2 Neuroscience2.5 Neurochemistry and neurophysiology

2.5.3 Effects of opioids and common recreational drugs on neurotransmission and links to mental health symptoms

1 min read1 figure

Written by Resident Doctor Committee · Published

Opioids

  • Opioid receptors couple mainly to Gi/o proteins, which reduce cyclic AMP, calcium entry and transmitter release.

  • Mu receptors give analgesia, reinforcement, respiratory depression and dependence, and kappa receptors give stress and aversion.

  • Opioids inhibit gamma-aminobutyric acid (GABA) inputs and so disinhibit ventral tegmental area dopamine cells.

  • Tolerance falls during abstinence, so resuming the previous dose risks overdose.

Follow the opioid to the mu receptor on the GABA interneurone: less GABA reaches the ventral tegmental dopamine cell, which is disinhibited and releases more dopamine in the nucleus accumbens. Drawn for MRCPsychiatrist

Stimulants

Drug

Action

Mental-health effects

Cocaine

Blocks dopamine, noradrenaline and serotonin transporters

Paranoia, hallucinations, post-binge low mood and craving

Amphetamines

Transporter substrates that reverse transport

Agitation, insomnia, stereotypy, psychosis

MDMA (methylenedioxymethamphetamine)

Releases serotonin, dopamine and noradrenaline

Mood and social changes, hyperthermia, serotonin toxicity

  • MDMA has a modest dependence liability, below cannabis and well below cocaine, despite genuine monoamine release and after-effects.

Cannabinoids

  • Exocannabinoids come from outside the body, from plants or synthesis, while endocannabinoids are made within it.

  • Related lipid mediators that do not bind CB1 or CB2 receptors are not cannabinoids.

  • Tetrahydrocannabinol (THC) partially activates CB1, altering presynaptic GABA and glutamate release.

  • Frequent high-potency THC use raises psychosis risk.

Alcohol, sedatives and GHB

  • Alcohol acts on GABA and glutamate systems, and its withdrawal seizures occur at 12 to 48 hours.

  • Gamma-hydroxybutyrate (GHB) gets its sedative, hypnotic and dependence-producing effects from weak agonism at the metabotropic GABA-B receptor, not the GABA-A benzodiazepine site.

Nicotine and caffeine

  • Nicotine activates nicotinic cation channels and dopamine circuits.

  • Caffeine blocks adenosine A1 and A2A receptors, and its withdrawal causes headache.

Psychedelics and dissociatives

  • Psilocybin is a classic serotonergic hallucinogen, converted to psilocin, whose 5-HT2A agonism and psychedelic effects closely resemble lysergic acid diethylamide (LSD).

  • Phencyclidine (PCP) and ketamine are N-methyl-D-aspartate (NMDA) glutamate receptor antagonists.

  • PCP impairs memory through NMDA antagonism, not through monoamine or cholinergic action.

  • NMDA blockade models both positive and negative features of schizophrenia.

Revision material for the MRCPsych examinations. Not clinical guidance, and not for use in patient care.

2.5.3 Effects of opioids and common recreational drugs on neurotransmission and links to mental health symptoms | MRCPsychiatrist