Patient Care

Treatment Considerations for Patients Using So-Called Legal Recreational Drugs

Issue 7 and Volume 40.

LEARNING Objectives

  • Learn the signs and symptoms associated with the latest fad recreational drugs.
  • Understand treatment considerations for each drug.
  • Realize that treatment can be complex due to polydrug use.

KEY Terms

  • Analogue: A drug intended to cause the same effects as a different drug.
  • Immunomodulatory: Able to change the functioning of the immune system.
  • Toxidrome: A syndrome that occurs as a result of drug toxicity.

The popularity of recreational drugs runs in cycles.1Decreased availability of high-profile drugs of abuse has created demand for synthetic or less-common alternatives. Few of these alternatives create a positive toxicological drug screen,2 leaving providers to play a guessing game of what drug their patient has used. Lack of identification means that toxicity is largely underreported.2

As alternatives are banned or made more difficult to obtain, others take their place; the variety of unregulated recreational drugs is unprecedented.3 Both the drug itself and the chemicals involved in production can cause a variety of symptoms, some of which may be unexpected. In the absence of pertinent medical history, drug use should always be considered as a potential cause for acute complaints.


Almost 12% of high school seniors in the United States have used synthetic cannabinoids in the past year,4and use appears to be most common among those under drinking age.5 These drugs are often simply called “spice” or “K2,” both also brand names.3 Spice is sprayed onto dried herbs and sold as incense. It has multiple selling points for minors—it’s inexpensive, legal, easily purchased, and with the label “not for human consumption,” a user may store and smoke spice without parents noticing.6

Spice often contains at least 10 different ingredients,3and the producers will often not list the psychoactive compounds responsible for the cannabis-like high on packaging.6 Different variations of spice produces different effects.3 Hundreds of synthetic cannabinoids exist;3 periodically an ingredient will be regulated, but new generation variants containing a slightly altered compound will then be released.5

Spice is smoked, creating a high that lasts 2–3 hours, leading most users to be able to lead a relatively normal life.6 However, users commonly combine drugs with cannabis, ketamine (used to ease coming down off of the drug) or kratom. Spice acts on the CB1 and CB2 receptors of the central nervous system, which creates the positive mood associated with cannabis.6,7 It also, however, creates the panic and other negative emotions associated with cannabis.

Cannabis is a partial agonist of affected receptors, while spice is a full agonist. This means a potential for both toxicity and overdose exists that doesn’t appear to exist with cannabis.7 Action on CB2 receptors in the immune system may also lead to immunomodulatory effects.7Spice inhibits GABA transmission more than cannabis, which causes the seizures occasionally seen with spice use.7

Spice is sprayed onto dried herbs and sold as incense. AP Photo/Kelley McCall

Spice is often mixed with vitamin E and clenbuterol, a sympathomimetic used off-label for weight loss or as a bronchodilator. This combination worsens sympathomimetic effects of the drug, including hypertension, tachycardia, nausea/vomiting, chest pain and, potentially, myocardial infarction.7

Spice toxicity has been reported,3 and deaths have occurred when combined with other drugs.8 Toxicity and death are believed to be underreported due to negative toxicology screens.5 A small study of head shops demonstrated that vendors describe spice as safe,9which may lead users into a false sense of safety. Unpleasant side effects include nausea/vomiting, paranoia, hyperactivity, abdominal pain/cramps and hallucinations.6 Hypertension, tachycardia and agitation are more severe symptoms.5 Psychological effects can be so severe that suicides have been attributed to use.5,7 Seizures and hyperthermia have occurred, especially when used with alcohol, and are associated with hyponatremia.7 Long-term effects of spice use aren’t well known, but it’s connected with cardiovascular, neurological and psychiatric symptoms.7 The extent to which spice users may become dependent to the drug is unknown.5

Most spice users who visit an ED are transported by EMS.7 Complaints generally involve behavioral emergencies such as paranoia, hallucinations or physical violence.7 Increased physical activity can cause rhabdomyolysis, which can cause renal failure.7Seizures can lead to anoxia, hyperthermia and acidosis; seizures secondary to drug use carry a mortality rate of up to 2% with additional risks of longterm end organ damage.7 Patients showing symptoms similar to excited delirium should be treated immediately with benzodiazepines and aggressive cooling.7 Sodium bicarbonate may be considered for rhabdomyolysis and acidosis when indicated in protocols.

Healthcare providers should remember that spice isn’t cannabis; it’s a synthetic mixture of drugs that may have unexpected and sometimes dangerous side effects.


Natural drugs used recreationally may create health problems; these drugs often become more dangerous and addictive when purified.8 This applies to kratom, from the plant Mitragyna speciosa. Also known as “biak-biak” or “Thom,” kratom is a commonly used drug in Malaysia and Thailand increasing in popularity in the U.S., Europe and areas that restrict alcohol use. Kratom is also a frequent cannabinoid substitute in spice.8,10

Kratom is used by chewing or smoking the leaves, drying the leaves and making pills, or through brewing leaves into tea. The mixture is done when it smells strongly; purity and dose is inconsistent.10 Effects are dose dependent. Small doses create a cocaine-like sense of increased endurance and energy.8 High doses create an opiate-like high, analgesia, the sensation of ease in social situations, and functions as an opiate substitute to control opiate or alcohol withdrawals (for which it may have a level of effectiveness, as over a third of users are ex-opiate or alcohol addicts).8,10

Traditionally, kratom is also used to treat a multitude of complaints from hypertension to overeating.8 Effects begin within several minutes and can last over an hour and a half.8 Few studies have been done on kratom use or toxicity; no toxic ranges exist,11 though limited animal studies demonstrate low toxicity.8 Studies have shown kratom users to perform worse than heroin users in visual-spatial tests,8 which may put them at higher risk for injury. Long-term kratom use is associated with skin darkening, weight loss and a generally ill appearance.8 No deaths have been attributed to the use of kratom alone, and health problems are poorly researched and based on individual case studies. Individual cases have attributed kratom use to jaundice,8 hypothyroidism8 and seizures unresponsive to benzodiazepines in one patient with a history of alcohol use.8,12

Kratom, when mixed with other drugs, may be dangerous. A common preparation, “4 × 100,” acts as an alcohol substitute. The preparation involves mixing kratom, caffeinated soda, cough syrup containing codeine or diphenhydramine, and either an anxiolytic, an analgesic or an antidepressant. The combination can be fatal to users.8 Death has also been attributed to kratom use when combined with benzodiazepines and cold medicine and with propylhexedrine (an ingredient used to treat nasal congestion found in nose sprays, also used recreationally with effects similar to ecstasy).11

Kratom creates severe dependence in over half of users within six months, and it appears the majority of users have tried unsuccessfully to quit.10 Withdrawal symptoms include cravings, irritability, pain, insomnia, fever, diarrhea, tremors and sweating.10 Psychosis was noted in one possible polydrug user.8 Withdrawals generally last 1–3 days but psychological symptoms last longer.10 Patients withdrawing from kratom should be treated symptomatically.


Salvia is a perennial herb and a member of the mint family. S divinorum is a type of salvia native to Oaxaca, Mexico, which contains salvinorin A. The plant, now called “salvia,” was traditionally used by the Mazatec Indians13 for its psychedelic effects and to treat headache, diarrhea and anemia.14 Salvia is a selective full agonist of opioid receptors13 and inhibits the release of dopamine while stimulating the release of noradrenaline.14 Also called “magic mint,” “Maria Pastora” and “seer’s sage,”15 salvia may be chewed to create a high almost immediately with effects lasting a half hour.14 A new user, especially one outside of his home environment, may experience a “bad trip” due to this unexpectedly rapid onset.14 Salvia is smoked for a less-intense effect,14 with an onset of one minute and lasting 15 minutes, or it may be drunk as a tea.16Salvia is inactivated in the gastrointestinal tract, so the amount of drug absorbed through the oral mucosa or lungs determines the amount of intoxication.2

A salvia high is intense even in small dosages and can be similar to that of LSD.13 Desired effects include hallucinations, synesthesia, a feeling of disconnect from oneself that may lead to an inability to interact, and the sensation of merging with objects, most commonly described by users as a dream-like state.13,14 Hallucinations can last up to two hours.2Common negative symptoms include panic, confusion, difficulty communicating or distinguishing real from imaginary, flushed skin, and occasionally tachycardia,14 with a hangover-like state following the high.13 Salvia doesn’t appear to significantly alter the blood pressure or heart rate of most users.14

Kratom is often sold legally in capsule form, but it can also be used by chewing or smoking the leaves or through brewing leaves into tea. Photo Wikimedia Commons/GamblinMan22

Although most workers at head shops warn customers of potential risks when asked,9 Internet sales tend to promote salvia as a non-addictive alternative to other drugs.14 It’s true that there’s a lack of data on the toxicity of salvia, but as with all drugs with negative toxicological screening, this lack of data doesn’t imply safety. It’s uncommon for users to seek emergency treatment for problems related to salvia use alone, but when they do it’s most often for a behavioral emergency.2 Persistent psychosis has occurred, sometimes lasting days, especially in those with psychiatric or polydrug use histories.14 Polydrug use intensifies salvia’s effects, is associated with seizures, and salvia use may contribute to other overdose deaths.15 This causes concern—the majority of salvia users use some type of other drug, many of whom are addicts.13,15 Those with mental health problems are also more likely to use salvia.15

Bath salts can be found as a powder, pill or capsule, and can contain a variety of ingredients, many not often listed on the packaging. Photo courtesy Drug Enforcement Administration

Benzodiazepines are useful for behavioral emergencies associated with salvia use.2 Activated charcoal may be effective if given within an hour of consumption.2 When a patient presents with severe symptoms the provider should strongly consider polydrug use and medical history. The effects of long-term salvia use are unknown.14 The average reported lifetime use is only 13 days, under half of users desire to use regularly, and it appears that the addictive potential of salvia is low.13,14When a user does become addicted, withdrawal symptoms appear to consist of mainly nausea/vomiting, diarrhea and abdominal pain,14 which should be treated symptomatically.


Bath salts, or “plant food,” is a generic term used for a wide variety of synthetic cathinones.3 A cathinone is an amphetamine analogue found in the leaf of the khat plant, which is traditionally chewed as a stimulant similar to coca, and which has been associated with longterm effects such as myocardial infarction, hypertension and dilated cardiomyopathy.17 Cathinone synthesis began in the 1920s with one drug (bupropion) in use medically as an antidepressant.17

The extent of bath salt use over the past few years is unprecedented.17 As a whole, bath salts remain “legal high” drugs because there are so many unregulated synthetic cathinones—when one becomes banned, another takes its place.17 A recent combination, called “flakka” or “gravel,” is currently enjoying popularity in the Southeast U.S. A few of the many popular ingredients include mephedrone (sold as plant fertilizer,17 this drug causes the user to have “a smell of cat wee”18 known as “mephedrone stink”17), methylone,19 or piperazine17 (an antihelmintic).

A survey of bath salts sold online showed that while some contained synthetic cathinones, others contained caffeine or local anesthetics, and still others contained scheduled drugs—and ingredients commonly didn’t match those listed on packaging.17 Further, one study of legal high drugs showed a change in the composition of active ingredients to be 25% over a six-month period.17 Additionally, most ecstasy tablets currently don’t contain MDMA but instead bath salts.17 For this reason providers need to keep in mind that a patient who believes he has used one drug may actually have taken another. Over a third of club-goers and a fifth of high school or college students in the United Kingdom have used bath salts.17 The drug appears as a powder, pill or capsule.19 It’s generally swallowed (through “bombing,” where it’s wrapped in cigarette paper and swallowed), smoked or snorted.20 Less often it’s injected, used per rectum or buccally.17,19 The drug acts as an amphetamine and stimulates the release of dopamine, norepinephrine and serotonin.20 Ideal effects are similar to that of ecstasy, with increased energy, libido, sociability and empathy.17,19,20 Effects last 1–12 hours depending on composition.19 Providers may note hypertension, tachycardia, diaphoresis, pupil dilation, bruxism, cold extremities and tremors.19 At least 20% of bath salt users experience negative effects during use.17 This is more likely with polydrug users, who compose the majority of bath salt users.17 Less severe symptoms include nausea/vomiting, dizziness, palpitations, short-term memory loss, abdominal pain, vision changes and hallucinations.17 The user may not recognize injury due to increased pain tolerance.

More severe adverse reactions include chest pain, palpitations, dyspnea, and a sympathomimetictoxidrome involving seizures, hypertension, tachycardia and altered level of consciousness.17Tachydysrhythmias, excited delirium, renal/hepatic failure, hyperthermia, cerebral edema and acute psychosis may occur.17,19 Diaphoresis and overhydration with water following vasopressin secretion can lead to hyponatremia.18 Death, including suicide, may occur.19 The majority of bath salt users who seek medical care do so for cardiac, neurologic or psychiatric symptoms.17 Over 2/3 of these patients will be agitated.17

Treatment of bath salt overdose is the same as that of amphetamines. Agitation, seizures, excited delirium or patients demonstrating the sympathomimetic toxidrome should be treated promptly with benzodiazepines.17Hyperthermic patients should be aggressively cooled—the provider should consider benzodiazepine administration to combat shivering if necessary. Oral water intake should be restricted or the patient administered hypertonic saline in the presence of suspected hyponatremia.17 Other symptoms should be treated as they occur. Bath salts are considered highly addictive,20 showing similar use patterns to cocaine.19Over 1/3 of users develop increased tolerance and continued use despite feeling out of control over their drug use.17 Users report strong cravings and the desire to re-dose frequently (“fiending”), with binges commonly lasting over 48 hours.17 Chronic use can lead to psychiatric problems.20 When an addict does stop using, withdrawals appear limited to psychological complaints.17,19


Although a provider may not be able to determine the synthetic drug used by a patient, treatment will be determined according to the class of drug that the synthetic attempts to mimic. When dealing with synthetic drugs, the provider should anticipate unexpected symptoms from the drug itself as well as from the synthesizing process. Polydrug use should always be a consideration in the overdose patient, as over 60% of those who seek treatment for drug use in the U.S. and of those arrested in some major cities in the U.S. are polydrug users. In patients with no pertinent medical history who present with altered level of consciousness, seizure, renal or hepatic problems, myocardial infarction, cerebrovascular accident or cardiac arrest, drug use should be considered.7

Cynthia H. Goss, BA, MICP, is a graduate student and a paramedic in Palm Springs, Calif.


1. Heimer R. Patterns of new drug emergence: A comment in light of ‘krokodil.’ Int J Drug Policy. 2013;24(4):275–277.

2. Babu K, Boyer EW, Hernon C, et al. Emerging drugs of abuse. Clin Pediatr Emerg Med. 2005;6:81–84.

3. Rosenbaum CD, Carreiro SP, Babu KM. Here today, gone tomorrow…and back again? A review of herbal marijuana alternatives (K2, Spice), synthetic cathinones (bath salts), kratom, Salvia divinorum, methoxetamine, and piperazines. J Med Toxicol. 2012;8(1):15–32.

4. Johnson LA, Johnson RL, Portier RB. Current “legal highs.” J Emerg Med. 2013;44(6):1108–1115.

5. Hu X, Primack BA, Barnett TE, et al. College students and use of K2: An emerging drug of abuse in young persons. Subst Abuse Treat Prev Policy. 2011;6:16.

6. Schifano F, Corazza O, Deluca P, et al. Psychoactive drug or mystical incense? Overview of the online available information on Spice products. Int J Cult Ment Health. 2009;2(2):137–144.

7. Bulbena-Cabre A, Dunn N, Kalantari H, et al. Drugs of abuse on the rise. Open Access Emerg Med. 2013;1(1):7.

8. Hassan Z, Muzaimi M, Navaratnam V, et al. From kratom to mitragynine and its derivatives: Physiological and behavioral effects related to use, abuse, and addiction. Neurosci Biobehav Rev.2013;37(2):138–151.

9. Pillay D, Kelly BD. Recreational drugs and health information provided in head shops. The Psychiatrist. 2010;34:100–102.

10. Singh D, Müller CP, Vicknasingam BK. Kratom (Mitragyna speciosa) dependence, withdrawal symptoms and cravings in regular users. Drug Alcohol Depend. 2014;139:132–137.

11. Neerman MF, Frost RE, Deking J. A drug fatality involving kratom.J Forensic Sci. 2013;58(Suppl 1):S278–S279.

12. Nelson JL, Lapoint J, Hodgman MJ, et al. Seizure and coma following kratom (Mitragyna speciosa) exposure. J Med Toxicol. 2010;6(4):424–426.

13. González D, Riba J, Bouso JC, et al. Pattern of use and subjective effects of Salvia divinorum among recreational users. Drug Alcohol Depend. 2006;85(2):157–162.

14. Zawilska JB, Wojcieszak J. Salvia divinorum: From Mazatec medicinal and hallucinogenic plant to emerging recreational drug. Hum Psychopharmacol.2013;28(5):403–412.

15. Wu LT, Woody GE, Yang C, et al. Recent national trends in Salvia divinorum use and substance-use disorders among recent and former Salvia divinorum users compared with nonusers. Subst Abuse Rehabil. 2011;2011(2):53–68.

16. Booth RE. ‘Krokodil’ and other home-produced drugs for injection: A perspective from Ukraine. Int J Drug Policy. 2013;24(4):277–278.

17. Prosser JM, Nelson LS. The toxicology of bath salts: A review of synthetic cathinones. J Med Toxicol. 2012;8(1):33–42.

18. Fort H. (Feb. 9, 2015.) Symptoms of mephedrone use: Sudden crying, extreme weight loss, and “a smell of cat wee.” The Mirror. Retrieved March 1, 2015, from

19. Winstock AR, Mitcheson L. New recreational drugs and the primary care approach to patients who use them. BMJ. 2012;344:e288.

20. Baumann MH, Partilla JS, Lehner KR. Psychoactive “bath salts”: Not so soothing. Eur J Pharmacol. 2013;698(1–3):1–5.