Designer Drugs: A Significant Public Health Challenge
Author: Bertha K. Madras, PhD
What Are Designer Drugs?
Designer drugs (“club drugs”, “party drugs”, “synthetic drugs”) are structurally similar to, but not identical to, conventional illegal psychoactive drugs. The majority of designer drugs are illegal to possess or sell for human consumption.
Production of these drugs has rapidly expanded over the past decade, because of technological advances, devious and aggressive marketing schemes, and globally accessible Internet sites. They are sold inexpensively and marketed, for example, as innocuous “research chemicals,” “bath salts,” “plant foods,” “incense,” and “plants” on various websites.
Frequently, the sites are impervious to legal sanctions, because of the time it takes to deliberate the evidence and shift newly designed drugs into a legally restrictive zone. The designer drug industry is in a race to outpace existing drug laws and undermine routine clinical drug testing. Users may misperceive the drugs as legal (majority are not legal), less hazardous than conventional street drugs (the majority are highly intoxicating and hazardous), more challenging to detect, and easier to evade routine clinical drug testing. Even though standard strip tests do not identify most of these drugs, the drugs or their metabolites are effortlessly isolated from biological samples, including hair samples, and can be identified from body fluids or hair in laboratories with analytical techniques. A large number of new, unregulated substances are being abused because of their psychoactive properties, often resulting in violent and unpredictable behavior.
Designer drugs are produced in laboratories by chemists creating drugs that can mimic drugs legally restricted for distribution and possession. They share one common trait: producing psychoactive effects—cannabis-like, psychomotor stimulation, dissociative anesthesia, or hallucinogenic. Some are designed to mimic THC (tetrahydrocannabinol) of marijuana, cocaine, cathinone, amphetamine, methamphetamine, ecstasy, ketamine, LSD (lysergic acid diethylamide), methaqualone, while others create complex and different sensations because of their hybrid structures, and complex mixture of substances. Most fall into two categories, the cathinone-based psychostimulants packaged as “bath salts” and synthetic cannabinoids sold as “Spice” or “K2.”
Examples of stimulants include mephedrone, methylone, MDPV. “Spice” or “K2” can contain synthetic cannabinoids of different types, including JWH-018, JWH-073, CP-47,497, and cannabicyclohexanol. They may evoke psychoactive effects similar to the parent drug, or elicit a more amplified, unique or life-threatening response. Infrequently, new drugs are designed or discovered that have neither precedent in medicinal chemistry nor a long history of abuse (e.g., SalvinorinA), yet may possess equal or greater abuse potential or health hazards.
Most of these psychoactive drugs are derived and modified from plant products, with the majority concocted by changing or inserting a few or many more atoms into the core structures of legal or illegal drugs. Clandestine chemists mine old sources of information (scientific journal articles, patents) to produce these drugs, or at times create entirely new drugs from existing ones. Modifications can drastically transform the psychobiology of the parent drug.
Legal Status of Designer Drugs
In 2011–2014, the United States Drug Enforcement Agency (DEA), in response to health crises, exercised its emergency scheduling authority to control distribution of newly emerging designer drugs: mephedrone, MDPV, and methylone, marketed as “bath salts” and “plant food” or “fake marijuana” products, and others were placed under the Controlled Substance Act. These emergency actions were taken to prevent an imminent threat to the public safety. They made possession and sale of these chemicals, or the products that contain them, illegal in the United States. More than 43 states and the U.S. armed forces have independently responded to emergencies and crises by taking action to control or ban synthetic drugs, along with counties and municipalities.
Health Hazards of Unregulated Designer Drugs
The unregulated production and packaging of two or more chemicals is a major concern.
Laboratory analyses of over 100 different “K2” cannabinoids products and other “bath salts” submitted to the Arkansas Designer Drug Research Consortium identified the inclusion of over 200 distinct chemicals in over 40 different combinations, including the cathinones MDPV, methylone, mephedrone, as well as caffeine, lidocaine, methamphetamine, levamisole, benzocaine, and synthetic cannabinoids.
There is no oversight of the manufacturing process, safety, purity, or other standards routinely imposed by the FDA. Without quality assurance and with deceptive labeling practices, compounds vary from product to product, from batch to batch and even contain “hot spots” within each packet. These untested multiple drugs in a single package are a great health risk to users, confuse emergency department physicians, and make it difficult if not impossible for the medical community to identify the key drugs that cause physical and mental distress in patients and to select effective antidotes.
The long-term physical and psychological effects of these products are unknown, but potentially severe, especially in our most vulnerable populations, teens and young adults. Regulatory oversight and control is based on the following considerations:
- Emergency room mentions of designer drugs (and deaths) from Poison Control Centers and from single case reports from physicians have escalated in recent years. These occurrences represent a significant public health and safety issue that requires regulatory intervention.
- The acute biological and behavioral effects and long term consequences are poorly understood: erring on the side of caution is sound public health policy. We do not know how they will react in the presence of other drugs in the body, what potentially toxic contaminants are in the marketed mixtures, what treatments for overdose crises or addiction are effective. Approved pharmacological antidotes do not exist and their projected biological targets can be far off the mark for the majority of these drugs. An extended period of time is needed before scientific evidence and public perception/use synchronize.
- The production of these “research chemicals” in clandestine laboratories precludes regulatory oversight on quality control. Designer drugs do not fulfill any of stringent criteria used in production of purity for pharmaceuticals, with no assurances that these compounds correspond to the ones “marketed.” With no legal standing and regulatory oversight, even if claims or documentation are produced for drug purity or quality, there is absolutely no guarantee that claims accurately reflect the quality of the material. Without regulatory oversight, individuals’ adverse responses to the drugs generally emerge only during crises, with critical information gleaned from emergency rooms, physicians, and surveys rather than from controlled clinical trials.
The drugs most found in “bath salts” are substituted cathinones, derived from the chemical in Khat.
“Bath salts” are disguised as plant foods, insect repellent, bath salts, stain removers, and sold under brand names, and as powders. Cocaine- and amphetamine-like psychostimulant drugs of abuse, mephedrone, methylone, and pyrovalerone analogs, including MDPV, and naphyrone are some of the constituents in “bath salts.”
Clinical symptoms reported by healthcare providers involve the majority of organ systems: psychiatric, neurological, gastrointestinal cardiac, pulmonary, renal, eyes, ear, nose, and throat. These drugs may produce psychostimulation, “empathic responses,” chest pain, increased blood pressure and heart rate, agitation and life-threatening cardiovascular crises, aggression, dizziness, memory loss, seizures, blurred vision, anxiety, hallucinations, depression, dysphoria, euphoria, fatigue, increased energy and decreased concentration, panic, extreme paranoia, and delusions. Other reported effects include palpitations, shortness of breathe, chest pain, dry mouth, abdominal pain, anorexia, vomiting, erectile dysfunction, discoloration of the skin, and muscular tension.
There is no consistent information on the addictive potential of these drugs, but based on the structures, their resemblance to amphetamines and cathinones and modes of action, it is likely that most will have addictive potential. Indeed frequent users report intense cravings tolerance, dependence, and strong withdrawal. According to the American Association of Poison Control Centers, bath salts exposure calls totaled 9,702 between January 1, 2010, and July 30, 2013, with most exposures (64 percent) occurring in the Midwest and Southeast regions.
“Spice” or “K2”—Synthetic Marijuana
“Spice” and “K2,” commonly called “herbal incenses,” are plant materials infused with synthetic cannabinoids and sold as “legal” alternatives to marijuana. When smoked, they mimic some of the effects of the psychoactive component of marijuana delta-9-tetrahydrocannabinol or THC. The popularity and abuse of these substances and associated products has spread rapidly since 2008.
These synthetic cannabinoids originally were confined to a few compounds, (e.g. JWH-018), but others rapidly followed. JWH-018, JWH-073, JWH-200, CP-47,497, and cannabicyclohexanol have been found alone or laced on products that are marketed as herbal incense. Easy access, undetectable by routine testing and a misperception that Spice is “natural” and harmless, have all fueled their use. “K2” and “Spice” are marketed as “herbal smoking mixtures,” “incense,” “herbal blends,” “air freshener,” and designated “not for human consumption.”
Most exposures (58 percent) occurred in the Midwest and Southeast regions. Numerous state public health departments, poison centers and private organizations have issued warnings on the dangers of synthetic cannabinoids. According to the American Association of Poison Control Centers, calls related to synthetic cannabinoids use totaled 16,923 between January 1, 2010, and July 30, 2013. Anecdotal self-reports, case reports and series suggest they are abused for their hallucinogenic effects.
Little is known about both the short- and long-term health effects of consuming these cannabinoids products, how long they stay in the body, long-term consequences, or toxicity. Their potential health risks may be as, or more serious than those associated with marijuana. As they bind strongly to their targets (more so than THC or endocannabinoids), they may produce severe psychotic effects (anxiety, paranoia, hallucinations), heart attacks in the vulnerable, along with other symptoms uncommon with marijuana: seizures, high blood pressure, and vomiting. Some of the metabolites of these compounds do not activate cannabinoids receptor signaling, but prevent it, causing the opposite effect of endocannabinoids or marijuana.
With evidence of abuse and adverse health effects on a national scale, state public health and poison centers have issued warnings of herbal incense products containing these synthetic cannabinoids. Acutely, “Spice” reportedly produces pleasant and euphoric sensations and also anxiety, psychomotor agitation, cognitive impairment, palpitations. Emergency departments report that individuals exposed to synthetic cannabinoids can manifest severe symptoms, including anxiety and panic attacks, tremors, generalized convulsions, psychosis, heart palpitations and elevated pulse, severe gastrointestinal distress, tremors, blurred peripheral vision, nausea, and persistent vomiting with retching.
Other symptoms of toxicity can endure for as long as 10 hours and may include delirium, impaired coordination, sleeplessness, seizures, palpitation, agitation, headache, paranoid hallucinations, confusion, mood disorders, and psychotic symptoms that can persist long after the last dose. Rapid heart rate, loss of consciousness, diarrhea, nausea, and vomiting have been documented. Some have reported withdrawal symptoms including elevated blood pressure, restlessness, drug craving, nightmares, sweating, nausea, tremors and headache, palpitation, insomnia, headache, diarrhea, and vomiting.
Because these substances act through the same molecular target as THC, the main active ingredient of marijuana, it can be reasonably expected that their physical dependence liability will be similar. Additional concerns include reports of new-onset of psychosis in otherwise healthy males reportedly smoking synthetic cannabinoids frequently and reports of the drugs exacerbating psychotic episodes.
Designer drugs are emerging as serious public health challenges. Their rise in popularity, access from multiple sources, production of acute psychological distress, toxicity and potentially long term harmful effects, ability to evade standard drug tests, require a massive public education campaign and strategies for deterrence in healthcare systems.