Table 4. Summary of psychoactive substance effects

Table 4. Summary of psychoactive substance effects

Substance primary mechanism of action tolerance and withdrawal prolonged use
Ethanol Increases the inhibitory effects of GABA and decreases the excitatory effects of glutamate. Reinforcing effects probably related to increased activity in mesolimbic dopamine pathway. Tolerance develops due to increased metabolism in the liver, and changes to receptors in the brain.
Withdrawal from chronic use can include shaking, perspiration, weakness, agitation, headache, nausea, vomiting, seizures, delirium tremens.
Altered brain function and structure, particularly in prefrontal cortex; cognitive impairments; decreased brain volume.
Hypnotics and sedatives Facilitate the actions of endogenous inhibitory neurotransmitters. Tolerance develops rapidly to most effects (except anti-convulsant), due to changes in brain receptors.
Withdrawal characterized by anxiety, arousal, restlessness, insomnia, excitability, seizures.
Memory impairment.
Nicotine Activates nicotinic cholinergic receptors. Increases dopamine synthesis and release. Tolerance develops through metabolic factors, as well as receptor changes. Withdrawal characterized by irritability, hostility, anxiety, dysphoria, depressed mood, decreased heart rate, increased appetite. Health effects due to smoking are welldocumented; difficult to dissociate effects of nicotine from other components of tobacco.
Opioids Activates receptors called mu and delta opioid receptors. These receptors are abundant in brain areas involved in responses to psychoactive substances, such as in the mesolimbic dopamine pathway. Tolerance occurs due to short-term and long-term receptor changes, and adaptations in intracellular signalling mechanisms.
Withdrawal can be severe and is characterized by watering eyes, runny nose, yawning, sweating, restlessness, chills, cramps, muscle aches.
Long-term changes in opioid receptors and peptides; adaptations in reward, learning, stress responses.
Cannabinoids Activates cannabinoid receptors. Also increases dopamine activity in the mesolimbic pathway. Tolerance develops rapidly to most effects.
Withdrawal is rare, perhaps due to long halflife of cannabinoids.
Long-term exposure to cannabis may produce long-lasting cognitive impairment. Risk of exacerbation of mental illness is also present.
Cocaine Cocaine blocks the uptake of transmitters such as dopamine, thereby prolonging its effects. Perhaps short-term acute tolerance occurs. There is not much evidence of withdrawal, however, depression is common among dependent persons who stop using the drug Cognitive deficits, abnormalities in specific regions of the cortex, impairments in motor function, and decreased reaction times have been found.
Amphetamines Increases release of dopamine from nerve terminals and inhibits the reuptake of dopamine and related transmitters. Tolerance develops rapidly to behavioural and physiological effects. Withdrawal is characterized by fatigue, depression, anxiety and intense craving for the drug. Sleep disturbances, anxiety, decreased appetite; alterations in brain dopamine receptors, regional metabolic changes, motor and cognitive impairments (13, 14).
Ecstasy Increased serotonin re lease and blockade of reuptake. Tolerance may develop in some individuals. Most common withdrawal symptoms are depression and insomnia. Damages brain serotonin systems, leads to behavioural and physiological consequences. Long-term psychiatric and physical problems such as impairments of memory, decision- making and selfcontrol, paranoia, depression and panic attacks (15, 16).
Inhalants Most likely affects inhibitory transmitters, similarly to other sedatives and hypnotics. Mesolimbic dopamine activated. Some tolerance develops, but is difficult to estimate. There is increased susceptibility to seizures during withdrawal. Changes in dopamine receptor binding and function; decreased cognitive function; psychiatric and neurological problems.
Hallucinogens Different substances in this class act on different brain receptors, such as serotonin, glutamate, and acetylcholine receptors. Tolerance develops rapidly to physical and psychological effects. There is no evidence of withdrawal. Acute or chronic psychotic episodes, flashbacks or re-experiencing of substance effects long after substance use.

Source: WHO  Neuroscience of Psychoactive Substance Use and Dependence, Summary (2004),
Global use of psychoactive substances and burden to health, p.18-19

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Psychoactive Drugs homePsychoactive Drugs Tobacco, Alcohol, and Illicit Substances
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Figure 3. A terminal button and synapse

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Table 4. Summary of psychoactive substance effectsTable 4. Summary of psychoactive substance effects

Figure 5. Mesolimbic dopamine pathway

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Box 2: Criteria for substance use dependence in ICD-10