Review of Therapeutics
New Drugs of Abuse
Drug abuse is a common problem and growing concern in the United States, and over the past decade, novel or atypical drugs have emerged and have become increasingly popular. Recognition and treatment of new drugs of abuse pose many challenges for health care providers due to lack of quantitative reporting and routine surveillance, and the difficulty of detection in routine blood and urine analyses. Furthermore, street manufacturers are able to rapidly adapt and develop new synthetic isolates of older drugs as soon as law enforcement agencies render them illegal. In this article, we describe the clinical and adverse effects and purported pharmacology of several new classes of drugs of abuse including synthetic cannabinoids, synthetic cathinones, salvia, desomorphine, and kratom. Because many of these substances can have severe or life-threatening adverse effects, knowledge of general toxicology is key in recognizing acute intoxication and overdose; however, typical toxidromes (e.g., cholinergic, sympathomimetic, opioid, etc.) are not precipitated by many of these agents. Medical management of patients who abuse or overdose on these drugs largely consists of supportive care, although naloxone may be used as an antidote for desomorphine overdose. Symptoms of aggression and psychosis may be treated with sedation (benzodiazepines, propofol) and antipsychotics (haloperidol or atypical agents such as quetiapine or ziprasidone). Other facets of management to consider include treatment for withdrawal or addiction, nutrition support, and potential for transmission of infectious diseases.
Drug abuse is a common problem and growing concern in the United States, and over the past decade, novel or atypical drugs have emerged and become increasingly popular. Staying current with the new drugs of abuse can be challenging for health care practitioners due to lack of quantitative reporting and surveillance, and the difficulty of detection in routine blood and urine analyses. Furthermore, street manufacturers are able to rapidly adapt and develop new synthetic isolates of older drugs as soon as law enforcement agencies render them illegal.
“Legal highs” are widely advertised in head shops and gas stations, and through the Internet. These agents are marketed as legal alternatives that produce similar effects as illicit drugs; however, many of these substances can cause severe or life-threatening adverse effects. The Synthetic Drug Abuse Prevention Act of 2012 was enacted to combat this issue, banning several of the most common isolates of synthetic cannabinoids and cathinones.
Recognition and treatment of new drugs of abuse pose many challenges for health care providers. Knowledge of general toxicology is key in recognizing acute intoxication and overdose; however, typical toxidromes are not precipitated by many of these agents. Furthermore, toxicity may be difficult to diagnose because most new designer drugs are not detected with conventional drug testing. Therefore, the purpose of this article is to describe the pharmacology, clinical and adverse effects, and reported literature on several new classes of drugs of abuse.
An estimated 23.9 million Americans 12 years or older are current illicit drug users. The National Institute on Drug Abuse estimates that overall use of tobacco, alcohol, and illicit drugs results in $600 billion annually in costs related to crime, health care, and lost work productivity. Use of illicit drugs alone accounts for $193 billion of the total. The illicit drugs routinely surveyed include marijuana, hashish, cocaine, heroin, hallucinogens, inhalants, and prescription-type psychotherapeutics used nonmedically; many newer illicit drugs of abuse are not currently tracked or reported, and thus it is difficult to capture the burden that new drugs of abuse place on society.
General Approach to Illicit Drug Users
Although intoxication with new drugs of abuse may be difficult to diagnose and treat, treatment of these patients should be approached similarly to that of other toxicology cases. General management should consist of supportive care combined with a detailed history and physical examination that may be difficult to perform due to altered mental status. The mnemonic ABCDEFG can be used to guide clinicians (Table 1). This approach combines basic emergency medical care (airway, breathing, and circulation [ABC]) with specific toxicology management, including decontamination (D) and enhanced elimination (E) methods, antidote administration (focused therapy [F]), and toxicologist or poison control center consultation (“get tox help” [G]). History should specifically address type of ingestion, time of exposure, cumulative amount, and route of administration. Furthermore, evaluation of multiple drugs of abuse, prescription opioid medications, and over-the-counter agents should be considered because coingestion is common. Clinicians should be aware of the classic drug toxidromes (e.g., cholinergic, sympathomimetic, opioid) and toxic vital signs (e.g., tachycardia, hyperthermia, hypotension) but should also realize the limitations due to confounding factors and atypical presentations with newer agents.[4, 5] Many toxicologic ingestants can be treated with specific antidotes. However, with the exception of the effects of desomorphine and kratom potentially being reversed by the μ-opioid antagonist naloxone, reversal agents have not been identified for new drugs of abuse.
Table 1. General Management of Toxicology Cases
|F||Focused therapy (antidote administration)|
|G||“Get tox help” (toxicologist or poison control center consultation)|
Diagnosis of new drugs of abuse is also particularly challenging. Routine blood and urine screening tests do not detect most of these agents, although desomorphine is structurally similar to opioids and therefore may be detected as such. Some new agents can be sent to laboratories capable of mass spectrometry or gas or liquid chromatography for detection.[6, 7] However, clinical utility of these tests is limited due to turnaround time and lack of a single test to collectively detect all new drugs of abuse. Diagnostic evaluation should include appropriate laboratory parameters including particular attention to electrocardiogram and electrolyte abnormalities. An understanding of common drugs of abuse in specific geographic locations may help narrow the differential diagnosis.
Synthetic cathinones, commonly referred to as “bath salts,” are analogs of naturally occurring cathinones such as Catha edulis (khat). Khat is native to Yemen and eastern Africa, where indigenous people have been chewing the fresh leaves for hundreds of years. Cathinone is the main psychoactive agent in khat, and it produces a stimulant effect resulting in increased alertness, energy, and libido, and appetite suppression and euphoria.[10, 11] Although the World Health Organization does not consider khat to be a seriously addicting drug of abuse, chewing the agent has been linked to peptic ulcers, myocardial infarction, dilated cardiomyopathy, stroke, and death.[7, 12]
Synthetic cathinones were initially developed in the 1920s for therapeutic purposes, and in recent years these agents have become drugs of abuse. Widespread use began in Europe in the early 1990s and then gained popularity in the United States, with at least 30 chemical compounds in existence and many street names (Table 2). Commercially available cathinones include bupropion for smoking cessation and depression, and diethylpropion for appetite suppression.[7, 12] In 1993, cathinone was classified as a Schedule I controlled substance by the Drug Enforcement Agency (DEA). The Synthetic Drug Abuse Prevention Act of 2012 amended the Controlled Substances Act to make several cannabimimetic substances and hallucinogens Schedule I controlled substances. U.S. poison control centers began receiving calls related to “bath salts” in 2010, with a peak in volume in mid-2011. In 2011, 6137 exposures to synthetic cathinones were reported, followed by 2691 exposures in 2012 and only 995 exposures in 2013. This decrease should be interpreted with caution because providers may have become more familiar with the treatment of synthetic cathinone abuse or overdose, and they may be less likely to call poison control centers for assistance.
Table 2. Common Street Names and Active Compounds of New Drugs of Abuse
|Synthetic cathinones[9, 11]||Khat, Bath salts, Meow meow, MCAT, Ivory wave Bubbles, Vanilla sky, Cloud 9, Explosion, White lightning||Methcathinone Ethylone, Mephedrone, MethedroneMethylenedioxypyrovalerone (MDPV) NaphyroneButylone 4-Fluoromethcathinone Brephedrone Pyrovalerone|
|Synthetic cannabinoids||Spice (including variants such as Spice Gold, Spice Diamond, Spice Silver) K2, Krypton, Aztec Fire, Bombay Blue, Fake Weed, Yucatan Fire||JWH-015JWH-018JWH-073JWH-210CP-47,497CP-55,490HU-210|
|Salvia||Diviner's Sage, Mystic Sage, Sally D, Magic Mint||Salvinorin A|
|Kratom||Biak-biak, Ketum, Kahuam, Ithang, Thom||Mitragynine|
|Krokodil||Krokodil, Crocodile, Zoombie Drug||Desomorphine|
Low cost and inability to detect these agents with conventional laboratory parameters makes them particularly appealing to illicit drug users. Synthetic cathinones are sold in smoke shops, head shops, gas stations, and convenience stores, and on the Internet as bath salts, plant food, jewelry cleaner, research chemicals, and herbal extracts under many street names (Table 2). Chemically unrelated to Epsom salts or household cleaning products, they are ambiguously labeled with the statement “not for human consumption.”
Synthetic cathinones are available as white or light brown powder, pills, or capsules. Doses range from a few milligrams to more than 1 g. The most common routes of administration include nasal insufflation (“snorting”) and oral ingestion; however, rectal, gingival, inhalation, smoking, parenteral (intravenous and intramuscular), “bombing” (wrapping powder in cigarette paper and swallowing it), and “keying” (insufflating powder off the surface of a key) have been reported.[7, 10, 12]
The mechanism by which synthetic cathinones exhibit an effect is similar to other stimulants through functionally changing monoamine transporters through which the neurotransmitters serotonin, dopamine, and norepinephrine are taken up from central synaptic clefts, resulting in increased postsynaptic neurotransmission. Each agent has variable effects and potency on serotonin, dopamine, and norepinephrine, and serum concentration does not predict toxicity.
Advertised effects of synthetic cathinones include euphoria, increased energy, openness, empathy, alertness, and increased libido. Duration of action, dosing, and time of onset of symptoms vary with routes of administration and purity of the product.[7, 12] Users report the onset of psychoactive effects as between 10 and 45 minutes and duration between 2 and 4 hours, depending on route of administration. No published human data on the pharmacokinetics and pharmacodynamics of the synthetic cathinones exist. Mephedrone is metabolized via phase I and II reactions involving various hepatic cytochrome P450 (CYP) isoenzymes including CYP2C19, CYP2D6, and CYP1A2.
The most common clinical findings reported to poison centers include agitation, confusion, hallucinations, tachycardia, hypertension, mydriasis, tremor, and fever. Additional serious effects reported include rhabdomyolysis, electrolyte abnormalities, renal failure, seizures, and death. Exposure may precipitate a sympathomimetic toxidrome including agitation, psychosis, hypertension, tachycardia, and seizures. Hyperthermia, hyponatremia, and acute renal failure have also been reported.[12, 18] Aggressive violent behavior, paranoia, and hallucinations are more frequently reported compared with amphetamines. Multiple case reports describe an “excited delirium” after using synthetic cathinones.[11, 15] Other case reports have shown compartment syndrome, suicide, and sudden cardiac death with synthetic cathinone use.[19, 20] A physical withdrawal syndrome occurs in cyclic binge users about 4 hours after the last dose is taken. Users have reported short periods of sleepiness, irritability, depression, and anxiety followed by sleep lasting days, increased appetite, and insomnia lasting up to 2 weeks.
Synthetic cathinones cannot be readily detected with routine testing, and no correlation of concentration with clinical effects has been reported. Exposure is a clinical diagnosis; therefore, history and physical examination findings are key. Synthetic cathinone intoxication should be suspected in a patient with acute onset altered mental status, excited delirium, renal failure, and sympathomimetic symptoms.
The management of intoxication is symptomatic and supportive. Physical restraints should be used with caution. Parenteral benzodiazepines may be considered for treatment of agitation and may also be beneficial for prevention or treatment of seizures or concomitant alcohol withdrawal. Alternative sedatives include propofol or dexmedetomidine. Antipsychotics including haloperidol may be used in severe cases but may worsen hyperthermia. Hyperthermia can be treated with aggressive cooling techniques. Hypertonic saline and water restriction may be used for hyponatremia. Cardiac ischemia is treated as it would be by any other cause except that β-blockers should not be used.
Synthetic cannabinoids, first produced in 1967, have been increasing in popularity over the past decade. Initially used as a drug of abuse in Europe in the mid-2000s, synthetic cannabinoids were identified in the United States in 2008. Similar to synthetic cathinones, these products are widely accessible. They are frequently marketed as incense in foil packets bearing the words “not for human consumption” and may be inhaled, ingested, and injected. They produce similar psychotropic effects to marijuana that contains the active component Δ9-tetrahydrocannabinol (THC). However, synthetic cannabinoids are structurally unrelated to THC and bind to cannabinoid receptors with an affinity of up to 100–800 times that of THC.[7, 24] As a class, these agents are multiplying in number, with hundreds of compounds and combinations already developed. The incidence of abuse of these novel compounds is increasing every year, with abuse increasing through 2011 but decreasing in 2013 in adolescents. As of February 2014, 22 synthetic cannabinoids have been placed under permanent or temporary Schedule I status. Table 2 lists common synthetic cannabinoid compounds and street names.
Synthetic cannabinoids exhibit increased cannabinoid effects compared with THC due to increased binding affinity, full receptor agonism, and active metabolites. Cannabinoid-1 (CB1) receptors are located in the peripheral and central nervous systems, specifically in the dorsal root ganglion of the spine and cortical and subcortical regions of the brain. CB1 receptors modulate the neurotransmitters glutamate and γ-aminobutyric acid. Cannabinoid-2 (CB2) receptors are expressed in immune tissue and the central nervous system, and they may affect pain and emesis. Both CB1 and CB2 receptors are affected by synthetic cannabinoids in varying ratios, with CB1 agonism producing a greater psychoactive effect. The paucity of information on the chemical content of these agents may lead to an unpredictable effect based on CB1:CB2 binding affinity. Similarly, little information exists regarding their pharmacokinetics and toxicokinetics. Onset and duration appear to be similar to marijuana but vary based on the product ingested. In one study, participants who had inhaled the cannabinoid receptor agonist JWH-018 had a detectable serum concentration within 5 minutes of exposure, which then decreased significantly over the next 3 hours. The participants subjectively reported the effects to last between 6 and 12 hours. JWH-018 is thought to undergo CYP oxidation, glucuronidation, and subsequent renal elimination. Metabolites vary in activity on the CB1 receptor in particular, potentially leading to unpredictable effects.[1, 30]
Synthetic cannabinoid consumers are frequently marijuana users and may be drawn to the reported similar psychotropic effects including euphoria and alteration in mood and sensorium.[7, 32] Adverse effects include anxiety, paranoia, sedation, hallucinations, psychosis, and seizures that may be more intense due to full-receptor agonism and increased binding affinity.[1, 31, 32] Of these, psychosis and anxiety tend to be the most reported. Cardiovascular symptoms may include tachycardia and hypertension, and, rarely, arrhythmias and myocardial infarction.[1, 7, 31, 33] Other adverse effects include nausea, vomiting, and acute kidney injury.[7, 33, 34] As such, synthetic cannabinoids do not fit a classically defined toxidrome.
Long-term effects, addiction, and withdrawal potential are difficult to characterize; however, parallels may be drawn from data on long-term marijuana use. Long-term users may be at increased risk for new-onset and relapse of psychosis and reduced brain volume and emotional processing.[23, 30] Furthermore, cognitive deficits including decreased attention, verbal learning, and memory were reported with chronic marijuana use.[30, 36] In a review of 41 studies, an association was found between synthetic cannabinoid use and the triggering of a psychotic event in vulnerable patients. One case report described an apparent instance of withdrawal in a patient who inhaled the product “Spice Gold” daily over 8 months. The patient had attempted abstinence previously and experienced sweating, unrest, tremor, and gastrointestinal symptoms. During admission to a hospital for detoxification, the patient experienced drug craving, nightmares, unrest, sweating, hypertension, and headache. For treatment of these symptoms, the patient received clonidine, the hypnotic zopiclone, and promethazine.
The largest age group of exposures to synthetic cannabinoid occurs in adolescents, with up to 40% of users 19 years or younger. A case series characterized adolescent users as mostly male (91%) with an average age of 17.3 years. In this group of 11 youths at a hospital addiction treatment center, all reported subjective feelings of euphoria while intoxicated, with 9 (82%) reporting negative mood changes. All patients described memory impairment. No long-term effects of synthetic cannabinoids were reported.
Care of the synthetic cannabinoids–intoxicated patient is largely supportive.[7, 28, 33, 39] In cases where a large quantity of ingestion is suspected, gastrointestinal decontamination may be considered. Benzodiazepines may play a role in the treatment of seizures and psychomotor agitation; antipsychotics may alternatively be used for agitation.[35, 39]
Salvia is a hallucinogen derived from the plant Salvia divornorum Lamiaceae, a member of the mint family, native to Mexico, which has been used in Mazatecan culture for centuries.[7, 40] In recent years, increased use has been observed in the United States. Touted as a legal alternative to marijuana, the DEA is considering giving salvia Schedule I classification, thus rendering it illegal. At least 20 states have implemented legislation placing regulatory controls on salvia. Common street names are listed in Table 2.
Recently, salvia has become more readily available to consumers due to distribution through head shops and the Internet. The Substance Abuse and Mental Health Services Administration annual survey of drug use in the United States showed that the overall rate of current illicit drug use in 2012 among persons aged 12 years or older was 23.9 million (9.2% of the U.S. population). However, hallucinogens only accounted for about 1 million (0.4%) of the population.
The mechanism through which Salvinorin A, the active plant component of salvia, causes hallucinations and altered sense of self differs from other hallucinogens (lysergic acid diethylamide [LSD] and psilocybin [“magic mushrooms”]) that are serotonin agonists. Salvia stimulates κ-opioid receptors, with little effect on μ-opioid receptors. One study exploring the dose-dependent effects of salvia demonstrated that the rewarding effect was antagonized by pretreatment with a CB1 receptor antagonist and κ-opioid antagonist, suggesting that salvia also modulates the endocannabinoid system.
Salvinorin A can be absorbed buccally through manual chewing of salvia, or the leaves can be crushed to extract a liquid that can be ingested or smoked. Oral ingestion, however, is limited due to first-pass metabolism and enzymatic degradation. A self-reported survey of 500 participants showed that the preferred route of administration was smoking or vaporization (92.6%); the mean ± SD duration of action was reported to be 14.1 ± 12.8 minutes. An inhaled dose of only 200–500 μg produces an onset of effect within 30 seconds, and the degree of hallucination was frequently described as “intense” by respondents.
The potential harm and degree of dependence from recreational salvia use is unclear. Chronic ingestion in rats and mice did not demonstrate cardiac abnormalities or histologic changes in several vital organs, suggesting the toxicity is relatively low. A retrospective review of 10 years of poison control data revealed only 37 cases of salvia use, all of which were intentional. Sixteen (43%) of the 37 cases reported concomitant exposures to other psychoactive agents. The most common symptoms recognized after isolated salvia use were confusion or disorientation, hallucinations, giddiness, dizziness, flushed sensation, and tachycardia. Vital sign abnormalities were present in only two patients (hypertension and tachycardia). Benzodiazepine administration for agitation was the most common therapeutic intervention reported. Several human case reports have reported acute psychosis secondary to salvia exposure,[45, 46] which may allude to its ability to exacerbate, precipitate, or unveil psychiatric disorders. Clinicians should consider salvia exposure in cases of acute psychosis refractory to traditional medical care.
Kratom is a tropical tree with opioid-like properties native to Thailand, Malaysia, Indonesia, Myanmar, and Papua New Guinea. Its bitter leaves are chewed to alleviate musculoskeletal pain and to increase energy, appetite, and sexual desire.[47, 48] It has been used in the treatment of hypertension, diarrhea, and cough. Recently, it has gained increased recognition in Western countries as a “natural alternative” for those who self-treat chronic pain and as a remedy for opioid withdrawal; reports of its use as an opiate substitute date back to 1836.
Kratom is a nonprescription herbal medication available on the Internet or in head shops. It is sold as leaves, powder, extract, capsule, pellet, or gum, and it can be smoked, chewed, or consumed as a tea. It has been suggested as a replacement for methadone because it is affordable, does not require physician supervision, and does not carry the stigma of methadone use. Many countries have banned or restricted kratom use. The DEA has listed kratom as a medication with no legitimate medical use; however, it has not been assigned Schedule I status.[47, 51, 52]
Reports of kratom use are rising; however, the number of kratom exposures remains small in the United States. It is difficult to establish the epidemiology because typical drug abuse metrics do not exist. In 2013 a retrospective study of the Texas Poison Control Network Database revealed no kratom exposures between 1998 and 2008, two exposures in 2009, one in 2010, four in 2012, and seven from January–September 2013. According to the System to Retrieve Information from Drug Evidence and the National Forensic Laboratory Information System, mitragynine—the primary active alkaloid in kratom—was reported once in 2010, 44 times in 2011, and 81 times in the first 6 months of 2012.
Kratom contains more than 40 alkaloids that interact with opioid and monoaminergic receptors but is structurally distinct from opioids. Mitragynine is likely responsible for its opioid-like effects. Mitragynine is an agonist of multiple receptors: the opioid receptors μ, κ, and Δ, as well as adenosine-2a, postsynaptic α-2, dopamine-2s, and serotonin receptors. Its action on α2-adrenergic agonists may mimic adjunctive therapies for opioid withdrawal such as clonidine.
Onset of effect occurs 5–10 minutes after ingestion and duration is 2–5 hours. At low to moderate doses (1–5 g), mild stimulant effects include increased sociability, alertness, and energy; moderate to heavy usage (5–15 g) produces opioid-like effects.[52, 53] Adverse effects are similar to opioids including nausea, vomiting, constipation, respiratory depression, itching, sweating, dry mouth, increased urination, anorexia, and palpitations. Neurologic effects include hallucinations, psychosis, seizures, and agitation.
Serious toxicity is rare and usually involves relatively high doses (more than 15 g) or coingestants.[50, 51] A 64-year-old man experienced multiple witnessed seizures requiring intubation 30 minutes after ingesting a tea made with kratom and Datura stramonium. Datura, commonly known as jimson weed, itself has rarely been associated with seizures. A 43-year-old man experienced a generalized tonic-clonic seizure lasting 5 minutes after he combined kratom with 100 mg of modafinil. This patient self-treated his opioid withdrawal with a tea made from kratom 4 times/day without significant adverse effects until he added modafinil in an attempt to improve alertness. Seizures and coma were reported in a 32-year-old man after kratom use, although coingestants were not reported. Cases of jaundice and pruritus after massive chronic exposure to kratom (14–21 g/day for 14 days) and severe primary hypothyroidism, potentially through reduction in the normal response of the thyroid gland to thyroid-stimulating hormone, have been reported.
Fatalities typically involve coingestants. There are several case reports of death resulting from “Krypton,” a powder mixture containing mitragynine and O-desmethyltramadol, the active metabolite of tramadol and a μ-receptor agonist.[1, 51, 57, 58] Autopsy examination revealed pulmonary edema in all cases, implying respiratory depression as cause of death. Furthermore, a fatality resulted from the combined use of kratom and propylhexedrine, an α-agonist and amphetamine-like stimulant found in nasal decongestant inhalers. Propylhexedrine, nicknamed “stovetop speed,” is similar to modafinil and primarily abused intravenously. Autopsy findings also showed pulmonary edema.
Kratom has addiction potential; in animal models, both mitragynine and 7-α-hydroxymitragynine produced a state of dependence when given for 5 days. Similar to opioids, individuals build tolerance with heavy use. One user who initially gained 4 hours of euphoria with a single 4-g dose eventually built such a tolerance that he needed 40 g/day in divided doses to avoid symptoms of withdrawal. Withdrawal has been described as less intense but more protracted than with prescription opioids; symptoms may include abdominal pain, diarrhea, sweating, and irritability. Treatment parallels opioid withdrawal, and patients may respond to opioid replacement therapy. There are a few case reports of supervised detoxification. One describes the use of dihydrocodeine (an opioid agonist) 60 mg 4 times/day and lofexidine (an α-adrenergic antagonist) 0.2 mg twice/day, titrating downward over 4 days. Buprenorphine/naloxone has been used as an opioid replacement.
Management of kratom overdose is similar to management of opioid overdose. Although animal literature provides conflicting results with respect to the utility of naloxone in reversing its effects, given its safety profile, naloxone should be considered if acute kratom overdose with respiratory depression is suspected.[1, 62]
Desomorphine, better known as krokodil for the skin lesions that plague its users, is an opioid analog that behaves pharmacologically similarly to heroin. First synthesized in the United States in 1932 as an alternative to morphine,[63, 64] it has been used commercially in Switzerland under the brand name Permonid. Its popularity in Russia and other European countries as a less expensive alternative to heroin has been increasing since it was first reported in 2002. New reports of use in the United States including Missouri, Arizona, Utah, and Illinois have occurred.
Desomorphine is a μ-receptor agonist and synthetic derivative of morphine.[63, 65] Analgesic effects are roughly 10 times that of morphine and therefore stronger than heroin. In an early comparison of desomorphine with morphine in patients with cancer, a 1:10 dosing ratio of desomorphine to morphine was used. At this dose, it was found to have a similar analgesic effect to morphine and similar occurrence of nausea and vomiting. Desomorphine has a more rapid onset of action (1–2 min) and shorter duration of action (1–2 hrs) than morphine, leading to increased potential for addiction, abuse, and withdrawal.[65, 67] In 1936 the effects of desomorphine withdrawal were observed in six patients with terminal cancer. After 3 weeks of desomorphine use, the patients experienced withdrawal symptoms if the drug was withheld for as little as 4 hours. Short duration of action in drug abusers results in a perpetual cycle of acquiring supplies, preparing the drug, and administering the drug. Desomorphine is synthesized in at-home laboratories through a process similar to that of methamphetamine production. It involves chemicals that are low cost, readily available, and highly toxic. Minimal laboratory equipment is needed, and doses can be made in less than an hour.
The adverse effects of desomorphine itself are typical of opioids. Due to variable chemical composition and the high degree of contamination of the final product, regular use results in near-immediate damage to vasculature, muscle, and bone, which may quickly progress to tissue necrosis and gangrene at the injection site. The severity of skin necrosis and muscle breakdown make way for a host of other systemic adverse effects including bacteremia, osteomyelitis, meningitis, speech and motor skill impairments, liver and kidney damage, venous ulcers, and skin eschars.[63, 67] Due to these health concerns, average survival from first use of desomorphine is reported to be 2 years.
Very limited data exist regarding treatment and management of patients who are addicted to or who acutely ingest large doses of desomorphine. The only published case report of desomorphine use in the United States is that of a 30-year-old man admitted with pain, swelling, and ulceration of the thigh after use for the past 6–7 months. He was noted to have painful necrotic ulcers on his thigh, and 2 months earlier, he had noticed swelling of his left little finger, which later turned black and autoamputated. The relationship between desomorphine use and the patient's necrotic events was suspicious but could not be confirmed.
Due to the lack of scientific data, treatment of desomorphine overdose and adverse effects largely consists of supportive care, opioid antagonism (naloxone administration), and precautions for opioid withdrawal. Although no published literature exists on withdrawal, mixed opiate agonists/antagonists such as buprenorphine/naloxone may be considered. Acute overdose should be approached similarly to heroin overdose and include naloxone for reversal of opioid agonism. Abusers should be screened for communicable diseases including human immunodeficiency virus and hepatitis. Additionally, patients often require intensive psychiatric care, thorough nutrition evaluations, and both physical and psychiatric rehabilitation.
Abuse of new designer drugs is a national problem whose rate of development is outpacing that of legislation. Clinicians should familiarize themselves with management principles of these new agents. Medical management of patients who abuse or overdose on these drugs largely consists of supportive care, although naloxone may be used as an antidote for desomorphine overdose. Symptoms of aggression and psychosis may be treated with sedation (benzodiazepines, propofol) and antipsychotics (haloperidol or atypical agents such as quetiapine or ziprasidone). Other facets of management to consider include treatment for withdrawal or addiction, nutrition support, and potential for transmission of infectious diseases.
The authors would like to acknowledge Christina Hantsch Bardsley, MD, FACEP, FAACT, FACMT, for her help in developing the content of this article.