Bath Salts and Synthetic Cannabinoids: A Review

Synthetic Cathinones ("Bath Salts")

Cathinones derived from the khat plant (Catha edulis) have been used recreationally for centuries. Chewing the leaves and twigs of the plant produces amphetamine-like euphoric effects. In 2006, there were 10 million khat users worldwide. The list of synthetic cathinones is long: butylone, dimethylcathinone, ethcathinone, ethylone, 3- and 4- flouromethcathinone, mephedrone, methedrone, methlenedioxypyrovalerone (MDPV), methylone and pyrovalerone, among others. Bupropion is the only cathinone derivative that has a medical indication in the U.S. and Europe. The first synthetic cathinone, methcathinone, was produced in 1928. Methcathinone was previously used in Russia as an antidepressant, also known as “Cat” and “Jeff” when used recreationally. The United Nations Convention listed cathinones as a schedule 1 substance in 1988 and the United States did so in 1993. Mephedrone, another type of synthetic cathinone, came from Europe to the U.S. in 2009. U.S. poison control centers received 12 times as many calls involving “bath salt” exposure in the first six months of 2011 than in all of 2010. The number of seizures from synthetic cathinones increased from 14 in 2009 to 290 in 2010. In September 2011, the DEA scheduled three synthetic cathinones as schedule one (mephedrone, methylone, and MDPV). Manufacturers sell the drugs as bath salts, plant food, insecticides, chicken feed additives, or research chemicals with names like Energy and Meow. They also label them as “not for human consumption” to avoid legal regulation and prosecution. The synthetic cathinones can be found on the internet, in smoke shops, and gas stations. Multiple deaths related to bath salts exposure have been reported internationally and in the medical literature, raising concerns as the drug becomes more popular in the U.S. Synthetic cathinones are usually sold as a white or brown powder, but capsules and tablets are also available.

The method of ingestion varies, but synthetic cathinones are most commonly nasally inhaled or ingested. Rectal administration (known as “booty bombing” or “keystering”), gingival delivery, inhalation and intramuscular or intravenous injection have all been reported. “Bombing” is wrapping powder in cigarette paper and swallowing it. “Keying” is dipping a key into powder and inhaling it. Synthetic cathinones are mostly excreted via the urine and can be measured via gas or liquid chromatography-mass spectrometry in the blood, urine and stomach contents. They can also be analyzed in hair.

There are limited data on pharmacokinetics and pharmacodynamics of synthetic cathinones. The cathinone stimulant from the khat plant has been manipulated with biochemical substitutions creating a new class of drugs with variable potency. These synthetic cathinones are beta ketophenethylamines, which are structurally similar to amphetamines. Cathinone derivatives, however, tend to be more hydrophilic, which decreases their ability to cross the blood-brain barrier. They have been shown to inhibit the reuptake of dopamine, serotonin, and norepinephrine. Based on animal models, amphetamine derivatives increase synaptic concentrations of biogenic amines (norepinephrine, dopamine, and serotonin) by two primary mechanisms. The first is by inhibiting monoamine uptake transporters. The second is by causing the release of neurotransmitters from intracellular stores via changing the vesicular pH or inhibiting the vesicular monoamine transport (VMAT2) receptor. The mechanism of different synthetic cathinones varies. Methylone acts less on VMAT2 receptors compared to other amphetamine derivatives. It is a competitive inhibitor of norepinephrine reuptake but a noncompetitive inhibitor of dopamine and serotonin receptors. Mephedrone causes a greater increase in brain dopamine concentration and was noted to have a faster return to baseline level of neurotransmitters compared to MDMA. Pyrovalerone inhibits norepinephrine and dopamine reuptake, but has little effect on serotonin uptake.

The symptoms reported by users include euphoria, alertness, energy, talkativeness, increased sexual arousal, and the compulsion to re-dose frequently. Some case reports describe extremely aggressive and psychotic behavior with increased physical strength, as sometimes described in PCP intoxication. The clinical effects of synthetic cathinone intoxication are consistent with sympathomimetic toxicity and include hypertension, tachycardia, hyperthermia, dehydration, and psychomotor agitation. The patients may also report palpitations, headache, chest pain, trismus, bruxism, tremors, insomnia, and paranoia. Although much can be drawn from the structural and chemical similarities between synthetic cathinones and amphetamines, continued studies are needed to understand the particular properties including the long-term effects of synthetic cathinones.

Currently, routine urine drug screening for amphetamines is not able to detect synthetic cathinones, although they may cause false positive methamphetamine screens. However, both GC-MS and LC -MS testing kits are commercially available for some synthetic cathinones including mephedrone, MDPV, and methylone. The synthetic cathinones are mostly excreted via the urine, but can be measured in the blood, hair, urine and stomach contents.

Supportive care is the mainstay of therapy based on management of other sympathomimetic conditions. Aggressive sedation with benzodiazepines is indicated for agitation, seizures, tachycardia, and hypertension. Extreme hypertension that persists despite benzodiazepines may be treated with titratable vasodilators. Beta blockers should be avoided due to the potential to cause unopposed alpha-adrenergic stimulation, worsening the hypertension. Significant hyperthermia may require passive or active cooling. All moderately to severe symptomatic patients should have an electrocardiogram (ECG), be placed on a cardiac monitor, and receive serial temperature checks. Lab studies including electrolytes, renal and liver function tests, cardiac markers and creatine kinase should be considered, as should testing for coingestants or adulterants. Asymptomatic patients with no other suspected coingestions or psychiatric symptoms generally may be discharged. In a case series of 35 patients who presented to the ED after using bath salts, 26% were admitted to an intensive care unit.

American Academy of Emergency Medicine. 2012;19(2):19-22. © 2012  American Academy of Emergency Medicine