Cathinones are synthetic derivatives of a stimulant found in the khat plant, Catha edulis, that are used by ingestion, inhalation, smoking, or injection. Their chemical structure and toxic effects are the similar to amphetamine (eg, agitation, seizures, hypertension, hyperthermia). Diagnosis is by history and physical examination, with ECG to monitor for complications. Toxicity is managed with intravenous benzodiazepines for agitation, hypertension, and seizures, and external cooling measures for hyperthermia.
The khat plant (Catha edulis) is native to the Horn of Africa region in East Africa and to the Arabian peninsula. Its leaves contain cathinone, an amphetamine derivative. For centuries, inhabitants in those areas have chewed the leaves for euphoriant and stimulant effects. Synthetic variations that are more potent than khat leaves have become drugs of abuse. They are often referred to as "bath salts" because of their resemblance to Epsom salts (mineral salts commonly used in a hot bath to relax muscles).
Cathinones are formed by adding a carbonyl group on the ethylamine portion of phenethylamine 2 carbons away from the amine. Adding this functional group increases the lipophilicity and rigidity of the molecule. The clinical importance of increasing lipophilicity is that cathinone and its derivatives are able to distribute from the vasculature into tissues such as the brain and heart more rapidly.
The most commonly reported synthetic cathinones used by symptomatic individuals are mephedrone and methylenedioxypyrovalerone, which are also common contaminants in MDMA. One cathinone derivative, bupropion, is a therapeutic medication used to treat depression.
Synthetic cathinones are used by ingestion, snorting, smoking, and injection. Reported use of synthetic cathinones increased several thousand-fold from 2010 to 2011 (1). Worldwide seizure of related compounds by drug enforcement authorities increased significantly in early 2017 over a comparable time period in 2016.
The main street name for cathinones is Bath salts; other names include Bloom and Cloud Nine.
Reference
1. Karila L, Megarbane B, Cottencin O, Lejoyeux M. Synthetic cathinones: a new public health problem. Curr Neuropharmacol. 2015;13(1):12-20. doi:10.2174/1570159X13666141210224137
Pathophysiology of Cathinone Use
Cathinones increase the release of catecholamines leading to a hyperadrenergic state, like other amphetamine derivatives. In theory, increased lipophilicity should lead to more neurotoxicity and cardiotoxicity. The wide variation in dosing makes it challenging to compare the toxicity of synthetic cathinones with each other or other substances.
The structural diversity of synthetic cathinones makes it difficult to make general statements about their properties. There are no published data on the pharmacokinetics or pharmacodynamics of synthetic cathinones in humans. Limited animal studies have reported that, in comparison to MDMA, mephedrone increases the concentration of dopamine more but increases the concentration of serotonin less (1). Pyrovalerone inhibits norepinephrine and dopamine reuptake but has little effect on serotonin reuptake.
Routes of use are ingestion, inhalation, smoking, and injection.
Pathophysiology reference
1. Winstock AR, Mitcheson LR, Deluca P, Davey Z, Corazza O, Schifano F. Mephedrone, new kid for the chop?. Addiction. 2011;106(1):154-161. doi:10.1111/j.1360-0443.2010.03130.x
Signs and Symptoms of Cathinone Toxicity
Signs of acute toxicity resemble those from other amphetamines, including agitation, hyperactivity, seizures, hypertension, tachycardia, and hyperthermia (1).
Severe toxicity may include tachydysrhythmias (eg, ventricular tachycardia), status epilepticus, and rhabdomyolysis.
Symptoms and signs reference
1. Prosser JM, Nelson LS. The toxicology of bath salts: a review of synthetic cathinones. J Med Toxicol. 2012;8(1):33-42. doi:10.1007/s13181-011-0193-z
Diagnosis of Cathinone Toxicity
History and physical examination
ECG
The diagnosis of cathinone toxicity is usually made by history and physical examination, when a patient reports ingestion of what they believe to be a cathinone (or "bath salts") and demonstrates restlessness, agitation, tachycardia, or mydriasis. Send-out serum and urine test are available. As with send-out tests for other illicit substances, antemortem testing should only be done when there is a suspicion for stimulant toxicity. A medical toxicologist should be involved in interpreting the results. The relationship between serum concentrations of cathinones and clinical effects has not been determined.
Treatment of Cathinone Toxicity
For acute ingestion within 2 hours, oral activated charcoal
IV benzodiazepines as initial therapy, additional medications as needed for severe agitation or cardiovascular effects
For hyperthermia, external cooling methods (eg, ice bath, evaporative cooling)
Benzodiazepines are used to treat the sympathomimetic toxidrome, central nervous system excitation, including agitation and seizures, and also to control tachycardia and hypertension. External cooling methods are used in patients who are hyperthermic. Management is similar to amphetamine toxicity, and is discussed in detail separately.
Chronic Use of Cathinones
There is little research into withdrawal from synthetic cathinones. In one study, 25% of people using mephedrone reported urges or cravings to continue using but no physical withdrawal symptoms (1).
Chronic use reference
1. Winstock AR, Mitcheson LR, Deluca P, Davey Z, Corazza O, Schifano F. Mephedrone, new kid for the chop?. Addiction. 2011;106(1):154-161. doi:10.1111/j.1360-0443.2010.03130.x
Key Points
Cathinones are synthetic derivatives of a stimulant found in the plant Catha edulis. Their chemical structure is similar to amphetamine.
Toxic effects include agitation, seizures, hypertension, and hyperthermia, with possible life-threatening complications such as ventricular dysrhythmias, hyperthermia, cerebral edema, and status epilepticus.
Diagnose with history and physical examination. Evaluate for cardiac arrhythmias with ECG.
For patients ingested cathinones within the previous 2 hours and who can safely tolerate liquids, treat with activated charcoal. Activated charcoal is not a treatment for other routes of use (eg, inhalation, smoking, injection).
Treat with benzodiazepines IM or IV to control central nervous system excitement, hypertension, and tachycardia. Additional medications as needed for severe agitation or cardiovascular effects.
For hyperthermia, treat with external cooling methods (eg, ice bath).
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