Cannabis -vs- Depression
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212061: Extensive work has established that noradrenergic inputs from the locus ceruleus provide a major excitatory drive to the DRn, which is mediated by α1-ARs. Activation of these receptors increases the excitability of DRn 5-HT neurons by inducing membrane depolarization (Aghajanian, 1985; Pan et al., 1994) and reducing the amplitude of after hyperpolarizing potential (Pan et al., 1994). In addition to these excitatory effects, the present study shows that activation of postsynaptic α1-ARs enhances 2-AG release, which in turn reduces the strength of glutamate synapses onto DRn 5-HT neurons (Fig. 8). Combined, these studies indicate that the noradrenergic modulation of 5-HT neurons is more complex than initially thought and that α1-AR signaling in the DRn exerts a bidirectional control on the excitability of 5-HT neurons. The bidirectional control exerted by α1-AR could play an important role in maintaining the activity of 5-HT neurons within desirable range and prevent excessive excitation of DRn 5-HT neurons, especially during heightened arousal (e.g., stress), which is characterized by increased noradrenergic tone (Krugers et al., 2012). As such, the reduction of eCB signaling and the impairment of α1-AR LTD induced by chronic stress may lead to an abnormal increase in the excitability of DRn 5-HT neurons and persistent alteration of central 5-HT transmission. Furthermore, the impairment of eCB signaling in the DRn could mediate, at least in part, some of the behavioral consequences of chronic stress exposure, such as depression-like behaviors. It is noteworthy that pharmacological manipulation that increases eCB signaling has been shown to block chronic stress-induced depression-like behaviors (Zhong et al., 2014).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4002665: The purpose of this review is to examine human and preclinical data that are relevant to the following hypotheses. The first hypothesis is that deficient CB1R-mediated signaling results in symptoms that mimic those seen in depression. The second hypothesis is that activation of CB1R-mediated signaling results in behavioral, endocrine and other effects that are similar to those produced by currently used antidepressants. The third hypothesis is that conventional antidepressant therapies act through enhanced CB1R mediated signaling. Together the available data indicate that activators of CB1R signaling, particularly inhibitors of fatty acid amide hydrolase, should be considered for clinical trials for the treatment of depression.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866040: The antidepressant action of cannabis as well as the interaction between antidepressants and the endocannabinoid system has been reported. This study was conducted to assess the antidepressant-like activity of Δ9-THC and other cannabinoids. Cannabinoids were initially evaluated in the mouse tetrad assay to determine doses that do not induce hypothermia or catalepsy. The automated mouse forced swim (FST) and tail suspension (TST) tests were used to determine antidepressant action. At doses lacking hypothermic and cataleptic effects (1.25, 2.5, and 5 mg/kg, i.p.), both Δ9-THC and Δ8-THC showed a U-shaped dose response with only Δ9-THC showing significant antidepressant-like effects at 2.5 mg/kg (p < 0.05) in the FST. The cannabinoids cannabigerol (CBG) and cannabinol (CBN) did not produce antidepressant-like actions up to 80 mg/kg in the mouse FST, while cannabichromene (CBC) and cannabidiol (CBD) exhibited significant effect at 20 and 200 mg/kg, respectively (p < 0.01). The antidepressant-like action of Δ9-THC and CBC was further confirmed in the TST. Δ9 -THC exhibited the same U-shaped dose response with significant antidepressant-like action at 2.5 mg/kg (p < 0.05) while CBC resulted in a significant dose dependent decrease in immobility at 40 and 80 mg/kg doses (p < 0.01). Results of this study show that Δ9-THC and other cannabinoids exert antidepressant-like actions, and thus may contribute to the overall mood-elevating properties of cannabis.
https://www.ncbi.nlm.nih.gov/pubmed/24923339: Anxiety and depression are pathologies that affect human beings in many aspects of life, including social life, productivity and health. Cannabidiol (CBD) is a constituent non-psychotomimetic of Cannabis sativa with great psychiatric potential, including uses as an antidepressant-like and anxiolytic-like compound. The aim of this study is to review studies of animal models using CBD as an anxiolytic-like and antidepressant-like compound. Studies involving animal models, performing a variety of experiments on the above-mentioned disorders, such as the forced swimming test (FST), elevated plus maze (EPM) and Vogel conflict test (VCT), suggest that CBD exhibited an anti-anxiety and antidepressant effects in animal models discussed. Experiments with CBD demonstrated non-activation of neuroreceptors CB1 and CB2. Most of the studies demonstrated a good interaction between CBD and the 5-HT1A neuro-receptor.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823358: Cannabidiol (CBD) is another major component of C. sativa that exhibits a somewhat different pharmacology compared with that of Δ9-THC (Mechoulam et al., 2007). CBD is usually described as a non-psychoactive compound that inhibits some behavioural effects of Δ9-THC, such as catalepsy in rats (Formukong et al., 1988) and psychotomimetic and anxiogenic effects in humans (Zuardi et al., 1982). CBD, however, has been shown to induce antipsychotic- and anxiolytic-like activity in preclinical and clinical studies (Zuardi et al., 1982; 2006; Guimarães et al., 1990; Resstel et al., 2006). More recently, our group showed that systemic administration of CBD was able to attenuate the development of stress-induced behavioural consequences (Resstel et al., 2009), raising the possibility that CBD could also be useful for treating psychiatric disorders thought to involve impairment of stress-coping mechanisms, such as depression.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334711: This preliminary study raises the possibility that endocannabinoids play a role in blood pressure regulation in depressives with higher blood pressure, and suggests an interrelationship among endocannabinoids, depression and cardiovascular risk factors in women.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1253627: The hippocampal dentate gyrus in the adult mammalian brain contains neural stem/progenitor cells (NS/PCs) capable of generating new neurons, i.e., neurogenesis. Most drugs of abuse examined to date decrease adult hippocampal neurogenesis, but the effects of cannabis (marijuana or cannabinoids) on hippocampal neurogenesis remain unknown. This study aimed at investigating the potential regulatory capacity of the potent synthetic cannabinoid HU210 on hippocampal neurogenesis and its possible correlation with behavioral change. We show that both embryonic and adult rat hippocampal NS/PCs are immunoreactive for CB1 cannabinoid receptors, indicating that cannabinoids could act on CB1 receptors to regulate neurogenesis. This hypothesis is supported by further findings that HU210 promotes proliferation, but not differentiation, of cultured embryonic hippocampal NS/PCs likely via a sequential activation of CB1 receptors, Gi/o proteins, and ERK signaling. Chronic, but not acute, HU210 treatment promoted neurogenesis in the hippocampal dentate gyrus of adult rats and exerted anxiolytic- and antidepressant-like effects. X-irradiation of the hippocampus blocked both the neurogenic and behavioral effects of chronic HU210 treatment, suggesting that chronic HU210 treatment produces anxiolytic- and antidepressant-like effects likely via promotion of hippocampal neurogenesis.