GPCR)<unk> s bind with neurological<unk>  receptors to provoke analgesic, sedative, and euphoric effects.<unk> ’s function by stimulating specific G-protein coupled receptors distributed throughout the body—including the brain, skin and spinal cord. Three of the major<unk>  receptors include mu, kappa, delta, and nociception, each playing a role in eliciting the effects associated with<unk> s. An<unk>  results from over-activation of these receptors, which can cause permanent brain damage from cerebral hypoxia or neurotoxicity. Mu receptors have an analgesic effect on the brain, and are found in various parts of the nervous system including the cerebral cortex and thalamus. They can be found in the nucleus accumbens, the pleasure centre of the brain, as well as the amygdala. Kappa receptors, in the hypothalamus, produce a similar analgesic effect. They bind with dynorphins to stimulate anti-reward effects —dysphoria— and other negative effects of withdrawal. While mu receptors are the source of addiction, kappa receptors contribute to continued abuse. They generate dysphoria in response to increasing stress levels via corticotropin-releasing factor (CRF). This increases erratic shifts in mood during withdrawal period and can prompt relapse. Delta receptors, found in the basal ganglia of the limbic system, have been shown to reduce anxiety by binding with enkephalins, although this requires further research. The most recent addition to these receptors are nociception<unk>  receptors. Although they have been determined to be receptors to certain ligands from<unk> s, their role has not yet fully understood. When<unk> s are ingested, the ligand binds to these constitutively active receptors to reduce neural activity. This is accomplished by inhibiting adenylyl cyclase and cyclic AMP, which are necessary for communication within the central nervous system. There is research indicating that<unk> s reduce pain by disrupting ion channels and vesicle fusion. Prolonged exposure to<unk> s can cause these receptors to become internalized, leading to increased tolerance and increased<unk>  use.
Opioid overdose
Stroke
Nicotine withdrawal
Alcohol intoxication
Benzodiazepine overdose
Hypoglycemia
Carbamate poisoning
Head injury