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Readable research linked to original sources
Browse normalized, publication-ready research with direct links to its evidence and source.
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Readable research linked to original sources
Browse normalized, publication-ready research with direct links to its evidence and source.
37 articles
Newest firstSeveral essential physiological systems express voltage-gated potassium channels within the KV7 family (comprising KV7.1-7.5), sometimes also co-assembled with auxiliary subunits in the KCNE family (comprising KCNE1-5). An ongoing challenge to KV7 drug development is creating subtype-selective compounds to limit adverse effects. Prior work has shown that the antiepileptic cannabidiol (CBD), a pan-KV7 modulator, in…
Open article record in new tab ↗BackgroundSynaptic dysfunction underlies early sensorimotor and cognitive deficits in Huntington's disease (HD) and precedes the degeneration of striatal spiny projection neurons and cortical pyramidal neurons. Movement selection and motor learning, which are impaired early in HD, are regulated by connections between the motor cortex, basal ganglia and thalamus. In particular, plasticity at corticostriatal synapse…
Prenatal cannabis exposure (PCE) has been associated with altered prefrontal cortex (PFC) activity and connectivity in adulthood, potentially increasing the risk of psychopathology later in life. This risk is thought to involve a complex interplay between the endocannabinoid and dopaminergic systems. We investigated the transcriptional regulation of genes associated with these systems in an animal model of PCE dur…
In this study, we have examined the neuroprotective effects of cannabidiolic acid (CBDA) in models of Alzheimer's disease (AD). We used in vitro electrophysiological recording in hippocampal slices and performed proteomic analysis of cortical tissue from APPswe/PS1dE9 (APP/PS1) mice. In wild-type (WT) slices from C57BL6 mice, acute treatment with CBDA (10 μM) did not alter levels of hippocampal long-term potentiat…
Deficits in learning and memory are some of the most commonly reported symptoms following a traumatic brain injury (TBI). We will examine whether the neural basis of these deficits stems from alterations to bidirectional synaptic plasticity within the hippocampus. Although the CA1 subregion of the hippocampus has been a focus of TBI research, the dentate gyrus should also be given attention as it exhibits a unique…
Synthetic cannabinoid receptor agonists (SCRAs) is a large group of structurally diverse designer drugs (analogues of controlled substances) associated with intense and sometimes fatal intoxication. Cardiac symptoms including tachycardia and arrhythmia are common consequences of SCRA consumption. However, little is known about the mechanisms through which SCRAs may perturb cardiac rhythm. Here we used electrophysi…
Open article record in new tab ↗The lateral habenula (LHb) integrates cortical and basal forebrain (BF) input to control monoaminergic outflow and is implicated in depression, anxiety, impulsivity, and aversion. Although cannabis withdrawal is associated with negative affect and heightened anxiety, LHb involvement is not established. Here, effects of withdrawal from the psychoactive cannabis constituent Δ 9 -tetrahydrocannabinol (Δ 9 -THC) on LH…
Cannabinoids have shown potential in drug-resistant epilepsy treatment; however, we lack knowledge on which cannabinoid(s) to use, dosing, and their pharmacological targets. This study investigated (i) the anticonvulsant effect of Cannabidiol (CBD) alone and (ii) in combination with Delta-9 Tetrahydrocannabinol (Δ9-THC), as well as (iii) the serotonin (5-HT)1A receptor's role in CBD's mechanism of action. Seizure…
Background Genotype-positive patients who suffer from the cardiac channelopathy Long QT Syndrome (LQTS) may display a spectrum of clinical phenotypes, with often unknown causes. Therefore, there is a need to identify factors influencing disease severity to move towards an individualized clinical management of LQTS. One possible factor influencing the disease phenotype is the endocannabinoid system, which has emerg…
There are no known drugs or drug combinations that promote substantial central nervous system axonal regeneration after injury. We used systems pharmacology approaches to model pathways underlying axonal growth and identify a four-drug combination that regulates multiple subcellular processes in the cell body and axons using the optic nerve crush model in rats. We intravitreally injected agonists HU-210 (cannabino…
Open article record in new tab ↗JWH-073 is a synthetic cannabinoid (SCB) that is illegally marketed within an "herbal blend", causing psychoactive effects more intense than those produced by Cannabis. Users report that JWH-073 causes less harmful effects than other SCBs, misrepresenting it as a "safe JWH-018 alternative", which in turn prompts its recreational use. The present study is aimed to investigate the in vivo pharmacological activity on…
Open article record in new tab ↗Introduction Tobacco use is in part a gendered activity, yet neurobiological studies outlining the effect by nicotine on the female brain are scarce. The aim of this study was to outline acute and sub-chronic effects by nicotine on the female rat brain, with special emphasis on neurotransmission and synaptic plasticity in the dorsolateral striatum (DLS), a key brain region with respect to the formation of habits.…
Open article record in new tab ↗Background CA1, as a major structure involved in learning and memory, has been shown to be affected by tramadol addiction. Both orexin and endocannabinoid receptors express in CA1 and play an important role in drug dependency. The aim of this study was to evaluate the modulatory effects of orexin-2 (OX2R) and endocannabinoid-1 (CB1R) receptors on neuronal activity in CA1, in response to tramadol in rats. Materials…
Open article record in new tab ↗There are no known drugs or drug combinations that promote substantial central nervous system axonal regeneration after injury. We used systems pharmacology approaches to model pathways underlying axonal growth and identify a four-drug combination that regulates multiple subcellular processes in the cell body and axon using the optic nerve crush model in rats. We intravitreally injected agonists HU-210 (cannabinoi…
Open article record in new tab ↗Cannabis use is associated with known cardiovascular side effects such as cardiac arrhythmias or even sudden cardiac death. The mechanisms behind these adverse effects are unknown. The aim of the present work was to study the cellular cardiac electrophysiological effects of cannabidiol (CBD) on action potentials and several transmembrane potassium currents, such as the rapid (IKr) and slow (IKs) delayed rectifier,…
Open article record in new tab ↗Patients with a serious mental illness often use cannabis at higher rates than the general population and are also often diagnosed with cannabis use disorder. Clinical studies reveal a strong association between the psychoactive effects of cannabis and the symptoms of serious mental illnesses. Although some studies purport that cannabis may treat mental illnesses, others have highlighted the negative consequences…
Open article record in new tab ↗Cortical circuit dysfunction is thought to be an underlying mechanism of schizophrenia (SZ) pathophysiology with normalization of aberrant circuit activity proposed as a biomarker for antipsychotic efficacy. Cannabidiol (CBD) shows potential as an adjunctive antipsychotic therapy; however, potential sex effects in these drug interactions remain unknown. In the present study, we sought to elucidate sex effects of C…
Cannabis use is associated with cardiovascular adverse effects ranging from arrhythmias to sudden cardiac death. The exact mechanism of action behind these activities is unknown. The aim of our work was to study the effect of cannabidiol (CBD), tetrahydrocannabinol and 11-nor-9-carboxy-tetrahydrocannabinol on cellular cardiac electrophysiological properties including ECG parameters, action potentials, hERG and IKr…
IntroductionLow voltage-activated T-type calcium channels (T-type ICa), CaV3.1, CaV3.2, and CaV3.3 are opened by small depolarizations from the resting membrane potential in many cells and have been associated with neurological disorders including absence epilepsy and pain. {Delta}9-tetrahydrocannabinol (THC) is the principal psychoactive compound in Cannabis and also directly modulates T-type ICa, however, there…
Open article record in new tab ↗BACKGROUND AND PURPOSE Consumption of Synthetic Cannabinoid Receptor agonists (SCRAs) is associated with severe adverse reactions including seizures, arrhythmias and death, but the molecular mechanisms surrounding SCRA toxicity are not yet established. These disease-like symptoms are also synonymous with altered T-type calcium channel activity which controls rhythmicity in the heart and brain. This study examined…