Psychoactive Drugs Tobacco, Alcohol, and Illicit Substances

3. How does drug addiction affect the functioning of the brain?

• 3.1 What is drug addiction?
• 3.2 What brain mechanisms are affected?
• 3.3 How do different psychoactive drugs act in the brain?

3.1 What is drug addiction?

The source document for this Digest states:

As defined by ICD-10, substance dependence includes six criteria (see Box 2); a person with at least three of these is diagnosable as "dependent". The criteria used by the American Psychiatric Association are similar.

As can be seen from Box 2, the two criteria most easily measured biologically are the third and fourth: withdrawal --- the occurrence of unpleasant physical and psychological symptoms when use of the substance is reduced or discontinued, and tolerance --- the fact that increased amounts of the substance are required to achieve the same effect, or that the same amount produces less effect. The other four criteria for dependence include elements of cognition, which are less accessible to biological measurement, but are becoming measurable using improved neuroima ging techniques. It is also important to keep in mind that the criteria for dependence include health and social consequences.

Source & ©: WHO  Neuroscience of psychoactive substance use and dependence, Summary (2004),
Substance use and dependence in relation to neuroscience, p. 12

Neuroanatomy, neurobiology, and pharmacology

Substance dependence is a disorder of altered brain function brought on by the use of psychoactive substances. These substances affect normal perceptual, emotional and motivational processes in the brain. However, as with any disorder specific to an organ or system, one must first understand the normal function of that organ or system to understand its dysfunction. Because the output of the brain is behaviour and thoughts, disorders of the brain can result in highly complex behavioural symptoms. The brain can suffer many types of diseases and traumas, from neurological conditions such as stroke and epilepsy, to neurodegenerative diseases such as Parkinson disease and Alzheimer disease, and infectious or traumatic brain injuries. In each of these cases, the behavioural output is recognized as being part of the disorder.

Similarly, with dependence, the behavioural output is complex, but is mostly related to the short-term or long-term effects of substances on the brain. The tremors of Parkinson disease, the seizures of epilepsy, even the melancholy of depression are widely recognized and accepted as symptoms of underlying brain pathology.

Substance dependence has not previously been recognized as a disorder of the brain, in the same way that psychiatric and mental illnesses were previously not viewed as such. However, with recent advances in neuroscience, it is clear that substance dependence is as much a disorder of the brain as any other neurological or psychiatric illness. New technologies and research provide a means to visualize and measure changes in brain function from the molecular and cellular levels, to changes in complex cognitive processes that occur with short-term and long-term substance use.

Major advances in neuroscience research on substance dependence have come from the development and use of techniques that allow the visualization of brain function and structure in the living human brain, known as neuroimaging techniques. Using these techniques, researchers can see what happens from the level of receptors to global changes in metabolism and blood flow in various brain regions. Images can be observed when substances are administered, to see where they act in the brain, and also following long-term substance use to observe the effects on normal brain functions. One example of an imaging technique is magnetic resonance imaging (MRI), which uses magnetic fields and radio waves to produce high-quality two- or three-dimensional images of brain structures (10-12). The brain can be imaged with a high degree of detail. Although MRI gives only static pictures of brain anatomy, functional MRI (fMRI) can provide functional information about brain activity by comparing oxygenated and deoxygenated blood.

Another important and useful imaging technique is positron emission tomography (PET) (10-12). PET scans provide information about the metabolic activity in a certain brain region. Most commonly, a person is injected with a radioactive compound that can be followed through the bloodstream in the brain. This can be visualized as two- or three-dimensional images, with different colours on a PET scan indicating different levels of radioactivity (blues and greens indicating areas of lower activity, and yellows and reds indicating areas of higher activity). Using different compounds, PET scans can be used to show blood flow, oxygen and glucose metabolism, and drug concentrations in the tissues of the living brain.

Source & ©: WHO  Neuroscience of psychoactive substance use and dependence, Summary (2004),
Summary (2004), Neuroanatomy, neurobiology, and pharmacology, p.13-15

3.2 What brain mechanisms are affected?

The source document for this Digest states:

Brain mechanisms: neurobiology and neuroanatomy

The brain is highly organized into a number of different regions with specialized functions. A region of the brain known as the hindbrain contains structures that are vital to the maintenance of life, such as centres that control breathing and wakefulness. The midbrain is a region that contains many areas that are important to a discussion of substance dependence, as these regions are involved in motivation and learning about important environmental stimuli, and reinforcing behaviours that lead to pleasurable and life-sustaining consequences, such as eating and drinking. The forebrain is more complex, and in humans the cerebral cortex of the forebrain is highly developed to give the ability for abstract thought and planning, and for associations of thoughts and memories. Specific regions of the forebrain have been shown by brain imaging techniques to be activated by stimuli that induce ‘‘cravings’’ in people with substance dependence, and other regions have been shown to function abnormally in people following acute or chronic substance use and dependence.

Communication in the brain takes place between the individual cells or neurons. The neurons communicate with one another through chemical messengers which are released at synapses (see Fig. 3). When one neuron is excited, an electrical signal is sent from the cell body, down an elongated process known as an axon, which can extend short distances to nearby neurons, or can extend long distances to other brain regions. At the end of the axon is a terminal button. To communicate the message from the terminal button of one axon, to the next neuron, a space must be crossed. This space is known as the synapse or synaptic cleft. Chemical messengers are released from the neuron sending the message, or presynaptic neuron, to the receiving, or postsynaptic neuron. These chemicals, or neurotransmitters have specific structures and functions, and which chemical is released depends upon the type of neuron. Some of the more well-studied neurotransmitters that are relevant to psychoactive substances are dopamine, serotonin, norepinephrine, GABA, glutamate and the endogenous opioids.

Figure 3. A terminal button and synapse

Figure 4. Two types of chemical synapses

The brain contains dozens of different types of chemical messengers. Each specific neurotransmitter binds to a specific receptor, like a lock to a key (see Fig. 4). Binding of neurotransmitter to receptor can result in a number of different changes in the postsynaptic membrane. Receptors are named according to the type of neurotransmitter that they bind preferentially, for example, dopamine receptors and serotonin receptors. There are also many subtypes of each type of receptor. Psychoactive substances are able to mimic the effects of naturally occurring or endogenous neurotransmitters, or to interfere with normal brain function by blocking normal function, or by altering the normal storage, release and removal of neurotransmitters. One important mechanism by which psychoactive substances act is to block the reuptake of a neurotransmitter after it is released from the presynaptic terminal. Reuptake is a normal mechanism by which the transmitter is removed from the synapse by the presynaptic membrane. By blocking reuptake, the normal effects of the neurotransmitter are exaggerated. Psychoactive substances that bind and enhance the function of receptors are known as agonists, whereas those that bind to block normal function are known as antagonists.

Source & ©: WHO  Neuroscience of psychoactive substance use and dependence, Summary (2004),
Brain mechanisms: neurobiology and neuroanatomy, p.15-16

3.3 How do different psychoactive drugs act in the brain?

The source document for this Digest states:

The most common psychoactive substances can be divided into depressants (e.g. alcohol, sedatives/hypnotics, volatile solvents), stimulants (e.g. nicotine, cocaine, amphetamines, ecstasy), opioids (e.g. morphine and heroin), and hallucinogens (e.g. PCP, LSD, cannabis).

Different psychoactive substances have different ways of acting in the brain to produce their effects. They bind to different receptor types, and can increase or decrease the activity of neurons through several different mechanisms. Consequently, they have different behavioural effects, different rates of development of tolerance, different withdrawal symptoms, and different short-term and long-term effects (Table 4). However, psychoactive substances do share similarities in the way they affect important regions of the brain involved in motivation, and this is a significant feature with regard to the theories of the development of substance dependence.

Table 4. Summary of psychoactive substance effects

Source & ©: WHO  Neuroscience of psychoactive substance use and dependence, Summary (2004),
Psychopharmacology of dependence for different substance classes, p.17-19