Meow-Meow, Ivory Wave, Russian River, Powdered Rush. You might not understand these nicknames, but there's a good chance you have patients who do. They refer to a new designer drug comprising various psychoactive chemicals, including mephedrone (4-methylmethcathinone) and MDPV (3,4-methylenedioxypyrovalerone). Aggressively marketed on the Internet and available in head shops as “bath salts,” these drugs initially gained popularity in Europe in the late 2000s because they were easy to get, legal and cheap. They were known collectively as “legal highs.”
Consider this presentation of a 27-year-old woman from Altoona, Pa. The police brought her to an emergency department (ED) after she and her boyfriend called, stating there was an unknown assailant in their home. The couple also claimed there was a dead body in their house and they were about to be killed. Upon investigation, it was apparent that they were both suffering delusions and that neither claim was true.
In the ED, the woman was tachycardic, diaphoretic, paranoid and anxious. She had a disorganized thought process and poor memory of the time period prior to admission. Her labs and radiology were unremarkable, including a negative drug screen. She was admitted and managed with risperidone and improved over the next 24 hours. She then admitted to a five- to six-day binge of “Powdered Rush,” purchased from a local head shop. By hospital day five her delusions and hallucinations had resolved, and she was stable for discharge on a taper of risperidone (11. Antonowicz JL, Metzger AK, Ramanujam SL. Paranoid psychosis induced by consumption of methylenedioxypyrovalerone: two cases.Gen Hosp Psychiatry. May 25, 2011. Epub ahead of print.).
While this patient survived, “bath salts” have been implicated in multiple deaths. A case study published in March 2011 reported the death of a man found off the coast of the Isle of Wight who was believed to have jumped off a cliff. He had taken “Ivory Wave” two days before and, according to his family, had been experiencing extreme hallucinations and psychoses (22. Durham M. Ivory wave: the next mephedrone?Emerg Med J. March 15, 2011. Epub ahead of print.). There have been multiple case reports of patients presenting to emergency departments with sympathomimetic toxidromes, as well.
These incidents have raised international concern and led to the ban of “bath salts” in several European countries. The United Kingdom banned them in April 2010—notably, it was the first generic ban of a group of cathinones based on the chemical structure (33. Morris K. UK places generic ban on mephedrone drug family. Lancet. 2010;375:1333-1334.).
Yet the drugs have made their way to the United States in the last three years and have rapidly gained in popularity. According to data from the American Association of Poison Control Centers, there were 303 documented calls about “bath salts” in 2010. From Jan. 1 through July 31, 2011, there were 4,137 calls.
Mephedrone and MDPV are derivatives of cathinone, a naturally occurring stimulant extracted from the khat plant (catha edulis) grown in the Middle East and East Africa. Cathinone is thought to be manufactured in bulk quantities in China, Pakistan and India and packaged and distributed in intermediate locations in Eastern Europe (44. Rannazzisi JT. Statement before the Subcommittee on Health, Committee on Energy and Commerce, United States House of Representatives, at a hearing entitled “Legislative Hearing to Address Bioterrorism, Controlled Substances and Public Health Issues.” July 21, 2011.).
The substance is packaged as a white or tan crystalline powder. In addition to being sold as “bath salts,” it is also marketed as “fertilizer” or “plant food” and is labeled as “not for human consumption” to avoid scrutiny by the Food and Drug Administration. (Just Google “bath salts” and you will see a vast array of creative packaging.) The drug can be ingested orally by swallowing, or by “bombing” (wrapping the powder in cigarette papers and swallowing). It can also be snorted, smoked, or administered intravenously or rectally (55. Drug Enforcement Administration Drug Fact Sheet. Bath Salts or Designer Cathinones (Synthetic Stimulants)., 66. Psychonaut Web Mapping Research Group. Mephedrone Report. Created March 4, 2009. Last updated March 1, 2010., 77. Psychonaut Web Mapping Research Group. MDPV Report. Created March 4, 2009. Last updated June 8, 2010.).
Structurally similar to other stimulants like cocaine, ecstasy (MDMA) and methamphetamine, the chemicals in “bath salts” are thought to cause dopamine release from the nucleus accumbens. A study on rat models by Hadlock and colleagues (88. Hadlock GC, Webb KM, McFadden LM, et al. 4-Methylmethcathinone (mephedrone): neuropharmacological effects of a designer stimulant of abuse. J Pharmacol Exp Ther. 2001;339:530-536.) demonstrated that mephedrone inhibits dopamine and serotonin uptake. MDPV is also thought to be a dopamine and norepinephrine reuptake inhibitor (99. Schecter A. Feds arrest ten in first ever “bath salts” bust. June 29, 2011.).
When the drugs are taken recreationally, the desired effects include euphoria, sociability, intensification of sensory experiences, sexual arousal, mood enhancement, and hallucinations. “Bath salts” are said to be smoother “coming up and coming down” than MDMA and don't involve a hangover. On average, the user begins to feel effects 10 to 20 minutes after taking the drugs, with a peak at 45 to 60 minutes. The effects wear off after about two hours (66. Psychonaut Web Mapping Research Group. Mephedrone Report. Created March 4, 2009. Last updated March 1, 2010., 77. Psychonaut Web Mapping Research Group. MDPV Report. Created March 4, 2009. Last updated June 8, 2010.), at which time there is a strong urge to re-dose. Though information is limited and long-term effects aren't known, anecdotal accounts indicate that the paranoid effects can be longer lasting.
The adverse effects are similar to other stimulants of the central nervous system, resulting in cardiac and neurologic toxicities including tachycardia, chest pains, vasoconstriction, ischemia, increase in mean body temperature, dehydration, flu-like symptoms, peripheral neuropathy, ulcerations in the mouth/nose from ingestion, anxiety, paranoia, hallucinations, seizures, delusions, anxiety, dysphoria, depression, rhabdomyolysis, and serotonin syndrome. Negative side effects are reported to increase with heavy use.
Standard drug screens are negative. Also, “bath salts” are often used in combination with other substances like alcohol, marijuana, cocaine, or heroin, which makes identification more difficult. However, they can be detected on gas chromatography/ mass spectroscopy (1010. Penders TM, Gestring R. Hallucinatory delirium following use of MDPV: “Bath Salts”. Gen Hosp Psychiatry. 2011;33:525-6.).
Management is supportive. Case reports have described the use of antipsychotics to manage the delusional behaviors and hallucinations and high doses of benzodiazepines to subdue aggressive behaviors (11. Antonowicz JL, Metzger AK, Ramanujam SL. Paranoid psychosis induced by consumption of methylenedioxypyrovalerone: two cases.Gen Hosp Psychiatry. May 25, 2011. Epub ahead of print., 22. Durham M. Ivory wave: the next mephedrone?Emerg Med J. March 15, 2011. Epub ahead of print., 1010. Penders TM, Gestring R. Hallucinatory delirium following use of MDPV: “Bath Salts”. Gen Hosp Psychiatry. 2011;33:525-6., 1111. Centers for Disease Control and Prevention. Emergency department visits after use of a drug sold as “bath salts”—Michigan, November 13, 2010-March 31, 2011. MMWR. 2011;60:624-627., 1212. Ross EA, Watson M, Goldberger B. “Bath Salts” intoxication. N Engl J Med. 2011;365:967-968., 1313. Smith C, Cardile AP, Miller CO. Bath salts as a “legal high”. Am J Med. April 22, 2011. Epub ahead of print., 1414. Wood DM, Davies S, Puchnarewicz M, et al. Recreational use of mephedrone (4-methylmethcathinone, 4-MMC) with associated sympathomimetic toxicity. J Med Toxicol. 2010;6:327-330.). A Sept. 8, 2011 letter to the editor of the New England Journal of Medicine agreed with the above and added that physical restraints also may be indicated to prevent self-harm or harm to others (1212. Ross EA, Watson M, Goldberger B. “Bath Salts” intoxication. N Engl J Med. 2011;365:967-968.). The letter authors describe “bath salts” as having the worst characteristics of LSD, PCP, ecstasy and cocaine.
The legal challenge
The problem with designer drugs is that they have similar effects to, but are structurally distinct from, other controlled substances. Endless structural variations can be made that do not change the drugs pharmacologically but allow them to evade legal control. Labeling the drugs as “plant food,” “not for human consumption” and “novelty” also helps to circumvent law enforcement.
As of Oct. 7, 2011, 31 U.S. states have banned “bath salts” (44. Rannazzisi JT. Statement before the Subcommittee on Health, Committee on Energy and Commerce, United States House of Representatives, at a hearing entitled “Legislative Hearing to Address Bioterrorism, Controlled Substances and Public Health Issues.” July 21, 2011.). Methcathinone, an analogue of mephedrone, is already classified as a Schedule I drug, and some incidents have been prosecuted under the Federal Analog Act of the Controlled Substances Act. For example, the New York division of the DEA arrested multiple distributors of “bath salts” in June 2011 in a large sting operation in Manhattan and Brooklyn (1212. Ross EA, Watson M, Goldberger B. “Bath Salts” intoxication. N Engl J Med. 2011;365:967-968., 1515. Goodnough A, Zezima K. An alarming new stimulant, sold legally in many states.The New York Times. July 16, 2011., 1616. McKenzie-Mulvey E. Ten arrested in New York “bath salts” round up. DEA news release. June 28, 2011.).
On October 21, 2011, the Drug Enforcement Agency (DEA) used its emergency authority to make the possession and sale of methylenedioxypyrovalerone, mephedrone and methylone—and any products that contain them—illegal for at least a year, while it considers whether the substances should be controlled permanently.
Hospitalists must be aware of trends in this rapidly evolving designer drug market, which can elude our screens and laws. We need to know what patients might be taking in order to ask specific questions in our histories. In doing so, we will be better able to diagnose, treat and counsel on adverse effects.