Reduced anxiety-like behaviour induced by genetic and pharmacological inhibition of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) is mediated by CB1 receptors.

“Anandamide and 2-arachidonoyl glycerol, referred to as endocannabinoids (eCBs), are the endogenous agonists for the cannabinoid receptor type 1 (CB1). Several pieces of evidence support a role for eCBs in the attenuation of anxiety-related behaviours, although the precise mechanism has remained uncertain…

 The fatty acid amid hydrolase (FAAH), an enzyme responsible for the degradation of eCBs, has emerged as a promising target for anxiety-related disorders, since FAAH inhibitors are able to increase the levels of anandamide and thereby induce anxiolytic-like effects…

The present work provides genetic and pharmacological evidence supporting the inhibition of FAAH as an important mechanism for the alleviation of anxiety.

 In addition, it indicates an increased activation of CB1 receptors as a mechanism underlying the effects of FAAH inhibition in two models of anxiety.”

http://www.ncbi.nlm.nih.gov/pubmed/17709120

The endogenous cannabinoid anandamide has effects on motivation and anxiety that are revealed by fatty acid amide hydrolase (FAAH) inhibition

“Converging evidence suggests that the endocannabinoid system is an important constituent of neuronal substrates involved in brain reward processes and emotional responses to stress.. It is known that the endocannabinoid system plays a modulatory role in emotional states such as anxiety and fear. Several studies utilizing rodent models of anxiety or depression showed that FAAH inhibition produced anxiolytic-like effects and anti-depressant-like effects…

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213536/

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.”

http://www.ncbi.nlm.nih.gov/pubmed/16541083

Anxiolytic effect of cannabidiol derivatives in the elevated plus-maze.

“1.In order to assess the presence of anxiolytic properties in cannabidiol (CBD) derivatives HU-219, HU-252 and HU-261, these drugs were tested in rats submitted to the elevated plus-maze model of anxiety.

 2. Additional groups received diazepam or CBD. HU-219 (0.03-1 mg/kg) and CBD (5 mg/kg) significantly increased the percentage of open arm entries without changing the total number of entries, an anxiolytic-like effect.

 3. Both HU-252 and HU-261 increased the percentage of time spent in open arms and the total number of entries, but only at the dose of 1 mg/kg.

4. Diazepam (2.5 mg/kg) increased both the percentage of entries and time spent on open arms and the total number of entries.

5. The results confirm previous findings with CBD and indicate that its derivative HU-219 may possess a similar anxiolytic-like profile.

6. Results from HU-252 and HU-261 are less apparent and suggest that the compounds may increase general exploratory activity in a limited range of doses.”

http://www.ncbi.nlm.nih.gov/pubmed/7913072

Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients

“Generalized Social Anxiety Disorder (SAD) is one of the most common anxiety conditions with impairment in social life. Cannabidiol (CBD), one major non-psychotomimetic compound of the cannabis sativa plant, has shown anxiolytic effects both in humans and in animals. This preliminary study aimed to compare the effects of a simulation public speaking test (SPST) on healthy control (HC) patients and treatment-naïve SAD patients who received a single dose of CBD or placebo…

Pretreatment with CBD significantly reduced anxiety, cognitive impairment and discomfort in their speech performance, and significantly decreased alert in their anticipatory speech. The placebo group presented higher anxiety, cognitive impairment, discomfort, and alert levels when compared with the control group…

…because of the absence of psychoactive or cognitive effects, to its safety and tolerability profiles, and to its broad pharmacological spectrum, CBD is possibly the cannabinoid that is most likely to have initial findings in anxiety translated into clinical practice…

… the effects of a single dose of CBD, observed in this study in the face of one of the main SAD’s phobic stimuli, is a promising indication of a rapid onset of therapeutic effect in patients with SAD.”

.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079847/#bib17

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

Safety and side effects of cannabidiol, a Cannabis sativa constituent.

“Cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, has multiple pharmacological actions, including anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, little is known about its safety and side effect profile in animals and humans. This review describes in vivo and in vitro reports of CBD administration across a wide range of concentrations, based on reports retrieved from Web of Science, Scielo and Medline. The keywords searched were “cannabinoids”, “cannabidiol” and “side effects”. Several studies suggest that CBD is non-toxic in non-transformed cells and does not induce changes on food intake, does not induce catalepsy, does not affect physiological parameters (heart rate, blood pressure and body temperature), does not affect gastrointestinal transit and does not alter psychomotor or psychological functions. Also, chronic use and high doses up to 1,500 mg/day of CBD are reportedly well tolerated in humans. Conversely, some studies reported that this cannabinoid can induce some side effects, including inhibition of hepatic drug metabolism, alterations of in vitro cell viability, decreased fertilization capacity, and decreased activities of p-glycoprotein and other drug transporters. Based on recent advances in cannabinoid administration in humans, controlled CBD may be safe in humans and animals. However, further studies are needed to clarify these reported in vitro and in vivo side effects.”