EXPERT ANALYSIS AT THE NPA PSYCHOPHARMACOLOGY UPDATE

LAS VEGAS (FRONTLINE MEDICAL NEWS) – People who use spice, bath salts, and other so-called designer drugs may present with symptoms that resemble numerous psychiatric conditions, including schizophrenia, anxiety disorders, and depression.

“Given the recent emergence of designer drugs, the long-term consequences of their use have not been extensively studied and are relatively unknown,” Dr. William M. Sauve said at the annual psychopharmacology update held by the Nevada Psychiatric Association.

Dr. Sauve, medical director of TMS NeuroHealth Centers of Richmond and Charlottesville, both in Virginia, said designer drugs have grown in popularity in recent years because they are perceived as legal alternatives to illicit substances. In addition, their detection by standard drug toxicology screens is limited.

In October 2011, components of designer drugs, including synthetic cannabinoids and the major constituents of bath salts, were categorized as emergency Schedule I substances. In July 2012, President Obama signed the Synthetic Drug Abuse Prevention Act , which doubled the time that a substance may be temporarily assigned to Schedule I, from 18 months to 36 months.

“Under federal law, any chemical that is similar to a classified drug and is meant to be used for the same purposes is considered to be classified,” Dr. Sauve said. However, designer drugs “get labeled ‘not for human consumption’ and can be sold out in the open and camouflaged under names such as ‘stain remover,’ ‘research chemicals,’ and even ‘insect repellent.’ That’s why it’s very difficult for the law to catch up with these things. Active ingredients are also a moving target.”

He discussed three types of these designer drugs: synthetic cannabinoids, bath salts, and krokodil.

Synthetic cannabinoids mimic THC

Also known as spice, K2, and incense, these substances began to appear in the United States in 2008 and are mostly used by males. Primarily inhaled, these substances are meant to mimic the effects of tetrahydrocannabinol (THC). They work by decreasing levels of gamma-aminobutyric acid (GABA) and by increasing levels of glutamate and dopamine. “Serotonin levels can also be affected indirectly by endocannabinoid control of GABA and glutamate release,” he added.

Unlike marijuana, which is a partial agonist at the cannabinoid 1 (CB-1) receptor, synthetics are full agonists at the CB-1 receptor, “so as you use it, it will hit every receptor until you have maximal stimulation, and it may have 800 times greater affinity than THC,” he said. Signs and symptoms of acute intoxication can be wide ranging, from agitation and dysphoria to paranoia and tachycardia, and can last up to 6 hours. While commercial tests are available to detect synthetic cannabinoid metabolites, formulations change so often that “most tests quickly become obsolete,” Dr. Sauve said. He noted that intoxication with spice should be suspected in patients who present with bizarre behavior, anxiety, agitation, and/or psychosis in those with no known psychiatric history. Intravaneous benzodiazepines can be used for agitation and seizures. While knowledge of their long-term impact is lacking, synthetic cannabinoids may increase the risk of subsequent psychosis by threefold, he said, and kidney failure has been reported in several cases.

Bath salts widely available

Also labeled as “plant food,” “pond water cleaner,” “novelty collector’s items,” and “not for human consumption,” these stimulants began to be used in the United States in 2010, and are widely available online and in smoke shops. Users have a median age of 26 years, Dr. Sauve said, and are mostly male.

Bath salts may be comprised of methcathinones, especially synthetic cathinones. Natural cathinones are found in khat, a root from a shrub that is chewed upon primarily by people in North Africa. Bath salts also may contain methamphetamine analogues, which can be synthesized from ephedrine and pseudoephedrine. These include methylone (similar to MDMA, or ecstasy), mephedrone (similar to methamphetamine), and methylenedioxypyrovalerone (similar to cocaine). Bath salts can be inhaled, injected, snorted, swallowed, or inserted into the rectum or vagina, and effects occur in doses of 2-5 mg. Pharmacological effects vary and may include increased plasma norepinephrine, sympathetic effects, serotonin syndrome, and increased dopamine. He also noted that the transition from recreational to addictive use “may occur in a matter of days.”

Signs of toxicity with bath salts, Dr. Sauve continued, include the following: disorientation and agitation; dilated pupils with involuntary eye movements; lockjaw and teeth grinding; rapid, inappropriate, incoherent speech; being emotionally, verbally, or physically abusive, and having elevated liver enzymes and/or liver failure.

Treatment is primarily supportive and may include sedatives for anxiety, agitation, aggression, tremors, seizures, and psychosis. Physical restraints may be necessary.

Krokodil not seen much in U.S.

Formally known as desomorphine, this substance is synthesized from codeine and became popular in Russia after a crackdown on heroin there in 2010, Dr. Sauve said. The ingredients for krokodil synthesis include tablets containing codeine, caustic soda, gasoline, hydrochloric acid, iodine from disinfectants, and red phosphorus from matchboxes. While desomorphine is believed to be highly addictive, “all the other sequelae of krokodil are generally thought to be a result of phosphorus” and other substances. No good data exist in the prevalence of its use, he said. “We’re not really seeing this much in the United States, because it’s way too easy to get Oxycontin and heroin [here].”

Dr. Sauve reported that he is a consultant to Avanir Pharmaceuticals and Otsuka Pharmaceutical. He also reported being a member of the speakers bureau or receiving honoraria from Avanir Pharmaceuticals, Otsuka Pharmaceutical, and Sunovion Pharmaceuticals.

dbrunk@frontlinemedcom.com

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