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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.
65 articles
Newest firstThe G-protein-coupled receptor cannabinoid receptor 2 (CB2R) initiates a key signaling pathway in mammalian physiology and pathophysiology. CB2R signaling holds significant therapeutic potential in ameliorating many pathologies, particularly in inflammatory conditions, neurodegenerative disorders, fibroproliferative and ocular diseases. CB2 modulators have been studied for their anti-inflammatory and tissue protec…
Open article record in new tab ↗TRPV2 is the least studied member of the vanilloid TRP subfamily despite its emerging relevance in cancer metastasis, pain, and inflammation. Although several small-molecule TRPV2 modulators have been reported, including the natural products piperlongumine (PL) and cannabidiol, all lack selectivity, complicating the interpretation of phenotypic readouts and functional insights into the role of the channel in healt…
Cannabinoid Receptor 2 (CB2) is a promising therapeutic target for modulating inflammation. Canonical signalling responses to receptor ligands are critically dependent on cell surface receptor expression. However, it is also now appreciated that intracellular G protein-coupled receptors can contribute to signalling responses and influence functional outcomes. Therefore, understanding how the subcellular distributi…
Epigenetic alterations are key contributors to Alzheimer's disease (AD), driving age-related cognitive decline. This study explores the combined neuroprotective effects of G9a histone methyltransferase inhibition (via UNC0642) and cannabinoid receptor activation (CB1R: ACEA; CB2R: JWH133) in AD models. We used HEK-293T cells and hippocampal neurons to demonstrate that G9a inhibition selectively enhances CB1R-media…
GPR55 is an orphan G protein-coupled receptor (GPCR) and represents a promising drug target for cancer, inflammation, and metabolic diseases. The endogenous activation of lipid GPCRs can be solely mediated by membrane components and different lipids have been proposed as endogenous activators of GPR55, such as cannabinoids and lysophosphatidylinositols. Here, we determine high-resolution cryo-electron microscopy s…
Activation of cannabinoid CB1 receptors (CB1R) by agonists induces analgesia but also induces cognitive impairment through the heteromer formed between CB1R and the serotonin 5HT2A receptor (5HT2AR). This side effect poses a serious drawback in the therapeutic use of cannabis for pain alleviation. Peptides designed from the transmembrane helices of CB1R, which are predicted to bind 5HT2AR and alter the stability o…
The assembly of tau into filaments defines tauopathies, a group of neurodegenerative diseases including Alzheimer's disease (AD), Pick's disease (PiD), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP). The seeded aggregation of tau has been modeled in cell culture using pro-aggregate modifications such as truncation of N- and C-termini and point mutations within the microtubule-binding rep…
Open article record in new tab ↗CB1 and CB2 cannabinoid receptors are members of the GPCR superfamily that modulate the effects of endocannabinoids. CB1 is the most abundant CB receptor in the central nervous system, while CB2 is present both peripherally and in the brain. CB2 plays a role in inflammation, as well as neurodegenerative and psychiatric disorders. To identify new ligands for CB2, we screened a library of FDA-approved drugs for acti…
Phytocannabinoids (pCBs) from Cannabis sativa represent an important class of bioactive molecules, potentially useful for the treatment of a wide range of diseases. Their efficacy is due to their ability to interact with multiple targets of the endocannabinoid system, including the thermosensitive transient receptor potential (Thermo-TRPs), namely TRPV1-4, TRPA1, and TRPM8 channels. Previously, we demonstrated a s…
Improper use of drugs in both animal and human therapy, such as doxycycline (DOX), lead to the accumulation of residues in edible animal tissues as well as in the environment. Plant-derived compounds reduce the adverse effects of drugs. This study aimed to evaluate the effect of cannabidiol (CBD) in two concentrations: lower (1.56 µg/mL) (DOX + C1) and higher (3.125 µg/mL) (DOX + C2) on the cytotoxicity of doxycyc…
Open article record in new tab ↗Objectives Cannabidiol (CBD) is a phytocannabinoid with great potential in clinical applications. The mechanism(s) of action of CBD require further investigation. Previous studies suggested that adenosine A2A receptors (A2ARs) could play a role in CBD-induced effects. Here, we evaluated the ability of CBD to modify the function of A2AR. Methods We used HEK-293T cells transfected with the cDNA encoding the human A2…
The growing awareness and need to protect public health, including food safety, require a thorough study of the mechanism of action of veterinary drugs in consumers to reduce their negative impact on humans. Inappropriate use of veterinary drugs in animal husbandry, such as tiamulin, leads to the appearance of residues in edible animal tissues. The use of natural substances of plant origin, extracted from hemp (Ca…
TRPV3 represents both temperature- and ligand-activated transient receptor potential (TRP) channel. Physiologically relevant opening of TRPV3 channels by heat has been captured structurally, while opening by agonists has only been observed in structures of mutant channels. Here, we present cryo-EM structures that illuminate opening and inactivation of wild-type human TRPV3 in response to binding of two types of ag…
Cannabidiol (CBD), the main non-psychotropic phytocannabinoid produced by the Cannabis sativa plant, blocks a variety of cardiac ion channels. We aimed to identify whether CBD regulated the cardiac pacemaker channel or the hyperpolarization-activated cyclic nucleotide-gated channel (HCN4). HCN4 channels are important for the generation of the action potential in the sinoatrial node of the heart and increased heart…
Open article record in new tab ↗The cannabinoid receptor type 1 (CB1R) is pivotal within the endocannabinoid system regulating various signaling cascades with effects in appetite regulation, pain perception, memory formation, and thermoregulation. Still, understanding of CB1R's cellular signaling, distribution, and expression dynamics is very fragmentary. Real-time visualization of CB1R is crucial for addressing these questions. Selective drug-l…
Δ9-Tetrahydrocannabinol (THC) is the primary psychoactive component of cannabis which is being increasingly consumed by pregnant people. In humans, THC is sequentially metabolized in the liver to its circulating metabolites 11-hydroxy-THC (11-OH-THC, psychoactive) and 11-nor-9-carboxy-THC (THC-COOH, non-psychoactive). Human and macaque data show that fetal exposure to THC is considerably lower than the correspondi…
Open article record in new tab ↗The Cannabis sativa plant has been used for centuries as a recreational drug and more recently in the treatment of patients with neurological or psychiatric disorders. In many instances, treatment goals include relief from posttraumatic disorders, anxiety, or to support treatment of chronic pain. Ligands acting on cannabinoid receptor 1 (CB1R) are also potential targets for the treatment of other health conditions…
The cannabinoid receptor 1 (CB1R) regulates synaptic transmission in the central nervous system, but also has important roles in the peripheral organs controlling cellular metabolism. While earlier generations of brain penetrant CB1R antagonists advanced to the clinic for their effective treatment of obesity, such molecules were ultimately shown to exhibit negative effects on central reward pathways that thwarted…
Purpose AMB-FUBINACA is a synthetic cannabinoid receptor agonist (SCRA) which is primarily metabolised by hepatic enzymes producing AMB-FUBINACA carboxylic acid. The metabolising enzymes associated with this biotransformation remain unknown. This study aimed to determine if AMB-FUBINACA metabolism could be reduced in the presence of carboxylesterase (CES) inhibitors and recreational drugs commonly consumed with it…
This protocol describes using fluorescence recovery after photobleaching (FRAP) of a superecliptic pHluorin (SEP)-diacylglycerol lipase α (DAGLα) to measure membrane-bound DAGLα mobility in dendritic shafts of primary cultured cortical mouse neurons. This could serve as an excellent tool to analyze endocannabinoid-mediated synaptic plasticity. We have used this protocol to show that DAGLα surface dynamics play an…
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