CB-1

The synthetic forms of delta-9-tetrahydrocannabinol (Δ9 -THC), dronabinol or nabilone, have been approved to treat several indications. However, due to safety concerns their clinical utility remains limited. Consequently, there is a need for developing cannabinoid (CB) ligands that display better behavioral pharmacological profiles than Δ9 -THC. Here, we utilized drug discrimination methods to compare the interoceptive effects of CB ligands that vary in potency, efficacy, and selectivity at the CB receptors, including two ligands, AM411 and AM4089, that show CB1 partial agonist-like actions in vitro...

With the increased popularity and societal acceptance of marijuana and cannabidiol (CBD) use in humans, there is an interest in using cannabinoids in veterinary medicine. There have been a few placebo-controlled clinical trials in dogs suggesting that cannabis-containing extracts are beneficial for dogs with inflammatory diseases such as osteoarthritis, and there is growing interest in their immunosuppressive potential for the treatment of immune-mediated diseases. Since cannabinoids exhibit anti-inflammatory and immunosuppressive effects in many species, the purpose of these studies was to examine whether the plant-derived cannabinoids, CBD and Δ9 -tetrahydrocannabinol (THC), would also suppress immune function in canine peripheral blood mononuclear cells (PBMCs)...

Repeated exposure to psychostimulants, such as amphetamine, causes a long-lasting enhancement in the behavioral responses to the drug, called behavioral sensitization.1 This phenomenon involves several neuronal systems and brain areas, among which the dorsal striatum plays a key role.2 The endocannabinoid system (ECS) has been proposed to participate in this effect, but the neuronal basis of this interaction has not been investigated.3 In the CNS, the ECS exerts its functions mainly acting through the cannabinoid type-1 (CB1 ) receptor, which is highly expressed at terminals of striatal medium spiny neurons (MSNs) belonging to both the direct and indirect pathways...

New psychoactive substances (NPS) targeting cannabinoid receptor 1 (CB 1 ) pose a significant threat to society as recreational abusive drugs that can avoid detection and have higher physiological side effects. These physiological side effects of NPS are shown to be linked to the higher β -arrestin signaling. We hypothesize that the difference in conformational dynamics of the NPxxY motif causes the distinct downstream signaling of NPS contrary to the classical cannabinoids. To compare the dynamic effects of the NPS and classical cannabinoid binding on the NPxxY conformational ensemble, we simulate (un)binding process of NPS MDMB-Fubinaca and classical cannabinoid HU-210 from CB 1 using unbiased and biased molecular dynamics simulations...

BACKGROUND: The endocannabinoid system is active in nervous and immune cells and involves the expression of two cannabinoid receptor genes (CB1 and CB2), along with endogenous endocannabinoid ligands, 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide (anandamide), and their synthetic enzymes. Cannabidiol (CBD) is a non-intoxicating exogenous cannabinoid agonist derived from plants that, at high doses, has received FDA approval as an anticonvulsant for epileptic seizures, and at low doses is marketed as a food-grade supplement for improved mental health, sleep quality, and immunological function...

Despite S-doped C3 N4 can exhibit more efficient photo-reactivity than pure C3 N4 , there is still some space to further improve the detaching efficiency of electron-hole and enhance the photocatalytic efficiency of S-C3 N4 . The construction of heterojunction is an effective method to promote the photocatalytic efficiency. ZnIn2 S4 , as a novel photocatalyst, its VB (1.37 V) and CB (- 1.09 V) can match with S-C3 N4 . Therefore, we hope to construct the ZnIn2 S4 /S-C3 N4 heterojunction for boosting the photocatalytic activity of S-C3 N4 ...

Endocannabinoid system (ECS), which composed of its ligands and receptors, widely distributes in peripheral tissues and nerve system. Through complex regulating mechanisms, ECS exerts a variety of biological functions including analgesia. Its utility in analgesic regulation has attracted extensive attention, and the related achievements have also been transformed into clinical practice. With the deepened understanding of the essence of pain, as well as the advances in research techniques, quantity of research evidences showed that ECS could be regulated by acupuncture treatment and exerted analgesic effect in inflammatory pain, neuropathic pain and other related diseases, and the mechanism had also been revealed gradually...

Cannabinoids exert pleiotropic effects on the brain by engaging the cannabinoid CB1 receptor (CB1 R), a presynaptic metabotropic receptor that regulates key neuronal functions in a highly context-dependent manner. We have previously shown that CB1 R interacts with growth-associated protein of 43 kDa (GAP43) and that this interaction inhibits CB1 R function on hippocampal excitatory synaptic transmission, thereby impairing the therapeutic effect of cannabinoids on epileptic seizures in vivo. However, the underlying molecular features of this interaction remain unexplored...

INTRODUCTION: Widespread use of Fluoroquinolones (FQs) has led to the development of its resistance in clinical isolates of Mycobacterium tuberculosis. However, in Mycobacterium tuberculosis, phenotypic resistance to FQs has been shown to be heterogeneous, ranging from low-level resistance to high-level resistance. This stratification in resistance has important implications for the inclusion of moxifloxacin (Mfx) in the treatment regimen. The World Health Organization recommends the use of GenoType MTBDRsl assay as the initial test for detecting resistance conferring mutations (both high and low) to FQs in patients with confirmed MDR-RR TB...

Molecular interactions between anorexigenic leptin and orexigenic endocannabinoids, although of great metabolic significance, are not well understood. We report here that hypothalamic STAT3 signaling in mice, initiated by physiological elevations of leptin, is diminished by agonists of the cannabinoid receptor 1 (CB1 R). Measurement of STAT3 activation by semi-automated confocal microscopy in cultured neurons revealed that this CB1 R-mediated inhibition requires both T cell protein tyrosine phosphatase (TC-PTP) and β-arrestin1 but is independent of changes in cAMP...

Clostridium butyricum (CB) is known to promote growth, enhance immunity, promote digestion, and improve intestinal health. In this study, we investigated the effects of CB in the feed on growth performance, digestion, and intestinal health of juvenile spotted sea bass. To provide a theoretical basis for the development and application of CB in the feed of spotted sea bass, a total of 450 spotted sea bass with an initial body weight of (9.58 ± 0.05) g were randomly divided into six groups. Gradient levels with 0, 0...

Hemopressin and related peptides have shown to function as the endogenous ligands or the regulator of cannabinoid receptors. The previous studies demonstrated that the endocannabinoid system played important roles in modulating several physiological functions such as sleep, olfaction, emotion, learning and memory, and reward behaviors. Mouse VD-hemopressin (α) [(m)VD-HPα], an 11-residue peptide derived from the α1 chain of hemoglobin, was recently presumed as a selective agonist of the CB1 receptor...

Background: N-linoleyltyrosine (NITyr), one of the anandamide analogs, exerts activity via the endocannabinoid receptors (CB1 and CB2 ), which showed anti-tumor effects in various tumors. Therefore, we speculated that NITyr might show anti-non-small cell lung cancer (NSCLC) effects via the CB1 or CB2 receptor. The purpose of the investigation was to reveal the anti-tumor ability of NITyr on A549 cells and its mechanisms. Methods: The viability of A549 cells was measured by MTT assay, and the cell cycle and apoptosis were both examined by flow cytometry; in addition, cell migration was tested by wound healing assay...

Nabilone, a synthetic analogue of delta-9-Tetrahydrocannabinol, is an agonist of cannabinoid receptors (CB-1 and CB-2) approved to treat chemotherapy-induced vomiting refractory to antiemetics. Its use in patients with refractory vomiting due to gastrointestinal dysmotility (GID) has not been reported. Our study aims are to assess nabilone usefulness and side-effects in patients with refractory vomiting due to GID. Patients prescribed nabilone at St. Mark's intestinal rehabilitation unit (January 2017 to September 2022) due to GID vomiting have been retrospectively reviewed...

Cannabis use disorder (CUD) is widespread, and there is no pharmacotherapy to facilitate its treatment. AEF0117, the first of a new pharmacological class, is a signaling-specific inhibitor of the cannabinoid receptor 1 (CB1 -SSi). AEF0117 selectively inhibits a subset of intracellular effects resulting from Δ9 -tetrahydrocannabinol (THC) binding without modifying behavior per se. In mice and non-human primates, AEF0117 decreased cannabinoid self-administration and THC-related behavioral impairment without producing significant adverse effects...

BACKGROUND AND PURPOSE: The type 1 cannabinoid receptor (CB1 ) is amongst the most abundant G-protein coupled receptors in brain. Allosteric ligands bind to a different site on receptors than the orthosteric ligand and can have effects that are both unique to the allosteric ligand and/or modulate orthosteric ligand activity. We aim to propose a unified mathematical model to describe the interaction effects of the allosteric ligand ORG27569 (ORG) and the orthosteric agonist CP55940 (CP) on CB1 ...

Synthetic cannabinoid receptor agonists (SCRAs) constitute the largest and most defiant group of abuse designer drugs. These new psychoactive substances (NPS), developed as unregulated alternatives to cannabis, have potent cannabimimetic effects and their use is usually associated with episodes of psychosis, seizures, dependence, organ toxicity and death. Due to their ever-changing structure, very limited or nil structural, pharmacological, and toxicological information is available to the scientific community and the law enforcement offices...

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Several pieces of evidence suggest that the monoaminergic theory of depression cannot fully explain all behavioral and neuroplastic changes observed after antidepressant chronic treatment. Other molecular targets, such as the endocannabinoid system, have been associated with the chronic effects of these drugs. In the present study, we hypothesized that the behavioral and neuroplastic effects observed after repeated treatment with the antidepressants (AD) Escitalopram (ESC) or venlafaxine (VFX) in chronically stressed mice depend on CB1 receptor activation...

Melanoma is one of the deadliest forms of cancer. Most melanoma deaths are caused by distant metastases in several organs, especially the brain, the so-called melanoma brain metastases (MBMs). However, the precise mechanisms that sustain the growth of MBMs remain elusive. Recently, the excitatory neurotransmitter glutamate has been proposed as a brain-specific, pro-tumorigenic signal for various types of cancers, but how neuronal glutamate shuttling onto metastases is regulated remains unknown. Here, we show that the cannabinoid CB1 receptor (CB1 R), a master regulator of glutamate output from nerve terminals, controls MBM proliferation...