Effects

Psychoactive drugs operate by temporarily affecting a person's neurochemistry, which in turn causes changes in a person's mood, cognition, perception and behavior. There are many ways in which psychoactive drugs can affect the brain. Each drug has a specific action on one or more neurotransmitter or neuroreceptor in the brain.

Drugs that increase activity in particular neurotransmitter systems are called agonists. They act by increasing the synthesis of one or more neurotransmitters, by reducing its reuptake from the synapses, or by mimicking the action by binding directly to the postsynaptic receptor. Drugs that reduce neurotransmitter activity are called antagonists, and operate by interfering with synthesis or blocking postsynaptic receptors so that neurotransmitters cannot bind to them.

Exposure to a psychoactive substance can cause changes in the structure and functioning of neurons, as the nervous system tries to re-establish the homeostasis disrupted by the presence of the drug (see also, neuroplasticity). Exposure to antagonists for a particular neurotransmitter can increase the number of receptors for that neurotransmitter or the receptors themselves may become more responsive to neurotransmitters; this is called sensitization. Conversely, overstimulation of receptors for a particular neurotransmitter may cause a decrease in both number and sensitivity of these receptors, a process called desensitization or tolerance. Sensitization and desensitization are more likely to occur with long-term exposure, although they may occur after only a single exposure. These processes are thought to play a role in drug dependence and addiction. Physical dependence on antidepressants or anxiolytics may result in worse depression or anxiety, respectively, as withdrawal symptoms. Unfortunately, because clinical depression (also called major depressive disorder) is often referred to simply as depression, antidepressants are often requested by and prescribed for patients who are depressed, but not clinically depressed.

Affected neurotransmitter systemsedit

The following is a brief table of notable drugs and their primary neurotransmitter, receptor or method of action. Many drugs act on more than one transmitter or receptor in the brain.

Neurotransmitter/receptor	Classification	Examples
Acetylcholine	Cholinergics (acetylcholine receptor agonists)	arecoline, nicotine, piracetam
	Muscarinic antagonists (acetylcholine receptor antagonists)	scopolamine, benzatropine, dimenhydrinate, diphenhydramine, doxylamine, atropine, quetiapine, olanzapine, most tricyclics
	Nicotinic antagonists (acetylcholine receptor antagonists)	memantine, bupropion
Adenosine	Adenosine receptor antagonists	caffeine, theobromine, theophylline
Dopamine	Dopamine reuptake inhibitors (DRIs)	cocaine, bupropion, methylphenidate, St John's wort, and certain TAAR1 agonists like amphetamine, phenethylamine, and methamphetamine
	Dopamine releasers	Cavendish bananas, TAAR1 agonists like amphetamine, phenethylamine, and methamphetamine
	Dopamine receptor agonists	pramipexole, Ropinirole, L-DOPA (prodrug), memantine
	Dopamine receptor antagonists	haloperidol, droperidol, many antipsychotics (e.g., risperidone, olanzapine, quetiapine)
	Dopamine receptor partial agonists	LSD, aripiprazole
gamma-Aminobutyric acid (GABA)	GABA reuptake inhibitors	tiagabine, St John's wort, vigabatrin, deramciclane
	GABA receptor agonists	ethanol, niacin, barbiturates, diazepam, clonazepam, lorazepam, temazepam, alprazolam and other benzodiazepines, zolpidem, eszopiclone, zaleplon and other nonbenzodiazepines, muscimol, phenibut
	GABA receptor antagonists	thujone, bicuculline
Norepinephrine	Norepinephrine reuptake inhibitors	St John's wort, most non-SSRI antidepressants such as amoxapine, atomoxetine, bupropion, venlafaxine, quetiapine, the tricyclics, methylphenidate, SNRIs such as duloxetine, venlafaxine, cocaine, tramadol, and certain TAAR1 agonists like amphetamine, phenethylamine, methamphetamine.
	Norepinephrine releasers	ephedrine, PPA, pseudoephedrine, amphetamine, phenethylamine, methamphetamine
	Norepinephrine receptor agonists	clonidine, guanfacine, phenylephrine
	Norepinephrine receptor antagonists	carvedilol, metoprolol, mianserin, prazosin, propranolol, trazodone, yohimbine, olanzapine
Serotonin	Serotonin receptor agonists	methylphenidate, LSD, psilocybin, mescaline, DMT
	Serotonin reuptake inhibitors	most antidepressants including St John's wort, tricyclics such as imipramine, SSRIs such as fluoxetine, sertraline and citalopram, and SNRIs such as duloxetine and venlafaxine, cocaine, tramadol, and certain TAAR1 agonists like amphetamine, tryptamine, and methamphetamine
	Serotonin releasers	fenfluramine, MDMA (ecstasy), tryptamine
	Serotonin receptor antagonists	ritanserin, mirtazapine, mianserin, trazodone, cyproheptadine, memantine, atypical antipsychotics (e.g., risperidone, olanzapine, quetiapine)
AMPA receptor	AMPA receptor positive allosteric modulators	aniracetam, CX717, piracetam
	AMPA receptor antagonists	kynurenic acid, NBQX, topiramate
Cannabinoid receptor	Cannabinoid receptor agonists	JWH-018
	Cannabinoid receptor partial agonists	Anandamide, THC, cannabidiol, cannabinol
	Cannabinoid receptor inverse agonists	Rimonabant
	Anandamide reuptake inhibitors	LY 2183240, VDM 11, AM 404
FAAH enzyme	FAAH enzyme inhibitors	MAFP, URB597, N-Arachidonylglycine
Melanocortin receptor	Melanocortin receptor agonists	bremelanotide
NMDA receptor	NMDA receptor antagonists	ethanol, ketamine, PCP, DXM, Nitrous Oxide, memantine
GHB receptor	GHB receptor agonists	GHB, Amisulpride, T-HCA
Sigma receptor	Sigma-1 receptor agonists	cocaine, DMT, DXM, fluvoxamine, ibogaine, opipramol, PCP, methamphetamine
	Sigma-2 receptor agonists	methamphetamine
Opioid receptor	μ-opioid receptor agonists	morphine, heroin, oxycodone, codeine
	μ-opioid receptor partial agonists	buprenorphine
	μ-opioid receptor inverse agonists	naloxone
	μ-opioid receptor antagonists	naltrexone
	κ-opioid receptor agonists	salvinorin A, butorphanol, nalbuphine, pentazocine, ibogaine
	κ-opioid receptor antagonists	buprenorphine
Histamine receptor	H1 histamine receptor antagonists	diphenhydramine, doxylamine, mirtazapine, mianserin, quetiapine, olanzapine, meclozine, dimenhydrinate, most tricyclics
Monoamine oxidase	Monoamine oxidase inhibitors (MAOIs)	phenelzine, iproniazid, tranylcypromine, selegiline, rasagiline, moclobemide, isocarboxazid, Linezolid, benmoxin, St John's wort, coffee, garlic
Melatonin receptor	Melatonin receptor agonists	ramelteon
Imidazoline receptor	Imidazoline receptor agonists	apraclonidine, clonidine, moxonidine, rilmenidine
Orexin receptor	Orexin receptor agonists	modafinil
	Orexin receptor antagonists	SB-334,867, SB-408,124, TCS-OX2-29, suvorexant