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Readable research linked to original sources
Browse normalized, publication-ready research with direct links to its evidence and source.
Loading articles data…
Readable research linked to original sources
Browse normalized, publication-ready research with direct links to its evidence and source.
11 articles
Newest firstOpioid use disorder (OUD) remains a major public health crisis, underscoring the urgent need for safer and more effective treatments. Cannabinoid CB2 receptor (CB2R) agonists show therapeutic promise for neuropsychiatric disorders and pain, with minimal psychoactive effects by themselves, but their potential in treating OUD is not well defined. Here, we report that MRI-2594, a novel, highly selective CB2R agonist,…
Open article record in new tab ↗Co-administration of cannabinoids and opioids has been shown to enhance analgesic effects. However, the underlying mechanisms remain unclear. One hypothesis suggests that cannabinoid CB1 receptors (CB1R) and mu-opioid receptors (MOR) interact at the cell membrane or intracellular signaling level. This study aimed to test this hypothesis by examining CB1R-MOR colocalization and assessing whether the deletion of one…
Open article record in new tab ↗Abstract The cannabinoid CB2 receptor (CB2R) has emerged as a promising therapeutic target for pain and central nervous system disorders, yet its brain expression has remained controversial due to low basal levels and the lack of reliable antibodies. Previous green fluorescent protein (GFP) reporter mouse lines have produced conflicting findings, possibly because GFP was either randomly inserted into the genome or…
Open article record in new tab ↗G protein-coupled receptor 55 (GPR55) has been thought to be a putative cannabinoid receptor. However, little is known about its functional role in cannabinoid action and substance use disorders. Here we report that GPR55 is predominantly found in glutamate neurons in the brain, and its activation reduces self-administration of cocaine and nicotine in rats and mice. Using RNAscope in situ hybridization, GPR55 mRNA…
Open article record in new tab ↗Preclinical research has demonstrated the efficacy of CB1 receptor (CB1R) antagonists in reducing drug-taking behavior. However, clinical trials with rimonabant, a CB1R antagonist with inverse agonist profile, failed due to severe adverse effects, such as depression and suicidality. As a result, efforts have shifted towards developing novel neutral CB1R antagonists without an inverse agonist profile for treating s…
Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors that regulate gene expression. Δ9-tetrahydrocannabinol (Δ9-THC) is a PPARγ agonist and some endocannabinoids are natural activators of PPARα and PPARγ. However, little is known regarding their cellular distributions in the brain and functional roles in cannabinoid action. Here, we first used RNAscope in situ hybridization and imm…
Open article record in new tab ↗Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors that regulate gene expression. Δ 9 -tetrahydrocannabinol (Δ 9 -THC) is a PPARg agonist and some endocannabinoids are natural activators of PPAR a and PPARg. Therefore, both the receptors are putative cannabinoid receptors. However, little is known regarding their cellular distributions in the brain and functional roles in cannabi…
Open article record in new tab ↗Cannabinoid CB1 receptors (CB1Rs) have been major targets in medication development for the treatment of substance use disorders. However, clinical trials with rimonabant, a CB1R antagonist/inverse agonist, failed due to severe side effects. Here, we evaluated the therapeutic potential of PIMSR, a neutral CB1R antagonist lacking an inverse agonist profile, against cocaine's behavioral effects in experimental anima…
Recent research indicates that brain cannabinoid CB2 receptors are involved in drug reward and addiction. However, it is unclear whether β-caryophyllene (BCP), a natural product with a CB2 receptor agonist profile, has therapeutic effects on methamphetamine (METH) abuse and dependence. In this study, we used animal models of self-administration, electrical brain-stimulation reward (BSR) and in vivo microdialysis t…
Open article record in new tab ↗Metabotropic glutamate receptor 5 (mGluR5) antagonism inhibits cocaine self-administration and reinstatement of drug-seeking behavior. However, the cellular and molecular mechanisms underlying this action are poorly understood. Here we report a presynaptic glutamate/cannabinoid mechanism that may underlie this action. Systemic or intra-nucleus accumbens (NAc) administration of the mGluR5 antagonist 2-methyl-6-(phe…
Open article record in new tab ↗Cannabis can be rewarding or aversive. Cannabis reward is believed to be mediated by activation of cannabinoid CB1 receptors (CB1Rs) on GABAergic neurons that disinhibit dopaminergic neurons in the ventral tegmental area (VTA). However, little is known about the mechanisms underlying cannabis aversion in rodents. In the present study, CB1Rs are found not only on VTA GABAergic neurons, but also on VTA glutamatergic…
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