Common (>10% therapeutic + recreational users):

• Sedation, drowsiness, daytime sleep inertia
• Nausea, vomiting (especially at higher doses)
• Headache
• Dizziness, ataxia
• Enuresis (bedwetting) at therapeutic doses — sleep-architecture-related
• Sleepwalking / parasomnia (Xyrem labeled side effect)
• Hyponatremia (Xyrem specifically — high sodium load → fluid retention → dilutional hyponatremia; partially mitigated by Xywav's lower-sodium formulation)
• Weight loss, decreased appetite

Less common (1-10%):

• Confusion, disorientation
• Anxiety, depression (paradoxical at therapeutic doses)
• Hypertension, palpitations
• Tremor, paresthesia
• Memory impairment, blurred vision
• Sleep apnea worsening (contraindicated in untreated severe sleep apnea)

Rare-serious (<1% but central to risk profile):

• Respiratory depression / arrest — dose-dependent; nearly universal at >5-7 g recreational doses; especially severe with alcohol or other CNS depressants. No specific reversal agent (naloxone, flumazenil ineffective). Supportive airway management is the only acute therapy.
• Death — primarily from respiratory depression in polysubstance overdose. >90% of GHB-related deaths in published forensic series involve other substances (alcohol, opioids, benzodiazepines, methamphetamine). Number-of-deaths underestimated due to LC-MS detection requirement (immunoassays miss GHB in postmortem toxicology unless specifically requested).
• Severe physical dependence within 1-3 weeks of around-the-clock dosing (chemsex pattern). Dependence at less frequent dosing emerges over 1-3 months.
• Withdrawal seizures (5-15% of withdrawal presentations across cohorts).
• Withdrawal delirium (>50% of untreated cases; reduced to <10% with pharmaceutical GHB tapering).
• Benzodiazepine-resistant withdrawal — different receptor target; standard alcohol-withdrawal protocols often fail. Pharmaceutical GHB substitution + taper is European standard-of-care.
• Withdrawal-related death — case-reported in untreated severe withdrawal (autonomic crisis, hyperthermia, rhabdomyolysis, multi-organ failure).
• Aspiration pneumonia in unconscious vomiting users (acute toxicity).
• Rhabdomyolysis (chronic agitation in withdrawal).
• Acute liver failure (rare; case reports in chronic high-dose GBL — possibly related to industrial-grade purity issues).
• Acute psychosis (case reports — chronic high-dose users + during withdrawal).
• Status epilepticus (rare; documented in severe withdrawal).

Specific watch periods (clinical context only):

• First 30 minutes after dose: acute respiratory depression risk — especially if alcohol co-ingested or dose miscalculated.
• Days 1-7 of regular use: tolerance signs emerging (re-dosing pressure).
• Weeks 1-3 of round-the-clock dosing: physical dependence often established.
• First 24-72 hours of attempted discontinuation: peak autonomic + delirium + seizure risk.
• Months 1-6 post-discontinuation: PAWS (post-acute withdrawal syndrome) — anxiety, sleep disruption, anhedonia.