As physicians working in acute care centers or emergency departments, it’s a daily challenge dealing with patients who are intoxicated. But as new street drugs emerge in the community this challenge is even more difficult. Street drugs or designer drugs, are those drugs that are produced by “street pharmacists” at home or in clandestine laboratories. The goal of these drugs is to mimic the most common general classes of drugs that are abused. These new designer drugs are more easily found and affordable than their counterparts, most of them can be found on the internet or local smoke shops, and are considered “legal highs”. Because the street drug’s chemical composition is different from those that they try to mimic, in most cases the US DEA has no jurisdiction over them. At the same speed that the DEA is developing laws to govern these new chemicals, the street pharmacists can easily change the chemical composition,  thus  avoiding the DEA’s jurisdiction. To be prepared to manage intoxications from these new designer drugs, the physician must have a strong knowledge of the common drugs of abuse toxidromes. It’s impossible in the length of this article to discuss all the common designer drugs.  I will discuss those that mimic the most common general classes of drugs of abuse; Synthetic Cannabinoids, Synthetic Cathinones and opioid analogues.  

Synthetic Cannabinoids

Cannabis (Marijuana) is one of the most widely illicit substances worldwide. In the past few years Cannabis has becomes  more widely decriminalized, and even legal in most of the states. With legalization comes taxation, which has led to an increased cost for users. In the last decade, Synthetic Cannabinoids (SCs) have gained popularity as a legal, more affordable alternative to natural Cannabis. The first SC was produced in 1967, and non classical SCs were produced in the 1960’s and 1980’s to have similar effects to cannabis. Hundreds of different SCs have been developed since then, and in 2008 an emergence of SCs as drugs of abuse was noted. Street pharmacists are frequently changing the chemical composition and developing new SCs, which makes development of standardized tests and pharmacokinetic profiles extremely difficult.  The SCs has been to able to avoid legal ramifications because it’s chemical composition is different from natural cannabis. 

Synthetic Cannabinoids are sprayed onto dried vegetable matter and sold as incense at convenience stores and smoke shops. The packaging has little information regarding the chemical composition and are label “ Not for Human Consumption”.  These products are sold under a variety of street names, the most common include: Spice, K2, Fake Weed, and many others. The use of SCs have become more widespread in the last 5 years, and calls to Poison Control Centers have tripled in the last few years. It’s most commonly used by inhaling by smoking or vaping, but ingestion has also been reported. Most users are in their early 20’s. SCs are only similar to natural Cannabis in their appearance and not their chemical composition.  Scs users report a quicker peak and shortened duration of effects when compared to those by natural Cannabis. A wide range of chemical effects have been reported including: tachycardia, agitation, drowsiness, confusion, hallucinations, hypertension, dizziness, chest pain and seizures. More severe clinical effects have been observed in SCs users than those of natural Cannabis, with up to 7.3% being life threatening. No specific test is recommended or indicated for suspected SCs use, routine qualitative drug testing for THC will generally be negative. Laboratory testing and management should be directed by the clinical presentation. No specific antidote exists for SCs and treatment should be symptom based and goal-directed supportive care. 

Bath Salts 

Synthetic Cathinones , commonly known as Bath Salts have recently emerged as a popular drug of abuse. Synthetic Cathinones are structurally similar to amphethamines and catecholamines. Cathinones are naturally found on the leaves of the Khat plant, common in Africa and the Arabian Peninsula. Cathinones appear to be the main constituent responsible for the amphetamine-like effects obtained from chewing the leaves of the Khat plant. Synthetic Cathinones are derivatives of natural cathinones with various chemical alterations that affects the  pharmacodynamics, thus keeping them out of reach of the US DEA. The first synthetic Cathinones were developed in the 1920’s and continued production thru the 1970’s. Some were used as treatment for depression. In the 1990’s abuse outbreaks started to appear in the US and Europe, but it wasn’t until 2007-2008 that it’s use became mainstream. The increase in popularity of Synthetic Cathinones was driven by the lack of availability and poor quality of other recreational stimulants, combined with it’s internet availability and no legal regulation. Today they are easily found in smoke shops and on the internet. They are marketed under different names including: Bath Salts, Vanilla Sky, Khat, MCAT, Energy-I and many others. 

There are many legislative measures in place to remove these “ legal highs” from the market, but calls to the Poison Control Centers related to Bath Salts have continued to increase since their emergence. Screening of these calls has revealed that 54% of users are under the age of 30. Synthetic Cathinones are most commonly snorted or ingested, but can also be administered IV, IM or per-rectum. Duration of action, dosing and time of onset can vary with the route of administration. Each Synthetic Cathinone has variable effects on neurotransmitters with differing potency and pharmacokinetics. Synthetic Cathinones create amphetamine-like effects such as tachycardia, hypertension and euphoria, but the most common effects include hallucinations, confusion, mydriasis, tremors and fever. Reported serious clinical effects include rhabdomyolysis, renal failure, seizures and even death. Synthetic Cathinones have been associated with fatal arrhythmias and ST-elevation. As with most designer drugs, there is not specific testing indicated in the management of Synthetic Cathinones, and testing should be directed towards the clinical symptoms. Despite the structural similarities with amphetamines, routine qualitative drug testing for amphetamines are typically negative. Even though benzodiazepines can be helpful in those patients presenting with extreme agitation, there is no specific antidote and the treatment should be goal-directed and supportive. 

Krokodil

Krokodil, Crocodile, Crok or Flesh-eating heroine, its a homemade, injectable, semisynthetic opioid, analogue of desomorphine. Desomorphine was first synthesized in 1932 and marketed for the treatment of postsurgical pain under the name of Permonid™️. It was removed from the US market in 1952 for being highly addictive. Desomorphine is a stronger analgesic and sedative when compared to Morphine, but has a faster onset and shorter half-life, which increases it’s addictive power. 

Krokodil was first reported in Siberia in 2002, where it  quickly spread throughout the urban centers of Eastern Europe, claiming on average 30,000 deaths a year. In recent years it’s use has started to appear in North America. The homemade production of Krokodil yields a liquid that it’s ready for consumption, instead a crystal form. Similar to heroin and morphine, it can be used IV, IM or PO. The homemade production of Krokodil is a very crude process were codeine tablets are boiled in paint thinner, ethyl acetate or gasoline, as a diluting agent. The resulting mixture is a brown liquid which has a  strong acidic ph. Desomorphine is the main active opioid of this mixture, which has sedative and analgesic effects that  are 8 to 15 times stronger than morphine. The onset of action is 2-3 minutes with a short duration of 2 hours. Because of its short duration, frequent dosing is necessary, leading to binge patters that can last for days. Users can show addiction effects 5-10 days after their first use. For those addicted, death typically occurs within 2-3 years. The Krokodil substance is an impure contaminated liquid with high concentrations of toxic and corrosive chemicals. Upon injection it causes ulcers, phlebitis, green tissue discoloration and desquamation, resembling crocodile skin, which give the drug its name. Gangrene will ensue with repeated use of Krokodil. Amputation often occurs, even with aggressive IV antibiotics and wound care. The injection of Krokodil will also cause burst of  coronary arteries, septicemia, pneumonia and meningitis. The effects of Krokodil exposure are not limited to localizing injuries, but also causes neurological, endocrine and organ damage. In acute intoxication management, Krokodil responds will respond to naloxone. 

 It can be daunting for providers to keep up with the challenges of the new illicit designer drug market. Not only is there no specific testing for identification or antidote, but the clinical presentation can be different each time because the chemical composition is often changed to avoid legal detection. Providers must relay on their knowledge of the common drugs of abuse toxidromes and have a high index of suspicion to identify and manage these new designer drugs of abuse. 

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