Tag Archives: anti-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

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

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

Cannabinoid effects on anxiety-related behaviours and hypothalamic neurotransmitters.

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“The aim of the present study was to examine the effects of the cannabinoid agonist CP 55,940 and the antagonist SR 141716A, alone and in combination, on rat exploratory and anxiety-like behaviour in the holeboard and elevated plus-maze tests. A further aim was to evaluate the effects of these treatments on hypothalamic neurotransmitters. Animals treated with CP 55,940 doses of 0.125 and 0.1 mg/kg exhibited less exploration and an increase in anxiety-like behaviour accompanied by great motor inhibition. No hypoactivity was seen at 0.075 mg/kg dosage, but anxiety and neophobic responses persisted, indicating independent and specific effects. Motor activity effects induced by CP 55,940 were reversed by pretreatment with SR 141716A (3 mg/kg). Surprisingly, when administered on its own, the antagonist also induced a reduction in exploratory parameters and an increase in anxiety-like responses. These apparently similar effects might be caused by different neural mechanisms. Finally, CP 55,940 increased hypothalamic dopamine and serotonin levels. These increases might be involved in the activation of the hypothalamic-pituitary-adrenal axis described for cannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/11566149

Cannabinoid type 1 receptors and transient receptor potential vanilloid type 1 channels in fear and anxiety-two sides of one coin?

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“The transient receptor potential vanilloid type 1 channel (TRPV1; originally vanilloid receptor VR1) is activated in peripheral terminals of nociceptive fibers by noxious heat, low pH, and natural products such as capsaicin, the pungent ingredient of red-hot chilli peppers. Evidence has been accumulating that TRPV1 is expressed also in the brain, where it seems to be involved in antinociception, locomotor control, and regulation of affective behaviors. This ion channel might be activated by arachidonoyl ethanolamide (anandamide), the endogenous agonist of the cannabinoid type 1 (CB(1)) receptor. However, while CB(1) activation leads to a decrease in intracellular calcium and attenuation of synaptic transmission, anandamide binding to TRPV1 results in elevated calcium levels and potentiated synaptic transmission. This suggests a tripartite regulatory system with antagonistic effects of CB(1) and TRPV1, which are tied together by the same endogenous ligand. Such a system may have important implication for the modulation of behavioral responses. The present commentary elaborates on this interplay between CB(1) receptors and TRPV1 channels in the context of fear- and anxiety-related behaviors.”

http://www.ncbi.nlm.nih.gov/pubmed/21906661

Effects of delta9-tetrahydrocannabinol on reward and anxiety in rats exposed to chronic unpredictable stress.

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“The aim of this study was to examine how exposure to chronic unpredictable stress (CUS) will affect reward function and anxiety after acute administration of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) in rats…

…both the low and the high dose of Delta(9)-THC exerted anxiolytic-like effects…

The present results provide clear evidence for an anxiolytic effect of Delta(9)-THC both in stressed and in nonstressed animals…”

http://www.ncbi.nlm.nih.gov/pubmed/19406854

Impaired action of anxiolytic drugs in mice deficient in cannabinoid CB1 receptors.

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“The role of cannabinoid CB(1) receptors in the action of anxiolytics was examined. Deletion of CB(1) receptors resulted in increased anxiety-like behaviours… Our findings reveal that CB(1) receptors are involved in the regulation of emotional responses, and play a pivotal role in the action mechanism of anxiolytics. They suggest that alterations in the functional activity of the CB(1) receptor may be related to the emergence of anxiety disorders, and may affect treatment with anxiolytics.”

http://www.ncbi.nlm.nih.gov/pubmed/15081793

Involvement of the opioid system in the anxiolytic-like effects induced by Delta(9)-tetrahydrocannabinol.

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Recent studies have shown that several pharmacological actions induced by cannabinoids, including antinociception and reward, involve the participation of the endogenous opioid system. The present study was designed to examine the possible involvement of the different opioid receptors in the anxiolytic-like responses induced by Delta(9)-tetrahydrocannabinol (THC)…

The administration of a low dose of THC produced clear anxiolytic-like responses…

CONCLUSIONS:

These results demonstrate that the endogenous opioid system is involved in the regulation of anxiety-like behaviour by cannabinoids and provide new findings to clarify further the interaction between these two neuronal systems.”

http://www.ncbi.nlm.nih.gov/pubmed/12185408