Abstract   Depression and pain co-exist in almost 80% of patients and are associated with impaired health-related quality of life, often contributing to high mortality. However, the majority of patients who suffer from the comorbid depression and pain are not responsive to pharmacological treatments that address either pain or depression, making this comorbidity disorder a heavy burden on patients and society. In ancient times, this depression-pain comorbidity was treated using extracts of the Cannabis sativa plant, known now as marijuana and the mode of action of Δ9-tetrahydrocannabinol, the active cannabinoid ingredient of marijuana, has only recently become known, with the identification of cannabinoid receptor type 1...

Abstract   The present review synthetically describes the currently advanced hypotheses for a neurobiological basis of depression, ranging from the classical monoaminergic to the more recent neurotrophic hypothesis. Moreover, the Authors review the available preclinical and clinical evidence suggesting a possible role for the endocannabinoid system in the physiopathology of depression. Indeed, in spite of the reporting of conflicting results, the pharmacological enhancement of endocannabinoid activity at the CB1 cannabinoid receptor level appears to exert an antidepressant-like effect in some animal models of depression. On the contrary, a reduced activity of the endogenous cannabinoid system seems to be associated with the animal model of...

Abstract 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...

Although previously thought of as the peripheral cannabinoid receptor, it is now accepted that the CB2 receptor is expressed in the central nervous system on microglia, astrocytes and subpopulations of neurons. Expression of the CB2 receptor in the brain is significantly lower than that of the CB1 receptor. Conflicting findings have been reported on the neurological effects of pharmacological agents targeting the CB2 receptor under normal conditions. Under inflammatory conditions, CB2 receptor expression in the brain is enhanced and CB2 receptor agonists exhibit potent anti-inflammatory effects. These findings have prompted research into the CB2 receptor as a possible target for the treatment of neuroinflammatory...

Bipolar affective disorder is often poorly controlled by prescribed drugs. Cannabis use is common in patients with this disorder and anecdotal reports suggest that some patients take it to alleviate symptoms of both mania and depression. We undertook a literature review of cannabis use by patients with bipolar disorder and of the neuropharmacological properties of cannabinoids suggesting possible therapeutic effects in this condition. No systematic studies of cannabinoids in bipolar disorder were found to exist, although some patients claim that cannabis relieves symptoms of mania and/or depression. The cannabinoids ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD) may exert sedative, hypnotic, anxiolytic, antidepressant, antipsychotic and anticonvulsant effects....

Medicine continues to struggle in its approaches to numerous common subjective pain syndromes that lack objective signs and remain treatment resistant. Foremost among these are migraine, fibromyalgia, and irritable bowel syndrome, disorders that may overlap in their affected populations and whose sufferers have all endured the stigma of a psychosomatic label, as well as the failure of endless pharmacotherapeutic interventions with substandard benefit. The commonality in symptomatology in these conditions displaying hyperalgesia and central sensitization with possible common underlying pathophysiology suggests that a clinical endocannabinoid deficiency might characterize their origin. Its base hypothesis is that all humans have an underlying endocannabinoid tone that is...

Anxiety and related disorders are the most common mental conditions affecting the North American population. Despite their established efficacy, first-line antidepressant treatments are associated with significant side effects, leading many afflicted individuals to seek alternative treatments. Cannabis is commonly viewed as a natural alternative for a variety of medical and mental health conditions. Currently, anxiety ranks among the top five medical symptoms for which North Americans report using medical marijuana. However, upon careful review of the extant treatment literature, the anxiolytic effects of cannabis in clinical populations are surprisingly not well-documented. The effects of cannabis on anxiety and mood symptoms have been examined in...

Cannabidiol (CBD) is a major phytocannabinoid present in the Cannabis sativa plant. It lacks the psychotomimetic and other psychotropic effects that the main plant compound D9 -tetrahydrocannabinol (THC) being able, on the contrary, to antagonize these effects. This property, together with its safety profile, was an initial stimulus for the investigation of CBD pharmacological properties. It is now clear that CBD has therapeutic potential over a wide range of non-psychiatric and psychiatric disorders such as anxiety, depression and psychosis. Although the pharmacological effects of CBD in different biological systems have been extensively investigated by in vitro studies, the mechanisms responsible for its therapeutic potential...

Recent evidence suggests that the cannabinoid receptor subtype 2 (CB2) is implicated in anxiety and depression disorders, although few systematic studies in laboratory animals have been reported. The aim of the current experiments was to test the effects of the CB2 receptor potent-selective agonist β-caryophyllene (BCP) in animals subjected to models of anxiolytic- and antidepressant-like effects. Therefore effects of BCP (50 mg/kg) on anxiety were assessed using the elevated plus maze (EPM), open field (OF), and marble burying test (MBT). However for depression, the novelty-suppressed feeding (NSF), tail suspension test (TST), and forced swim tests (FST) were used. Results indicated that adult mice receiving...