“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.”
Tag Archives: anxiety
Cannabinoid-related agents in the treatment of anxiety disorders: current knowledge and future perspectives.
“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.”
Cannabinoid effects on anxiety-related behaviours and hypothalamic neurotransmitters.
“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.”
Cannabinoid type 1 receptors and transient receptor potential vanilloid type 1 channels in fear and anxiety-two sides of one coin?
“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.”
Effects of the cannabinoid receptor ligands on anxiety-related effects of d-amphetamine and nicotine in the mouse elevated plus maze test.
“The purpose of the experiments was to examine the anxiety-related effects of d-amphetamine and nicotine, and the possible involvement of the endocannabinoid system…
These results provide evidence that the endogenous cannabinoid system is involved in the anxiety-related responses to d-amphetamine and/or nicotine.”
The efficacy and safety of nabilone (a synthetic cannabinoid) in the treatment of anxiety.
“The anxiolytic properties of nabilone, a synthetic cannabinoid resembling the natural cannabinoids, were studied in 25 outpatients suffering from anxiety. The drug was compared with a placebo in a double-blind manner over a 28-day treatment period. Patients were seen weekly by the physician and were rated by the Hamilton Rating Scale for Anxiety and the Patient’s Global Evaluation as well as by patient-rated evaluations. The results of the study showed a dramatic improvement in anxiety in the nabilone group when compared with placebo (P less than 0.001). Side effects reported were dry mouth, dry eyes, and drowsiness. Patients did not report any of the subjective “altered state” experience of marihuana.”
Cannabinoid CB1 receptors of the rat central amygdala mediate anxiety-like behavior: interaction with the opioid system.
“Cannabinoids, which are the active compounds of marijuana, produce some pharmacological effects similar to the opioids. In addition, there are functional interactions between the cannabinoid and opioid systems. In this study, we investigated the effects of intraperitoneal (i.p.) injection of opioid drugs on responses induced by intracentral amygdala (intra-CeA) microinjection of cannabinoid CB1 receptor agents in rats, using the elevated plus maze test of anxiety…
In conclusion, the results may indicate an anxiolytic-like effect for cannabinoid CB1 receptors of the CeA and the existence of an interaction between the cannabinoid and the opioid systems in the modulation of anxiety.”
Cat odour-induced anxiety–a study of the involvement of the endocannabinoid system.
“Recent evidence suggests the involvement of the endocannabinoid (EC) system in the regulation of anxiety.The aim of present work was to study the role of the EC system in cat odour-induced anxiety in rats… Exposure to cat odour induces anxiogenic-like effect on the behaviour in rats… Relation of predator odour-induced anxiety to the inhibition of the EC system in the amygdala and PAG is supported by behavioural studies where blockade of CB1 receptors by rimonabant induces anxiogenic-like action.”
Predator threat stress promotes long lasting anxiety-like behaviors and modulates synaptophysin and CB1 receptors expression in brain areas associated with PTSD symptoms.
“Several studies have suggested that changes in hippocampal, prefrontal cortex and amygdaloid complex function are associated with the main symptoms of Posttraumatic Stress Disorder (PTSD). Predator exposure can mimic some aspects of PSTD such as hyperarousal and chronic anxiety…
The present work evaluated whether the long lasting behavioral effects evoked by predator exposure are associated to long-term changes in the expression of the Cannabinoid receptor 1 (CB1) and the synaptic protein SYP in brain areas…
Our results suggested that predator exposure causes long-lasting anxiogenic effects associated with hyperactivation of amygdaloid complex and modulation of CB1 receptor in brain areas related to PTSD symptoms.”
Acute stress increases circulating anandamide and other N-acylethanolamines in healthy humans.
“Stress plays an important role in psychiatric disorders, and preclinical evidence indicates that the central endocannabinoid system modulates endocrine and neuronal responses to stress. This study aimed to investigate the effect of acute stress on circulating concentrations of endocannabinoids (eCBs) in healthy humans…
…stress increased serum concentrations of AEA and the other NAEs immediately after the stress period…These results indicate that stress increases circulating NAEs in healthy human volunteers.
This finding supports a protective role for eCBs in anxiety. Further research is needed to elucidate the function of these lipid mediators, and to determine the mechanisms that regulate their appearance in the circulation.”