drugs are agonists at the 5-ht2 receptors; this is thought to be the central component of their hallucinogenic properties. activation of 5-ht2a may be particularly important for hallucinogenic activity. however, repeated exposure to hallucinogens leads to rapid tolerance, likely through down-regulation of these receptors in specific target cells. research suggests that hallucinogens affect many of these receptor sites around the brain and that through these interactions, hallucinogenic substances may be capable of inducing positive introspective experiences. the current research implies that many of the effects that can be observed occur in the occipital lobe and the frontomedial cortex; however, they also present many secondary global effects in the brain that have not yet been connected to the substance's biochemical mechanism of action. dissociative hallucinogens another class of hallucinogens, known as dissociatives, includes drugs such as ketamine, phencyclidine (pcp), and salvia divinorum. drugs such as these are thought to interact predominantly with glutamate recpetors within the brain. specifically, ketamine is thought to block nmda receptors that are responsible for signalling in the glutamate pathways. ketamine's more tranquilizing effects can be seen in the central nervous system through interactions with parts of the thalamus by inhibition of certain functions. ketamine has become a major drug of research for the treatment of depression. these antidepressant effects are thought to be related to the drug's action on the glutamate receptor system and the relative spike in glutamate levels, as well as its interaction with mtor, which is an enzymatic protein involved in catabolic processes in the human body. phencyclidine's biochemical properties are still mostly unknown; however, its use has been associated with dissociation, hallucinations, and in some cases seizures and death. salvia divinorum, a plant native to mexico, has strong dissociative and hallucinogenic properties when the dry leaves are smoked or chewed. the qualitative value of these effects, whether negative or positive, has been observed to vary between individuals with many other factors to consider. hypnotics hypnotics are often used to treat the symptoms of insomnia or other sleep disorders. benzodiazepines are still among the most widely prescribed sedative-hypnotics in the united states today. certain non-benzodiazepine drugs are used as hypnotics as well. although they lack the chemical structure of the benzodiazepines, their sedative effect is similarly through action on the gabaa receptor. they also have a reputation of being less addictive than benzodiazepines. melatonin, a naturally-occurring hormone, is 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 activate potassium ion channels. many cb1 receptors are located on axon terminals, where they act to inhibit the release of various neurotransmitters. in combination, these chemical actions work to alter various functions of the central nervous system, including the motor system, memory, and various cognitive processes. opioids the opioid category of drugs – including drugs such as heroin, morphine, and oxycodone – belong to the class of narcotic analgesics, which reduce pain without producing unconsciousness but do produce a sense of relaxation and sleep, and at high doses may result in coma and death. the ability of opioids (both endogenous and exogenous) to relieve pain depends on a complex set of neuronal pathways at the spinal cord level, as well as various locations above the spinal cord. small endorphin neurons in the spinal cord act on receptors to decrease the conduction of pain signals from the spinal cord to higher brain centers. descending neurons originating in the periaqueductal gray give rise to two pathways that further block pain signals in the spinal cord. the pathways begin in the locus coeruleus (noradrenaline) and the nucleus of raphe (serotonin). similar to other abused substances, opioid drugs increase dopamine release in the nucleus accumbens. opioids are more likely to produce physical dependence than any other class of psychoactive drugs, and can lead to painful withdrawal symptoms if discontinued abruptly after regular use. stimulants cocaine is one of the more common stimulants and is a complex drug that interacts with various neurotransmitter systems. it commonly causes heightened alertness, increased confidence, feelings of exhilaration, reduced fatigue, and a generalized sense of well-being. the effects of cocaine are similar to those of amphetamines, though cocaine tends to have a shorter duration of effect. in high doses or with prolonged use, cocaine can result in a number of negative effects, including irritability, anxiety, exhaustion, total insomnia, and even psychotic symptomatology. most of the behavioral and physiological actions of cocaine can be explained by its ability to block the reuptake of the two catecholamines, dopamine and norepinephrine, as well as serotonin. cocaine binds to transporters that normally clear these transmitters from the synaptic cleft, inhibiting their function. this leads to increased levels of neurotransmitter in the cleft and transmission at the synapses. based on in-vitro studies using rat brain tissue, cocaine binds most strongly to the serotonin transporter, followed by the dopamine transporter, and then the norepinephrine transporter. amphetamines tend to cause the same behavioral and subjective effects of cocaine. various forms of amphetamine are commonly used to treat the symptoms of attention deficit hyperactivity disorder (adhd) and narcolepsy, or are used recreationally. amphetamine and methamphetamine are indirect agonists of the catecholaminergic systems. they block catecholamine reuptake, in addition to releasing catecholamines from nerve terminals. there is evidence that dopamine receptors play a central role in the behavioral responses of animals to cocaine, amphetamines, and other psychostimulant drugs. one action causes the dopamine molecules to be released from inside the vesicles into the cytoplasm of the nerve terminal, which are then transported outside by the mesolimbic dopamine pathway to the nucleus accumbens. this plays a key role in the rewarding and reinforcing effects of cocaine and amphetamine in animals, and is the primary mechanism for amphetamine dependence. psychopharmacological research main articles: psychoactive substances and psychiatric medication in psychopharmacology, researchers are interested in any substance that crosses the blood–brain barrier and thus has an effect on behavior, mood, or cognition. drugs are researched for their physiochemical properties, physical side effects, and psychological side effects. researchers in psychopharmacology study a variety of different psychoactive substances, including alcohol, cannabinoids, club drugs, psychedelics, opiates, nicotine, caffeine, psychomotor stimulants, inhalants, and anabolic–androgenic steroids. they also study drugs used in the treatment of affective and anxiety disorders, as well as schizophrenia. clinical studies are often very specific, typically beginning with animal testing and ending with human testing. in the human testing phase, there is often a group of subjects: one group is given a placebo, and the other is administered a carefully measured therapeutic dose of the drug in question. after all of the testing is completed, the drug is proposed to the concerned regulatory authority (e.g. the u.s. fda), and is either commercially introduced to the public via prescription, or deemed safe enough for over-the-counter sale. though particular drugs are prescribed for specific symptoms or syndromes, they are usually not specific to the treatment of any single mental disorder. a somewhat controversial application of psychopharmacology is "cosmetic psychiatry": persons who do not meet criteria for any psychiatric disorder are nevertheless prescribed psychotropic medication. the antidepressant bupropion is then prescribed to increase perceived energy levels and assertiveness while diminishing the need for sleep. the antihypertensive compound propranolol is sometimes chosen to eliminate the discomfort of day-to-day anxiety. fluoxetine in nondepressed people can produce a feeling of generalized well-being. pramipexole, a treatment for restless leg syndrome, can dramatically increase libido in women. these and other off-label lifestyle applications of medications are not uncommon. although occasionally reported in the medical literature, no guidelines for such usage have been developed. there is also a potential for the misuse of prescription psychoactive drugs by elderly persons, who may have multiple drug prescriptions.