Special Feature
Pharmacologically Facilitated Sexual Assault: A Review of "Date Rape" Drugs
By Jacob W. Ufberg, MD
During the last several years, drug-facilitated sexual assault has received increased media exposure and public attention. Among the major reasons for this are the emergence of several relatively new drugs that are easily procured, have a rapid onset of action, and produce anterograde amnesia—making them ideal agents for perpetrators of this crime. Although several agents have been identified as date rape drugs, this article focuses on three newer agents: flunitrazepam, gamma-hydroxybutyrate, and ketamine.
Flunitrazepam
A sedative-hypnotic, flunitrazepam (Rohypnol) is an intermediate-to-long acting benzodiazepine that is banned in the United States, but manufactured legally by Hoffman-LaRoche in Europe and Latin America, where it is used for the treatment of anxiety and insomnia. Based on weight, it is 10 times more potent than diazepam. Flunitrazepam, like other benzodiazepines, acts as an indirect gamma-aminobutyric acid (GABA) agonist. The effects of flunitrazepam are similar to those of other benzodiazepines, and its hypnotic and amnestic effects predominate over its anxiolytic, muscle relaxant, and anticonvulsant effects.
Flunitrazepam was originally manufactured in clear plastic blister packs, available as individually wrapped, 2 mg tablets embossed with the name Roche and the number two in a circle. Legally manufactured flunitrazepam has been reformulated to create an easily identifiable blue color when dissolved in clear beverages, and a haziness in colored beverages. However, illicitly manufactured flunitrazepam remains colorless, odorless, and tasteless when dissolved.1 Common street names include Roofies, Rochies, Roches, Rope, Mexican Valium, R-2, and Roach-2, among others.
Following oral ingestion, flunitrazepam is 80-90% absorbed by the gastrointestinal tract. Onset of action is within 30 minutes, with peak blood levels achieved in approximately one hour. Flunitrazepam exerts its effects for up to eight hours, and has an elimination half-life of approximately 20 hours. It is hepatically metabolized, with active metabolites that are excreted in the urine; therefore, renal insufficiency will result in accumulation of metabolites and prolonged duration of action.
Symptoms of intoxication resemble those of other benzodiazepines. They include sedation, disinhibition, amnesia, muscular relaxation, respiratory depression, and possibly hypotension. Fatalities due to flunitra-zepam overdose are rare unless the drug is taken with alcohol.2 Emergency department (ED) treatment includes assessment of the ABCs, activated charcoal, symptomatic treatment, and consideration of the benzodiazepine antagonist flumazenil.3
Recognition of flunitrazepam toxicity is aided by un-derstanding the usual course of events. During most drug-facilitated sexual assaults, a person at a bar or a party unknowingly ingests a beverage in which a 2 mg tablet of flunitrazepam has been dissolved. Later, the person may awaken partially clothed or nude in a strange place, with little or no memory of the events that occurred. Routine toxicologic testing may not detect flunitrazepam.
Gamma-Hydroxybutyrate (GHB)
Gamma-hydroxybutyrate (GHB) is a short-chain fatty acid derivative of GABA. It is found naturally in human serum, binding in the CNS mainly at a GHB-specific receptor site, and more weakly to the GABA receptor. It is a CNS depressant that is abused as a euphoriant and/or as an anabolic agent (purported to enhance muscle strength and growth hormone release despite no evidence as to its anabolic effects in humans). It is banned in the United States with the exception of FDA-approved research trials; however, it has been used clinically outside of the United States for anesthesia, and treatment of narcolepsy and opiate and alcohol addiction.4
GHB is easy to synthesize from common ingredients, with recipes available on the internet and in underground literature. Chemical precursors of GHB, include gamma-butyrolactone (GBL), 1,4 butanediol, and pine needle oil. Any of these chemicals can be readily converted to GHB in a home laboratory. The most common of these, GBL, is marketed as a dietary supplement in many health food stores under the names Blue Nitro and RenewTrient. Following ingestion, GBL is bioconverted to GHB, and has greater bioavailability than GHB. GHB may be produced in a powdered or a liquid form. When mixed in a drink, it is colorless and odorless and may have a salty taste or be tasteless.1 Common street names for GHB include Grievous Bodily Harm, Liquid Ecstasy, Easy Lay, Salty Water, G-Riffick, Gamma-G, Soap (it is produced from GBL using a saponification reaction), and Georgia Home Boy, among others.
Following oral ingestion, GHB is rapidly absorbed. It is not protein-bound, and it readily crosses the blood-brain barrier. Onset of action occurs within 15 minutes, and duration of action typically is between one and three hours. GHB has an elimination half-life of 27 minutes. The typical euphoric dose of GHB is 10-25 mg/kg. An oral dose of 25 mg/kg of GHB initiates REM sleep, and 60 mg/kg typically induces coma. The primary route of GHB elimination of is through cellular respiration with elimination of carbon dioxide.
GHB intoxicated patients present with a profound decrease in level of consciousness. Emesis is common, and may continue several hours after the sedative effects have worn off. Many patients also may have mild hypothermia, bradycardia, hypoventilation, and anterograde amnesia.5 An unusual feature of GHB intoxication is agitation upon stimulation despite prolonged hypoxia or apnea. ED treatment of GHB intoxication includes airway protection and ventilation support if necessary, treatment of symptomatic bradycardia with atropine, and treatment for co-ingestions. Most patients will awaken spontaneously within three hours. There is evidence to indicate that neostigmine or physostigmine may reverse the CNS-depressant effects of GHB, and these agents may be considered in severe cases.1,4,5
When used in drug-facilitated sexual assault, victims typically ingest a beverage to which GHB has been added. The drug induces a rapid decrease in level of consciousness, and usually produces complete anterograde amnesia, such that the victim will not remember the assault even if she remained conscious throughout. Like flunitrazepam, routine toxicologic testing will not detect GHB.
Ketamine
Ketamine is a rapid-acting general anesthetic that is a derivative of phencyclidine. It produces profound anesthesia and analgesia while preserving respiratory function and airway protective reflexes. It is used mainly for procedural sedation in the United States, but is used for general anesthesia in third world countries where extensive anesthetic equipment is not available. Ketamine’s mechanism of action is complex; it interacts with multiple binding sites including opioid, NMDA, glutamate, nicotinic, muscarinic, and monoaminergic receptors. The analgesic effects are partially mediated by the opioid m-receptor. However, most of ketamine’s analgesic, amnestic, and neurologic effects are due to non-competitive antagonism of the NMDA receptor.6
Recreational users of ketamine and perpetrators of drug-facilitated sexual assault generally obtain the drug through theft from sources such as hospitals or veterinary clinics.6 It is manufactured by Parke-Davis and is available commercially in vials containing 10, 50, or 100 mg per mL. Recreational abusers mix ketamine with cocaine, amphetamines, flour, talc, or vitamins in order to achieve a dissociative hallucinatory state. It can be taken through intravenous, intramuscular, intranasal, or oral routes, with the oral route being used in acquaintance rape. Street names include Special K, K, Super Acid, Green (the color of crystalline ketamine), Purple (the color when mixed with vitamin B12), and Super C.7
Following oral ingestion, peak plasma concentrations occur within 30-45 minutes. It has a high volume of distribution, and is approximately 12% protein-bound, with an elimination half-life of two hours. It is metabolized in the liver, with active metabolites that are one-sixth to one-tenth as potent as ketamine. Renal insufficiency may prolong the duration of action, as the kidney excretes the metabolites.
Ketamine intoxication produces profound analgesia, catalepsy, and amnesia. The patient may have nystagmus, and corneal reflexes remain intact. Patients appear to be awake, but are non-communicative and lack physical control. The airway remains patent and the patient maintains respiratory effort, although mild respiratory depression may be present. Salivary and tracheobronchial secretion is stimulated. Ketamine increases heart rate, blood pressure, and cerebral blood flow, leading to increased intracranial pressure. Adverse events include moderate-to-severe emergence reactions, hypertensive crisis, respiratory depression, laryngospasm, stridor, dystonia, and seizures.7
ED treatment of ketamine intoxication is mostly supportive. Airway control and ventilatory support must be considered, but usually are not necessary. Naloxone can be considered for reversal of opioid-dependent effects. Seizures can be treated in the standard fashion. Dystonia can be treated with diphenhydramine or benztropine. Hypersecretion can be reversed with atropine or glyco-pyrrolate. Emergence reactions should be treated with reassurance, a dark, quiet room, and benzodiazepines. Hypertensive crisis can be treated with alpha- and beta-blockade and verapamil. Consideration must be given to possible co-ingestants. Gastric decontamination can be performed for recent ingestions or co-ingestants. There is no known antidote for ketamine.7
Similar to flunitrazepam and GHB, patients who are sexually assaulted after ingesting ketamine will have little or no recollection of the event. Routine toxicology screens do not test for ketamine. Assays for serum ketamine levels exist, although they are not commonly available in most institutions.
Summary
Drug-facilitated sexual assault is becoming increasingly common. Flunitrazepam, GHB, and ketamine are being used with increasing frequency due to their rapid onset of action, and the production of disinhibition, muscular control loss, and profound anterograde amnesia. Emergency physicians should be aware of these drugs, their effects, the clinical presentation of acutely intoxicated patients, and treatment modalities, as well as the fact that these agents are not detected on routine toxicologic screening. In cases of drug-facilitated sexual assault, physicians should contact their local or state police crime laboratory or a private laboratory in their area. It also is important to note that urine samples that have been refrigerated or frozen can be tested days or weeks later.
References
1. Schwartz RH, et al. Drug-facilitated sexual assault (date rape’). South Med J 2000;93:558-561.
2. Drummer OH, et al. Death involving the benzodiaze-pine flunitrazepam. Am J Forensic Med Pathol 1993;14:238-243.
3. Schwartz RH, Weaver AB. Rohypnol, the date rape drug. Clin Pediatr 1998;37:321-822.
4. Li J, et al. A tale of novel intoxication: A review of the effects of gamma-hydroxybutyric acid with recommendations for management. Ann Emerg Med 1998;31:729-736.
5. Chin RL, et al. Clinical course of gamma-hydroxybutyrate overdose. Ann Emerg Med 1998;31:716-722.
6. Weir E. Raves: A review of the culture, the drugs, and the prevention of harm. CMAJ 2000;162:1843-1848.
7. Ellenhorn MJ, et al, eds. Ellenhorn’s Medical Toxico-logy. 2nd ed. Baltimore, MD: Williams and Wilkins; 1997:1179-1181.
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