Consciousness-Altering Drugs

Four drug categories: depressants, stimulants, opioids, hallucinogens — each with its own receptor/neurotransmitter mechanism, all capable of activating the same reward circuitry.
Depressants (alcohol, barbiturates, benzodiazepines) increase GABA receptor activity, opening a chloride channel → hyperpolarization → brain inhibition. Alcohol also raises dopamine (mild euphoria) and causes alcohol myopia at high doses; chronic abuse can cause Wernicke-Korsakoff syndrome.
Stimulants (amphetamines, cocaine, MDMA) raise synaptic dopamine/norepinephrine/serotonin. Amphetamines promote release AND block reuptake; cocaine only blocks reuptake. MDMA combines amphetamine-like and hallucinogenic effects.
Opiates (naturally occurring: morphine, codeine) and opioids (semisynthetic: oxycodone, hydrocodone, heroin) bind opioid receptors, reducing pain and producing euphoria; overdose causes respiratory suppression. Methadone treats opioid use disorder.
Hallucinogens (LSD, mushrooms) act through poorly understood, largely serotonergic mechanisms. Marijuana (THC) acts at cannabinoid, glycine, and opioid receptors and can look stimulant-, depressant-, or hallucinogen-like.
Addiction is driven specifically by the mesolimbic pathway (VTA → nucleus accumbens, connected via the medial forebrain bundle) — one of four dopaminergic pathways, activated by all addictive substances plus gambling and falling in love.

Alcohol myopia: A short-sighted view of consequences produced by high-dose alcohol's broad disruption of brain activity.
Wernicke-Korsakoff syndrome: Thiamine (B1) deficiency from chronic alcohol abuse causing severe memory impairment, mental status changes, and motor skill loss.
Nigrostriatal pathway: Dopaminergic pathway (substantia nigra → striatum) governing motor planning.
Mesolimbic pathway: The reward pathway (VTA → nucleus accumbens) driving addiction; activated by drugs, gambling, and love.
Mesocortical pathway: Dopaminergic pathway (VTA → cortex) affecting cognition and affect.
Tuberoinfundibular pathway: Dopaminergic pathway (hypothalamus → pituitary) regulating prolactin release.

Barbiturates	Benzodiazepines
Increase the duration each GABA-A chloride channel opening lasts	Increase the frequency the GABA-A chloride channel opens
Narrower safety margin, higher overdose risk	Less susceptible to overdose (but still risky with alcohol)

Amphetamines	Cocaine
Promote release of dopamine, norepinephrine, serotonin AND block reuptake	Only blocks reuptake of dopamine, norepinephrine, serotonin

Opiates	Opioids
Naturally occurring (morphine, codeine)	Semisynthetic derivatives (oxycodone, hydrocodone, heroin)
Both bind opioid receptors: decreased pain, euphoria; overdose → respiratory suppression	Same mechanism and overdose risk as opiates

Same receptor (GABA-A), different mechanism: barbiturates = duration of opening, benzodiazepines = frequency of opening — this is why barbiturates carry higher overdose risk.
Amphetamines both release AND block reuptake of monoamines; cocaine blocks reuptake only — similar effects, different mechanism.
'Opiate' and 'opioid' are not interchangeable — natural vs. semisynthetic.
Only the mesolimbic pathway is 'the addiction pathway' — don't assume every dopaminergic pathway drives addiction.

Why do barbiturates carry a higher overdose risk than benzodiazepines, even though both increase GABA activity?

A patient overdoses on heroin and stops breathing. What mechanism explains this?

Which dopaminergic pathway specifically underlies addiction, and what are its components?

Why doesn't marijuana fit cleanly into one drug category?

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