Elsevier

The Lancet

Volume 365, Issue 9477, 18–24 June 2005, Pages 2137-2145
The Lancet

Review
Recognition and management of complications of new recreational drug use

https://doi.org/10.1016/S0140-6736(05)66737-2Get rights and content

Summary

Use of illicit drugs in clubs and large dance parties (so-called raves) is a burgeoning cultural trend. Such recreational drug use is associated with several medical complications, both acute and longlasting. Although few, if any, of the drugs currently used in recreational venues are truly new, their patterns and context of use have changed (a great deal in some instances). For some of these substances, this cultural repackaging of the drug experience has resulted in various medical disorders that have previously gone undocumented. This review aims to help treating physicians recognise and manage complications associated with the use of new drugs in clubs, including methylenedioxymethamfetamine, ephedrine, γ-hydroxybutyrate; γ-butyrolactone, 1,4-butanediol, flunitrazepam, ketamine, and nitrites. We also alert researchers to specific toxic effects of club-drugs on which more basic information is needed.

Section snippets

Common strategies

Club-drug toxic effects should be considered in the differential diagnosis when a previously healthy individual (typically a young adult) has a history of acute change in mental status, especially if they have come from or recently attended a social event. Agitation and raised heart rate, blood pressure, or temperature might suggest recent use of stimulants or ketamine, whereas lethargy, bradycardia, and respiratory depression could indicate recent ingestion of a sedative-hypnotic drug such as

MDMA (ecstasy)

Structurally related to the psychostimulant metamfetamine and the hallucinogen mescaline (figure 1), MDMA produces a mixture of stimulant and mild psychedelic effects. In the developed world, use of the compound is increasing at a rate higher than that of most other recreational drugs.5, 6 With college students and young adults in the USA, MDMA has become very popular, and lifetime prevalence rates range from 10% to 15%.6 Like other sympathomimetic drugs that readily cross the blood-brain

Hyperpyrexia

Severe, potentially fatal hyperthermia has been described after MDMA use, especially following excessive exertion in warm, crowded settings such as dance clubs or raves.11, 12 The possibility of MDMA ingestion should be aggressively pursued in any young adult who presents with an acutely altered mental status and a raised temperature because this disorder can result in several serious complications if left untreated, including disseminated intravascular coagulation, rhabdomyolysis, hepatic and

Hyponatraemia

Pronounced hyponatraemia is another life-threatening complication of MDMA. It is thought to be caused by MDMA-induced secretion of antidiuretic hormone or by excessive water consumption (due to overzealous efforts to ward off dehydration).15, 16 The disorder should be considered in all patients with suspected recent exposure of MDMA and with psychiatric or neurological symptoms. Initial symptoms can include nausea, drowsiness, vomiting, headache, muscle cramps, and weakness, which can progress

Rhabdomyolysis

Rare, substantial rises in the amounts of serum creatine kinase (>25 000 IU/L) have also been noted after MDMA use.18 These increases are usually due to rhabdomyolysis (secondary to hyperthermia, prolonged dancing, or seizures) but can take place in the absence of muscular damage. Presentation varies but could include diarrhoea and general muscle aches. Urinalysis shows dark urine, proteinuria, and no evidence of pronounced haematuria (although a urine test for haemoglobin could cross-react

Hepatoxicity

Hepatotoxicity due to MDMA is rare and can range from mild, self-limited episodes to fulminant hepatotoxicity needing transplantation.11, 19 Some cases seem to be related to necrosis, secondary to hyperthermia. Others seem to result from a direct action of MDMA on hepatic tissue. Most patients present with progressive jaundice and weight loss that could recur if exposed to MDMA again. Some individuals present the disorder in acute crisis within hours of MDMA ingestion. Treatment should be

Neuropsychiatric dysfunction

Occasionally, MDMA can also produce severe, longlasting neuropsychiatric complications including atypical psychosis, depression, and anxiety disorders.8, 10, 20 Some neuropsychiatric complications can develop acutely or shortly after MDMA ingestion, whereas other symptoms can emerge weeks or months afterwards and be longlasting. For example, many but not all research studies have shown that MDMA users with no overt psychiatric diagnoses have subtle cognitive deficits that persist with prolonged

Ephedrine

Ephedrine is another amfetamine analogue that is sometimes used recreationally. Until recently, the compound was widely promoted for weight loss, body-building, and increased energy.4, 25 In clubs and parties, ephedrine-containing products are sometimes sold as herbal ecstasy. Both synthetically and botanically derived formulations of ephedrine are readily available (table). As with MDMA, adverse effects of ephedrine-containing products generally are overstimulation of the CNS and sympathetic

γ-hydroxybutyrate

γ-hydroxybutyrate and its precursors, γ-butyrolactone and 1,4-butanediol (figure 2), are CNS-suppressant drugs that are analogues of γ-aminobutyric acid (GABA), the major inhibitory transmitter in the CNS.27 In addition to binding to GABA receptors, γ-hydroxybutyrate affects endogenous opioid, dopamine, and serotonin systems.28 γ-hydroxybutyrate, γ-butyro lactone, and 1,4-butanediol are pharmacologically related and probably act via similar CNS mechanisms. γ-hydroxybutyrate is endogenously

γ-butyrolactone

γ-butyrolactone, a precursor of γ-hydroxybutyrate (figure 2), is readily converted into γ-hydroxybutyrate without sophisticated laboratory methods or equipment. Also, once ingested, γ-butyrolactone is metabolised into γ-hydroxybutyrate by a peripheral lactonase.27 γ butyrolactone has also been marketed as a health supplement, under various brand names (table). Pharmacological and toxic effects of γ-butyrolactone resemble those of γ-hydroxybutyrate;27, 30, 34, 37 thus the precursor is also

1,4-butanediol

1,4-butanediol (table) is an aliphatic alcohol that, similar to γ-hydroxybutyrate, occurs endogenously in trace amounts.28, 39 Once ingested, it is converted to γ hydroxybutyrate by dehydrogenase enzymes (figure 2). 1,4-butanediol is used in industrial solvents and, as mentioned earlier, in various health supplements. Subjective and toxic effects of 1,4-butanediol are similar to those of γ-hydroxybutyrate and γ-butyrolactone.27, 39 Features of 1,4-butanediol overdose that could be more

Flunitrazepam

Flunitrazepam (table) is abused for its intoxicant and relaxant effects, and has become known as a date-rape drug because sexual predators use it to chemically incapacitate their victims. Flunitrazepam is a highly effective benzodiazepine-GABA-receptor-complex agonist with pharmacology similar to other benzodiazepines.40, 41, 42 It has excellent oral bioavailability, and is highly lipophilic. The benzodiazepine-GABA-receptor complex is thought to mediate the muscle relaxant, anxiolytic,

Ketamine

Ketamine (table) is a non-competitive N methyl-D-aspartate (NMDA) receptor antagonist and therefore blocks the actions of the excitatory aminoacids, glutamate and aspartate. It was introduced as a general anaesthetic drug in the late 1960s to replace phencyclidine, which had developed a reputation for unpleasant, post-anaesthetic emergence reactions. In addition to the action of ketamine on NMDA receptors, the drug exerts mild to moderate sympathomimetic effects by blocking the reuptake of

Nitrites

The nitrites (amyl, butyl, and isobutryl nitrite) are volatile, clear, amber-coloured liquids that have had a history of abuse for more than three decades, especially in gay and bisexual men.54, 55 However, in the past few years, nitrites have gained popularity in dance clubs, where they are used alone or in combination with other drugs. Nitrites are used recreationally for the rapid onset of their psychoactive and physical effects, which include a so-called high feeling, a slowed sense of

Research priorities

Our review addresses a difficult and complex topic, in which requisite data are often not yet available. In future years, research is needed on pharmacological interactions in the development of club-drug toxic effects. Other research priorities include the possible role of previous club-drug use in the subsequent development of neuropsychiatric illness, effective treatment and better understanding of drug-induced heat stroke, improved knowledge of the characteristics that render some

Conclusions

Recognition and treatment of complications of new recreational club-drugs can be very challenging. These difficulties notwithstanding, certain common strategies are helpful. In the emergency department, after instituting no-harm measures (panel), management should be guided by the assumption of polydrug intoxication, and treating physicians should be vigilant for emerging toxic effects due to either drug combination or incipient withdrawal. Additionally, if several complications coexist and

Search strategies and selection criteria

Archival articles and reviews were identified through a computerised search of Medline from 1966, to May, 2004, with “methylenedioxymethamphetamine”, “ephedrine”, “gammahydroxy-butyrate”, “gamma butyrolactone”, “1,4-butanediol”, “flunitrazepam”, “ketamine”, and “nitrites” as index terms. We selected reports dealing with acute and long-term adverse effects of these drugs and their management. Reports were reviewed by the authors who have expertise in neurology, psychiatry, pharmacology,

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