often used over the counter (OTC) to treat insomnia and jet lag. This hormone appears to be excreted by the pineal gland early during the sleep cycle and may contribute to human circadian rhythms. Because OTC melatonin supplements are not subject to careful and consistent manufacturing, more specific melatonin agonists are sometimes preferred. They are used for their action on melatonin receptors in the suprachiasmatic nucleus, responsible for sleep-wake cycles. Many barbiturates have or had an FDA-approved indication for use as sedative-hypnotics, but have become less widely used because of their limited safety margin in overdose, their potential for dependence, and the degree of central nervous system depression they induce. The amino-acid L-tryptophan is also available OTC, and seems to be free of dependence or abuse liability. However, it is not as powerful as the traditional hypnotics. Because of the possible role of serotonin in sleep patterns, a new generation of 5-HT2 antagonists are in current development as hypnotics. Cannabis and the cannabinoids Cannabis consumption produces a dose-dependent state of intoxication in humans. There is commonly increased blood flow to the skin, which leads to an increased heart rate and sensations of warmth or flushing. It also frequently induces increased hunger. Iversen (2000) categorized the subjective and behavioral effects often associated with cannabis into three stages. The first is the "buzz", a brief period of initial responding where the main effects are lightheadedness or slight dizziness, in addition to possible tingling sensations in the extremities or other parts of the body. The "high" is characterized by feelings of euphoria and exhilaration characterized by mild psychedelia as well as a sense of disinhibition. If the individual has taken a sufficiently large dose of cannabis, the level of intoxication progresses to the stage of being "stoned", and the user may feel calm, relaxed, and possibly in a dreamlike state. Sensory reactions may include the feeling of floating, enhanced visual and auditory perception, visual illusions, or the perception of the slowing of time passage, which are somewhat psychedelic in nature. There exist two primary CNS cannabinoid receptors, on which marijuana and the cannabinoids act. Both the CB1 receptor and CB2 receptor are found in the brain. The CB2 receptor is also found in the immune system. CB1 is expressed at high densities in the basal ganglia, cerebellum, hippocampus, and cerebral cortex. Receptor activation can inhibit cAMP formation, inhibit voltage-sensitive calcium ion channels, and