“Cannabinoids participate in the modulation of numerous functions in the human organism, increasing the sense of hunger, affecting carbohydrate and lipid metabolism, and controlling systemic energy balance mechanisms. Moreover, they influence the endocrine system functions, acting via two types of receptors, CB1 and CB2. The aim of the present study was to examine the number, distribution and activity of ghrelin and somatostatin producing endocrine cells in the pancreas of rats after a single administration of selective CP 55,940 agonist of CB1 receptor. The study was performed on 20 rats. Neuroendocrine cells were identified by immunohistochemical reactions, involving specific antibodies against ghrelin and somatostatin. The distribution and number of ghrelin- and somatostatin-immunoreactive cells were separately studied in five pancreas islets of each section. A performed analysis showed a decreased number of somatostatin-immunoreactive cells and a weak immunoreactivity of ghrelin and somatostatin containing neuroendocrine cells in the pancreatic islets of experimental rats, compared to control animals. The obtained results suggest that a single administration of a selective CP 55,940 agonist of CB1 receptor influences the immunoreactivity of endocrine cells with ghrelin and somatostatin expression in the pancreas islets.”
Tag Archives: cannabinoid
The endocannabinoid system in the regulation of emotions throughout lifespan: a discussion on therapeutic perspectives.
“Alterations in emotion regulation processes may form the basis of psychopathologies. The endocannabinoid (eCB) system, composed of endogenous ligands, the enzymatic machinery in charge of their metabolism and the specific metabotropic receptors, has emerged as a major neuromodulatory system critically involved in the control of emotional homeostasis and stress responsiveness. Data from animal models indicate that the eCB system plays a key role in brain development, and is probably involved in the control of emotional states from early developmental stages.
The present review summarizes the latest information on the role of the eCB system in emotionality and anxiety-related disorders throughout the lifespan. Putative therapeutic strategies based on the pharmacological modulation of this system will be discussed.
Given the fact that the pharmacological modulation of the eCB system has recently arisen as a promising strategy in the management of anxiety and mood disorders, the potential efficacy of this pharmacological approach (i.e. blockers of the catabolic pathway) will be discussed, as well as pharmacological alternatives such as modulators of cannabinoid receptors other than the classical CB1 receptor, or administration of other plant-derived compounds (e.g. cannabidiol).”
Role of endocannabinoid system in the ventral hippocampus of rats in the modulation of anxiety-like behaviours.
“The effects of unilateral intra-ventral hippocampus injection of URB597, a fatty acid amid hydrolase inhibitor, and AM251, a selective CB(1) receptor antagonist, on anxiety-related behaviours using elevated plus-maze test of anxiety were evaluated in the present study. Possible involvement of GABAergic system in those effects of URB597 was also evaluated. Injection of URB597 at the doses of 0.01, 0.1 and 1 microg/rat showed significant anxiogenic-like effects at 0.1 and 1 microg/rat. However, intra-ventral hippocampus injection of AM251 at the doses of 0.001, 0.01 and 0.1 microg/rat did not produce any significant effect in the elevated plus-maze. The ineffective doses of selective GABA(A) receptor antagonist, bicuculline (2 microg/rat) and selective GABA(B) receptor antagonist, phaclofen (1 microg/rat) on anxiety-related behaviours were also injected with URB597 (0.1 microg/rat). The present data showed that neither bicuculline nor phaclofen affected the anxiogenic-like effects of URB597. The results showed that injection of URB597 into the ventral hippocampus may be anxiogenic and GABAergic system may not be involved in its anxiogenic-like effects.”
An Endocannabinoid Signaling System Modulates Anxiety-like Behavior in Male Syrian Hamsters
“An endocannabinoid signaling system has not been identified in hamsters.
We examined the existence of an endocannabinioid signaling system in Syrian hamsters using neuroanatomical, biochemical and behavioral pharmacological approaches.
The distribution of cannabinoid receptors was mapped and membrane fatty-acid amide hydrolase (FAAH) activity and levels of fatty-acid amides were measured in hamster brain. The impact of cannabinoid CB1 receptor blockade and inhibition of FAAH was evaluated in the elevated plus maze, rota-rod test and models of unconditioned and conditioned social defeat.
Results
A characteristic heterogeneous distribution of cannabinoid receptors was detected in hamster brain..
Endocannabinoids engage functional CB1 receptors in hamster brain to suppress anxiety-like behavior and undergo enzymatic hydrolysis catalyzed by FAAH. Our results further suggest that neither unconditioned nor conditioned social defeat in the Syrian hamster is dependent upon cannabinoid CB1 receptor activation.”
The endocannabinoid nervous system: unique opportunities for therapeutic intervention.
“The active principle in marijuana, Delta(9)-tetrahydrocannabinol (THC), has been shown to have wide therapeutic application for a number of important medical conditions, including pain, anxiety, glaucoma, nausea, emesis, muscle spasms, and wasting diseases. Delta(9)-THC binds to and activates two known cannabinoid receptors found in mammalian tissue, CB1 and CB2. The development of cannabinoid-based therapeutics has focused predominantly on the CB1 receptor, based on its predominant and abundant localization in the CNS.
Like most of the known cannabinoid agonists, Delta(9)-THC is lipophilic and relatively nonselective for both receptor subtypes.
Clinical studies show that nonselective cannabinoid agonists are relatively safe and provide therapeutic efficacy, but that they also induce psychotropic side effects. Recent studies of the biosynthesis, release, transport, and disposition of anandamide are beginning to provide an understanding of the role of lipid transmitters in the CNS. This review attempts to link current understanding of the basic biology of the endocannabinoid nervous system to novel opportunities for therapeutic intervention.
This new knowledge may facilitate the development of cannabinoid receptor-targeted therapeutics with improved safety and efficacy profiles.”
Anxiolytic-like effect induced by the cannabinoid CB1 receptor agonist, arachydonilcyclopropylamide (ACPA), in the rat amygdala is mediated through the D1 and D2 dopaminergic systems.
“In the present study the influence of the dopaminergic system(s) of the amygdala on the anxiolytic-like effect of the cannabinoid CB1 receptor agonist arachydonilcyclopropylamide (ACPA) in male Wistar rats was investigated. An elevated plus-maze test of anxiety was used to assess anxiety-like behaviors…
It can be concluded that the dopaminergic system of the amygdala may be involved, at least partly, in the anxiolytic-like effects induced by ACPA in the rat amygdala.”
Anxiolytic-like properties of the anandamide transport inhibitor AM404.
“The endocannabinoids anandamide and 2-arachidonoyglycerol (2-AG) may contribute to the regulation of mood and emotion. In this study, we investigated the impact of the endocannabinoid transport inhibitor AM404 on three rat models of anxiety..
These results support a role of anandamide in the regulation of emotion and point to the anandamide transport system as a potential target for anxiolytic drugs.”
Modulation of anxiety through blockade of anandamide hydrolysis.
“The psychoactive constituent of cannabis, Delta(9)-tetrahydrocannabinol, produces in humans subjective responses mediated by CB1 cannabinoid receptors, indicating that endogenous cannabinoids may contribute to the control of emotion. But the variable effects of Delta(9)-tetrahydrocannabinol obscure the interpretation of these results and limit the therapeutic potential of direct cannabinoid agonists. An alternative approach may be to develop drugs that amplify the effects of endogenous cannabinoids by preventing their inactivation. Here we describe a class of potent, selective and systemically active inhibitors of fatty acid amide hydrolase, the enzyme responsible for the degradation of the endogenous cannabinoid anandamide. Like clinically used anti-anxiety drugs, in rats the inhibitors exhibit benzodiazepine-like properties in the elevated zero-maze test and suppress isolation-induced vocalizations. These effects are accompanied by augmented brain levels of anandamide and are prevented by CB1 receptor blockade.
Our results indicate that anandamide participates in the modulation of emotional states and point to fatty acid amide hydrolase inhibition as an innovative approach to anti-anxiety therapy.”
Pot Compound Reduces Anxiety
“According to clinical trial data published online in The Journal of Psychopharmacology, the administration of the non-psychoactive component of marijuana [cannabinoid cannabidiol (CBD)] reduces anxiety in subjects with social anxiety disorder (SAD).
The anti-anxiety activity of oral doses of CBD in ten subjects was assessed by investigators at the University of Sao Paulo in Brazil in a double blind, placebo-controlled trial.
Researchers concluded, “CBD reduces anxiety in SAD and that this is related to its effects on activity in limbic and paralimbic brain areas.”
This study is the first clinical trial to investigate the effects of cannabinoid cannabidiol on human pathological anxiety and its underlying brain mechanisms.
Previous studies in the context of CBD have suggested that the compound possesses anti-inflammatory activity, anti-cancer activity, and neuroprotective effects – among other therapeutic properties.
The study “Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report,” appeared online in The Journal of Psychopharmacology.”
Antianxiety effect of cannabidiol in the elevated plus-maze.
“In order to assess the presence of anxiolytic properties in cannabidiol (CBD) the drug was tested in an elevated plus-maze model of anxiety, in rats. Doses of 2.5, 5.0 and 10.0 mg/kg significantly increased the entry ratio (open/total number of entries), an anxiolytic-like effect. CBD at a dose of 20.0 mg/kg was no longer effective. None of the doses of CBD used changed total number of entries, a measure of total exploratory activity. Diazepam (2.0 mg/kg) also caused an anxiolytic-like effect in this model.
These results indicate that CBD causes a selective anxiolytic effect in the elevated plus-maze, within a limited range of doses.”