The primary rating instrument used to assess depressive symptoms in this study was the Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item clinician-rated scale with total scores ranging from 0 (no depressive features) to 60 (maximum score). The primary endpoint was the change from baseline in MADRS score at Week 6. The key secondary instrument was the Clinical Global Impression-Bipolar-Severity of Illness scale (CGI-BP-S), a clinician-rated scale that measures the subject's current illness state on a 7-point scale, where a higher score is associated with greater illness severity.
The areas of the brain where cannabinoid receptors are most prevalently located are consistent with the behavioral effects produced by cannabinoids. Brain regions in which cannabinoid receptors are very abundant are the basal ganglia , associated with movement control; the cerebellum , associated with body movement coordination; the hippocampus , associated with learning , memory, and stress control; the cerebral cortex , associated with higher cognitive functions; and the nucleus accumbens , regarded as the reward center of the brain. Other regions where cannabinoid receptors are moderately concentrated are the hypothalamus , which regulates homeostatic functions; the amygdala , associated with emotional responses and fears ; the spinal cord , associated with peripheral sensations like pain; the brain stem , associated with sleep , arousal , and motor control; and the nucleus of the solitary tract , associated with visceral sensations like nausea and vomiting . 
Benzodiazepine therapy can give rise to physiologic and psychologic dependence based on the drug's dosage, duration of therapy and potency. 1 Thus, dependence will develop sooner (such as in one to two months) in a patient who is taking a high dosage of a high-potency agent such as alprazolam than in a patient who is receiving a relatively low dosage of a long-acting, low-potency agent such as chlordiazepoxide. As a result of physiologic dependence, withdrawal symptoms emerge with rapid dose reduction or abrupt discontinuation of the drug.