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Image data from Nutt D, King LA, Saulsbury W, et al. Lancet. 2007; 369(9566):1047-53.

Drugs of Abuse: What Clinicians Need to Know

Larissa Mooney, MD | June 28, 2017 | Contributor Information

New Drugs of Abuse

According to the United Nations Office on Drugs and Crime (UNODC), drug use is shifting to new markets, and the number of new psychoactive substances is on the rise. These newer drugs of abuse include bath salts, synthetic marijuana (e.g. K2, Spice), salvia, methoxetamine, fentanyl, carfentanil, synthetic piperazines, dextromethorphan (DXM), ecstasy (Molly), kratom, anabolic steroids, cough syrups containing codeine, and even energy drinks.[1-3] In the slides that follow, learn about these latest psychoactive substances, along with key guidance on recognition and management in clinical practice.

Image courtesy of Thinkstock.

Drugs of Abuse: What Clinicians Need to Know

Larissa Mooney, MD | June 28, 2017 | Contributor Information

Bath Salts

"Bath salts" are synthetic compounds related to cathinone, a stimulant found in the khat plant. Sold as white or off-white powders or crystals, they are often misleadingly labeled to avoid detection.[1] (They are not bath salts meant to be used while bathing.) Bath salts may be ingested, insufflated (snorted or inhaled), or smoked, and intoxication produces stimulant effects similar to amphetamines. Bath salts have various trade names (e.g. Ivory Wave, Vanilla Sky, Bloom, Cosmic Blast). Sympathomimetic effects (eg, elevated pulse and blood pressure; diaphoresis; agitation; and, with long-term or heavy use, psychosis) may predominate. Overdose deaths have also been reported.[4] Supportive care for the observed sympathomimetic effects and altered mental status should include benzodiazepines for sedation. If hallucinations are present, a quiet environment devoid of auditory and visual sources of stimulation may help. Neuroleptics may also be indicated if agitation or psychotic symptoms are present.

Image adapted from www.narcocheck.com and U.S. Drug Enforcement Administration (background).

Drugs of Abuse: What Clinicians Need to Know

Larissa Mooney, MD | June 28, 2017 | Contributor Information

Flakka (alpha-PVP)

Shown is the color key to a synthetic cathinones identification test.

Alpha-PVP, or "Flakka", is a synthetic cathinone chemically related to bath salts. Rates of use rose in recent years in Florida and other areas of the U.S. Alpha-PVP is a white or pink foul-smelling crystal that may be smoked, injected, or vaporized. Users experience stimulant effects similar to cocaine or methamphetamine, but effects are typically more intense and may last for days. Users may present in an "excited delirium" marked by agitation, paranoia and hallucinations. Medical consequences may include hypertension, hyperthermia, rhabdomyolysis, acute renal failure and myocardial infarction. Deaths by self-injury or homicide have been reported in association with use of this substance.[5]

Image courtesy of Kelley McCall/Associated Press.

Drugs of Abuse: What Clinicians Need to Know

Larissa Mooney, MD | June 28, 2017 | Contributor Information

Synthetic Cannabinoids (e.g. K2, Spice)

Synthetic cannabinoids are herbal mixtures that produce effects similar to those of marijuana. Marketed under the names Spice, K2, Scooby Snax, Kick, Chill Zone, Sensation, Chaos, Aztec Thunder, Red Merkury, and Zen, synthetic marijuana contains chemical compounds responsible for its psychoactive effects. Spice products often contain dried plant materials and are commonly smoked but may also be orally ingested. Liquid forms are increasingly popular when used in electronic cigarette devices. Synthetic cannabinoids do not resemble THC (tetrahydrocannabinol) in chemical structure but are often marketed as "safe" alternatives that are undetected in urine during drug screens. Clinical effects are variable, ranging from euphoria and relaxation to effects stronger than those associated with marijuana, including significant paranoia, hallucinations, and agitation resulting in self-harm. Severe medical consequences have also been reported in some users, including tachycardia, vomiting, seizures, and myocardial ischemia. Supportive care and a quiet environment devoid of stimulation, in addition to benzodiazepines as needed for sedation, may be helpful.[6]

Image courtesy of Wikimedia Commons.

Drugs of Abuse: What Clinicians Need to Know

Larissa Mooney, MD | June 28, 2017 | Contributor Information

Salvia

Salvia (Salvia divinorum) is a psychoactive plant whose active ingredient is salvinorin A.[1] Users reportedly use this substance for its hallucinogenic properties by chewing or smoking the leaves, by brewing in a tea, or by using as a tincture (dissolving in alcohol and drinking). Users may experience short-lasting dissociative and visual experiences, often with a religious theme. Unlike other hallucinogens, Salvia divinorum is not historically associated with serotonin syndrome, but its kappa opioid receptor agonist effects may cause dysphoria, sedation, analgesia, GI hypomotility, and aversion. If hallucinations are part of the presentation, a quiet environment devoid of auditory and visual sources of stimulation may help. Benzodiazepines may be used in cases of severe agitation.[7]

Image from Di Rocco JR, During A, Morelli PJ, et al. J Med Case Rep. 2011; 5:18. [Open Access] PMID: 21247417, PMCID: PMC3038953.

Drugs of Abuse: What Clinicians Need to Know

Larissa Mooney, MD | June 28, 2017 | Contributor Information

Energy Drinks

The image is an electrocardiogram from a 14-year-old boy showing narrow-complex tachycardia with atrial fibrillation and sporadic atrial flutter. The patient came into the ED after running a race with a history of drinking a large quantity of highly caffeinated drinks during the previous day.[8]

Energy drinks contain caffeine (1,3,7-trimethylxanthine) and may be consumed to excessive quantities, resulting in caffeine toxicity.[9] Energy drinks are marketed widely to teens and young adults and may contain up to 500 mg of caffeine (equivalent to 4-5 cups of coffee), in addition to guarana (which contains caffeine) sugars, and other ingredients.[10] Clinical effects corresponding to caffeine's adenosine receptor antagonism may include mild nausea or protracted vomiting (corresponding to the dose ingested), elevated heart rate and blood pressure, headaches, anxiety, cardiac dysrhythmias, or seizures. Mixing energy drinks with alcohol has been a growing trend, increasing risks from intoxication. Supportive care should include intravenous fluid resuscitation, antiemetics, and sympatholytics.[9]

In 2017, a snortable form of chocolate (Coco Loko) containing similar ingredients that are found in energy drinks including ginkgo biloba, taurine, guarana, and cacao powder became available in the US and has raised health concerns.[11]

Image courtesy of Thinkstock.

Drugs of Abuse: What Clinicians Need to Know

Larissa Mooney, MD | June 28, 2017 | Contributor Information

Methoxetamine

Methoxetamine (MXE) is an analog of ketamine, and both drugs have structural similarity to PCP (phencyclidine).[1] Clinical effects related to NMDA receptor antagonism mirror those of ketamine and other dissociative anesthetics, including hallucinations and out-of-body experiences. The most common routes of administration include nasal insufflation and oral ingestion, but injection and sublingual use have also been reported. Physical exam findings may include mydriasis, tremor, ataxia, slurred speech, agitation, tachycardia, and hypertension. Care is supportive.[10]

Image courtesy of Wikimedia Commons.

Drugs of Abuse: What Clinicians Need to Know

Larissa Mooney, MD | June 28, 2017 | Contributor Information

Synthetic Piperazines

Synthetic piperazines have stimulant properties and include multiple compounds: BZP, CPP, MBZP, MeBP, MeOPP, MeP, and TFMPP. These drugs have been used most commonly in nightclub and rave scenes as alternatives to ecstasy and other amphetamines. Brand names include Benzo Fury, Head Rush, Exotic Super Strong, and XXX Strong as Hell. The sympathomimetic clinical effects may be similar, and users may report euphoria, anxiety, palpitations, paranoia, or hallucinations. Vomiting, seizures, QT prolongation, or hyponatremia are possible toxic effects. Supportive care may include intravenous fluids, cooling measures, and benzodiazepines as needed for sedation.[1]

Image courtesy of Thinkstock.

Drugs of Abuse: What Clinicians Need to Know

Larissa Mooney, MD | June 28, 2017 | Contributor Information

Fentanyl and Carfentanil

The highly potent synthetic opioids fentanyl and carfentanil have been linked with increasing numbers of overdose deaths, fueling the United States opioid epidemic. Whereas fentanyl may be used medically as an opioid analgesic, carfentanil is a large animal anesthetic that is 10,000 times more potent than morphine. Both agents are being distributed within illicit drug markets and used to "cut" heroin and other opioids sold on the street to intensify their effects. Due to their potency, even small quantities may cause respiratory depression and death.[12] A recent dangerous combination of fentanyl, carfentanil, heroin and another synthetic opioid, U-47700, has been labeled "gray death", as it is responsible for a series of overdose fatalities in several states.[13] Clinicians treating possible opioid or heroin overdoses should consider this trend, as increasing doses of the opioid antagonist naloxone may be necessary to reverse respiratory depression.[14]

Image courtesy of Wikimedia Commons.

Drugs of Abuse: What Clinicians Need to Know

Larissa Mooney, MD | June 28, 2017 | Contributor Information

Dextromethorphan (DXM)

Dextromethorphan (DXM) is one of the active ingredients in over-the-counter cough medications and is available in liquid and capsule/tablet formulation. Recreational use of DXM is most common in teens and has been referred to as Robotripping, in reference to Robitussin, and using Skittles or Triple C's because of the red-pill formulation in Coricidin Cough & Cold products. At higher doses, DXM acts as an NMDA receptor antagonist, causing clinical effects similar to those of ketamine or PCP, including euphoria, dissociative effects (ie, feeling detached from one's body), hallucinations, nystagmus, vomiting, tachycardia, or hypertension. Supportive care should include checking for salicylate or acetaminophen intoxication, as cough syrup preparations are often co-formulated. If the product is co-formulated with diphenhydramine, look for evidence of sodium channel blockade on the ECG (manifested as QRS prolongation and/or an abnormal R wave in aVR).[15] Treatment for sodium channel blockade toxicity includes intravenous sodium bicarbonate.

Image courtesy of Thinkstock.

Drugs of Abuse: What Clinicians Need to Know

Larissa Mooney, MD | June 28, 2017 | Contributor Information

Promethazine-Codeine Cough Syrup

Use of codeine-containing cough syrup has been a popular among youth because of its affordability and accessibility. When mixed with soda, the combination is also referred to as Syrup, Purple Drank, Sizzurp, and Lean. Codeine is an opioid with cough suppressant effects, and in higher doses, it causes relaxation and euphoria. Promethazine HCl is an antihistamine that has additional sedating effects. Codeine-containing syrup is commonly used in combination with alcohol to enhance its effects. Treatment should include supportive care, airway management, and an opioid antagonist (eg, naloxone) in cases of overdose. Investigation for evidence of salicylate toxicity and acetaminophen is also indicated, as cough syrup products are often co-formulated with these ingredients.[16,17]

Image courtesy of Thinkstock.

Drugs of Abuse: What Clinicians Need to Know

Larissa Mooney, MD | June 28, 2017 | Contributor Information

MDMA (Ecstasy or Molly)

MDMA (methylene-dioxy-methamphetamine) is commonly known as Ecstasy or, more recently, as Molly. It has been most popular in the nightclub and "rave" scenes. Taken orally in capsules or tablets, MDMA has both sympathomimetic and hallucinogenic effects. Users report feelings of euphoria, empathy, increased energy, emotional closeness, and altered perceptions. Clinically, signs of serotonin syndrome may be observed (hyperthermia, hypertension, tachycardia, altered mental status, hyperreflexia, clonus, and/or muscle rigidity), as well as bruxism (users have been known to use pacifiers). MDMA may also cause hyponatremia either directly or secondary to excessive water intake (in the context of all-night dancing).[18] Supportive care should include intravenous fluid resuscitation, benzodiazepines as needed for sedation, and possible cooling in severe cases of hyperthermia.

Image courtesy of Wikimedia Commons.

Drugs of Abuse: What Clinicians Need to Know

Larissa Mooney, MD | June 28, 2017 | Contributor Information

Kratom

Kratom is a Southeast Asian tropical tree with weak opioid effects. It has been used to treat chronic pain and opioid withdrawal, but use of Kratom for its psychoactive effects is also on the rise. Kratom is often smoked or brewed in a tea, but users may also chew the leaves. Reportedly, users experience stimulant-like effects at lower doses and opioid effects at higher doses, including withdrawal symptoms upon discontinuation of use. Withdrawal symptoms may be treated with supportive care and opioid replacement therapy; opioid antagonists (ie, naloxone) may be indicated in cases of overdose. Kratom has addiction potential, and medications approved for the treatment of opioid use disorder (e.g. buprenorphine/naloxone) may be considered if clinically indicated.[3,19]

Image from Wikimedia Commons (left) and Rosenfeld GA, Chang A, Poulin M, et al. J Med Case Rep. 2011;5:138. [Open Access] PMCID: PMC3079674, PMID: 21470406 (right).

Drugs of Abuse: What Clinicians Need to Know

Larissa Mooney, MD | June 28, 2017 | Contributor Information

Anabolic Steroids

Shown (right) is a core liver biopsy from a 50-year-old patient who, following two months of methandrostenolone use, presented with weight loss, anorexia, and abdominal pain. The black arrows point to bile filled canaliculi and the white arrows point to bile in the hepatocytes.[20]

Anabolic steroids are synthetic analogs of testosterone. They are used medically to treat hormone problems or delayed puberty in men, or muscle wasting from some diseases. Athletes and bodybuilders may use steroids to enhance muscle mass and improve athletic performance, often in excessive doses. Commonly referred to as "roids" or "juice," brand names include Androsterone, Winstrol, Oxandrin, Dianabol, and Equipoise. Users may consume steroids orally or via intramuscular injection. Cycling is a common use pattern involving weeks of use followed by rest periods in order to reduce tolerance. Stacking refers to use of multiple steroids, with or without other supplements, to maximize their efficacy. Psychiatric manifestations of use may include aggression, violence (roid rage), mania, psychosis, or suicidal ideation. Symptoms of dependence and withdrawal may be observed. Medical consequences of prolonged steroid use include liver or renal damage, elevated blood pressure, hypercholesterolemia, and cardiomegaly. In men, steroid abuse may cause testicular atrophy or gynecomastia; women may experience male-pattern baldness, hirsutism, and menstrual cycle abnormalities. Treatment involves supportive care targeting hormonal imbalances and withdrawal symptoms, in addition to tapering and discontinuation of steroids.[21]

Images courtesy of Wikimedia Commons/Hendrike (top) and the US Drug Enforcement Administration (DEA) (bottom left and right).

Drugs of Abuse: What Clinicians Need to Know

Larissa Mooney, MD | June 28, 2017 | Contributor Information

Heroin

Data from the National Institute on Drug Abuse (NIDA) indicate that between 2002 and 2015, mortality due to heroin overdose increased six-fold.[22] There were 12,989 deaths related to heroin in 2015 alone, a 562% increase from 1999.[23,24] Moreover, nearly half of young injection heroin users reported using prescription opioid agents prior to initiating heroin use, some of whom noted that heroin is cheaper and easier to obtain than prescription narcotics.[25] Thus, the rise in heroin-related mortality appears to be one of the many consequences of the excessive prescription of narcotic agents, which has led to the current prescription opioid overdose epidemic.[23]

In response to the epidemic of heroin use, cities across the United States are installing safe-injection sites, supervised injection centers where users can control their dosing and intake. Other initiatives to deter IV heroin abuse outright include increasing access to Suboxone and prescribing Naloxone to users and their families so that opioid overdoses can be reversed: a potentially lifesaving treatment (Sanburn).

Physical findings of heroin use include pupillary miosis, mild hypotension, and bradycardia.[26] Overdose can lead to respiratory depression and lethargy that can progress to hypoxia, hypercarbia, and coma; respiratory depression also greatly increases the risk for aspiration pneumonia.[26] Other complications include infection with human immunodeficiency virus (HIV) and/or hepatitis C virus (HCV), endocarditis, chronic constipation, and hepatorenal disease.[25,26,27]

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