It has long been a practice, particularly among street-level dealers, to "cut" cocaine with diluents in order to increase profits. In the past, cuts have commonly been fairly innocuous materials, such as lactose, mannitol, or niacinamide, chosen because they match the appearance of cocaine, or chemicals such as benzocaine, lidocaine, or procaine, chosen because they cause a localized numbing effect similar to that produced by cocaine. However, in recent years there has been an upsurge in the use of more pharmacologically active chemicals as cocaine adulterants, including compounds such as acetaminophen, atropine, caffeine, hydroxyzine, methylephedrine, diltiazem, methylphenidate (Ritalin), and phenacetin.^{[DEA microgram 2004] [Vroegop 2009] [Elias 2007]} One of the more concerning adulterants that has become increasingly prevalent over the last few years is levamisole, a pharmaceutical veterinary dewormer and a research immunomodulator.

Cocaine Adulterants

Acetaminophen (Paracetamol, APAP) Common analgesic and fever reducer, can cause liver damage at higher doses, particularly when combined with alcohol. Atropine (rare) Anti-muscarinic with various clinical applications. Severe adverse effects possible, including amnesia, disorientation, visual disturbances, ataxia, tachycardia, disturbed speech, difficulty swallowing, restlessness, urinary retention, psychoses, and coma at high doses. Caffeine Common stimulant. Cornstarch (rare) Used as a low-end adulterant. Easily detected and dangerous if injected. Diltiazem Calcium channel blocker used in cardiovascular disease. Can cause adverse cardiovascular reactions, fainting, vomiting, nausea, and diarrhea. Hydroxyzine Sedative, anxiolytic, antihistamine. Can cause dizziness. Lactose Milk sugar. One of the most common substances used over the last century to cut cocaine. Levamisole Anthelmintic (de-wormer) and immunomodulator, can cause nausea, diarrhea, and dizziness. Increasingly found in cocaine supplies, associated with cases of reversible immune system dysfunction. Lidocaine, Procaine Local anesthetics, used as cocaine diluents to mimic the numbing effect of cocaine. Can cause nausea, vomiting, dizziness, tremors, and convulsions. Lidocaine's presence in cocaine seems to be in decline. Mannitol (Mannite) A sugar alcohol and a diuretic that characteristically makes cocaine adulterated with it more sweet tasting. Methylephedrine A stimulant chemical. Phenacetin Analgesic and fever reducer, withdrawn by the U.S. FDA in 1983 because of possible carcinogenicity and kidney toxicity. Increasingly found as a primary adulterant in illicit cocaine. Acetaminophen is a metabolite of phenacetin. Quinine An odorless, bitter chemical used to cut cocaine and heroin. Dangerous when injected. Talc (magnesium trisilicate) A soft mineral, pharmacologically inert. Easy to detect and very dangerous to inject. References # Brunt TM, Rigter S, Hoek J, et al. "An analysis of cocaine powder in the Netherlands". Addiction. 2009;104(5):798-805. Gottlieb A. "The Pleasures of Cocaine". The Twentieth Century Alchemist. 1976.

Although levamisole has been a known adulterant in cocaine since at least 2002,^{[SAMHSA 2009]} on September 21, 2009, the U.S. Substance Abuse and Mental Health Services Administration (SAMHSA) made the surprising announcement that levamisole had been found in "over 70 percent of the illicit cocaine analyzed [by the DEA] in July. In addition, a recent analysis in Seattle, Washington found that almost 80 percent of the individuals who test positive for cocaine also test positive for levamisole."^{[SAMHSA 2009]}

Following the SAMHSA alert, the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) also sent out an email alert, which claimed that levamisole was found in over 50% of cocaine samples tested in the United Kingdom and the Netherlands during a period in 2009.^{[Ventura 2009]} Previous reports by the DEA and testing conducted by a number of other organizations had shown levamisole present in cocaine, but in a much smaller percentage of tested samples than reported by the DEA in August/September 2009. For example, in October 2008, the DEA reported detecting levamisole in 30% of the bricks of cocaine that they analyzed,^{[DEA Microgram Oct 2008]} and Health Canada reported 11% of cocaine samples from April to December 2008 were contaminated with levamisole.^{[Zhu 2009]}

Beginning in late August 2009, a surge of media stories warned about negative health effects and deaths associated with levamisole as a cocaine adulterant, with Google News showing 606 stories in September alone. The death of a popular DJ and Los Angeles club owner, Adam Goldstein "DJ AM", in late August kept the issue in the news because autopsy-related forensic toxicology results included levamisole among a long list of other drugs detected.

As a cocaine adulterant, levamisole is dangerous primarily because it suppresses the immune system of those who are exposed to it. It is also possible that levamisole interacts with cocaine's stimulant effects and increases acute cardiovascular toxicity, though this is still speculation based on levamisole metabolites (such as aminorex [Erowid Note: December 2010, new research suggests this hypothesis is wrong. See ¹.) that have been found to occur in horses. Such metabolites have not been confirmed in humans.

Though it has been used therapeutically in humans for decades, levamisole can cause agranulocytosis (acute neutropenia), a blood disorder characterized by the disappearance of certain types of white blood cells necessary for the proper functioning of the immune system. Agranulocytosis/neutropenia can result in a wide range of problems associated with a weakened immune system including infections throughout the body, high fever, chills, swollen glands, painful sores, and wounds that don't heal. Left untreated, the condition can result in death. Agranulocytosis can be treated if detected and diagnosed properly.

Because the symptoms of agranulocytosis can be so wide-ranging, because it is an unusual condition, and because levamisole contamination of cocaine is a relatively new problem, it is essential that those seeking medical care for a condition like high fever be honest with their health care providers about the illicit substances they have taken, in order to improve their chances of being diagnosed properly and recovering quickly.

It is likely that people whose immune systems are already compromised by disease or genetic background are more susceptible to the risk of agranulocytosis from levamisole exposure.

Levamisole's half-life in blood plasma is short, less than six hours, but its immune suppression can last much longer. This makes it difficult to positively diagnose that a patient's agranulocytosis is a result of levamisole exposure, as blood or urine tests may come back negative for levamisole even when immune suppression has resulted from levamisole ingestion. Medical centers are currently forced to rule out other causes of immune problems such as HIV (AIDS), leukemias, and parvovirus. If the patient admits to cocaine use or has used cocaine recently enough that levamisole is still present in their blood or urine, some tests for unlikely conditions may be avoided.^{[Babu 2009]}

As of Oct 1, 2009, there is no nationwide data on the number of cases of levamisole poisoning. Many health care providers are unaware of the problem, though poison control centers and the U.S. Centers for Disease Control are currently on the lookout for new cases.

For most pharmacologically active adulterants, the potential risks related to interactions with cocaine (and/or with each other) are unknown. Additionally, none of those compounds--when used medicinally in humans--are insufflated or smoked, and there may be increased risks based on such routes of consumption. A paper by Brunt et al. in 2009 analyzed data about street cocaine use in the Netherlands and found that "Adulterated cocaine was associated more frequently with reported adverse effects than unadulterated cocaine."^{[Brunt et al. 2009]}

Unfortunately, the nature of black market substances makes it difficult or impossible to be sure that any sample of street cocaine is free from adulterants.

The DEA's message is simply "Don't use cocaine; it's a dangerous drug",^{[Knierim, 2009]} a position criticized by those who see drug prohibition as the cause of the difficulties, similar to the problems associated with contaminated and low-quality alcohol during the U.S. alcohol Prohibition of the 1920s.^{[Sullum 2009]}

Levamisole is an antihelminthic (dewormer, anti-parasitic) used in large livestock and aquarium fish. Levamisole is also an antineoplastic (a drug that inhibits abnormal cell growth that can produce potentially malignant tumors) used in the treatment of colo-rectal cancer in humans. However, this use has been discontinued in the United States and many other countries. It acts on the central and peripheral nervous systems, and has cholinesterase inhibitory properties. Side effects from therapeutic doses of levamisole include nausea, diarrhea, dermatitis, taste perversion, fatigue, vomiting, arthralgia, infection, leucopenia,^{[PDR 1998]} and much more rarely agranulocytosis.

According to the DEA, levamisole--as well as other adulterants--is apparently present in some shipments of cocaine intercepted before they are broken up for further distribution to consumers. Considering that, in one batch, only 6% by weight of the total product sold as cocaine was levamisole, it seems possible it is more than simply a bulking agent. One theory is that levamisole or other adulterants boost the effects of cocaine, permitting material to pass for higher-quality product despite additional cuts made down the line. Another theory is that levamisole or other adulterants are added as chemical signatures used to track distribution of material.^{[Fucci 2007]} It may be that levamisole has been used because it has similar solubility properties to cocaine and therefore is difficult to remove and has not previously been considered a serious health hazard. As of October 1, 2009, there is no definitive answer as to why it is used as a cocaine adulterant.

Unfortunately, there is no currently available easy, on-site test to determine if street cocaine is adulterated with levamisole. DanceSafe.org has indicated that they are working on a field test that can be used, but it is not yet available. Thin Layer Chromatography (TLC) could be used by trained individuals to check for contaminants, but requires the use of lab standards and is therefore impractical for the general public.

As of September 2009, EcstasyData.org is accepting submissions of cocaine samples in capsules, which will be analyzed by a lab that can identify levamisole. Testing costs $120 per submitted sample, which must be paid by the submitter. Unfortunately, the DEA currently restricts testing and does not allow the lab to quantify the amount of contaminants in street drugs. So far, EcstasyData has received one cocaine sample, sent from Butte, Montana, which was found to contain levamisole. (Update: As of August 2017, 34 samples tested by EcstasyData have contained levamisole. The percentage of samples containing levamisole declined dramatically in January of 2016.)

Data from the following countries is not inclusive of all levamisole findings, but represents a brief survey of information available showing how widespread levamisole-tainted cocaine is.

AUSTRALIA # -- From 70 seizures, 59% of cocaine seized during 2005 and 2006 was of Colombian origin. Adulterants found included levamisole (10% of adulterated seizures), which was noted as the "most interesting" along with diltiazem and hydroxyzine, "as they had not been observed previously in border-level seizures of cocaine".^{[Australian Federal Police 2005/6]}

CANADA # -- Zhu et al. reported in February 2009: that, "Levamisole contaminated [...] 11% of cocaine samples tested in Alberta, Canada, from April to December 2008.".^{[Zhu et al 2009]} In January 2009, Alberta Health Services reported that the public health department had become aware of cases of agranulocytosis related to cocaine and levamisole. 67% of the cases were females, with the first confirmed case in August 2008, and the first "probable case" in April 2007. Following hospitalizations in Alberta, public health notices went out in several Canadian cities, warning about tainted cocaine and the symptoms to watch for.

COLOMBIA # -- Multiple batches of cocaine sourced from or tested in Colombia have contained levamisole. In February 2009 a Miami, Florida DEA lab tested a magazine page that was coated with a thick plastic "protective" covering that they determined contained cocaine and levamisole. The page had originated from Bogotá, Colombia.^{[DEA Microgram February 2009]}

FRANCE (& BELGIUM) # -- Samples in which levamisole was detected in 2004 were seized in Guyana, the Antilles, and a shipment coming from Venezuela. Système National d'Identification des Toxiques et Substances (SINTES) reported seizures of levamisole-tainted cocaine in Belgium.^{[OFDT 2005]} Their data shows that levamisole is a less common adulterant (present in only 11-12% of seized cocaine) than phenacetin, diltiazem, caffeine, and hydroxyzine, though it is slightly more common than lidocaine and procaine. All of these are showing up increasingly in adulterated samples, with the exception of lidocaine, which is waning.^{[OFDT 2008]}

GUYANA # -- In February 2009 a New York City DEA lab received 192 churros (fried pastries) that arrived at JFK Airport from Guyana. Each churro contained a plastic-wrapped cylinder of cocaine adulterated with levamisole.^{[DEA Microgram Feb 2009]}

ITALY # -- Italian seizures (published in 2007, without stating when analysis was conducted) showed "trace amounts of hydroxyzine and levamisole". It was not clear whether they were co-present.^{[Fucci 2007]}

JAMAICA # -- In April 2009 the DEA reported seizing two packages shipped from Jamaica to addresses in Chesapeake and Portsmouth, Virginia, that contained a total of 323 grams of material, containing cocaine, caffeine, and levamisole.^{[DEA Microgram Apr 2009]}

THE NETHERLANDS # -- The best data comes from a study published in 2009 that examined samples submitted for analysis to the Dutch Drugs Information and Monitoring System (DIMS) between 1999 and 2007. DIMS permits consumers to turn in material, provide information on what it was sold as and what its effects were, and receive results on the material's contents one week later. According to the Dutch research, 2004 was the year levamisole was first found as an adulterant, the same year it was detected in France and Belgium. The Dutch data shows an increase in the percentage of samples containing levamisole between 2004 and 2007 (from 0.6% to 11.6% of samples). Reported adverse effects were likelier in cocaine adulterated with diltiazem, hydroxyzine, and phenacetin. However, the diluents procaine and lidocaine, and the adulterants caffeine and levamisole, were not associated with a higher likelihood of adverse effects.^{[Brunt et al. 2009]}

SPAIN # -- During Summer 2009, the risk reduction group Energy Control detected levamisole in two samples of cocaine that came from Granada, a province in the south of Spain.^{[Ventura 2009]}

SWITZERLAND # -- Two cocaine samples from Zürich subject to quantitative analysis by the harm reduction group Safer Clubbing Switzerland found: 1) cocaine (51.8%), phenacetin (44.2%), and levamisole (3.3%), and: 2) cocaine (21.6%), phenacetin (41.9%), levamisole (3.3%), and caffeine (0.5%).^{[Ventura 2009]} A Swiss harm reduction group reported in private communication to Erowid that they are commonly testing for levamisole in 2009 and are seeing around 75% of the cocaine they test adulterated with levamisole, though it only constituties 3-4% of the total mass of "cocaine" powder. They report that phenacetin is even more common and often makes up 30-50% of the powder sold as cocaine. This group first found levamisole in cocaine samples in 2008.^{[Buecheli 2009]}

UNITED KINGDOM # -- Levamisole was first detected in the United Kingdom in April 2005; it was found in cocaine-positive urine collected from deceased individuals.^{[Morley et al. 2006]} Fourteen such cases between 2005 and 2006 were examined; 13 of the decedents were male and "known drug abusers". At the time, the researchers had personal-communication intelligence about levamisole-contaminated cocaine seizures in Australia, Europe, and North America. Over a period of one week, when the researchers were collecting urine samples among people in rehab, of those who tested positive for cocaine, no levamisole was detected in the urine samples.

UNITED STATES # -- Data regarding the first appearance of levamisole in cocaine, as reported by the DEA, is not entirely clear. In a 2008 paper, a graph shows April 2005 as the first year that levamisole is present in "Cocaine HCl Bricks".^{[Casale et al. 2008]} However, a 2005 paper refers to material analyzed "over approximately the past two years" and "containing various amounts of levamisole", which could refer to samples analyzed as early as 2003.[Valentino et al. 2005] The September 2009 SAMHSA report suggests that the DEA had been detecting levamisole as early as 2002. In Delaware, as early as September 2005, it was mentioned that there had been fatalities "from this drug as well as from crack".^{[Delaware Health Alert Network 2005]}