“Endocannabinoids (eCBS) are involved in the stress response and alterations in eCB signaling may contribute to the etiology of mood disorders.
Exposure to chronic mild stress (CMS), a model of depression, produces downregulation of the CB1 receptor (CB1) in the hippocampus of male rats.
These results effectively demonstrate that CMS significantly alters hippocampal eCB-mediated neurotransmission and synaptic plasticity.”
“The nucleus accumbens (NAc) is a critical component of the reward circuitry, and dysfunction of the NAc may account for anhedonia and other symptoms of depression.
The endocannabinoid (eCB) system regulates mood, emotion, motivation, appetite, body weight, and cognition.
Here, we investigated whether alterations in endocannabinoid (eCB) signaling in the NAc contribute to depression-like behaviors induced by chronic unpredictable stress (CUS) in mice.
These results suggest that downregulation of eCB signaling in the NAc occurs after CUS and contributes to the pathophysiology of depression.”
“Cannabis is commonly used to alleviate symptoms of negative affect. However, a paucity of research has examined the acute effects of cannabis on negative affect in everyday life.
The current study provides a naturalistic account of perceived changes in symptoms of depression, anxiety, and stress as a function of dose and concentration of Δ9tetrahydrocannabinol (THC) and cannabidiol (CBD).
Cannabis is commonly used to alleviate depression, anxiety, and stress. Indeed, one of the most commonly reported motives for cannabis use is to cope with stress, with 72% of daily cannabis users reporting use of cannabis to relax or relieve tension.
Results from the present study indicate that medical cannabis users report a substantial and significant reduction in symptoms of negative affect shortly after using cannabis.”
https://www.ncbi.nlm.nih.gov/pubmed/29656267
https://www.sciencedirect.com/science/article/pii/S0165032718303100
“Cannabidiol (CBD) is a component of Cannabis sativa that has a broad spectrum of potential therapeutic effects in neuropsychiatric and other disorders. However, few studies have investigated the possible interference of CBD on the sleep-wake cycle.
The aim of the present study was to evaluate the effect of a clinically anxiolytic dose of CBD on the sleep-wake cycle of healthy subjects in a crossover, double-blind design.
The drug did not induce any significant effect.
Different from anxiolytic and antidepressant drugs such as benzodiazepines and selective serotonin reuptake inhibitors, acute administration of an anxiolytic dose of CBD does not seem to interfere with the sleep cycle of healthy volunteers. The present findings support the proposal that CBD do not alter normal sleep architecture.
Cannabidiol may play a therapeutic role in sleep regulation.
We found no differences between CBD and placebo in respect to polysomnographic findings or cognitive and subjective measures in a sample of healthy subjects. Unlike widely used anxiolytic and antidepressant drugs such as benzodiazepines and SSRIs, the acute administration of an anxiolytic dose of CBD does not appear to interfere with the sleep cycle of healthy volunteers. Future studies should address the effects of CBD on the sleep-wake cycle of patient populations as well as evaluate the chronic effects of CBD in larger samples of patients with sleep and neuropsychiatric disorders.”
https://www.ncbi.nlm.nih.gov/pubmed/29674967
https://www.frontiersin.org/articles/10.3389/fphar.2018.00315/full
“Early-life stress (ELS) creates life-long vulnerability to stress-related anxiety disorders through altering stress and fear systems in the brain.
The endocannabinoid system has emerged as an important regulator of the stress response through a crosstalk with the glucocorticoid system, yet whether it plays a role in the persistent effects of ELS remains unanswered. By combining, behavioral, pharmacological and biochemical approaches in adult male rats, we examined the impact of ELS on the regulation of endocannabinoid function by stress and glucocorticoids.
These findings suggest that ELS results in an uncoupling of glucocorticoid-endocannabinoid signaling in the hippocampus, which, in turn, relates to alterations in stress regulation of memory recall. These data provide compelling evidence that ELS-induced deficits in the glucocorticoid-endocannabinoidcoupling following stress could predispose susceptibility to stress-related psychopathology.”
“Long term exposure to stress has been demonstrated to cause neuroinflammation through a sustained overproduction of free radicals, including nitric oxide, via an increased inducible nitric oxide synthase (iNOS) activity.
Similar to nitric oxide, endocannabinoids are synthesised on demand, with preclinical observations suggesting that cannabinoid receptor agonists and endocannabinoid enhancers inhibit nitrergic activity.
RESULTS:
The results demonstrate that pre-treatment with PF-3845 rapidly ameliorates plasma corticosterone release at 60 minutes of stress. An increase in endocannabinoid signalling also induces an overall attenuation in iNOS, tumor necrosis factor-alpha convertase, interleukin-6, cyclooxygenase-2, peroxisome proliferator-activated receptor gamma mRNA, and the transactivation potential of NF-κB in the hippocampus.
These results suggest that enhanced endocannabinoid levels in the dorsal hippocampus have an overall anti-nitrosative and anti-inflammatory effect following acute stress exposure.”
“We examined the effects of essential oil from legal (THC <0.2% w/v) hemp variety on the nervous system in 5 healthy volunteers. GC/EIMS and GC/FID analysis of the EO showed that the main components were myrcene and β-caryophyllene.
The experiment consisted of measuring autonomic nervous system (ANS) parameters; evaluations of the mood state; and electroencephalography (EEG) recording before treatment, during treatment, and after hemp inhalation periods as compared with control conditions. The results revealed decreased diastolic blood pressure, increased heart rate, and significant increased skin temperature.
The subjects described themselves as more energetic, relaxed, and calm.
The analysis EEG showed a significant increase in the mean frequency of alpha (8-13 Hz) and significant decreased mean frequency and relative power of beta 2 (18,5-30 Hz) waves. Moreover, an increased power, relative power, and amplitude of theta (4-8 Hz) and alpha brain waves activities and an increment in the delta wave (0,5-4 Hz) power and relative power was recorded in the posterior region of the brain.
These results suggest that the brain wave activity and ANS are affected by the inhalation of the EO of Cannabis sativa suggesting a neuromodular activity in cases of stress, depression, and anxiety.”
“Endocannabinoids are involved in depressive and anxious symptoms and might play a role in stress-associated psychiatric disorders.
While alterations in the endogenous cannabinoid system have been repeatedly found in patients with posttraumatic stress disorder (PTSD), this system has been mostly neglected in borderline personality disorder (BPD). However, there is first evidence for elevated serum levels of the endocannabinoids arachidonylethanolamide (AEA) and 2-arachidonyl-sn-glycerol (2-AG) in BPD patients compared to healthy controls and PTSD patients.
In this study, hair endocannabinoids were analyzed, reflecting long-term endocannabinoid concentrations. We assessed AEA concentrations as well as 2-AG and the 2-AG main isomer 1-AG (1-AG/2-AG) in hair in women with BPD (n = 15) and age- and education-matched healthy women (n = 16).
We found significantly reduced log AEA in BPD patients compared to healthy women (p = .03) but no differences in log 1-AG/2-AG concentrations. In addition, there was no association between 1-AG/2-AG and hair cortisol, but we found a non-significant correlation between hair concentrations of AEA and cortisol (p = .06).
Our data indicate altered long-term release of endogenous cannabinoids in women with BPD depending on type of endocannabinoid. AEA has been suggested to modulate the basal activity of the endocannabinoid system and seems to attenuate depressive and anxious symptoms. Thus, chronically reduced AEA might contribute to psychiatric symptoms in BPD.”
https://www.ncbi.nlm.nih.gov/pubmed/29546791
https://www.tandfonline.com/doi/abs/10.1080/10253890.2018.1451837?journalCode=ists20
“Repeated injections of cannabidiol (CBD), the major non-psychotomimetic compound present in the Cannabis sativa plant, attenuate the anxiogenic effects induced by Chronic Unpredictable Stress (CUS). The specific mechanisms remain to be fully understood but seem to involve adult hippocampal neurogenesis and recruitment of endocannabinoids.
Here we investigated for the first time if the behavioral and pro-neurogenic effects of CBD administered concomitant the CUS procedure (14 days) are mediated by CB1, CB2 or 5HT1A receptors, as well as CBD effects on dendritic remodeling and on intracellular/synaptic signaling (fatty acid amide hydrolase – FAAH, Akt, GSK3β and the synaptic proteins Synapsin Ia/b, mGluR1 and PSD95).
After 14 days, CBD injections (30 mg/kg) induced anxiolytic responses in stressed animals in the elevated plus-maze and novelty suppressed feeding tests, that were blocked by pre-treatment with a CB1 (AM251, 0.3 mg/kg) or CB2 (AM630, 0.3 mg/kg), but not by a 5HT1A (WAY100635, 0.05 mg/kg) receptor antagonist. Golgi staining and immunofluorescence revealed that these effects were associated with an increase in hippocampal neurogenesis and spine density in the dentate gyrus of the hippocampus. AM251 and AM630 abolished the effects of CBD on spines density. However, AM630 was more effective in attenuating the pro-neurogenic effects of CBD. CBD decreased FAAH and increased p-GSK3β expression in stressed animals, which was also attenuated by AM630.
These results indicate that CBD prevents the behavioral effects caused by CUS probably due to a facilitation of endocannabinoid neurotransmission and consequent CB1/CB2receptors activation, which could recruit intracellular/synaptic proteins involved in neurogenesis and dendritic remodeling.”
https://www.ncbi.nlm.nih.gov/pubmed/29510186
https://www.sciencedirect.com/science/article/pii/S0028390818301023
“Cannabidiol (CBD) is thought to have therapeutic potential for treating psychiatric conditions that affect cognitive aspects of learning and memory, including anxiety and post-traumatic stress disorder (PTSD).
Studies have shown that CBD enhances extinction of fear memory when given after conditioning. This led us to hypothesize that CBD, if administered prior to fear conditioning, might modulate cognitive learning and memory processes in additional ways that would further guide its potential use for treating PTSD.
Therefore, we designed a study to investigate effects of CBD on fear learning and memory when administered to mice prior to administering a trace fear conditioning protocol which imposes cognitive demands on the learning and memory process.
Overall, the memory-modulating effects of a single pre-conditioning dose of CBD, which we show here, demonstrate the need to more fully characterize its basic effects on memory, suggest caution when using it clinically as an anxiolytic, and point to a need for more research into its potential as a therapeutic for treating memory-loss disorders.”
https://www.ncbi.nlm.nih.gov/pubmed/29432803
https://www.sciencedirect.com/science/article/pii/S1074742718300224