Cocaine and Amphetamines


As stimulants, cocaine and amphetamines activate both the sympathetic and central nervous systems to heighten arousal, increase behavioural activation, and, when delivered rapidly to the brain, create the so‐called flash or rush followed by a long‐lasting state of euphoria. Cocaine, derived from coca leaves, and amphetamines, a group of synthetic compounds whose molecular structure resembles adrenalin, increase the level of norepinephrine (noradrenalin) and dopamine in the synapse. As part of the brain's reward circuit, dopamine neurons play a critical role in drug craving. The stimulant properties of cocaine and amphetamines have been known for centuries, but illicit manufacturing techniques now produce versions of these drugs that can be smoked or injected to enhance their pleasurable effects. Repeated drug use changes the way that neurons in the reward circuit process information. The end result is a fundamental change in brain circuitry that increases the likelihood of addiction.

Key Concepts:

  • Cocaine occurs naturally in coca leaves, which have been chewed for centuries to increase feelings of energy.

  • The amphetamines were modelled after ephedrine, a plant‐derived alkaloid that improves breathing and has stimulating effects on behaviour.

  • Cocaine and amphetamines activate the sympathetic nervous system by increasing the synaptic level of norepinephrine.

  • The rewarding or pleasurable effects of these drugs involve an increase in dopamine, a transmitter released in key areas of the forebrain.

  • Cocaine increases synaptic norepinephrine and dopamine by blocking the transporter proteins that removes these catecholamine transmitters from the synapse.

  • The amphetamines increase synaptic norepinephrine and dopamine by forcing the transporters to operate in reverse.

  • A direct increase in dopamine transmission in the nucleus accumbens, a part of the limbic forebrain, is common to many drugs of abuse and appears to be a key mechanism leading to addiction.

  • With repeated use of these drugs, long‐lasting changes occur in the accumbens and other key forebrain nuclei to promote drug craving and relapse.

  • Medically, cocaine is used as a local anaesthetic, whereas some amphetamines are used as treatment for narcolepsy and attention‐deficit‐hyperactivity disorder.

  • Caffeine and other xanthines are not as powerful in stimulating behaviour and act by blocking receptors for adenosine, a purine nucleotide.

Keywords: dopamine; drug abuse; norepinephrine; nucleus accumbens; synaptic transmission

Figure 1.

Mechanism of action of amphetamine at a catecholamine synapse. (a) and (b) Catecholamines are released from vesicles into the synapse and bind to a transporter protein, which also binds the sodium ion. The transporter uses the sodium ion gradient to carry the catecholamine back inside the neuron terminal (reuptake) where the catecholamine can be stored in the vesicle for re‐release or inactivated by monoamine oxidase. (c) and (d) In the presence of amphetamine, which structurally resembles the catecholamines, the transporter binds amphetamine and transports it inside the neuron terminal where amphetamine can displace catecholamines from the vesicles and also inhibit monoamine oxidase. (e) and (f) The amphetamine‐induced increase in freely available catecholamines inside the neuron terminal allows the transporter to bind catecholamines while it is facing inward. With a low level of intracellular sodium, the transporter quickly flips to the extracellular position carrying the catecholamine to the outside of the neuron.



Aghajanian GK and Sanders‐Bush E (2002) Serotonin. In: Davis KL, Charney D, Coyle JT and Nemeroff C (eds) Neuropsychopharmacology: The Fifth Generation of Progress, pp. 15–34. Philadelphia, PA: Lippincott‐Williams‐Wilkins.

Angrist B and Sudilovsky A (1978) Central nervous system stimulants: historical aspects and clinical effects. In: Iversen LL, Iversen SD and Snyder SH (eds) Stimulants, Handbook of Psychopharmacology, vol. 11, pp. 99–165. New York: Plenum Press.

Aston‐Jones G (1985) Behavioral functions of locus coeruleus derived from cellular attributes. Physiology and Psychology 13: 118–126.

Cho AK (1990) Ice: a new dosage form of an old drug. Science 249: 631–634.

Cornish JW and O'Brien CP (1996) Crack cocaine abuse: an epidemic with many public health consequences. Annual Review of Public Health 17: 259–273.

Courtwright DT (2001) Forces of Habit: Drugs and the Making of the Modern World. Cambridge, MA: Harvard University Press.

Feldman RS, Meyer JS and Quenzer LF (1997) Principles of Neuropsychopharmacology. Sunderland, MA: Sinauer Associates.

Gainetdinov RR and Caron MG (2002) Monoamine transporters: their role in maintaining neuronal homeostasis. In: Reith MEA (ed.) Neurotransmitter Transporters: Structure, Function, and Regulation, pp. 171–192. Totowa, NJ: Humana Press.

Grace AA (2002) Dopamine. In: Davis KL, Charney D, Coyle JT and Nemeroff C (eds) Neuropsychopharmacology: The Fifth Generation of Progress, pp. 120–132. Philadelphia, PA: Lippincott‐Williams‐Wilkins.

Karch SB (1998) A Brief History of Cocaine. Boca Raton, FL: CRC Press.

Koob GF and LeMoal M (2006) Neurobiology of Addiction. San Diego, CA: Academic Press.

Koob GF, Sanna PP and Bloom FE (1998) Neuroscience of addiction. Neuron 21: 467–476.

Kuhar M (2012) The Addicted Brain: Why We Abuse Drugs, Alcohol, and Nicotine. Upper Saddle River, NJ: FT Press.

Moore RY and Bloom FE (1979) Central catecholamine neuron systems: anatomy and physiology of the norepinephrine and epinephrine systems. Annual Review of Neuroscience 2: 113–168.

Randrup A and Munkvad I (1967) Stereotyped activities produced by amphetamine in several animal species and man. Psychopharmacologia 11: 300–310.

Rasmussen N (2008) On Speed: The Many Lives of Amphetamine. New York: New York Univeristy Press.

Seiden LS, Sabol KE and Ricaurte GA (1993) Amphetamine: effects on catecholamine systems and behaviour. Annual Review of Pharmacology and Toxicology 32: 639–677.

Sulzer D, Maidment NT and Rayport S (1993) Amphetamine and other weak bases act to promote reverse transport of dopamine in ventral midbrain neurons. Journal of Neurochemistry 60: 527–535.

Further Reading

Hyman SE and Malenka RC (2001) Addiction and the brain: the neurobiology of compulsion and its persistence. Nature Reviews Neuroscience 2: 695–703.

Koob GF and Volkow ND (2009) Neurocircuitry of addiction. Neuropsychopharmacology 111: 1–22.

Nestler EJ (2004) Historical review: molecular and cellular mechanisms of opiate and cocaine addiction. Trends in Pharmacological Sciences 25: 210–218.

Robinson TE and Berridge KC (2003) Addiction. Annual Reviews of Psychology 54: 25–53.

Thomas MJ, Kalivas PW and Shaham Y (2002) Neuroplasticity in the mesolimbic dopamine system and cocaine addiction. British Journal of Pharmacology 154: 3277–3342.

Volkow ND, Baler RD and Goldstein RZ (2011) Addiction: pulling at the neural threads of social behaviors. Neuron 69: 599–602.

Wise RA and Kiyatkin EA (2011) Differentiating the rapid actions of cocaine. Nature Reviews Neuroscience 12: 479–484.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Rebec, George V(Aug 2012) Cocaine and Amphetamines. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000042.pub3]