“The endocannabinoid (eCB) system is an important regulator of the stress response and mediates several stress-related behaviors, including anxiety. Despite anatomical evidence that eCBs interact with the principle stress peptide, corticotropin-releasing factor (CRF), few data exist that address functional interactions between these systems. Accordingly, we examined the effects of the CB1 receptor antagonist, AM251, on behavioral anxiety induced by (1) exogenous CRF, and (2) withdrawal from chronic cocaine exposure (mediated by CRF)… Our findings suggest that the anxiogenic effects of CRF and cocaine withdrawal are mediated, at least in part, by CB1 receptor transmission, and provide evidence in support of eCB-CRF interactions that are independent of the hypothalamic-pituitary-adrenal axis.”
Category Archives: Endocannabinoid System
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.”
Anti-Aversive Effects of Cannabidiol on Innate Fear-Induced Behaviors Evoked by an Ethological Model of Panic Attacks Based on a Prey vs the Wild Snake Epicrates cenchria crassus Confrontation Paradigm
“Research on the interaction between different compounds extracted from the plant Cannabis sativa (Cannabis) and the endocannabinoid system has revealed a series of ligands that selectively bind to cannabinoid receptors. The activation of this system causes a wide spectrum of responses, some of which could be potentially therapeutic. Recently, much attention has been given to cannabidiol (CBD), a major constituent of Cannabis that is unable to mimic all of the effects of the plant but has a wide range of pharmacological effects. In the elevated plus-maze, this drug produces an anxiolytic-like effect…
… attention has been given to the potential anxiolytic properties of cannabidiol, because of its complex actions on the endocannabinoid system together with its effects on other neurotransmitter systems. The aim of this study was to investigate the effects of cannabidiol on innate fear-related behaviors evoked by a prey vs predator paradigm…
These results show that cannabidiol modulates defensive behaviors evoked by the presence of threatening stimuli…
In summary, the data presented in this study suggest that the complex action of CBD on the endocannabinoid-mediated system, together with its putative effect on the serotonin-mediated system, could have a pivotal role in the regulation of emotional states and thus constitute a novel pharmacological target for anti-panic therapy.”
5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats.
“Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa which induces anxiolytic- and antipsychotic-like effects in rodents. These effects could be mediated by facilitation of the endocannabinoid system or by the activation of 5-HT(1A) receptors. As either of these mechanisms could promote adaptation to inescapable stress, the aim of the present work was to test the hypothesis that CBD would attenuate the autonomic and behavioural consequences of restraint stress (RS). We also investigated if the responses to CBD depended on activation of 5-HT(1A) receptors.
Cannabidiol (CBD)… cannabinoid generally found in relatively high concentrations in cannabis, exhibits a somewhat different pharmacology compared with THC. CBD attenuates the psychotomimetic and anxiogenic effects of THC in humans.
Moreover, systemic administration of CBD induced antipsychotic and anxiolytic-like effects…
CONCLUSION AND IMPLICATIONS:
The results suggest that CBD can attenuate acute autonomic responses to stress and its delayed emotional consequences by facilitating 5-HT(1A) receptor-mediated neurotransmission.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697769/
Differential role of anandamide and 2-arachidonoylglycerol in memory and anxiety-like responses.
“Cannabinoid agonists are potential therapeutic agents because of their antinociceptive and anxiolytic-like effects…
These results dissociate the role of anandamide and 2-arachidonoylglycerol in memory consolidation and anxiety and reveal the interest of cannabinoid receptor 2 as a novel target for the treatment of anxiety-related disorders.”
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.”
Mitigation of post-traumatic stress symptoms by Cannabis resin: a review of the clinical and neurobiological evidence.
“It is known from clinical studies that some patients attempt to cope with the symptoms of post-traumatic stress disorder (PTSD) by using recreational drugs. This review presents a case report of a 19-year-old male patient with a spectrum of severe PTSD symptoms, such as intense flashbacks, panic attacks, and self-mutilation, who discovered that some of his major symptoms were dramatically reduced by smoking cannabis resin. The major part of this review is concerned with the clinical and preclinical neurobiological evidence in order to offer a potential explanation of these effects on symptom reduction in PTSD.
This review shows that recent studies provided supporting evidence that PTSD patients may be able to cope with their symptoms by using cannabis products. Cannabis may dampen the strength or emotional impact of traumatic memories through synergistic mechanisms that might make it easier for people with PTSD to rest or sleep and to feel less anxious and less involved with flashback memories.
The presence of endocannabinoid signalling systems within stress-sensitive nuclei of the hypothalamus, as well as upstream limbic structures (amygdala), point to the significance of this system for the regulation of neuroendocrine and behavioural responses to stress.
Evidence is increasingly accumulating that cannabinoids might play a role in fear extinction and antidepressive effects. It is concluded that further studies are warranted in order to evaluate the therapeutic potential of cannabinoids in PTSD.”
Nutritional n-3 polyunsaturated fatty acids deficiency alters cannabinoid receptor signaling pathway in the brain and associated anxiety-like behavior in mice.
“N-3 polyunsaturated fatty acids (PUFAs) cannot be synthesized de novo in mammals and need to be provided by dietary means. In the brain, the main n-3 PUFA is docosahexaenoic acid (DHA), which is a key component of neuronal membranes. A low dietary level of DHA has been associated with increased risk of developing neuropsychiatric diseases; however, the mechanisms involved remain to be determined.
In this study, we found that long-term exposure to an n-3 deficient diet decreases the level of DHA in the brain and impairs the cannabinoid receptor signaling pathway in mood-controlling structures.
In n-3 deficient mice, the effect of the cannabinoid agonist WIN55,212-2 in an anxiety-like behavior test was abolished. In addition, the cannabinoid receptor signaling pathways were altered in the prefrontal cortex and the hypothalamus.
Consequently, our data suggest that behavioral changes linked to an n-3 dietary deficiency are due to an alteration in the endocannabinoid system in specific brain areas.”
Role in Anxiety Behavior of the Endocannabinoid System in the Prefrontal Cortex
“Increasing evidence that low doses of cannabinoid agonists reduce anxiety-like behaviors in mice and rats is being reported, thus suggesting an anxiolytic role for the endogenous cannabinoid signaling. In line with this hypothesis, pharmacological agents that enhance the endogenous cannabinoid signaling exert anxiolytic-like actions…
These findings support an anxiolytic role for physiological increases in AEA in the PFC, whereas more marked increases or decreases of this endocannabinoid might lead to an anxiogenic response due to TRPV1 stimulation or the lack of CB1 activation, respectively.”
The endocannabinoid system in the processing of anxiety and fear and how CB1 receptors may modulate fear extinction.
“The endocannabinoid system recently emerged as an important modulator of many neuronal functions. Among them, the control of anxiety and acquired fear represents nowadays one of the most interesting fields of research. Despite contrasting results obtained by the use of cannabinoid receptor agonists in experimental animals, there is growing evidence that the physiological activation of the endocannabinoid system plays a central role in the control of basal anxiety levels and in the modulation of fear responses. This review will summarise recent data on the role of the endocannabinoid system in most commonly used tests of anxiety and in the processing of acquired fear, with particular attention to its involvement in fear extinction. Finally, a neurobiological model possibly able to implement the role of the endocannabinoid system in these processes will be proposed.”