ABSTRACT
Objective: The use of medical cannabis among people with epilepsy (PWE) has been garnering increasing interest. In this scoping review, we aimed to summarize the literature on recreational/non-medical cannabis (NMC) use in PWE, focusing on the experience, habits, and beliefs of PWE regarding NMC. Methods: Four databases (OVID Medline, OVID Embase, Ovid APA PsycInfo, and Web of Science) were searched for studies describing NMC use in PWE. NMC was defined as cannabis products procured from sources other than by prescription. Studies that consisted in original research and that detailed the experience, habits, and/or beliefs of PWE regarding NMC use were included in the analysis. Data pertaining to study identification, demographics, NMC use, and epilepsy characteristics were extracted. Descriptive statistical analyses and reflexive thematic analyses were performed to map these data. Results: In total, 3,228 records were screened, and 66 were included for analysis: 45 had mainly adult samples, whereas 21 had mainly pediatric samples. Most studies were published after 2010, originated from the USA, and were cross-sectional. The median number of PWE using cannabis in these studies was 24.5 (1-37,945). No studies showcased elderly PWE, and most had predominantly Caucasian samples. The lifetime prevalence of NMC use in PWE was variable, ranging between 0.69 and 76.8%. Factors frequently associated with NMC use in PWE were male sex, younger adult age, and lower education status. Children with epilepsy took NMC primarily for seizure control, using high CBD/THC ratios, and only orally. Adults with epilepsy took NMC for various reasons including recreationally, using variable CBD/THC ratios, and predominantly through smoking. The majority of PWE across all studies perceived that NMC aided in seizure control. Other aspects pertaining to NMC use in PWE were rarely reported and often conflicting. Conclusion: The literature on NMC use in PWE is sparse and heterogeneous, with many salient knowledge gaps. Further research is necessary to better understanding the experience, habits, and beliefs of PWE pertaining to NMC.
ABSTRACT
Uncaria rhynchophylla is a plant highly used in the traditional Chinese and Japanese medicines. It has numerous health benefits, which are often attributed to its alkaloid components. Recent studies in humans show that drugs containing Uncaria ameliorate sleep quality and increase sleep time, both in physiological and pathological conditions. Rhynchophylline (Rhy) is one of the principal alkaloids in Uncaria species. Although treatment with Rhy alone has not been tested in humans, observations in rodents show that Rhy increases sleep time. However, the mechanisms by which Rhy could modulate sleep have not been comprehensively described. In this review, we are highlighting cellular pathways that are shown to be targeted by Rhy and which are also known for their implications in the regulation of wakefulness and sleep. We conclude that Rhy can impact sleep through mechanisms involving ion channels, N-methyl-d-aspartate (NMDA) receptors, tyrosine kinase receptors, extracellular signal-regulated kinases (ERK)/mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinase (PI3K)/RAC serine/threonine-protein kinase (AKT), and nuclear factor-kappa B (NF-κB) pathways. In modulating multiple cellular responses, Rhy impacts neuronal communication in a way that could have substantial effects on sleep phenotypes. Thus, understanding the mechanisms of action of Rhy will have implications for sleep pharmacology.
ABSTRACT
Sleep and sleep loss are affecting protein synthesis in the brain, but the contribution of translational control to wakefulness and sleep regulation remains poorly understood. Here, we studied the role of two suppressors of protein synthesis, the eukaryotic translation initiation factor 4E-binding proteins 1 and 2 (4E-BP1 and 4E-BP2), in sleep architecture and electroencephalographic (EEG) activity as well as in the EEG and molecular responses to acute sleep loss. The EEG of mice mutant for the genes encoding 4E-BP1 or 4E-BP2 (Eif4ebp1 and Eif4ebp2 knockout [KO] mice) was recorded under undisturbed conditions and following a 6-hour sleep deprivation (SD). The effect of SD on the expression of genes known to respond to SD was also measured in the prefrontal cortex of Eif4ebp1 and Eif4ebp2 KO mice. Eif4ebp1 KO mice differed from wild-type mice in parameters of wakefulness and sleep quantity and quality, and more subtly in the gene expression response to SD. For instance, Eif4ebp1 KO mice spent more time in slow-wave sleep (SWS) and showed altered baseline 24-h time courses of SWS delta (1-4 Hz) activity and sigma (10-13 Hz) activity. Eif4ebp2 KO mice differed from wild-type mice only for wakefulness and sleep quality, expressing changes in EEG spectral activity generally revealed during and after SD. These findings suggest different roles of effectors of translational control in the regulation of wakefulness and sleep and of synchronized cortical activity.
Subject(s)
Phosphoproteins , Wakefulness , Animals , Carrier Proteins , Electroencephalography , Eukaryotic Initiation Factors/metabolism , Mice , Mice, Knockout , Phosphoproteins/metabolism , Sleep/geneticsABSTRACT
Wakefulness and sleep are dynamic states during which brain functioning is modified and shaped. Sleep loss is detrimental to many brain functions and results in structural changes localized at synapses in the nervous system. In this review, we present and discuss some of the latest observations of structural changes following sleep loss in some vertebrates and insects. We also emphasize that these changes are region-specific and cell type-specific and that, most importantly, these structural modifications have functional roles in sleep regulation and brain functions. Selected mechanisms driving structural modifications occurring with sleep loss are also discussed. Overall, recent research highlights that extending wakefulness impacts synapse number and shape, which in turn regulate sleep need and sleep-dependent learning/memory.
