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What Are Designer Drugs and Legal Highs?
The terms “designer drugs” and “legal highs” are used to refer to substances such as synthetic marijuana and “bath salts” that are engineered in a laboratory to recreate or simulate the effects of traditional illicit drugs such as amphetamines, ecstasy, lysergic acid diethylamide (LSD), marijuana, ketamine, and others. Because their chemical structures are different from the drugs they are intended to mimic, designer drugs frequently escape regulation, making them easier to obtain by users.
Although encompassing a wide variety of substances with many different effects, designer drugs share a few general characteristics including:
- Opaque or misleading labeling information.
- Inconsistent ingredients and dosages from batch to batch.
- A lack of scientific or medical data on their safety profile and health risks.
- Ceaseless tinkering with molecular structure, or chemical components to stay ahead of the law.
Why Are Designer Drugs Popular?
The recent surge in popularity of designer drugs is partly due to aggressive online marketing as well as several misperceptions about these substances. Some mistaken beliefs about these drugs are:1,2
- There are no legal consequences for using them.
- Drug screening tests are unable to detect them.
- They are relatively safe when compared to illicit drugs.
Some people are attracted by the implication that, in contrast to illicit drugs, there are no criminal risks for using these substances. However, there has been a significant legislative effort in the US and other countries over the last 5 years to close the legal loopholes exploited by the makers of designer drugs, and the legal status of specific chemicals can change very quickly.1
Designer drugs can also be an attractive choice for individuals concerned about being screened for drug use because of the belief that these compounds are undetectable by drug tests.3 Although there is usually a lag after new designer drugs become available before drug testing is adjusted to detect them, drug test manufacturers have become much more vigilant in trying to keep pace with the proliferation of new substances,4, and there is no longer any guarantee of avoiding detection.
Finally, studies have shown that there is a perception among the general public that “legal highs” are safer than illicit drugs simply because they are legal.5 This is a dangerous misconception, because almost none of these compounds have been tested for safety in humans, and many have been reported to cause dangerous, even deadly, effects in some users. For this reason, some researchers and medical experts take issue with the term “legal high,” and they instead encourage the use of terms like “novel psychoactive substances” (NPS) or “novel psychoactive drugs”.1
Why Are These Drugs Legal?
Designer drugs are so numerous that they are difficult to categorize, although 2 classes—synthetic cannabinoids (marijuana substitutes) and synthetic cathinones (amphetamine and ecstasy substitutes)—are the most common. It is this overwhelming, constantly evolving variety that makes regulating these chemicals so difficult.
In 2009, there were 2 synthetic cannabinoids and 4 synthetic cathinones identified in the US. This number rose to 54 different synthetic cannabinoids and 31 synthetic cathinones by 2012. Worldwide, there were 348 known designer drugs being sold to drug users in 2013 according to the United Nations.6
Since most of these designer drugs are chemically different from the illicit drugs they are mimicking, they are frequently not covered by drug laws. New rules and regulations must be written to prohibit each new drug, or related group of drugs. This has led to a cat-and-mouse game in which no sooner have governments prohibited the latest batch of legal highs than illicit chemists produce new compounds not covered by the laws.7
It is important for people to know the facts about so-called “legal highs” in order to make informed decisions about their use. The following pages will briefly describe the effects and dangers of several large classes of designer drugs:
- Synthetic cannabinoids.
- Synthetic cathinones.
- Designer hallucinogens.
- Other legal highs that are substitutes for ketamine and opiates.
Synthetic Cannabinoids (Marijuana Substitutes)
What Are Synthetic Cannabinoids?
Synthetic cannabinoids are substances created in a laboratory that mimic the high caused by smoking or otherwise ingesting the marijuana (cannabis) plant. They are available in 2 main forms:
- Sprayed on dried plant material to be smoked.
- In a liquid that can be used in e-cigarettes and other types of vaporizers.
Synthetic cannabinoids first became available in Europe in the early 2000s as herbal mixtures that were labeled “incense” or “potpourri” and sold in head shops and convenience stores. Internet posts by users reported cannabis-like effects when these products were smoked.
It was initially thought that these effects were due to the bioactive herbs in the mixes, including Leonotis leonurus (Lion’s Tail) and Pedicularis densiflora (Indian Warrior), which do contain psychoactive chemicals. However, laboratory testing soon showed that synthetic cannabinoids had been sprayed on the plant material and were responsible for the highs produced by these herbal mixes.8
Common Street Names for Synthetic Cannabinoids
As of 2013, there were more than 100 different synthetic cannabinoids identified by the United Nations Office of Drug Control being sold to drug users.9 The technical names for these chemical substances are strings of letters and numbers such as JWH-018 and WIN55-212-2 that are confusing and difficult to remember.
Because of this, as well as the fact that the drug packaging never specifies the precise chemical composition, the drugs’ technical names are not well known to people outside of scientific and legal professions. Instead, synthetic cannabinoids are frequently referred to by street names such as “herbal incense”, “synthetic marijuana”, or “fake weed”.10
They are also known by the hundreds of brand names under which they are sold, including:
- Black Mamba.
Are Synthetic Cannabinoids Legal?
The legal status of synthetic cannabinoids is murky and constantly changing. Although synthetic cannabinoids have been around for over 20 years, it was only recently that they became a concern as recreational drugs.
In the U.S., the first report of products laced with synthetic cannabinoids occurred in 2008 when U.S. Customs and Border Protection seized a shipment of “Spice” for analysis in Dayton, Ohio.11 Because most synthetic cannabinoids are chemically distinct from delta-9-tetrahydrocannabinol (THC), the most important psychoactive ingredient in marijuana, the chemicals found in Spice were not covered by existing drug-control laws.12
Researchers originally developed synthetic cannabinoids to study the effects of marijuana on the brain,13 and the few scientists who were aware that these compounds existed considered them tools, not potential drugs of abuse. As a result, the authorities were unprepared for the rapid rise in popularity of synthetic cannabinoids—it would be several years before any federal or state regulations for drugs were in place.
As word spread about the intoxicating effects of herbal incense and potpourri mixes, their popularity increased rapidly, and websites marketing and selling synthetic cannabinoids proliferated. In 2010, the state of Kansas and the US military banned several specific compounds found in Spice and K2.14
In 2011, the Drug Enforcement Administration (DEA) placed a specific synthetic cannabinoid, called JWH-018, and 4 related drugs under Schedule I control. This rule made it illegal to manufacture or possess these compounds or any product that contained them.12
Although specific chemicals found in the original Spice formulations are now illegal, and new rules are being issued regularly to update the list of prohibited ingredients, the number of synthetic cannabinoids available is exploding. Only 2 new synthetic cannabinoids were found in 2009; in contrast, a total of 51 were identified in 2012.11
Each of these new compounds, if its chemical structure is sufficiently different from previously banned substances, requires a new rule to be issued before it can be declared illegal. Therefore, manufacturers in China and elsewhere are constantly tweaking and changing these drugs in order to stay one step ahead of the law and sell their products without repercussions.
Recent Research on Synthetic Cannabinoids
Marijuana is by far the most popular illicit drug in the United States, with 115 million Americans aged 12 or older having used it at least once in their lives.15 It is, therefore, unsurprising that marijuana substitutes enjoy a high level of popularity as well.
Besides the greater ease of obtaining synthetic cannabinoids due to their ambiguous legal status, these products are also less likely to be discovered by standard drug screening and may be perceived as safer due to their unregulated availability. Some recent statistics about synthetic cannabinoids include:
- The Monitoring the Future survey on adolescent drug use revealed that in 2011, the year that synthetic cannabis was banned by the DEA, 11.4% of US12th graders had used the drug in the previous year. This made it the 2nd most popular illicit drug among this age group behind marijuana.16
- The number of emergency room visits that involved synthetic cannabinoids increased from 11,406 in 2010 to 28,531 in 2011.17
- According to the United Nations Office on Drugs and Crime, over 50% of all new designer drugs identified between 2009 and 2013 were synthetic cannabinoids.9
- In the US, the largest group of synthetic cannabinoid users is composed of men aged 13-59 years who have a history of marijuana and other drug use.13
Natural cannabinoids, such as THC, and synthetic cannabinoids both cause their mental and physical effects primarily by binding to cannabinoid receptor 1 (CB1) on nerve cells in the brain and body. The major difference between THC and the chemicals found in herbal incense is how strongly they bind these CB receptors.18
For those synthetic cannabinoids that have been tested, the results have shown them to be between 2 to 100 times more potent than THC.13 The fact that the specific cannabinoids used in the earliest Spice products, such as JWH-018 and WIN55-212-2, were the ones that had been shown by scientists to bind CB1 receptors the best suggests that illegal drug manufacturers were searching scientific journals for information to help them decide which compounds to make and sell.19
Because of this greater potency, or increased binding affinity at the CB receptors, synthetic cannabinoids produce effects similar to marijuana, but with much greater intensity. Marijuana also contains cannabidiol, an ingredient that reduces anxiety, while synthetic cannabis products do not.20 This lack of built-in anxiolytic, or anxiety-quelling properties may help explain why Spice use sometimes leads to agitation, aggression, and anxiety more often than marijuana.21
What Are the Effects of Synthetic Cannabinoids?
Because there are so many different types of synthetic cannabinoids, and because none of them have ever been tested in controlled, clinical trials, it is difficult to know precisely how they will affect people after short- and long-term use. Indeed, because labels on products like Spice do not disclose their chemical ingredients or dosage, users are invariably taking a chance with their health whenever they use these drugs.
By using data from animal studies and individual case reports of human users, however, some general conclusions can be drawn regarding the use of synthetic cannabinoids. Many of these effects are similar to those caused by ingesting or smoking marijuana:8
- Euphoric high.
- Increased relaxation.
- Conjunctival injection (red eyes).
In addition to these effects, there are dangerous side effects specific to synthetic cannabinoids. These are largely due to the comparatively high potency of these substances, and are possibly manifestations of other unstudied chemical differences between the synthetics and standard marijuana. These effects are primarily responsible for the many emergency department visits due to Spice use and include:12
- Increased blood pressure.
- Extreme anxiety and agitation.
- Nausea and vomiting.
Serious Complications From Synthetic Cannabinoid Use
The lack of clinical trial data about synthetic cannabinoids and their short history of abuse mean that determining long-term effects is difficult. Although most side effects subsided after 1-2 days, some more serious effects have been reported, including:13
- Heart attack.
- Ischemic stroke.
- Acute kidney injury.
Dangerous psychiatric effects have been reported as well, including episodes lasting for weeks or months:13
- Thought disorder.
- Suicidal thoughts.
Dependence and Addiction
Finally, addiction to synthetic cannabinoids has been reported after a prolonged period of regular use and is characterized by withdrawal symptoms similar to marijuana including:22,23
- Disturbed sleep and vivid dreams.
- Muscle twitching and cramping.
Synthetic Cathinones (Stimulant Substitutes)
What Are Synthetic Cathinones?
Synthetic cathinones, commonly known as “bath salts,” are chemical derivatives of cathinone, a stimulant found in the khat plant (Catha edulis).24 These substances have fallen under recent scrutiny, as many of the designer drugs available today are synthetic cathinones—including some of the most popular legal highs.
Synthetic cathinones are sold as substitutes for illicit psychostimulants such as methamphetamine, cocaine, and ecstasy. Like synthetic cannabinoids and other common legal highs, synthetic cathinones are sold online, in head shops, and in convenience stores. These drugs are available in powder or crystalline form and can be eaten, insufflated (snorted), or injected.
Some of the more common synthetic cathinones include:
- Methylenedioxypyrovalerone (MDPV).
- ?- pyrrolidinopentiophenone (?-PVP).
In total, there are over 50 different synthetic cathinones that have been identified by law enforcement and health agencies around the world.
Common Street Names for Synthetic Cathinones
Synthetic cathinones are sold in packaging intended to avoid drug control laws by being labeled as “bath salts”—the most common street name for these chemicals. Other terms used on the labels to obscure the purpose of these substances include “plant food” and “jewelry cleaner”.24
Synthetic cathinones can also be found on the online market, and otherwise sold under dozens of brand names, including:
- Cloud Nine.
- Ivory Wave.
- Vanilla Sky.
Finally, there are a number of street names for particularly popular and widely available synthetic cathinones. These names serve as much more memorable and marketable substitutes for the complex chemical names of these drugs:
- Mephedrone—“Meph,” “Meow-meow,” “M-Cat,” “MMC Hammer,” “Bubbles”.
- ?-PVP—“Flakka,” “Gravel”.
Are Synthetic Cathinones Legal?
Like other “legal highs”, the legality of synthetic cathinones is constantly changing. When they first appeared in the US a decade ago, neither the manufacturing of, nor the possession of, synthetic cathinones was illegal unless they were not intended for human consumption.25 This is the reason all legal highs are prominently labelled “not for human consumption” even though that is their only intended purpose.
After the emergence of mephedrone, MDPV, and methylone as recreational drugs, the DEA enacted temporary bans in 2011, prohibiting the manufacture, sale, or possession of these drugs. The Synthetic Drug Abuse Prevention Act of 2012 made the bans on mephedrone and MDPV permanent, and the Synthetic Cathinones Control Act of 2013 permanently prohibited methylone and 14 other synthetic cathinones.26
The problem, as with many designer drugs, is that as quickly as the authorities outlaw specific cathinones, clandestine chemists and laboratories continue to create new drugs with chemical structures that are not covered by current legislation.
As of December 2013, the United Nations Office of Drug Control reported that 54 different synthetic cathinones were being sold around the world.9 Over 80% of those substances had been identified after July 2012, indicating an explosion of new cathinones just as the new prohibition laws passed in the U.S.
Recent Research on Synthetic Cathinones
Synthetic cathinones have been around for a long time. The first research paper describing mephedrone appeared in 1929, and MDPV was first created in 1967. Recreational use of these stimulants, however, was not known until they were “rediscovered” in the early 2000s and promoted as legal substitutes for ecstasy.27
Most of what is known about how synthetic cathinones work has been gleaned from laboratory and animal studies. This is due to the fact that these drugs were never tested in controlled human trials before they appeared on the market.
Experiments in human cells have shown that synthetic cathinones work by influencing the levels of the monoamine neurotransmitters—an important group of brain-signaling molecules that includes dopamine, serotonin, and norepinephrine.28 Studies in mice and rats have shown that the way a particular cathinone affects the balance of these neurotransmitters determines whether they have effects that mimic MDMA, methamphetamine, or cocaine.29
Examples of each type include:
- MDMA-like: mephedrone, methylone.
- Methamphetamine-like: cathinone, methcathinone.
- Cocaine-like: pyrovalerone, MDPV.
There is a lot of concern about how widespread synthetic cathinone is among the general public, but reliable data are difficult to obtain. Some important statistics about these drugs include:
- The Monitoring the Future survey on adolescent drug use has shown that the use of “bath salts” among US 12th graders has declined from 1.3% in 2012 to 0.9% in 2014. This decline coincided with an increase in the number of high school seniors who perceive using bath salts to be dangerous, from 39% in 2012 to 49% in 2014.16
- NMS Labs, a private drug testing company, reported that in 2014, the top 3 cathinones detected in the bio-samples they screened were: ?-PVP, ethylone, and methylone.30
- Poison control center calls involving bath salts increased from 302 in 2010 to 6,136 in 2012.27
What Are the Effects of Synthetic Cathinones?
The effects of synthetic cathinones vary among the different drugs in this class but are broadly similar to other psychostimulants such as cocaine, methamphetamine, and MDMA. The intended effects sought by users include.27
- Euphoric high.
- Raised levels of energy and alertness.
- Heightened sense of empathy and openness.
- Increased libido.
The negative effect profile also overlaps with other, more commonly abused stimulants and includes signs and symptoms such as:
- Jaw clenching.
- Dilated pupils; sensitivity to light.
- Reduced appetite.
- Increased body temperature and sweating.
- Rapid heart beat.
- Agitation and aggression.
- Anxiety and panic attacks.
Most of the negative side effects listed above are relatively mild and generally resolve themselves within hours or days after taking bath salts. There are also more dangerous, even lethal, consequences reported in those who use these drugs, such as:29
- Heart attack.
- Liver failure.
- Respiratory arrest.
- Suicidal thoughts and self-harming behaviors.
- Long-term cognitive impairment.
Dependence and Addiction
It is important to note that there is no reason to believe that synthetic cathinones are less dangerous than the illicit stimulants they mimic. Just as methamphetamine and cocaine can produce dependence and addiction in individuals who abuse them, so can cathinones.
In some instances, the designer substitute may be more dangerous than the original drug. Ecstasy tablets, for example, often contain the cathinone mephedrone instead of MDMA because both drugs produce similar effects in users. Mephedrone, however, also induces strong drug cravings in people—a key characteristic of an addictive drug—while MDMA does not.31
Finally, although many cases of human dependence on synthetic cathinones have been reported, animal experiments have helped to shed more light on their true addictive potential. Two recent studies showed that rats exerted more effort to get MDPV and ?-PVP (flakka) than they did for methamphetamine—one of the more highly addictive recreational drugs known.32
These results indicate that synthetic cathinones—far from being safe alternatives to cocaine and other drugs—may be even more dangerous and addictive.
Designer Hallucinogens (Psychedelic Substitutes)
What Are Designer Hallucinogens?
Hallucinogens, also known as psychedelics, are drugs that change an individual’s perception of their surrounding environment. The physical sensations—such as sight, sound, and touch—may be experienced as unreal, dreamlike, or even frightening.33 Hallucinogens may also distort:
- The perception of time.
- The notion of self (ego).
- The ability to think rationally.
The original hallucinogenic drugs were derived from plants and fungi or their extracts. Some of these botanically derived substances include psilocybin, which is found in over 200 species of mushrooms, and mescaline, which is derived from the peyote cactus. The original man-made hallucinogenic drug was lysergic acid diethylamide (LSD) in 1938. Since that time, chemists such as David Nichols and Alexander Shulgin (known as the “godfather of ecstasy”) have created hundreds of similar drugs—each with their own range of hallucinogenic effects.
There are 3 main subgroups of hallucinogens:
- Phenethylamines (mescaline).
- Tryptamines (psilocybin).
- Lysergamines (LSD).
Despite their distinct chemical structures, drugs from all three of these groups act on the brain via their interaction with various serotonin (5-HT) receptors—ultimately eliciting quite similar and characteristic effects.34
Common Street Names for Designer Hallucinogens
There are a huge number of different designer hallucinogens available under various names. However, in the past several years, 2 drugs and their derivatives in particular have grabbed the attention of medical and legal professionals with their widespread proliferation on the illicit drug scene.
The first of these is a drug that has the technical name 1-(8-bromobenzo[1,2-b;4,5-b’]difuran-4-yl)-2-aminopropane hydrochloride. This chemical is popularly known as bromo-dragonFLY because its chemical structure resembles an insect. It was first created in 1998 at Purdue University in the laboratory of David Nichols as a tool for brain research. This drug is also called:38
The second currently widespread group of designer hallucinogens consists of 2-(4-chloro-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine and its derivatives, better known as 25C-NBOMe, 25B-NBOMe, and 25I-NBOMe. These drugs are sold on the street as N-bomb, smiles, 25C, 25B, and 25I. Some of these drugs—with reportedly lethal toxicities—are being sold as LSD to unsuspecting users.35
Are Designer Hallucinogens Legal?
Like other “legal highs,” designer hallucinogens fall into a complex and constantly changing legal grey area. Even though these drugs produce similar effects in users, they have very different chemical structures, which means that existing laws and regulations may not cover them. Further confusing the issue, individual states and the federal government can have different laws in place, making possession of some of these chemicals legal in one place, but subject to stiff penalties in another.
Take, for example, the NBOMe group of compounds—made illegal under an emergency ruling by the DEA in late 2013 following the deaths of 19 people from these drugs in the previous year. The drugs were promptly classified under schedule I of the Controlled Substances Act, placing them under the most stringent prohibition with drugs such as heroin and ecstasy.36 However, such emergency controls are in effect for only 2 years, leaving the future legal status of these drugs uncertain.
Recent Research on Designer Hallucinogens
Although synthetic hallucinogens are similar to previously known hallucinogens in that they primarily target 5-HT receptors in the brain, much remains unknown about these compounds, as little scientific study has been conducted on them. None of the designer hallucinogens have undergone controlled human trials, but a small number of animal and human studies have started to shed some light on these drugs.
Experimenters using rats to test bromo-dragonFLY found that it may be as potent as LSD, a drug with an effective dose in humans as low as 30 micrograms—an alarmingly miniscule amount considering its powerful effects.37 Additionally, users have reported that the onset of bromo-dragonFLY effects can be delayed by as much as 6 hours and then last as long as 2 to 3 days.38
An Internet survey of nearly 450 users revealed that NBOMe drugs produced more “negative” effects than either LSD or psilocybin.3 These negative effects include potentially life-threatening toxic reactions , as well as self-harming behaviors.
Such reactions may be especially dangerous in users who mistakenly believe they are taking LSD instead of NBOMes.35 When taken by mouth using blotter paper, NBOMes cause numbness of the tongue and mouth.36 This numbness can serve as a warning sign to those who believe they’ve taken LSD that they’ve taken something else entirely.
What Are the Effects of Designer Hallucinogens?
Designer hallucinogens produce effects similar to other, more conventional psychedelic drugs such as psilocybin and LSD although, depending on the exact drug taken, the duration of these effects can vary considerably. Some of these include:3,33,36
- Acceleration of thought.
- Time distortion.
- Increased empathy.
- Increased energy.
- Severe confusion.
- Rapid heart rate.
Despite these similarities, there are some distinctions between conventional psychedelics and synthetic hallucinogens. Unlike typical hallucinogens, users of NBOMes have reported depersonalization, or the loss of the sense of self,3 an effect more often reported in dissociative drugs, such as ketamine.
Although there is little experimental data about the toxic effects of synthetic hallucinogens, many severe reactions in users have been reported in the medical literature. Some of the most common of these include:3,38
- Raised body temperature.
- Kidney failure.
- Self-harming behavior.
Dependence and Addiction
Though in existence for many years, conventional hallucinogens have not been reported to produce withdrawal symptoms and they are typically seen as having minimal addictive potential, unlike other drugs of abuse.39 This is likely because their effects decline rapidly with frequent use, and they have little effect in the ventral tegmental area of the brain (the “reward center”).7
These facts make it unlikely that synthetic hallucinogens will elicit a progression towards chemical dependence and addiction. These drugs do have some effects and toxicities that distinguish them from conventional psychedelics, however, so it is possible that there is a danger of addiction from using them.
It’s also important to note that while hallucinogens have been shown to have relatively less addictive potential than some of the more classically thought of “drugs of abuse,” such as cocaine and heroin, people may still begin to manifest signs of compulsive drug seeking and using behavior with these substances—compulsions that can have a detrimental impact on an individual’s overall quality of life. One more fact to consider: users of synthetics will also often use them in combination with other more addictive substances and may ultimately be compounding the associated problems of another substance use disorder.
Other Popular Legal Highs—Kratom and Methoxetamine (Opiate and Ketamine Substitutes)
What Are Kratom and Methoxetamine?
The term “kratom” technically refers to a group of plants distantly related to coffee and gardenia plants, but in the West, “kratom” is used for one particular, Southeast Asian species of plant—Mitragyna speciosa.
Kratom has a history of use in Thailand and neighboring countries going back hundreds of years, either by eating the leaves or using them to make a tea, and it is used as a stimulant, a painkiller, and a remedy for opiate withdrawal. This plant has now emerged in the United States as a legal high available as chopped leaves for brewing tea or compressed into tablets. It is promoted on various websites as an herbal remedy for pain and self-management of opiate withdrawal.40
Methoxetamine is a dissociative drug or dissociative anesthetic, which are a group of drugs that are similar to hallucinogens because they can alter perceptions and cause visual and auditory hallucinations. Dissociative drugs differ from so-called “psychedelic” hallucinogens like LSD and peyote by causing a distinct feeling of detachment, or dissociation, from oneself and the environment.33
Dissociative drugs such as phencyclidine (PCP) and ketamine were originally developed as anesthetics. Historically, recreational abuse of these substances has been commonplace. Consequently, there is a demonstrated demand for ketamine-like designer drugs—like methoxetamine—that are unregulated and perhaps easier to obtain from the illicit market.
Common Street Names for Kratom and Methoxetamine
Because kratom is not a controlled substance in the U.S. and is sought by users for specific purposes like pain management, it is most often marketed under this name. Alternative street names listed by the DEA are:41
Now one of the most widely available designer dissociative drugs, an underground chemist in the United Kingdom claims to have created methoxetamine while trying to develop a safer alternative to ketamine.42 Common street names for this drug include:43
- Legal ketamine.
Brand names of legal highs containing this drug are:
Are Kratom and Methoxetamine Legal?
As with other classes of designer drugs, the legality of kratom and methoxetamine is highly dependent on specific national or state laws, and legal status can change very quickly as governments and regulatory agencies seek to keep up with the proliferation of these substances.
Kratom is not a controlled substance in the U.S., and so is not subject to drug laws. However, the U.S. Food and Drug Administration (FDA) issued an import alert for kratom directing shipments to be seized due to health risks to users.44
The United Kingdom banned methoxetamine in February 2013. It currently remains unregulated in the U.S., though it is illegal to manufacture, sell, or purchase it for human consumption.7
Recent Research on Kratom and Methoxetamine
Pharmacological studies on kratom have shown that there are more than 20 biologically active chemicals in this plant. Several of these bind opioid receptors in the brain, which may explain kratom’s reputed ability to ease opioid withdrawal.40
Methoxetamine has been shown to act in a similar way to other dissociative drugs like PCP and ketamine by blocking NMDA receptors in the brain to produce its effects.45 In a survey of people attending gay-friendly nightclubs in Britain in 2011, 6.4% of those who had ever used “legal highs” reported using methoxetamine at least once,43 and a drug testing company reported that in 2014 methoxetamine was detected in 6% of the samples testing positive for designer drugs.30
What Are the Effects of Kratom and Methoxetamine?
Though few scientific studies have been conducted regarding the effects of this plant, user reports confirm that it produces an unusual mix of stimulant and opioid-like effects, though effects depend both on the individual user and the dose taken.40
Low doses produce stimulant effects like increased alertness and energy, though not as strong as amphetamines, while pain reduction, and sedation predominate at higher doses. These effects are reported to be either positive and euphoric, or unpleasant, depending on the individual.
Negative side effects reported in users of kratom include:46
- Anxiety and irritability.
The self-reported effects of methoxetamine vary significantly, with descriptions from users ranging from “euphoric” to “worst fear” to “near-death experience”.42 In general, the common effects of dissociative drugs include:33
- Disorientation and confusion.
- Nausea and vomiting.
- Changes in sensory perceptions.
- Feelings of detachment from self and environment.
- Increase in body temperature and heart rate.
- Memory loss.
At high doses, or when mixed with other drugs, dangerous and sometimes deadly side effects may occur including:
- Intense fright or fear.
- Panic attacks.
- Cardiac arrhythmias.
- Respiratory distress.
There may also be risks from long-term use of these drugs. Regular users of ketamine are known to be at risk of ulcerative cystitis of the bladder, abdominal pain, memory decline, and psychosis.7
Dependence and Addiction
The fact that kratom contains opioid-binding chemicals and has opioid-like effects raises the possibility that it may share opioid drugs’ characteristic of being highly addictive.
In Southeast Asia, where there is a much longer history of kratom use, tolerance and addiction are well known and have led to the plant being outlawed in many of these countries.46 More recently reports have surfaced in the West of individuals showing compulsive, heavy use of kratom and tolerance to its effects, suggesting that this drug has a significant potential to cause addiction.40
Ketamine and PCP are known to produce dependence and addiction among users. Individuals who use ketamine frequently report binging on the drug, or being unable to stop using it until it is gone.7 Many users of methoxetamine report similar binging experiences, as well feeling a desire to use the drug again as soon as possible.42 Based on this evidence, it is reasonable to consider that the designer dissociative drugs have a similar, significant potential for addiction.
The Rise of “Legal Highs” Online
One major reason for the proliferation of designer drugs and legal highs over the last decade has been their easy availability in retail outlets such as gas stations, head shops, convenience stores, and adult stores; however, the exploitation of the Internet by both sellers and users has arguably been the most important factor behind the rise of these drugs.
Internet sales have become such an important source of drugs, both legal and illegal, that specific federal penalties now exist for drug violations involving this medium.
Among drug consumers, the Internet offers a way to share knowledge and experiences about newly emerging designer drugs, and several surveys have shown that the Internet is the most popular source of information about recreational drugs. Because of this, awareness and demand for new legal highs can spread widely and rapidly. Unfortunately, like Wikipedia and other repositories of crowd-sourced information, this information is often biased and potentially inaccurate.47
Online retail websites have taken advantage of consumer interest in these drugs. It has been found that merely having a readily available and easy-to-use website can instill feelings of safety and trust in potential consumers.48 Additional strategies used by such sites to promote sales include:47
- Appealing branding and names for products (“Spice”, “Vanilla Sky”, etc.).
- Periodic discounts and special offers.
- Use of mainstream payment and shipping methods.
- Privacy protecting software.
The Internet makes designer drugs easily available and gives the sale of untested and unregulated drugs a veneer of legality and legitimacy, and there are many challenges for regulators in confronting this problem. Websites make identification of drug suppliers difficult and are scattered across international borders. A study in 2014 found 31 unique websites selling “bath salts”. The top 3 countries hosting these sites were the U.S., Germany, and the United Kingdom.48 Faced with these numbers and conflicting laws in differing jurisdictions, these websites are likely to continue selling their questionable products for the foreseeable future.
Warning Signs of Designer Drug Use
Traditional drug testing is of limited use when it comes to designer drugs. The constant influx of novel substances into the market means testing technology always lags behind the most recent crop of designer drugs, and the sheer number of compounds available makes it impossible to devise a test that detects them all. Indeed, the ability to defeat drug testing is one of the most commonly reported reasons that people give for using designer drugs, especially those being supervised by the legal system, like parolees, and members of the military.3
Because drug testing is of limited use, designer drug abuse may first be detected as part of a routine physical and mental status examination. Symptomatology may be used to help support existing clinical suspicion, with signs that include:
- Raised body temperature.
- Red eyes.
Other signs indicating possible designer drug use include:
- The presence of paraphernalia (like pipes or rolling papers).
- Perfume or cologne (to mask the smell of smoke).
- Foil packaging for products labelled “not for human consumption”.3
Additionally, heavy designer drug users may start to show signs of substance dependence or addiction. These can include:
- Sudden change in friends.
- Loss of interest in previously enjoyable activities.
- Money problems.
- Becoming angry when asked about drug use.
- Difficulties at school or work.
Although labeled “legal,” these drugs are still dangerous. Toxic side effects caused by designer drug use may ultimately require hospitalization or treatment, and addiction to a “legal high” can be just as devastating to a person’s life as being hooked on an illicit drug.
Treatment for Designer Drug Abuse and Addiction
As discussed above, there have been many reports of medical complications in association with designer drug intoxication. Most physical toxic effects of these drugs generally wane within a few days as the drugs leave the user’s body.3
Although temporary, some of these physical effects can be dangerous—or even life-threatening. When in doubt, it will be important to seek medical attention for the affected individual to ensure their safety.
Of the drugs discussed, physical toxicities are most common in situations involving synthetic cannabinoid and cathinone use, and can bring about symptoms such as:13,27
- Nausea and vomiting.
- Shortness of breath.
- Blood pressure instability.
- Heart rate instability.
- Sweating and chills.
- Chest pains.
- Muscle twitches and spasms.
- Body temperature fluctuations.
Designer drug use can have serious mental health ramifications—ranging from the short-term (during the acute intoxication phase) through to more serious and long-lasting impact, even when the drug is not being used. A few of these problematic psychiatric effects include:
Sometimes, as with physical toxicities, time is the most important treatment, and keeping users in a safe, quiet environment with medical observation is sufficient. However, in more severe cases, medical intervention with sedative, anti-anxiety, and antipsychotic drugs may be required.3 For the most severe cases, prolonged inpatient treatment is sometimes necessary.
As with most other drugs of abuse, the sudden discontinuation of designer drugs after a period of regular, heavy use often produces symptoms of withdrawal. Inpatient treatment at a detoxification facility can assist users through this difficult withdrawal period by offering observation and support by medical staff.
Withdrawal from synthetic cannabinoids may result in physical symptoms similar to that experienced by withdrawing marijuana users—such as headaches and vomiting. These symptoms are not life-threatening and can be treated with anti-nausea medications and intravenous fluids.3
Withdrawal from all classes of designer drugs can elicit psychological symptoms seen to arise throughout the detoxification process of many different types of drugs including:
Addiction is a disease in which a person compulsively uses a substance despite negative impacts on their life such as losing a job, being arrested, or becoming estranged from friends and family. People who have a designer drug addiction face the same barriers to becoming well as individuals addicted to conventional drugs, including:
- Difficulty being honest with themselves or others about their problem.
- Lack of motivation to do something about their addiction.
- Difficulty overcoming the addiction without outside help.
The treatment of designer drug addiction presents unique difficulties for physicians and mental health professionals for several reasons:3
- The heterogeneous family of designer drugs encompasses substances with vastly different physical and mental effects, including cannabinoids, stimulants, and hallucinogens.
- Each individual designer drug has existed for only short periods of time—a few years on average—and has been used by relatively small numbers of people, so there are very little data about the best treatment strategies for each substance.
- The use of designer drugs is highest among young people and people who use multiple different drugs—both of these groups tend to have less successful outcomes in drug treatment programs than other patients.
- Many designer drug users have an intermittent, rather than continuous, pattern of use, so they may be less likely to recognize their drug use as a problem.
There are no medications available to treat designer drug addictions, but the most effective treatments are likely to be similar to those used for other types of drug addiction. Treatment of club drug addiction could provide a good template for addressing the needs of a young population using many different drugs.49
Common interventions used in many inpatient and outpatient drug treatment facilities include:
- Cognitive-behavioral therapy.
- Group and individual counseling; support group participation.
- Education—which can include learning new coping mechanisms, as well as relapse prevention strategies.
Following successful completion of a drug treatment program, sober living facilities and peer support (12-Step) groups can continue as effective aftercare measures to help those recovering from designer drug addictions to maintain abstinence and rebuild their lives.
Designer drugs are a relatively new and dangerous phenomenon in society. It is critically important to spread awareness of the dangers of these substances in order allow people make informed decisions about using them, and help those who have developed addictions to get the help they need.
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