Background
Cathinones are originally found in the Khat plant from east Africa and have been chewed for centuries for their stimulant properties. However, once harvested, natural cathinones quickly break down into cathine, which is also a stimulant but much less potent than cathinone. This lead to the production of synthetic cathinones which have been used for decades in Russia. In 2010, their use became prevalent in North America. Bath salts are composed of several variations of synthetic cathinones, of which there are over 100 different ones in existence. They were designed to mimic the effects of methamphetamine and cocaine at a much cheaper price (6).
Nicknames
Synthetic Cathinones may also be called: bath salts, bath powder, meph, drone, 4-MMC, MCAT, MMCAT, bubbles, magic, meow, plant food, insect repellent, vacuum frshener, natural stain remover, potpourri, research chemicals, sub-coca, crab, rush, ivory wave, purple wave, red dove, blue silk, zoom, bloom, vanilla sky, white lighening, cloud nine, bluzzard, ocean snow, scarface, hurricane charlie, fine china, silver back, blue magic, heavenly soak (2,7)
Chemistry
Chemical structures of synthetic bath salt cathinones (8).
Components
The composition of bath salts is known to vary widely (6). Some of the common components include but are not limited to:
The figure to the left displays the similarity in structure of cathinones to amphetamines and methamphetamine (8).
The composition of bath salts is known to vary widely (6). Some of the common components include but are not limited to:
- Methcathinone (α-methylamino-propiophenone)
- Mephedrone (4-methymethcathinone)
- Methylone (3,4-methylenedioxy-N-methylcathinone)
- MDPV (3,4-methlenedioxypyrovalerone) (7,8).
The figure to the left displays the similarity in structure of cathinones to amphetamines and methamphetamine (8).
Pharmacology
Pharmacokinetics
Absorption/Administration
Bath salts can be administered in a number of ways (7):
Distribution
Distribution depends widely on the particular components of the bath salts used. Methcathinone is more polar than other components, and thus crosses the blood-brain barrier much more slowly than MDPV which is much more lipophilic. Since bath salts are fairly new to North America and the composition can vary greatly, data regarding specific volume of distribution and protein binding are limited (7).
Metabolism
The components of bath salts are 25% degraded by Phase I (CYP 450) and II reactions (7).
Elimination
75% of the components are excreted unchanged in the urine (7).
Absorption/Administration
Bath salts can be administered in a number of ways (7):
- Injection: intravenous and intramuscular injection provide are the fastest routes of administration
- Intranasal: this is the preferred route - it has a gradual onset but lasts for severe hours
- Oral, rectal and vaginal: these routes provide the slowest onset of action
Distribution
Distribution depends widely on the particular components of the bath salts used. Methcathinone is more polar than other components, and thus crosses the blood-brain barrier much more slowly than MDPV which is much more lipophilic. Since bath salts are fairly new to North America and the composition can vary greatly, data regarding specific volume of distribution and protein binding are limited (7).
Metabolism
The components of bath salts are 25% degraded by Phase I (CYP 450) and II reactions (7).
Elimination
75% of the components are excreted unchanged in the urine (7).
Effects
Mechanism of Action
Because the composition of bath salts is unpredictable, there are a number of different possible mechanisms of action (7):
Different synthetic cathinones have different affinities for different monoamine transporters. The composition of the bath salt used impacts the effects of the drug. For example, some cathinones have a higher affinity for norepinephrine transporters. This potentiates the sympathetic effects of norephinephrine and the signs and symptoms mimic those of amphetamine and cocaine use. Others have a higher affinity for serotonin transporters which potentiates the effects of serotonin. This causes the psychological symptoms such as delusions, hallucinations and paranoia that are characteristic of hallucinogen use. Excess dopamine is responsible for addiction potential, especially when it greatly exceeds serotonin levels (7).
Inhibiting monoamine oxidase A prevents the metabolism of serotonin and norephinephrine while inhibiting monoamine oxidase B prevents the metabolism of dopamine (7).
Desirable Effects
Using bath salts can cause patients to feel euphoric, alert, aroused, sociable, motivated and focused (2,7).
Undesirable effects
More than half of the users of bath salts have reported experiencing at least one adverse effect of which there are many (2,7).
Long term effects
Effects of chronic, regular use of "bath salts" can lead to persistent psychological effects. These can include depression, mood swings, restlessness, insomnia, bizarre behaviour, kidney damage or failure, rhabdomyolysis, suicide and death (2).
Because the composition of bath salts is unpredictable, there are a number of different possible mechanisms of action (7):
- Premature release of dopamine, serotonin and norephinephrine from neuronal cells
- Inhibition of monoamine transporters responsible for reuptake of dopamine, serotonin and norepinephrine
- Inhibition of monoamine oxidase A and B
Different synthetic cathinones have different affinities for different monoamine transporters. The composition of the bath salt used impacts the effects of the drug. For example, some cathinones have a higher affinity for norepinephrine transporters. This potentiates the sympathetic effects of norephinephrine and the signs and symptoms mimic those of amphetamine and cocaine use. Others have a higher affinity for serotonin transporters which potentiates the effects of serotonin. This causes the psychological symptoms such as delusions, hallucinations and paranoia that are characteristic of hallucinogen use. Excess dopamine is responsible for addiction potential, especially when it greatly exceeds serotonin levels (7).
Inhibiting monoamine oxidase A prevents the metabolism of serotonin and norephinephrine while inhibiting monoamine oxidase B prevents the metabolism of dopamine (7).
Desirable Effects
Using bath salts can cause patients to feel euphoric, alert, aroused, sociable, motivated and focused (2,7).
Undesirable effects
More than half of the users of bath salts have reported experiencing at least one adverse effect of which there are many (2,7).
- Neurological/Psychiatric: disorientation, confusion, anxiety, agitation, change in mental status, dilated pupils, nystagmus, rapid/inappropriate/incoherent speech, detachment from reality, paranoia, delusional, hallucinations, aggression, tremor, seizure, coma.
- Cardiovascular: sympathiomimetic effects; shortness of breath, palpitations, tachycardia, hypertension, hyperthermia, sweating, decreased circulation.
- Other: elevated liver enzymes, liver failure, dehydration, elevated cratinine phosphokinase, rhabdomyolysis, erectile dysfunction, urinary retention, anorgasmia, nausea and vomiting.
Long term effects
Effects of chronic, regular use of "bath salts" can lead to persistent psychological effects. These can include depression, mood swings, restlessness, insomnia, bizarre behaviour, kidney damage or failure, rhabdomyolysis, suicide and death (2).
Addiction Potential
It is unknown for certain if bath salts are addictive - they are still fairly new to North America. However, they possess many of the same characteristics as cocaine and amphetamine which can both be extremely addictive. Because of this and the dopamine release associated with bath salts, it is likely that it is addictive (2)
Toxicity
Intoxication
Patients experiencing bath salts intoxication often experience agitation, agression, psychosis, tachycardia and hyperthermia (8)
Overdose
Overdose often presents with symptoms similar to serotonin syndrome, neuroleptic malignant syndrome, anticholinergic toxidromes and sympathomimetic toxidromes. Psychotic behaviour has continued up to several days in some patients (7).
Withdrawal
Symptoms of withdrawal from bath salts are similar to other stimulants: intense cravings, depression, anxiety, irritability, lack of concentration, fatigue, nasal congestion and amnesia (2).
Patients experiencing bath salts intoxication often experience agitation, agression, psychosis, tachycardia and hyperthermia (8)
Overdose
Overdose often presents with symptoms similar to serotonin syndrome, neuroleptic malignant syndrome, anticholinergic toxidromes and sympathomimetic toxidromes. Psychotic behaviour has continued up to several days in some patients (7).
Withdrawal
Symptoms of withdrawal from bath salts are similar to other stimulants: intense cravings, depression, anxiety, irritability, lack of concentration, fatigue, nasal congestion and amnesia (2).
Treatments
Treatment is often supportive; there is no antidote for bath salts. Patients are often cooled to prevent hyperthermia from causing permanent damage such as rhabdomyolysis and renal failure (6,7,8).
Benzodiazepines
Midazolam or lorazepam help reduce tremors and agitation.
Antipsychotics
Rapid acting antipsychotics can be useful for controlling psychotic behaviour. However, it is important to choose one that does not lower seizure threshold and that is less likely to cause neuroleptic malignant syndrome (contributes to patient's hyperthermia).
Benzodiazepines
Midazolam or lorazepam help reduce tremors and agitation.
Antipsychotics
Rapid acting antipsychotics can be useful for controlling psychotic behaviour. However, it is important to choose one that does not lower seizure threshold and that is less likely to cause neuroleptic malignant syndrome (contributes to patient's hyperthermia).
Author: Lauren Elliott. BSc Pharm candidate, University of Waterloo. PHARM 415. Last Updated February 28, 2013