Category Archives: Anxiety

Enhancement of endocannabinoid signaling with JZL184, an inhibitor of the 2-arachidonoylglycerol hydrolyzing enzyme monoacylglycerol lipase, produces anxiolytic effects under conditions of high environmental aversiveness in rats.

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“Dysregulation in signaling of the endocannabinoid 2-arachidonoylglycerol (2-AG) is implicated in hyperresponsiveness to stress. We hypothesized that blockade of monoacylglycerol lipase (MGL), the primary enzyme responsible for 2-AG deactivation in vivo, would produce context-dependent anxiolytic effects in rats.

 These data warrant further testing of MGL inhibitors to elucidate the functional role of 2-AG in controlling anxiety and stress responsiveness. Our data further implicate a role for 2-AG in the regulation of emotion and validate MGL as a therapeutic target.”

http://www.ncbi.nlm.nih.gov/pubmed/21600985

The cannabinoid receptor CB₁ inverse agonist AM251 potentiates the anxiogenic activity of urocortin I in the basolateral amygdala.

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The basolateral amygdala is reported to play an important role in the neural bases of emotional processing… Based on these findings, we propose that urocortin and endocannabinoid signaling are part of an integrated neural axis modulating anxiety states within the basolateral amygdala. This article is part of a Special Issue entitled ‘Anxiety and Depression’.”

http://www.ncbi.nlm.nih.gov/pubmed/21736884

Chronic blockade of cannabinoid CB2 receptors induces anxiolytic-like actions associated with alterations in GABA(A) receptors.

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“The aim of this study was to explore the effects of CB(2) receptor agonist and antagonist in the regulation of anxiety-like behaviours…The opposing behavioural and molecular changes observed after chronic treatment… support the key role of CB(2) receptors in the regulation of anxiety. Indeed, the efficacy in reducing the anxiety of the spontaneously anxious strain of mice strengthens the potential of the CB(2) receptor as a new target in the treatment of anxiety-related disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/21838753

Overexpression of CB2 cannabinoid receptors decreased vulnerability to anxiety and impaired anxiolytic action of alprazolam in mice.

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“Overexpression of CB2r reduced anxiety-like behaviours in… mice…

 Our findings revealed that increased expression of CB2r significantly reduced anxiogenic-related behaviours, modified the response to stress and impaired the action of anxiolytic drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/20837564

Pharmacological and pharmacokinetic characterization of the cannabinoid receptor 2 agonist, GW405833, utilizing rodent models of acute and chronic pain, anxiety, ataxia and catalepsy.

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“To date, two cannabinoid receptors have been identified, CB1 and CB2. Activation of these receptors with non-selective cannabinoid receptor agonists reduces pain sensitivity in animals and humans. However, activation of CB1 receptors is also associated with central side effects… More recently, a role for selective CB2 agonists in pain modification has been demonstrated…a selective CB2 agonist, was recently reported to partially reverse the inflammation and hyperalgesia in a rat model of acute inflammation. In the current report, we extend the characterization and therapeutic potential of this compound…

 These data support the tenet that selective CB2 receptor agonists have the potential to treat pain without eliciting the centrally-mediated side effects associated with non-selective cannabinoid agonists…”

http://www.ncbi.nlm.nih.gov/pubmed/15814101

Role of endocannabinoid system in mental diseases.

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“In the last decade, a large number of studies using Delta9-tetrahydrocannabinol (THC), the main active principle derivative of the marijuana plant, or cannabinoid synthetic derivatives have substantially contributed to advance the understanding of the pharmacology and neurobiological mechanisms produced by cannabinoid receptor activation.

 Cannabis has been historically used to relieve some of the symptoms associated with central nervous system disorders. Nowadays, there are anecdotal evidences for the use of cannabis in many patients suffering from multiple sclerosis or chronic pain. Following the historical reports of the use of cannabis for medicinal purposes, recent research has highlighted the potential of cannabinoids to treat a wide variety of clinical disorders. Some of these disorders that are being investigated are pain, motor dysfunctions or psychiatric illness…

 Considering that cannabis or cannabinoid pharmaceutical preparations may no longer be exclusively recreational drugs but may also present potential therapeutic uses, it has become of great interest to analyze the neurobiological and behavioral consequences of their administration. This review attempts to link current understanding of the basic neurobiology of the endocannabinoid system to novel opportunities for therapeutic intervention and its effects on the central nervous system.”

http://www.ncbi.nlm.nih.gov/pubmed/15325960

New pharmacological treatment approaches for anxiety disorders.

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“New developments in the pharmacological treatment of anxiety disorders will have distinct backgrounds: characterization of pathophysiological processes including evolving techniques of genomics and proteomics will generate new drug targets. Drug development design will generate new pharmacological substances with specific action at specific neurotransmitter and neuropeptide receptors or affecting their reuptake and metabolism. New anxiolytic drugs may target receptor systems that only recently have been linked to anxiety-related behavior. This includes the N-methyl-D-aspartate (NMDA), S-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and the cannabinoid receptors. In addition, signal transduction pathways, neurotrophic factors, and gases such as nitric oxide or carbon monoxide may be new drug targets. Combining psychopharmacological and psychotherapeutical interventions is a further field where benefits for the treatment of anxiety disorders could be achieved. Although the road of drug development is arduous, improvements in the pharmacological treatment of anxiety disorders are expected for the near future.”

http://www.ncbi.nlm.nih.gov/pubmed/16594270

Facilitation of contextual fear memory extinction and anti-anxiogenic effects of AM404 and cannabidiol in conditioned rats.

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“The present study investigated the central effects of the eCB uptake/metabolism inhibitor AM404 and the phytocannabinoid cannabidiol (CBD) on the extinction of contextual fear memories in rats…

… In conclusion, CBD, a non-psychoactive phytocannabinoid could be an interesting pharmacological approach to reduce the anxiogenic effects of stress and promote the extinction of fear memories.”

http://www.ncbi.nlm.nih.gov/pubmed/18706790

Cannabinoid-related agents in the treatment of anxiety disorders: current knowledge and future perspectives.

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“Rich evidence has shown that cannabis products exert a broad gamut of effects on emotional regulation. The main psychoactive ingredient of hemp, Δ9-tetrahydrocannabinol (THC), and its synthetic cannabinoid analogs have been reported to either attenuate or exacerbate anxiety and fear-related behaviors in humans and experimental animals. The heterogeneity of cannabis-induced psychological outcomes reflects a complex network of molecular interactions between the key neurobiological substrates of anxiety and fear and the endogenous cannabinoid system, mainly consisting of the arachidonic acid derivatives anandamide and 2-arachidonoylglycerol (2-AG) and two receptors, respectively termed CB1 and CB2. The high degree of interindividual variability in the responses to cannabis is contributed by a wide spectrum of factors, including genetic and environmental determinants, as well as differences in the relative concentrations of THC and other alkaloids (such as cannabidiol) within the plant itself.

The present article reviews the currently available knowledge on the herbal, synthetic and endogenous cannabinoids with respect to the modulation of anxiety responses, and highlights the challenges that should be overcome to harness the therapeutic potential of some of these compounds, all the while limiting the side effects associated with cannabis consumption. In addition the article presents some promising patents on cannabinoid-related agents.”

http://www.ncbi.nlm.nih.gov/pubmed/22280339

Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects.

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“Cannabis (marijuana, hashish, or cannabinoids) has been used for medical and recreational purposes for many centuries and is likely the only medicine or illicit drug that has constantly evoked tremendous interest or controversy within both the public domain and medical research. Cannabinoids appear to be able to modulate pain, nausea, vomiting, epilepsy, ischemic stroke, cerebral trauma, multiple sclerosis, tumors, and other disorders in humans and/or animals.

Cannabis acts on 2 types of cannabinoid receptors, the CB1 and CB2 receptors, which are distributed mainly in the brain and immune system, respectively. In the brain, CB1 receptors are also targeted by endogenous cannabinoids (i.e., endocannabinoids) such as anandamide (AEA), 2-arachidonylglycerol, and arachidonylethanolamide…

…since adult hippocampal neurogenesis is suppressed following chronic administration of opiates, alcohol, nicotine, and cocaine, the present study suggests that cannabinoids are the only illicit drug that can promote adult hippocampal neurogenesis following chronic administration…

Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects.”  

https://www.jci.org/articles/view/25509

“University Of Saskatchewan Research Suggests Marijuana Analogue Stimulates Brain Cell Growth”  http://www.sciencedaily.com/releases/2005/10/051016083817.htm