view the role of their health care provider in providing information is important.

Methods: Participants with multiple sclerosis (MS) from the North American Research Committee on Multiple Sclerosis registry completed a supplemental survey on Δ9-tetrahydrocannabinol-containing cannabis use between March and April… Show more

Background and objectives: As cannabis products become increasingly accessible across the United States, understanding how patients obtain medical information on cannabis and view the role of their health care provider in providing information is important.

Methods: Participants with multiple sclerosis (MS) from the North American Research Committee on Multiple Sclerosis registry completed a supplemental survey on Δ9-tetrahydrocannabinol-containing cannabis use between March and April 2020. Participants reported dialogue with health care providers regarding cannabis use, information sources used to make product decisions, and expenditure on cannabis. Findings are reported using descriptive statistics.

Results: Overall, 3,249 participants responded (47% response rate), of whom 31% ever used cannabis and 20% currently used cannabis for MS. To determine presumed cannabis contents, respondents who had ever used cannabis (ever users) most often used dispensary-provided information (39%), word of mouth/dealer/friend (29%), and unregulated product labels (24%). For general information on cannabis for MS, ever users most often used dispensary staff (38%) and friends (32%). The primary source of medical guidance among ever users was most often "nobody or myself" (48%), followed by a dispensary professional (21%); only 12% relied on their MS physician, although 70% had discussed cannabis with their MS physician. Most current users (62%) typically sourced their cannabis from a dispensary. The most common factor in selecting a cannabis product was perceived quality and safety (70%).

Discussion: Participants most often received information on cannabis for MS from dispensaries, unregulated product labels, and friends; only a small proportion used health care providers. Evidence-based patient and physician education is needed. Show less

Background: As cannabis products become increasingly accessible across the United States, it is important to understand the contemporary use of cannabis for managing multiple sclerosis (MS) symptoms. Methods: We invited participants with MS from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry (aged 18 years or older) to complete a supplemental survey on cannabis use between March and April 2020. Participants reported cannabis use, treated symptoms, patterns… Show more

Background: As cannabis products become increasingly accessible across the United States, it is important to understand the contemporary use of cannabis for managing multiple sclerosis (MS) symptoms. Methods: We invited participants with MS from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry (aged 18 years or older) to complete a supplemental survey on cannabis use between March and April 2020. Participants reported cannabis use, treated symptoms, patterns, preferences, methods of use, and the factors limiting use. Findings are reported using descriptive statistics. Results: Of the 6934 participants invited, 3249 responded. Of the respondents, 31% reported having ever used cannabis to treat MS symptoms, with 20% currently using cannabis. The remaining 69% had never used cannabis for MS symptoms, for reasons including not enough data about efficacy (40%) and safety (27%), and concerns about legality (25%) and cost (18%). The most common symptoms current users were attempting to treat were spasticity (80%), pain (69%), and sleep problems (61%). Ever users (vs never users) were more likely to be younger, be non-White, have lower education, reside in the Northeast and West, be unemployed, be younger at symptom onset, be currently smoking, and have higher levels of disability and MS-related symptoms (all P < .001). Conclusions: Despite concerns about insufficient safety and efficacy data, legality, and cost, almost one-third of NARCOMS Registry respondents report having tried nonprescription cannabis products in an attempt to alleviate their symptoms. Given the lack of efficacy and safety data on such products, future research in this area is warranted. Int J MS Care. 2021;23:245-252. Show less

Since 2014, patients with severe treatment-resistant epilepsies (TREs) have been receiving add-on cannabidiol (CBD) in an ongoing, expanded access program (EAP), which closely reflects clinical practice. We conducted an interim analysis of long-term efficacy and tolerability in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) who received CBD treatment through December 2016. Results from this interim analysis support add-on CBD as an effective long-term treatment option in… Show more

Since 2014, patients with severe treatment-resistant epilepsies (TREs) have been receiving add-on cannabidiol (CBD) in an ongoing, expanded access program (EAP), which closely reflects clinical practice. We conducted an interim analysis of long-term efficacy and tolerability in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) who received CBD treatment through December 2016. Results from this interim analysis support add-on CBD as an effective long-term treatment option in LGS or DS. Show less

Our results demonstrate that CLB and N-CLB have significantly greater binding affinities for α2- vs. α1-receptor complexes, a difference not observed for CLN, for which no distinction between α2 and α1 receptors was observed. These results provide potential clues to a new understanding of the pharmacologic modes of action of CLB and N-CLB

BACKGROUND: The possibility that ɛ4 may modulate the effects of fitness in the brain remains controversial. The present exploratory FDG-PET study aimed to better understand the relationship among ɛ4, fitness, and cerebral metabolism in 18 healthy aged women (nine carriers, nine noncarriers) during working memory.

METHODS: Participants were evaluated using maximal level of oxygen consumption, California Verbal Learning Test, and FDG-PET, which were collected at rest and during completion… Show more

BACKGROUND: The possibility that ɛ4 may modulate the effects of fitness in the brain remains controversial. The present exploratory FDG-PET study aimed to better understand the relationship among ɛ4, fitness, and cerebral metabolism in 18 healthy aged women (nine carriers, nine noncarriers) during working memory.

METHODS: Participants were evaluated using maximal level of oxygen consumption, California Verbal Learning Test, and FDG-PET, which were collected at rest and during completion of the Sternberg working memory task.

RESULTS: Resting FDG-PET did not differ between carriers and noncarriers. Significant effects of fitness on FDG-PET during working memory were noted in the ɛ4 carriers only. High fit ɛ4 carriers had greater glucose uptake in the temporal lobe than the low fit ɛ4 carriers, but low fit ɛ4 carriers had greater glucose uptake in the frontal and parietal lobes.

CONCLUSIONS: We demonstrate that fitness differentially affects cerebral metabolism in ɛ4 carriers only, consistent with previous findings that the effects of fitness may be more pronounced in populations genetically at risk for cognitive decline.

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Physical activity interacts with genotype known to confer risk of Alzheimer's disease, apolipoprotein E4. Exercise improves cognition and alters synaptic proteins in mouse model of genetic risk.

Inflammation cascades change during the course of Alzheimer's disease. Physical exercise alters these changes and decreases some forms of amyloid associated with the progression of dementia.

Alzheimer's disease (AD) is characterized by the accumulation of plaques containing beta-amyloid (Abeta) and neurofibrillary tangles (NFTs) consisting of modified tau. Although Abeta deposition is thought to precede the formation of NFTs in AD, the molecular steps connecting these two pathologies is not known. Previous studies have suggested that caspase activation plays an important role in promoting the pathology associated with AD. To further understand the contribution of caspases in… Show more

Alzheimer's disease (AD) is characterized by the accumulation of plaques containing beta-amyloid (Abeta) and neurofibrillary tangles (NFTs) consisting of modified tau. Although Abeta deposition is thought to precede the formation of NFTs in AD, the molecular steps connecting these two pathologies is not known. Previous studies have suggested that caspase activation plays an important role in promoting the pathology associated with AD. To further understand the contribution of caspases in disease progression, a triple transgenic Alzheimer's mouse model overexpressing the anti-apoptotic protein Bcl-2 was generated. Here we show that overexpression of Bcl-2 limited caspase-9 activation and reduced the caspase cleavage of tau. Moreover, overexpression of Bcl-2 attenuated the processing of APP (amyloid precursor protein) and tau and reduced the number of NFTs and extracellular deposits of Abeta associated with these animals. In addition, overexpression of Bcl-2 in 3xTg-AD mice improved place recognition memory. These findings suggest that the activation of apoptotic pathways may be an early event in AD and contributes to the pathological processes that promote the disease mechanisms underlying AD.

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Physical exercise improves cognitive performance in aged mouse models of Alzheimer's.

Estrogen has been shown to increase endothelium-dependent vasodilation and expression of endothelial nitric oxide (NO) synthase (eNOS); however, the role of estrogen receptors in mediating estrogen effects on endothelial function remains to be elucidated. The purpose of this study was to test the hypothesis that estrogen modulates NO-dependent vasodilation of coronary arteries through its action on estrogen receptor-alpha (ER-alpha) to increase protein levels of eNOS and Cu/Zn superoxide… Show more

Estrogen has been shown to increase endothelium-dependent vasodilation and expression of endothelial nitric oxide (NO) synthase (eNOS); however, the role of estrogen receptors in mediating estrogen effects on endothelial function remains to be elucidated. The purpose of this study was to test the hypothesis that estrogen modulates NO-dependent vasodilation of coronary arteries through its action on estrogen receptor-alpha (ER-alpha) to increase protein levels of eNOS and Cu/Zn superoxide dismutase (SOD-1). Vasodilation to acetylcholine (ACh) and sodium nitroprusside was assessed in isolated coronary arteries from intact and ovariectomized female wild-type (WT) and ER-alpha knockout (ERalphaKO) mice. Protein levels for eNOS and SOD-1 were also evaluated. Vasodilation to ACh was not significantly altered in ERalphaKO mice compared with WT mice. Ovariectomy reduced responsiveness to ACh in ERalphaKO mice but not WT mice. Responses to sodium nitroprusside were not altered by disruption of ER-alpha or by ovariectomy. Supplementation with estrogen restored ACh-induced vasodilation in ovariectomized ERalphaKO mice. eNOS protein was reduced in ERalphaKO mice compared with WT mice. Ovariectomy caused a further reduction in eNOS protein in ERalphaKO mice, but this reduction was reversed by estrogen treatment. SOD-1 protein levels were increased by disruption of ER-alpha. Ovariectomy reduced SOD-1 protein in ERalphaKO mice, but this reduction was partially reversed by estrogen replacement. These results suggest that estrogen modulation of eNOS protein content is mediated in part through ER-alpha. NO-dependent responses are preserved in ERalphaKO mice, possibly through increased SOD-1 expression and enhanced bioavailability of NO.

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Pro-apoptotic members of the Bcl-2 family are identified in white matter and astrocytes in post-mortem cortex from fronto-temporal dementia patients.