3 Clinical psychopharmacology3.3 Pharmacodynamics
3.3.2.13 Novel psychoactive substances
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Written by Resident Doctor Committee · Published
Groups and mechanisms
Novel psychoactive substances are newly available or newly used compounds, often made to imitate established drugs or evade controls. Their identity, potency and composition are uncertain.
Group | Mechanism | Imitates |
|---|---|---|
Synthetic cannabinoids | Cannabinoid 1 receptor agonism, usually full rather than partial | Cannabis |
Synthetic cathinones | Monoamine release or reuptake blockade | Amphetamine, cocaine, ecstasy |
Phenethylamines and tryptamines | Serotonin 2A agonism | Psilocybin, mescaline |
Arylcyclohexylamines | N-methyl-D-aspartate receptor blockade | Ketamine, phencyclidine |
Designer benzodiazepines and gamma-hydroxybutyrate analogues | Gamma-aminobutyric acid A or B enhancement | Diazepam, gamma-hydroxybutyrate |
Nitazenes and fentanyl analogues | High-efficacy mu-opioid agonism | Heroin, fentanyl |
Clinical signs suggest a drug class, not an exact compound, because small structural changes alter potency, duration and metabolites.
Why imitations are more dangerous
Property | Consequence |
|---|---|
Higher affinity and efficacy | Large effects from quantities too small to see |
Release rather than reuptake blockade | Monoamines above physiological ceilings |
Slow dissociation or long-lived metabolites | Intoxication lasting days |
Off-target actions | Seizures and arrhythmia |
No moderating components | Synthetic cannabinoid products lack cannabidiol |
Synthetic cannabinoids are often more potent than cannabis and can cause psychosis, seizures, hyperthermia, kidney injury, cardiac complications and death.
Nitazenes can exceed fentanyl in potency; naloxone still works but may need repeating, with observation and respiratory support.
Supply hazards
Products may be mislabelled, vary between batches, contain several drugs or contaminants, and be unevenly mixed.
Counterfeit alprazolam or diazepam tablets may contain designer benzodiazepines or potent opioids.
Legal status, brand names and tablet stamps cannot establish contents or safety, so "legal high" is misleading.
Toxidromes
Pattern | Features |
|---|---|
Sympathomimetic | Agitation, sweating, mydriasis, tachycardia, hypertension, hyperthermia |
Serotonergic | Sweating, diarrhoea, hyperreflexia, clonus worse in the legs, rigidity |
Anticholinergic | Hot dry skin, mydriasis, urinary retention, absent bowel sounds, delirium |
Sedative | Ataxia, dysarthria, reduced consciousness, respiratory depression |
Dissociative | Dissociation, nystagmus, analgesia, rigidity |
Opioid | Reduced consciousness, slow breathing, miosis |
Sweating and active bowel sounds tell sympathomimetic toxicity apart from anticholinergic toxicity.
Severe opioid hypoxia can dilate the pupils, and mixed pictures are common.
Investigation and management
Routine immunoassays miss many novel drugs and can cross-react, so a negative screen does not exclude exposure.
Mass spectrometry detects only compounds in its reference libraries, and detection does not prove impairment or causation.
Monitor vital signs, temperature and consciousness; check glucose, electrocardiogram, creatine kinase, renal function and electrolytes; seek TOXBASE advice.
Treat stimulant agitation and seizures with benzodiazepines, severe hyperthermia with active cooling, and opioid toxicity with repeated naloxone.