Depressants
Substances that decrease central nervous system activity — alcohol, benzodiazepines, GHB, barbiturates. Includes fatal withdrawal risks.
Harm Reduction Notice: This site does not promote drug use. It provides evidence-based information to reduce harm. If you or someone you know is struggling with substance use, call SAMHSA: 1-800-662-4357 (free, confidential, 24/7). In an emergency, call 911. Naloxone saves lives — carry it.
Alcohol
Aliases: Ethanol, Booze, Liquor, Beer, Wine
Chemical Class: Simple alcohol (ethanol, CH3CH2OH) | Risk: high | Schedule: None (legal, regulated)
Mechanism: Positive allosteric modulator of GABA-A receptors (enhances inhibitory neurotransmission). Antagonist at NMDA glutamate receptors (reduces excitatory neurotransmission). Also affects opioid, serotonin (5-HT3), glycine, and nicotinic acetylcholine receptors. Increases dopamine release in nucleus accumbens via VTA disinhibition.
Onset/Duration by Route
| Route | Onset | Peak | Duration |
|---|
| Oral (empty stomach) | 15-30 min | 45-90 min | 2-5 hours |
| Oral (with food) | 30-60 min | 60-120 min | 3-6 hours |
Desired Effects: Anxiolysis and relaxation, Euphoria and disinhibition, Increased sociability, Muscle relaxation, Sedation (higher doses)
Adverse Effects: Impaired judgment and coordination, Slurred speech, Nausea, vomiting, Dehydration, Blackouts (anterograde amnesia), Aggression/emotional lability, Respiratory depression (high doses), Aspiration pneumonia risk
Overdose: BAC >0.30% = severe poisoning. BAC >0.40% = 50% fatality rate. Death from respiratory depression, aspiration, or cardiac arrhythmia. Treatment: supportive (airway management, IV fluids, thiamine, glucose). Recovery position if unconscious. NEVER leave an unconscious intoxicated person alone.
Dangerous Interactions
- Benzodiazepines (deadly): FATAL respiratory depression. Both are GABA-A modulators — effects are synergistic, not additive
- Opioids (deadly): FATAL respiratory depression. Leading cause of polysubstance overdose deaths
- GHB (deadly): Synergistic CNS depression; very narrow margin between recreational dose and fatal dose when combined
- Acetaminophen (Tylenol) (dangerous): Both are hepatotoxic. Chronic alcohol use depletes glutathione, making even therapeutic acetaminophen doses dangerous
- Cocaine (dangerous): Produces cocaethylene (more cardiotoxic, longer half-life)
- Antihistamines (caution): Additive sedation and impairment
Benzodiazepines
Aliases: Benzos, Xanax (alprazolam), Valium (diazepam), Klonopin (clonazepam), Ativan (lorazepam)
Chemical Class: Benzodiazepine (fused benzene + diazepine ring) | Risk: high | Schedule: IV
Mechanism: Positive allosteric modulators of GABA-A receptors at the benzodiazepine binding site. Increase the frequency of chloride channel opening (vs barbiturates which increase duration). This distinction gives benzos a wider therapeutic window than barbiturates. Different benzos vary in onset, duration, and potency based on lipophilicity and active metabolites.
Onset/Duration by Route
| Route | Onset | Peak | Duration |
|---|
| Oral (alprazolam) | 15-30 min | 1-2 hours | 4-6 hours |
| Oral (diazepam) | 15-45 min | 1-1.5 hours | 6-12 hours (active metabolites: days) |
| Oral (clonazepam) | 20-60 min | 1-4 hours | 6-12 hours |
| IV (midazolam) | 1-3 min | 3-5 min | 1-2 hours |
Desired Effects: Anxiolysis (primary medical use), Muscle relaxation, Sedation and sleep induction, Anticonvulsant effects, Euphoria (especially with rapid-onset benzos like alprazolam), Amnesia (procedural sedation)
Adverse Effects: Excessive sedation and drowsiness, Cognitive impairment and memory issues, Paradoxical disinhibition (aggression, impulsivity), Ataxia and falls (especially in elderly), Anterograde amnesia, Respiratory depression (especially combined with other depressants), Emotional blunting
Overdose: Benzodiazepines alone rarely fatal in overdose (wide therapeutic window). However, combined with opioids, alcohol, or other depressants, they are extremely lethal. Antidote: flumazenil (competitive antagonist at benzodiazepine binding site) — use cautiously as it can precipitate seizures in dependent individuals.
Dangerous Interactions
- Alcohol (deadly): FATAL respiratory depression. Both enhance GABA-A — synergistic effect
- Opioids (deadly): FATAL respiratory depression. #1 drug combination in overdose deaths
- GHB (deadly): Synergistic CNS depression
- Barbiturates (deadly): Overlapping GABA-A mechanism — extreme respiratory depression risk
- Z-drugs (zolpidem) (dangerous): Additive CNS depression via similar mechanism
WARNING: Fentanyl contamination risk. Always test your supply with fentanyl test strips.
GHB / GBL
Aliases: G, Liquid Ecstasy, Fantasy, Grievous Bodily Harm, Juice
Chemical Class: GHB: gamma-hydroxybutyric acid (endogenous). GBL: gamma-butyrolactone (prodrug) | Risk: extreme | Schedule: I (GHB), unscheduled/industrial (GBL)
Mechanism: GHB acts at GHB-specific receptors AND as a weak GABA-B receptor agonist. At recreational doses, GABA-B effects predominate (sedation, euphoria). GBL is rapidly converted to GHB by lactonase in the blood. Also modulates dopamine release (biphasic: inhibition at low doses, increase at moderate doses). Sodium oxybate (Xyrem) is pharmaceutical GHB for narcolepsy.
Onset/Duration by Route
| Route | Onset | Peak | Duration |
|---|
| Oral (GHB) | 15-30 min | 45-90 min | 1.5-3 hours |
| Oral (GBL) | 5-15 min | 30-60 min | 1-2.5 hours |
Desired Effects: Euphoria similar to alcohol but "cleaner", Disinhibition and sociability, Enhanced sensuality, Muscle relaxation, Deep sleep (at higher doses), Increased GH release (bodybuilding use)
Adverse Effects: Nausea and vomiting, Dizziness, Amnesia, Unconsciousness (G-hole) with very small dose increase above recreational level, Respiratory depression, Incontinence, Seizure-like myoclonus, Extremely steep dose-response curve
Overdose: GHB overdose presents as deep unconsciousness (GHB coma) with slow, shallow breathing. May look like sleep but is MEDICAL EMERGENCY. No antidote. Treatment: intubation if needed, supportive care. Most GHB-only overdoses resolve within 2-5 hours with supportive care. Adding alcohol or other depressants dramatically increases fatality rate.
Dangerous Interactions
- Alcohol (deadly): EXTREMELY DANGEROUS. Synergistic CNS depression. Tiny amount of alcohol can push therapeutic GHB dose into fatal range
- Benzodiazepines (deadly): Synergistic respiratory depression and unconsciousness
- Opioids (deadly): Fatal respiratory depression
- Ketamine (dangerous): Compounded CNS depression and vomiting while unconscious
Barbiturates
Aliases: Barbs, Downers, Phenobarbital, Secobarbital, Pentobarbital
Chemical Class: Barbituric acid derivatives | Risk: extreme | Schedule: II-IV (varies by compound)
Mechanism: Positive allosteric modulators of GABA-A receptors, increasing the DURATION of chloride channel opening (vs benzos which increase frequency). At high doses, can directly activate GABA-A receptors without GABA (explains narrower therapeutic window than benzos). Also block AMPA glutamate receptors.
Onset/Duration by Route
| Route | Onset | Peak | Duration |
|---|
| Oral (short-acting) | 15-40 min | 1-2 hours | 3-6 hours |
| Oral (long-acting, phenobarbital) | 30-60 min | 2-4 hours | 10-12 hours |
Desired Effects: Sedation and relaxation, Anxiolysis, Euphoria (at supratherapeutic doses), Sleep induction, Anticonvulsant effects
Adverse Effects: Extreme sedation, Respiratory depression (primary lethal mechanism), Cognitive and motor impairment, Paradoxical excitation, Hypotension, Hypothermia, Very narrow therapeutic window
Overdose: Extremely dangerous. Death from respiratory depression, cardiovascular collapse, and hypothermia. Lethal dose: 10x therapeutic for short-acting barbiturates. No specific antidote (unlike benzos). Treatment: intubation, activated charcoal (if early), supportive care, alkaline diuresis (phenobarbital).
Dangerous Interactions
- Alcohol (deadly): Synergistic respiratory depression — extremely small margin of safety
- Benzodiazepines (deadly): Both are GABA-A modulators
- Opioids (deadly): Fatal respiratory depression
- Antihistamines (dangerous): Additive CNS depression