5.5 Cannabis, GHB, Nitrites, and Nicotine Products
Key Takeaways
- Edible cannabis products are a leading cause of pediatric intensive care admission among recreational drug exposures, with young children developing ataxia, profound somnolence, and occasionally respiratory depression after delayed absorption.
- Gamma-hydroxybutyrate produces deep coma with preserved vital signs and an abrupt spontaneous awakening after 2 to 4 hours, and its withdrawal syndrome resembles severe alcohol withdrawal and may require very large benzodiazepine doses.
- Nicotine causes biphasic nicotinic effects: early vomiting, tachycardia, and hypertension, followed by weakness, bradycardia, and paralysis, and concentrated electronic cigarette liquid can deliver a lethal dose to a small child in a swallow.
- Volatile alkyl nitrites, used as inhalants, cause methemoglobinemia and syncope, while nitrite ingestion has caused fatal methemoglobinemia treated with methylene blue.
- Most single-substance cannabis exposures in adults need only reassurance and a quiet environment, so triage focuses on the child who ingested an edible, the patient with an unknown co-ingestant, and the synthetic cannabinoid user with agitation or seizures.
Cannabis and Delta-9-Tetrahydrocannabinol
Delta-9-tetrahydrocannabinol is a partial agonist at CB1 (central) and CB2 (peripheral immune) receptors. Partial agonism, plus the presence of cannabidiol in plant material, explains why natural cannabis has a wide margin of safety in adults.
Adults
Expected effects are euphoria, conjunctival injection, tachycardia, dry mouth, increased appetite, and impaired coordination and reaction time. Adverse presentations include panic and paranoia, acute psychosis, and cannabinoid hyperemesis syndrome: cyclical vomiting in a chronic heavy user who describes compulsive hot bathing for relief, often responsive to topical capsaicin, droperidol or haloperidol, and benzodiazepines rather than to standard antiemetics.
Children and Edibles
Edible products are the pediatric problem. They look like candy or baked goods, contain many adult doses per package, and absorb slowly so the child appears fine and then deteriorates.
- Onset after ingestion is 30 minutes to 3 hours, with peak effects at 2 to 4 hours and effects lasting 8 to 12 hours or longer.
- Young children present with ataxia, marked lethargy or coma, mydriasis, tachycardia, and sometimes hypotonia, apnea, or seizures.
- There is no reliable safe pediatric threshold: a single 10 mg edible serving can sedate a toddler, and many packages contain 100 mg or more of tetrahydrocannabinol.
- Management is airway assessment and observation; most children recover with supportive care, but respiratory depression mandates emergency evaluation for any symptomatic child.
Delta-8 and Related Semi-Synthetic Cannabinoids
Products labeled delta-8 or delta-10 tetrahydrocannabinol are chemically converted from hemp-derived cannabidiol, sold with little regulation, and frequently mislabeled for potency. Pediatric exposures behave like high-dose edible exposures.
Synthetic Cannabinoid Receptor Agonists
These are full agonists with far higher CB1 affinity and no cannabidiol, which is why they behave nothing like cannabis: severe agitation, psychosis, seizures, tachydysrhythmias, hypokalemia, acute kidney injury, myocardial ischemia, and death. Some batches have been adulterated with brodifacoum, producing severe coagulopathy. Treatment is benzodiazepines and supportive care, with coagulation studies if bleeding occurs.
Gamma-Hydroxybutyrate and Its Precursors
Gamma-hydroxybutyrate (GHB) is an endogenous neurotransmitter that acts at GHB receptors and, at higher concentrations, at GABA-B receptors. Two industrial chemicals are converted to GHB after ingestion: gamma-butyrolactone (GBL), found in some cleaners and solvents, and 1,4-butanediol, which is metabolized by alcohol dehydrogenase.
Acute Overdose
- Deep coma with relatively preserved vital signs, often with bradycardia, hypothermia, myoclonic jerks, and vomiting.
- A hallmark is abrupt, spontaneous awakening 2 to 4 hours after ingestion, sometimes with agitation, in a patient who appeared moribund.
- The steep dose-response curve means the difference between euphoria and apnea is small, and co-ingested ethanol markedly increases the risk.
- Management is airway protection and observation. Flumazenil and naloxone are ineffective. Persistent coma beyond about 6 hours should prompt a search for another cause.
Withdrawal
Daily users (often dosing every 2 to 4 hours around the clock) develop withdrawal within hours of the last dose: tremor, tachycardia, hypertension, insomnia, hallucinations, delirium, and seizures. It resembles severe alcohol withdrawal, can be fatal, and often requires very high cumulative benzodiazepine doses, sometimes with barbiturates or propofol.
Volatile Alkyl Nitrites ("Poppers")
Amyl, butyl, and isobutyl nitrite are inhaled as vasodilators and euphoriants.
- Inhalation causes flushing, headache, tachycardia, and syncope from abrupt vasodilation, and it is dangerous with phosphodiesterase-5 inhibitors.
- Ingestion causes clinically significant methemoglobinemia: cyanosis unresponsive to oxygen, chocolate-brown blood, and a pulse oximetry reading that plateaus near 85%. Treatment is methylene blue 1 to 2 mg/kg IV.
- Sodium nitrite purchased online has caused deaths in intentional ingestions; these patients need immediate methylene blue and often exchange transfusion if severe.
Nicotine and Tobacco Products
Nicotine is an agonist at nicotinic acetylcholine receptors at autonomic ganglia, the neuromuscular junction, and the central nervous system. Its toxicity is biphasic.
| Phase | Mechanism | Findings |
|---|---|---|
| Early (stimulation) | Ganglionic and central activation | Nausea and vomiting (often within 15 to 60 minutes), salivation, pallor, diaphoresis, tachycardia, hypertension, tremor, agitation, seizures |
| Late (blockade) | Persistent depolarization causes receptor blockade | Bradycardia, hypotension, weakness, fasciculations then flaccid paralysis, respiratory muscle failure, coma |
Product Content and Thresholds
| Product | Approximate Nicotine Content |
|---|---|
| One cigarette | 10 to 15 mg total (much is lost in smoke) |
| One cigarette butt | 5 to 7 mg |
| Chewing tobacco, 1 g | 6 to 8 mg |
| Nicotine gum or lozenge | 2 to 4 mg per piece |
| Nicotine pouch | 3 to more than 40 mg per pouch |
| Electronic cigarette liquid | Commonly 3 to 60 mg/mL; a 30 mL bottle at 36 mg/mL contains over 1,000 mg |
- Children who ingest about 0.2 mg/kg or more warrant medical evaluation if symptomatic, and many centers refer any swallow of liquid nicotine. Mild symptoms have appeared near 0.8 mg/kg, and the estimated lowest lethal oral dose for children under 5 is roughly 1 to 14 mg/kg. The older "60 mg is lethal in an adult" figure is now considered a substantial underestimate for adults.
- The dangerous exposures are concentrated electronic cigarette liquid (a swallow can far exceed a toddler's toxic dose, and dermal absorption from a spill also matters), pouches and lozenges, and multiple cigarette butts.
- Management is airway support and aggressive antiemetic and fluid therapy. Vomiting is partly protective. Activated charcoal binds nicotine but is often impractical because of emesis. Atropine treats symptomatic bradycardia and secretions; benzodiazepines treat seizures; assisted ventilation is required for paralysis.
Green Tobacco Sickness
Field workers harvesting wet tobacco absorb nicotine transdermally and develop nausea, vomiting, headache, dizziness, and weakness. Treatment is removal from exposure, skin washing, and rehydration.
Triage Summary
| Exposure | Home Observation Possible? | Key Action |
|---|---|---|
| Adult single-substance cannabis | Usually yes | Quiet environment, reassurance, follow-up call |
| Child with an edible or delta-8 product | No if any symptom; low-dose asymptomatic exposures may be observed with close follow-up | Watch for delayed onset up to 3 hours, then prolonged effects |
| Synthetic cannabinoid | No | Benzodiazepines, potassium, kidney function, coagulation if bleeding |
| GHB, GBL, 1,4-butanediol | No | Airway, expect abrupt awakening; investigate persistent coma |
| Nitrite ingestion | No | Co-oximetry, methylene blue |
| Concentrated nicotine liquid in a child | No | Emergency evaluation, antiemetics, monitoring for the late paralytic phase |
| One or two cigarette butts in a child | Often yes | Expect vomiting; follow-up call |
A 3-year-old ate an unknown number of cannabis gummies about 90 minutes ago. He is now markedly ataxic, difficult to keep awake, and has dilated pupils and a heart rate of 150. Which statement should guide the specialist's advice?
A 25-year-old is brought in comatose with a respiratory rate of 10, heart rate of 52, and normal blood pressure after a party. He has myoclonic jerks and vomits once. Three hours later he suddenly sits up, alert and agitated. Which exposure best explains this course?
A 2-year-old is found with an open 30 mL bottle of electronic cigarette refill liquid labeled 36 mg/mL; roughly 5 mL is missing. He weighs 13 kg and has already vomited twice. What is the calculated dose and the correct disposition?