Pat Pizzo, Director of Toxicology, Alere Toxicology Services


“Ladies and gentlemen, we’re at war,” Lance Dyer told an audience gathered for a community drug forum at Gwinnett Technical College in Lawrenceville, GA in December. “These are poisons,” he added, referring to synthetic marijuana. Dyer’s son Dakota, an otherwise successful and active teen, committed suicide after becoming a user of what was being promoted as a “new legal weed.”

Dakota’s tragic story is not the only one. In the last few years the public has become increasingly interested in a number of synthetic substances that mimic the affects of illicit drugs. Found online and in stores (as well as exchanged among friends and associates), these psychoactive herbs and chemicals come in many forms including what are known as “cannabimimetics,” so-called “designer drugs,” and plant material. They are not marketed as a means to getting high and are often labeled as herbal incense, plant food, or bath salts. Unfortunately, these substances are easily obtained, often smoked or ingested by people who think they are legal and safe, and carry with them serious and sometimes deadly consequences.

Cities, counties, states, and even the U.S. Drug Enforcement Agency (DEA) have enacted laws to prevent the retail sale and use of these products; however, the success of such laws as a deterrent is questionable. Many items containing synthetic marijuana and other mind-altering substances are still available online, and new compounds are regularly developed and marketed in innocuous ways.

The chemical structure of the molecules within these items can easily be altered to create different compounds with the same effects on humans. The term and concept of “research chemicals” was coined by some marketers of designer drugs. The idea was that the intent clause of the U.S. analogue drug laws could be avoided by selling the chemicals for “scientific research” rather than human consumption. People are still obtaining and using these highly dangerous products, and law and drug testing must hustle to keep up.


Cannabimimetics, often called Synthetic Cannabinoids or Synthetic Marijuana, are not new and are known to have the same affects on the brain as the active ingredient of marijuana – tetrahydrocannabinol or THC. Synthetic marijuana is most commonly marketed under brand names such as K2, Spice, MoJo, Black Mombo, Dragon Spice, and Yucatan Fire and in many other herbal incense blends where plant or herbal mixtures are sprayed with psychoactive chemicals. The plants and herbs include Blue or Pink Lotus water lilies, Lion’s Tail, Dwarf Skullcap, Indian Warrior, Siberian Motherwort, and Maconha Brava, which is also called “false marijuana.” Alone they have an effect on humans ranging from euphoria and relaxation to sexual stimulation, but when treated with synthetic cannabinoids they can create more intense or longer lasting highs. Often more than one synthetic cannabinoid
is added to the product. Available on the Internet as well as at head shops and gas stations, cannabimimetic products are sold as incense and labeled as “not for human consumption,” but people smoke and ingest them as a substitute for marijuana.

The active chemical compound in many of these products, JWH-018, was first synthesized in 1995 by John W. Huffman. It is only one of more than 470 synthetic cannabinoids and metabolites that have been prepared by Huffman and other scientists. Huffman is often quoted acknowledging the danger of smoking a product not intended for humans as a foolish action that could lead to death. “‘It’s like playing Russian roulette,” he is fond of saying in multiple sources. “You don’t know what it’s going to do to you.”

July 2012, President Obama signs Synthetic Drug Abuse Prevention Act, instituting a federal ban on 31 designer drugs. The original ban identified 15 synthetic marijuana drugs and 5 drug classes as Schedule 1 drugs. In May 2013, 3 new synthetic marijuana compounds were added to the emergency schedule 1 (temporary) ban by the DEA.

Synthetic Cannabinoids

What exactly are synthetic cannabinoids? They are a class of substances that are structurally diverse that bind to the cannabinoids receptors (CB1 and CB2) and produce similar psychoactive effects as cannabis. The synthetic cannabinoids actually show a greater affinity to the cannabinoids receptors than THC. This means the synthetic cannabinoids are often many times more potent than marijuana. HU-210, for example, is a synthetic marijuana compound thought to be 100-800 times more potent than THC.

The first synthetic cannabinoids compounds were identified in the United States in 2008. The Poison Control Center has been an excellent source to track the usage of the synthetic cannabinoids in the United States. Their data first showed a dynamic increase than a gradual decrease in synthetic marijuana use. Table 1
Table 1

As the chart shows, calls to poison centers have decreased. There are at least two possible explanations for this trend: first, decreases in overall usage related to heightened media exposure about the negative effects of these drugs combined with recent federal and state bans on the substances; and second, ‘chemists’ may have figured out relatively safer drugs to manufacture. Yet, a 2013 survey by the Center for Substance Abuse indicated that synthetic marijuana was the third most reported substance used by U.S. high school students in 2008—1-in-9 high school students admitted to using K2. Some users reported using synthetic marijuana to avoid a positive drug test and then admitted they returned to real marijuana use when not being subject to testing.

If we look at the choice of synthetic marijuana compounds used over the last three years it reveals a change in the popularity of certain compounds. In 2010, prior to the initial temporary ban of five compounds, the most popular brand was K2, which would typically contain any number of JWH compounds such as JWH018, JWH073 and JWH250. Very few brands of synthetic cannabinoids were available. In 2011, after the temporary ban was put in place, the selection of brands went from a few to a few hundred and the ingredients changed to compounds such as JWH081, JWH201, RCS4 and AM2201. In July 2012, the Synthetic Drug Abuse Prevention Act was signed identifying 15 synthetic marijuana compounds and 5 synthetic marijuana drug classes as Schedule 1 controlled substances. This created a 3rd generation of synthetic marijuana compounds and late 2012 brought the emergence of XLR-11, UR-144, AKB-48 and JWH122. As 2013 dawned the 4th generation of synthetic marijuana compounds emerged with active ingredients such as PB-22, BB-22 and 5F-PB-22. In May of 2013, the DEA passed a temporary ban on three additional synthetic marijuana compounds: UR-144, XLR11 and AKB-48, all 3rd generation compounds popular in 2012.

What will 2014 bring? With more than 450 compounds to choose from and the ability to develop new products, the list of possible compounds is nearly endless.

Effects on Users
How does the use of the synthetic marijuana compounds affect the user? Acute effects such as euphoria, sedation, nociception (the neural processes of encoding and processing noxious stimuli), perceptual distortions and appetite stimulation have been observed and documented. The duration of effects of the synthetic marijuana compounds is dependent on the specific compound chosen. Examples are listed in Table 2.

Table 2

Dr. Robert Kronstrand, SPFT WS9, Oct 2013 (1)
Synthetic marijuana compounds have been known to cause undesirable effects. Numerous researchers across the world have conducted studies or case reports of usage and found a variety of undesirable effects ranging from red eyes, dry mouth, appetite stimulation, thought disruption and sedation to sever effects such as hallucinations, delusions, aggression, arrhythmia, tachycardia, elevated blood pressure, nausea, vomiting, depressed locomotion and hypothermia (URL 44), kidney failure (XLR 11), seizures and loss of consciousness.

Research on the excretion patterns of the synthetic cannabinoids is limited because it is classified as “Not for Human Consumption.” De Jager published a study on one subject with a single intake of a synthetic marijuana compound and found the maximum excretion in the urine occurred approximately 2-3 hours after smoking and the maximum level detected was 10ng/mg.(2) Research in mice done by Poklis indicated the brain contained higher concentrations of JWH018 and JWH073 than the blood. (3)

Law, Legislators and Labs

Synthetic cannabinoids are here to stay. Law enforcement, legislators and laboratories will always be behind in providing information on these compounds. The producers of the illicit products can produce and publish information on the Internet at an alarming rate. Law enforcement must become aware of the new products and do a better job of lobbying legislators to pass laws. Even with the pressure the U.S. government received, it took three years to pass legislation making only 18 synthetic marijuana compounds and 5 synthetic marijuana drug classes Schedule 1 controlled substances.

Laboratories cannot test for all compounds. Before testing can be offered to clients a lab must acquire standards from a reliable source, develop methods and validate those methods. This process can require many months. If you wish to test for the synthetic cannabinoids be sure to check with your laboratory to learn what substances that lab can actually detect. Many labs offer immunoassay screening tests that will only detect 1st and possibly 2nd generation synthetic cannabinoids. Screening and confirmation with LC/MS/MS would offer detection of the largest number of compounds. Always check with your drug test provider to ensure you are knowledgeable on what compounds are actually being tested in both your screen and confirmation.

Designer Drugs
In addition to cannabimimetics, other chemicals being labeled as
“Designer Drugs,” including cathinone, piperazine, phenethylamines, and tryptamines, have become a major concern in the United States. In early 2000, a huge amount of designer drugs were sold over the Internet. To get around existing drug laws, chemists make designer drugs by modifying the molecular structure of a compound in an existing illicit drug or by finding new substances that mimic the affects of a currently illegal drug. They are manufactured and marketed as plant food or bath salts, and promotional material and packaging stipulate that they are not intended for human consumption. Yet, even at that people inhale or ingest them to gain stimulant effects similar to cocaine or methamphetamine. Just like cannabimimetics, these products can be purchased online or at convenience stores, truck stops, and head shops.

The most common chemical found in designer drugs is cathinone, and it can be used to make 43 other compounds by substituting elements in its structure. Cathinone is a plant native to West Africa, is usually chewed, and sells for $50 to $150 per plant. Designer drugs of this type have been recognized and banned in Australia and Europe for some time.

Mephedrone is one compound derived from cathinone and it is sold on the Internet as plant food. The effects of Mephedrone are similar to amphetamine and its use has been responsible for several deaths in the United Kingdom.

The most common derivative of cathinone, MDPV, is found in “bath salts.” MDPV mimics the effects of cocaine. Readily available in stores and online for $4 to $20 per package depending on the size, bath salts are snorted, smoked, or taken orally. The product package clearly indicates “Not for Human Consumption,” and the websites that sell these products have listed disclaimers such as:

“TERMS AND CONDITIONS: By entering the website of and ordering from you agree to our Terms of Service and use as expressed below. You also affirm and agree to the following: That you are 18 years of age or older. NO EXCEPTIONS!
Buyer agrees that any herbs, herbal blends, and or any other products on this site are legal to sell and/or purchase in your physical location or point of receipt of shipment. You agree to use our products for their intended purposes only. You waive without exception your right to hold Seller liable in any way for the misuse of Seller’s products.”

MDPV use can cause hallucinations, increased heart rate, seizures, paranoia, kidney failure, violent behavior, and death. Several fatalities in the United States have been directly linked to the use of MDPV, and the major abuse seems to be in the South and Midwest portions of the country. The Poison Control Center in Louisiana reported 234 calls concerning bath salts for the year 2010. In January of 2011, the same Poison Control Center reported 248 calls from 25 states concerning bath salts. More than 40 states have passed legislation to ban the use of bath salts. July 2012, President Obama signed the Synthetic Drug Abuse Prevention Act, instituting a Schedule 1 federal ban on two designer stimulant drugs and nine synthetic hallucinogens. MDPV and Mephedrone are the two designer stimulants.

Other Compounds

Other compounds not derived from cathinone are also considered designer drugs. Phenethylamines and Tryptamines are known as psychedelic amphetamines and have been around since the 1980’s. The DEA classified these as Schedule I; however, it has not stopped their use. Between 2004 and 2009, the DEA had 20 successful seizures across 13 states. Some of the main products in this classification are DOM, DOB, DOI, 2C-1,2C-B, and 2C-E. Europa, the common name of 2C-E, has recently been responsible for several deaths in the United States, and another product known as Bromo-Dragonfly has gained popularity on the West Coast. Another class of designer drugs that has been classified as Schedule I is Piperazine. The most frequently encountered derivatives of Piperazine are BZP, TFMPP, MDBP, and MeOPP.

Several of the drugs in the cathinone and piperazine family can be tested. At least one laboratory is testing for the following compounds: MDPV, Mephedrone, Bytylone, BZP, Cathinone, Ethylone, MBDB, mCPP, MDMA. MDEA, MDA, Methcathinone, TFMPP, and Methylone. The analysis is a screen by GC/MS, and a confirmation by GC/MS on a separate specimen.

Plant Material
A large number of plants will produce effects desired by individuals who wish to abuse drugs. Easily located and purchased through the Internet, Salvia Divinorum, also known as Diviner’s Sage, Ska María Pastora, or Seer’s Sage, is a psychoactive plant which can induce dissociative effects. It is a potent producer of “visions” and other hallucinatory experiences. The initial effect of Salvia Divinorum is believed to last for 2-5 minutes, but the after-effects can continue for hours. Several deaths have been attributed to the use of Salvia, and this plant has been banned in 17 states with 13 other states considering bans. It is legal for non-human consumption in four states, and legal for adults but illegal for minors in three states. One state has written legislation banning the manufacture, sale, or delivery of Salvinorin A, but possession of it remains legal.

Other plants as common as Kratom, Morning Glory seeds, Angel’s Trumpet, and Wormwood can produce the same effects as illicit drugs. Kratom, a plant native to Thailand and Malaysia, has been reported to have effects similar to both opiates and cocaine depending on the amount used. Morning Glory seeds when properly prepared have the active ingredient Lysergic Acid Amide (LSA) which acts as a psychedelic or hallucinogen. Angel’s Trumpet contains belladonna alkaloids, such as atropine and scopolamine, and acts as a hallucinogen. Wormwood is used to make Absinthe, and its active ingredient is Thujone. Thujone can cause effects such as disorientation, euphoria, and dreamlike states. The plant kingdom is very large, and we have just touched on some of the naturally occurring drug effects found in plants.

As indicated, many of these cannabimimetics, designer drugs, and plant materials used by recreational users to circumvent current drug laws have been made illegal themselves. In addition, laboratories are developing methods to detect these compounds for workplace
or criminal justice drug testing programs. Just as quickly as these products come into the recreational drug scene, governments and testing laboratories will have to address them.

Perhaps the biggest deterrent to the use of these substances is the danger involved in using them. User may think they are a safe and, in some instances legal replacement for illicit drugs without a clue regarding the potential deadly consequences. While the effects of the substances may be the same without the risk of punishment, anyone using a substance not intended for human consumption runs the risk of doing long-term damage to their health or ultimately ending their life.

Before being the Director of Toxicology at Alere, Pat Pizzo worked as a chemist in the Toxicology Lab for the Federal Bureau of Investigation in Washington, DC. She is a former member of the Federal Drug Testing Advisory Board, an Inspector for the National Laboratory Certification Program and the College of American Pathologist Forensic Urine Drug Testing Program, and Board Certified Forensic Examiner. She has been certified as an expert witness in Federal and State courts and has testified throughout the country.