cannabidiol and Depressive-Disorder--Major

Uncontrolled stress can lead to vascular injury, hypertension, arrhythmia, compromised immune system alteration in microbiota activity, and neurobehavioral changes, including depression. The gut microbiota has been recently developed, not only for major depressive disorders but also cardiovascular problems, as a therapeutic concern. Since then, >100 studies have studied the link between depression and cardiovascular disease (CVD), and have shown that depression is common (≈20%-35%) in patients with CVD, and seems to be indicative of negative heart effects in patients. Depressive symptoms patients have demonstrated an elevated platelet reactivity, reduced cardiac variability, and enhanced proinflammatory signals, which are all cardiovascular-related risk factors. The pathophysiology of depression-related CVD is nevertheless a challenge because of the heterogeneous depressive syndromes and the etiologies. The cardiovascular effects of tetrahydrocannabinol (THC) (the key psychotropic credential of cannabis) and endocannabinoids (THC endogenous equivalents which cause type 1 [CB1] and 2 [CB2] cannabinoids) have been extensively examined based on well-documented effects of marijuana smoke on blood pressure (BP) and heart rate (HR). Therefore, the aim of the review article is to establish the relationship of abnormal cannabidiols system-mediated cardiovascular protection in disrupted gut/brain axis associated depression to determine the translational potential of targeting abnormal cannabidiols receptors in clinical studies.

Topics: Brain; Cannabidiol; Cardiovascular System; Depressive Disorder, Major; Humans; Intestines

Adverse effects and lack of efficacy in a significant number of patients limit pharmaceutical interventions in youth psychiatry. This is exemplified by the fact that no medication is currently approved for the treatment of non-OCD anxiety disorders or major depressive disorder in young people younger than 18 years of age in Australia. Here, emerging biological therapies for youth with mental health problems are discussed. There is an urgent need for more research into biological interventions with acceptable risk-benefit balances. Omega-3 fatty acids, cannabidiol and N-acetylcysteine are currently being evaluated. If initial findings are confirmed, they may offer alternatives with more benign side-effect profiles than existing treatments.

Topics: Adolescent; Anxiety Disorders; Australia; Biological Therapy; Cannabidiol; Depressive Disorder, Major; Fatty Acids, Omega-3; Humans; Mental Health; Transcranial Magnetic Stimulation

The pathophysiology of major depressive disorder (MDD) is diverse and multi-factorial, yet treatment strategies remain limited. While women are twice as likely to develop the disorder as men, many animal model studies of antidepressant response rely solely on male subjects. The endocannabinoid system has been linked to depression in clinical and pre-clinical studies. Cannabidiolic Acid-Methyl Ester (CBDA-ME, EPM-301) demonstrated anti-depressive-like effects in male rats. Here, we explored acute effects of CBDA-ME and some possible mediating mechanisms, using a depressive-like genetic animal model, the Wistar-Kyoto (WKY) rat. In Experiment 1, Female WKY rats underwent the Forced swim test (FST) following acute CBDA-ME oral ingestion (1/5/10 mg/kg). In Experiment 2, Male and female WKY rats underwent the FST after injection of CB1 (AM-251) and CB2 (AM-630) receptor antagonists 30 min before acute CBDA-ME ingestion (1 mg/kg, males; 5 mg/kg, females). Serum levels of Brain-Derived Neurotrophic Factor (BDNF), numerous endocannabinoids and hippocampal Fatty Acid Amide Hydrolase (FAAH) levels were assessed. Results indicate that females required higher doses of CBDA-ME (5 and 10 mg/kg) to induce an anti-depressive-like effect in the FST. AM-630 blocked the antidepressant-like effect in females, but not in males. The effect of CBDA-ME in females was accompanied by elevated serum BDNF and some endocannabinoids and low hippocampal expression of FAAH. This study shows a sexually diverse behavioral anti-depressive response to CBDA-ME and possible underlying mechanisms in females, supporting its potential use for treating MDD and related disorders.

Topics: Animals; Brain-Derived Neurotrophic Factor; Cannabidiol; Depressive Disorder, Major; Disease Models, Animal; Endocannabinoids; Female; Male; Rats; Rats, Inbred WKY; Receptor, Cannabinoid, CB2

Topics: Bipolar Disorder; Cannabidiol; Depressive Disorder, Major; Humans; Mood Disorders

Major depressive disorder (MDD) affects millions of people worldwide. While the exact pathogenesis is yet to be elucidated, the role of neuro-immune signaling has recently emerged. Despite major advances in pharmacotherapy, antidepressant use is marred by limited efficacy and potential side effects. Cannabidiol (CBD), a phytocannabinoid, exerts antidepressant-like effects in experimental animals. This study investigated the impact of CBD on sickness behavior (SB), a measure of depressive-like response, and neuro-immune changes induced by lipopolysaccharides (LPS) in mice.. Socially isolated rodents were administered with LPS to trigger SB. and treated with CBD or its vehicle. Animals were submitted to forced swimming test, to evaluate depressive-like behavior, and to open field test, to evaluate locomotory activity. Immediately after behavioral analyses, animals were euthanized and had their hypothalamus, prefrontal cortex and hippocampus dissected, to proceed neurotrophins and cytokines analyses. ELISA was used to detect IL-1β, BDNF and NGF; and cytometric beads array to measure IL-2, IL-4, IL-6, IFN-γ, TNF-α and IL-10 levels.. CBD effectively prevented SB-induced changes in the forced swim test without altering spontaneous locomotion. This phytocannabinoid also partially reversed LPS-evoked IL-6 increase in both the hypothalamus and hippocampus. In addition, CBD prevented endotoxin-induced increase in BDNF and NGF levels in the hippocampus of SB animals.. Apparently, CBD prevents both behavioral and neuro-immunological changes associated with LPS-induced SB, which reinforces its potential use as an antidepressant which modulates neuroinflammation. This opens up potentially new therapeutic avenues in MDD.

Topics: Animals; Antidepressive Agents; Behavior, Animal; Brain; Brain-Derived Neurotrophic Factor; Cannabidiol; Cytokines; Depressive Disorder, Major; Disease Models, Animal; Illness Behavior; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Nerve Growth Factor; Neuroinflammatory Diseases

Anxiety disorders in young people are frequently comorbid with other mental disorders and respond unsatisfactorily to first-line treatment in many cases. Here, we report the case of a 20-year-old man with severe social anxiety disorder, major depressive disorder, insomnia and attenuated psychotic symptoms despite ongoing treatment with cognitive behavioural therapy and mirtazapine who was treated with adjunctive cannabidiol (CBD) in doses between 200 and 800 mg/day for 6 months. During treatment with CBD, he experienced subjective benefits to his anxiety, depression and positive symptoms during treatment that were confirmed by clinicians and by standardised research instruments. Findings from this case study add to existing evidence in support of the safety of CBD and suggest that it may be useful for young people with treatment refractory anxiety and for attenuated psychotic symptoms.

Topics: Adult; Cannabidiol; Cognitive Behavioral Therapy; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Dose-Response Relationship, Drug; Drug Monitoring; Humans; Male; Mirtazapine; Phobia, Social; Psychiatric Status Rating Scales; Psychotic Disorders; Psychotropic Drugs; Sleep Initiation and Maintenance Disorders; Treatment Outcome