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.