| Substance |
Primary action mechanism |
Tolerance and withdrawal |
Prolonged use |
| Ethanol |
Increases the inhibitory effects of GABA and decreases Glutamate’s excitatory effects. Reinforcement probably associated with higher activity in dopamine’s mesolimbic pathway. |
Tolerance development due to higher liver metabolism and receptor changes. Withdrawal symptoms may include shaking, perspiration, weakness, agitation, migraines, nausea, seizures, delirium tremens |
Changes in brain structure and function, namely pre-frontal cortex, cognitive disorders, decrease in brain volume. |
| Hypnotics and sedatives |
Facilitators of endogenous inhibitory neurotransmitters |
Quick tolerance development for the majority of effects due to brain receptor alterations. Withdrawal characterised by anxiety, wakefulness, restlessness, insomnia, excitability, seizures. |
Memory disturbances. |
| Opioids |
Activation of Mu and delta receptors in brain regions implicated in the response to psychoactive substances, like the mesolimbic pathway. |
Tolerance occurs due to short and long-term changes in receptors and intracellular signalling. Withdrawal can be severe and is characterized by transpiration, coryza, restlessness, shivers, cramps, muscle pain. |
Long term changes in peptides and opioid receptors. Adaptation to reward response, learning and stress. |
| Cannabinoids |
Activation of cannabinoid receptors. Also increase dopaminergic activity in the mesolimbic pathway. |
Quick tolerance development. Rare withdrawal, perhaps due to cannabinoid half-life |
Long term exposure to cannabis may produce durable cognitive impairment. There is also an increased risk for aggravating mental illness. |
| Cocaine |
Cocaine prevents the reuptake of transmitters, namely Dopamine, prolonging its effects. |
Possible short term acute tolerance. Not many evidences of withdrawal but depression is common in users. |
Cognitive deficits have been found, anomalies in specific regions of the cortex, motor function impairment, impaired reaction time. |
| Amphetamine |
Increase in Dopamine release while simultaneously inhibiting its reuptake. |
Tolerance develops quickly in regards to behavioural and physiological effects. Withdrawal includes fatigue, depression, anxiety and cravings. |
Sleep disorders, anxiety, loss of appetite, dopamine receptor changes, metabolic changes cognitive and motor impairments. |
| Ecstasy |
Increase in serotonin release and blockade of its reuptake. |
Tolerance may develop in some individuals. Most common symptoms are depression and insomnia. |
Damage on serotonergic systems, behavioural complications. Long term psychiatric and physical problems such as memory disorders, decision making, self-control, paranoia, depression, panic attacks. |
| Volatile substances |
Likely to act in a similar way as sedatives. Activation of mesolimbic dopamine. |
Tolerance somewhat difficult to evaluate. Withdrawal increases vulnerability to seizures. |
Changes in connection and function of dopamine receptors; impaired cognitive function; neurological and psychiatric problems. |
| Psychedelics |
Different types act on different brain receptors (serotonin, glutamate, acetylcholine). |
Tolerance develops quickly for both physical and psychological effects. No evidence of withdrawal. |
Acute psychotic episodes, and even chronic. Revival/relapse of the substance’s effects, long after its use. |
