A quarter of a century ago, it was relatively easy to stay current on drugs of abuse. Things rarely changed. When I started practicing in 1985, the major drugs available on the street had been the same for many years: Opiates, cocaine, and phencyclidine (PCP) being the mainstays. These had all been around for decades if not centuries, and they had all been used in medical practice. Extensive scientific literature — clinical and experimental — described their kinetics and toxicologic effects.
Salvia divinorum...Image Tools
Now all that has changed. While many hospitals still see plenty of cases of opiate and cocaine toxicity — and PCP seems to be making a comeback in some locales — there is a rapidly evolving group of new substances showing up in emergency departments in North America and Europe. These drugs have strange names that are still unfamiliar to many practitioners: Bromo-Dragonfly, 2C-B, mephedrone, K2, and salvia. New ones seem to pop up every few months. They are often manufactured in laboratories in distant parts of the world, and sold over the Internet as “plant food” or “research chemicals.”
Besides scattered case reports, there is scant scientific literature describing many of these agents, and most likely there will never be much more. Because the pace of manufacturing and marketing new street drugs is so accelerated, by the time good studies are completed and published, entirely new compounds will have supplanted the old ones. Increasingly, instead of looking to PubMed and the medical journals for information on current drugs of abuse, the curious physician must consult drug culture web sites such as Erowid (www.erowid.org) and NeuroSoup (www.neurosoup.com), which often have up-to-date information on even the newest agents. Although I will review some of the more recent drugs of abuse to emerge, be warned: By the time you finish reading this article, even newer drugs such as NRG-1 and naphyrone will have appeared. The effort to keep on top of them, both medically and legally, is endless.
Bromo-Dragonfly (BDF) is a phenethylamine derivative first synthesized just more than a decade ago in a laboratory at Purdue University in Indiana. It was intended as a laboratory agent to study the role of specific serotonin receptors. Although it has no known medical or industrial use, BDF is now sold over the Internet, where it is often labelled as a “plant food” or “research chemical.” Its effects can be devastating.
Bromo-Dragonfly got its nickname because its structure (see figure 1) resembles that of a giant insect; the two five-sided dihydrofuran rings being the wings, the six-sided benzene ring the body. Like many phenethylamines, BDF has a high affinity for the 5-HT2A serotonin receptors, and is a potent hallucinogen. It is also an alpha-1 agonist, capable of causing intense peripheral vasoconstriction, limb ischemia, and most likely, coronary vasospasm.
Although the toxicology of BDF has not been well studied, limited data and anecdotal reports seem to indicate that the drug is remarkable for its delayed onset to peak effect (up to six hours), and its prolonged duration (up to several days). Five cases have been reported in the literature, two of which resulted in death.
In the first case, an 18-year-old man experienced hallucinations after ingesting BDF and snorting an unknown white powder. Eight hours later, he became increasingly agitated, and was taken to an emergency department, where he had four seizures, and was found to be hypertensive and tachycardic. After treatment with lorazepam, the seizures ceased. The patient developed aspiration pneumonia, but was discharged on the fourth hospital day. Serum and urine drug tests were positive for BDF, ketamine, and cannabinoids. (J Med Toxicol 2009;5:226.)
This case illustrates the delay to peak effect that has been reported with BDF. Seizure activity and increased hallucinations did not occur until eight hours after ingestion. The authors argue convincingly that ketamine would not have caused these effects.
In another case, a 35-year-old man and his friend consumed Bromo-Dragonfly one evening. The next morning, the man was found by his brother to be markedly confused. The friend was dead. On arrival at the hospital, the patient had cold extremities and dilated pupils. Seizure activity was controlled with diazepam. Over the next several days, he developed hepatic insufficiency (thought to be ischemic) and increasing peripheral ischemia resistant to vasodilators. He eventually required amputation of all distal phalanges of his left hand. Urine drug tests confirmed the presence of BDF. (Lakartidningen 2008;105:1199).
This case vividly demonstrates the intense and catastrophic vasoconstriction that can be caused by BDF's alpha-1 adrenergic properties. Google images has horrifying photographs from the article documenting the extent of injury to this patient's left hand. (http://bit.ly/BromoHand)
Nexus (2C-B) is a synthetic phenethylamine that has appeared under a number of other street names, including Bees, Venus, Erox, Performax, Toonies, and Bromo mescaline. It also has been sold by dealers claiming it was Ecstasy. Supplied as white powder or a tablet, 2C-B is usually ingested or snorted. Nexus acts as an agonist at both the alpha-1 and 5-HT2 receptors. It apparently lacks any anesthetic properties because snorting the powder is reported to cause intense nasal pain lasting up to half an hour.
According to the National Drug Intelligence Center, Nexus causes euphoria, increased visual and tactile sensations, relaxation, synesthesia, and hallucinations that can range from mild to terrifying, depending on the dose. Onset occurs approximately 30 to 90 minutes after ingestion, and lasts four to eight hours.
Little reliable scientific literature details the effects or toxicology of Nexus. A recent paper from the University of California-San Francisco describes a 43-year-old woman who developed persistent neurological deficits, including encephalopathy and quadriparesis, after ingesting a liquid she was told contained 2C-B made from a recipe found on the Internet. Two days after ingestion, she experienced a severe pulsatile headache and mental status deterioration, followed by progressive weakness and hyperreflexia denoting upper motor neuron impairment. Extensive workup revealed cerebral infarction in watershed areas and diffuse focal narrowing of small, medium, and large cerebral vessels, but no evidence of infectious or autoimmune etiology. Unfortunately, no testing was done to confirm the presence of 2C-B, so it is not clear what drug or drugs (if any) caused her severe neurological manifestations. (Neurologist 2010;16:199.)
I could find very few scientific articles investigating the effects of 2C-B. For what it's worth, a paper from Auburn University in Alabama observed that feeding 2C-B to one-day-old chickens produced tremors and what was described as a very rigid, penguin-like posture. (Pharmacol Biochem Behavior 1995;51[2-3]:473.) Make of it what you will.
Mephedrone (4-methylmethcathinone; figure 2) is a relatively new arrival on the street-drug scene, having first appeared two or three years ago. It was recently banned in Great Britain, but is still unscheduled in the United States. According to Erowid, street names include Meow, Drone, Bubble, M-Cat, and Milton Keynes (when combined with ketamine). Mephedrone has a structure similar to cathinone (Khat).
Anecdotal reports suggest that mephedrone is a potent sympathomimetic agent, causing intense peripheral vasoconstriction. Many accounts describe anxiety, panic attacks, and paranoia after using mephedrone. Heavy use is reported to cause severe hallucinations. One media report — most likely apocryphal — mentions a user with hallucinations so bizarre that he ripped off his own scrotum. Fatalities have been reported from mephedrone use, although any cause and effect is not yet clear. The drug seems quite addictive.
A recent case report from Britain describes a 22-year-old man who purchased 4 g of mephedrone powder online. After ingesting 200 mg without producing any effect, he injected 3.8 grams into his thighs and quickly developed palpitations, chest pressure, and diaphoresis. On arrival at the hospital, he exhibited straightforward signs of sympathomimetic syndrome, with tachycardia (105 bpm), hypertension (177/111 mm Hg), and dilated pupils. He received 1 mg of oral lorazepam, and was discharged six hours after presentation. Urine and serum were both positive for 4-methylmethcathinone. (J Med Toxicol 1 April 2010 [epub].)
Back in the 1990s, a lab at Clemson University in South Carolina synthesized a number of cannabinoid analogues to facilitate research into the different types of cannabinoid receptors. The research led them to conclude that there were two major receptors: CB(1), found mainly in the central nervous system and responsible for the psychotropic effects of marijuana, and CB(2), found in T-cells, macrophages, and other parts of the immune system. “Street chemists,” possibly following recipes in the papers published by the Clemson group, cooked up some of these analogues, and used them to lace herbal mixtures and tobacco that were sold under such names as “K2” and “spice.”
While K2 has been banned in Missouri and in the military, it is still legal in many parts of the United States, and is readily available for purchase especially around college campuses. Little is known about the clinical effects of these analogues because the few scientific articles that have discussed them deal mostly with laboratory analysis. There are some reports that the psychotropic effects of K2 are much stronger than those usually associated with cannabis. One Missouri state representative who supported banning K2 opined, “This isn't Jerry Garcia's marijuana.”
By the way, a recent paper in the International Journal of Obesity studied the use of taranabant, a CB(1) antagonist, as a weight loss aid. (16 Feb 2010 [epub].) The paper reported that groups on varying doses of taranabant lost more weight than controls. Unfortunately, the study had to be stopped because of dose-related adverse effects, including dysphoria, depression, anxiety, and suicidal ideation.
Salvia divinorum is a perennial plant in the mint family used for centuries by the Mazatec Indians of Mexico in shamanistic rituals and divination ceremonies. The active ingredient, salvinorin A, causes vivid hallucinations, and is unique among hallucinogens because it does not contain nitrogen and does not affect the 5-HT2A serotonin receptor. Rather, salvinorin A selectively stimulates kappa opioid receptors found in the brain and spinal cord. Along with hallucinations, salvia also produces spinal anesthesia. Pretreating with naloxone can block both effects.
Although an amendment to the Controlled Substances Act was proposed in 2002 to make Salvia divinorum a Schedule I drug, it did not pass. While some states have passed statutes making possession of the herb against the law, S. divinorum is still legal in many parts of the country and readily available for purchase in a variety of outlets. Effects are usually short-lived, and there have been no reports in the medical literature of significant toxicity or fatalities. Searching YouTube using the term “salvia” will retrieve a large number of clips showing young people smoking what purports to be Salvia. Usually they laugh hysterically and seem to be experiencing visual hallucinations for six to eight minutes, after which time all overt effects suddenly disappear.
Dr. Gussow is a voluntary attending physician at the John H. Stroger Hospital of Cook County in Chicago (formerly Cook County Hospital), an assistant professor of emergency medicine at Rush Medical College, and a consultant to the Illinois Poison Center. He is also the editor of his own blog, The Poison Review (www.thepoisonreview.com).
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