Psychoactive drugs of misuse: rationalising the irrational

Drugs are chemical substances that modify biological responses by interacting with macromolecular targets such as receptors, ion channels, transporters, and enzymes. Pharmacodynamics describes the course of action of drugs leading to the physiological effect at a specific site in the body.
Drugs can be agonists or antagonists. Like the endogenous ligands, agonists always bind and activate the target to produce a cellular response. Agonist binding induces a conformational change which in turn...

Indirect-acting adrenergic agonists potentiate the effects of endogenous catecholamines through different mechanisms without directly binding to adrenoceptors.
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...

Drug dependence, abuse, and addiction are complex phenomena that can precipitate various abnormal states. Physical dependence refers to a state of pharmacological adaptation to a drug. This adaptation often results in tolerance—a reduced response to the drug after repeated administrations. When the drug use is abruptly stopped, withdrawal symptoms occur due to the body's need to readjust from the pharmacologically induced imbalance. However, tolerance and withdrawal symptoms do not necessarily...

Hallucinogens, also known as psychedelic drugs, are a class of substances known for their ability to alter perception, cognition, and emotions. Despite their profound effects on the mind, these drugs are non-addictive, setting them apart from many other abused substances. The mechanism of action of these drugs lies in their impact on the 5-HT2A receptor in the brain. Upon activation, this receptor couples to Gq-type G proteins, triggering a cascade that releases intracellular calcium. This...

Cognitive enhancers, also known as "smart drugs," are substances used to enhance memory, mental alertness, and concentration. These can be natural or synthetic and improve cognition in conditions like Alzheimer's disease (AD) and other neurodegenerative diseases. Some common examples include caffeine, amphetamines, methylphenidate, modafinil, arecoline, donepezil, vortioxetine, and piracetam. These enhancers work on the principle of synaptic plasticity and altered circuit function. They...

Psychoactive drugs impact brain function, influencing perception, mood, consciousness, cognition, and behavior. These substances are grouped based on their effects and the mechanisms by which they act.
Stimulants such as cocaine, amphetamines, and nicotine enhance brain activity, leading to increased alertness, attention, and energy. These drugs typically raise heart rate, blood pressure, and body temperature. While they can induce feelings of euphoria, their misuse can result in severe health...