Psychopharmacology of Drug of Abuse


    * Abuse: Self-administration of any drug in a culturally disapproved manner that causes adverse consequences.

    * Addiction: A behavioral pattern of drug abuse characterized by overwhelming involvement with the use of a drug (compulsive use), the securing of its supply, and a high tendency to relapse after discontinuation.

    * Dependence: The physiological state of neuroadaptation produced by repeated administration of a drug, necessitating continued administration to prevent the appearance of the withdrawal syndrome.

    * Reinforcement: The tendency of a pleasure-producing drug to lead to repeated self-administration.

    * Tolerance: Tolerance has developed when after repeated administration, a given dose of a drug produces a decreased effect, or conversely, when increasingly larger doses must be administered to obtain the effects observed with the original use.

    * Cross-tolerance and cross-dependence: The ability of one drug to suppress the manifestations of physical dependence produced by another drug and to maintain the physically dependent state.

    * Withdrawal: The psychological and physiological reactions to abrupt cessation of a dependence-producing drug.

    * Relapse: The reoccurrence on discontinuation of an effective medical treatment of the original condition from which the patient suffered.

    * Rebound: The exaggerated expression of the original condition sometimes experienced by patients immediately after cessation of an effective treatment.

    * Detoxification: The slow tapering of a drug that has caused dependence and would cause withdrawal if stopped too suddenly.

Mesolimbic Dopamine Pathway

The common pathway of reinforcement and reward, the mechanisms underlying addiction and dependence, is the mesolibmic dopamine pathway (MPD). MPD is known as the "pleasure center" of the brain as it regulated the dopamine, known as the "pleasure neurotransmitter". MPD is the site in the brain regulating natural highs such as intellectual accomplishments and athletic accomplishments as well as more explosive artificial highs as those induced by psychotropic drugs. Psychotropic drugs bypass brain’s neurotransmitters and directly stimulate endorphin (stimulated by heroin), anandamide (stimulated by marijuana) and dopamine (stimulated by cocaine) receptors. The risk of becoming abuser is related to the number of such receptors in one's brain. If one possesses fewer number of receptors, there will be a less pronounced effect at initial use, thus increased need to use more of the substance to obtain the desired effect, therefore there is a higher risk of abuse. Another explanation is that fewer number of receptors is an indicator of malfunctioning reward system and thus a higher intention to abuse the drug to restore the reward system.


Cocaine is a stimulant and a local anesthetic. It works by inhibiting monoamine transporters, especially dopamine. Cocaine also inhibits dopamine reuptake at the dopamine transporter and it releases dopamine by reversing the neurotransmitter out of the presynaptic neuron via monoamine transporters. Cocaine produces euphoria, reduces fatigue and sense of mental acuity. At high doses, cocaine leads to tremors, emotional lability, restlessness, irritability, paranoia, panic and repetitive stereotyped behavior. At higher doses, it leads to intense anxiety, paranoia, hallucinations, hypertension, tachycardia, ventricular irritability, hyperthermia and respiratory depression. In the case of a cocaine overdose, acute heart failure, stroke and seizures are observed. Repeated intoxication by cocaine leads to adaptation of the dopamine neuronal system and produces tolerance effects. Long-term use may lead to psychosis-like symptoms. In long-term use, when the effect of cocaine subsides, it leads to crashing symptoms, such as agitation, anxiety, fatigue, depression, exhaustion, hypersomnolence and hyperphagia. As one goes through withdrawal from cocaine, anergy, decreased interest, anhedonia and increased cocaine cravings are observed.


Amphetamine is a stimulant. It releases dopamine and some designer forms of amphetamine release serotonin. The effects of amphetamine are similar to those of cocaine. One difference is that euphoria following amphetamine intake is less intense but longer in duration. The intoxication of and overdose by amphetamine can be as serious as acute paranoid psychosis.


Hallucinogens such as magic mushroom, ecstasy, produce changes in one's sensory experiences. Following hallucinogen intake, one can experience visual illusions, hallucinations, visual trails, macropsia, micropsia, enhanced awareness of external/internal stimuli, emotional lability, subjective slowing of time, intensification of sound perception, depersonalization and derealization. At high doses, hallucinogens lead to impaired judgment, fear of losing one’s mind, anxiety, nausea, tachycardia, increased blood pressure and increased body temperature. These symptoms resemble those of a panic attack. At higher doses, hallucinogens may lead to delirium. Hallucinogens belong to one the most dangerous classes of drugs as tolerance can develop even after single dose of a hallucinogen.


Marijuana interacts with the brain's own cannabinoid receptors to trigger dopamine release from the mesolimbic reward system. It produces a sense of well-being, relaxation, friendliness, loss of temporal awareness, slowing of thought process, impairment of short-term memory and the feeling of achieving special insights. At high doses marijuana use leads to panic and toxic delirium. A serious complication of long-term use of marijuana is amotivational syndrome. This syndrome is seen mostly in daily or heavy users. The amotivational syndrome is characterized by the emergence of decreased motivation and ambition. It is linked to other socially and occupationally impairing symptoms, such as shortened attention span, poor judgment, easy distractibility, impaired communication skills, introversion, and diminished effectiveness in interpersonal situations. Personal habits deteriorate, and there may be a loss of insight and even feelings of depersonalization.

This document is composed by Yudit Namer, using the following reference:

Stahl, S. M. (2000). Essential Psychopharmacology: Neuroscientific Basis and Practical Application. New York: Cambridge University Press.