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.