Drugs and Human Performance Fact Sheets
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Carisoprodol (and Meprobamate)





Gamma-Hydroxybutyrate (GHB, GBL, and 1,4-BD)


Lysergic acid diethylamide (LSD)


Methamphetamine (and Amphetamine)

Methylenedioxymethamphetamine (MDMA, Ecstasy)

Morphine (and Heroin)

Phencyclidine (PCP)


Zolpidem (and Zaleplon, Zopiclone)

Biographical Sketches of Lead Authors and Main Contributors


Gamma-Hydroxybutyrate (GHB, GBL, and 1,4-BD)

GHB is a clear liquid, or a white powder with a soap-like texture. Precursor drugs such as gamma-butyrolactone (GBL) and 1,4 butanediol (1,4-BD) are clear liquids.


GHB: Sodium oxybate, Xyrem® oral solution; liquid X, liquid XTC, salt water, scoop, soap, grievous bodily harm, georgia home boy, G, G-caps, easy lay, everclear, vita G, degreaser + lye, smart drug, gamma-OH, Somatomax.

GBL: 2(3)-furanone dihydro; Blue Nitro, G3, Invigorate, Jolt, ReActive, REMForce, RenewTrient, Rest-eze, Revivarant, Verve, V35.

1,4-BD: tetramethylene glycol; Amino Flex, Enliven, FX, GHRE, Inner G, NRG3, Pine Needle Extract, Revitalize, Serenity, SomatoPro, Thunder Nectar, Zen.

Source: GHB was first synthesized in 1960 as an experimental GABA analog, and was classified as a food and dietary supplement and sold in health food stores in early 1990. It was available in tablet, capsule and liquid forms. In late 1990, the FDA banned over-the-counter sales of GHB in the U. S. In 1999, the FDA issued warnings on the dangers of its precursor drugs GBL and 1,4-BD. In early 2000, GHB was federally reclassified as a Schedule 1 controlled substance. GBL and 1,4-BD are not scheduled, however, GBL is classified as a list 1 chemical and a controlled substance analog, while 1,4-BD is listed as a controlled substance analog. GHB can be clandestinely made and the ingredients are available in kit form over the internet. GHB is made from GBL and a base (e.g. lye/NaOH), the mixture is heated, and vinegar is added to reduce the pH. Acetone can then be added and the mixture dried, resulting in GHB powder. GBL and 1,4-BD are commercially available as industrial solvents and are used as ingredients in cleaners, solvents, paint removers, and engine degreasers. They are also sold as “natural supplements” over the internet, and in some health food stores and gymnasiums, and are marketed as natural, non-toxic dietary supplements.

Drug Class: CNS depressant, sedative, anesthetic.

Medical and Recreational Uses: In Europe, GHB is used as an anesthetic adjunct and hypnotic agent, used to treat narcolepsy, and used to suppress symptoms of alcohol-dependence and opiate withdrawal syndrome. In the U. S., medically formulated sodium oxybate (Xyrem®) has been approved as a Schedule III controlled substance for the treatment of cataplexy (sudden loss of muscle tone associated with narcolepsy). Recreationally, GHB is used for its intoxicating effects (euphoria, reduced inhibitions, sedation), and by bodybuilders as an alternative to anabolic steroids. GBL and 1,4-BD rapidly convert to GHB within the human body following oral administration and are taken as GHB substitutes. They are marketed as anti-aging drugs, for weight loss, to treat insomnia, anxiety and depression, and as mood enhancers and energizers.

Potency, Purity and Dose:Clinical doses for alcohol withdrawal syndrome are 25-50 mg/kg every 12 hours (1.7-3.5 g/70 kg); sleep induction 20-30 mg/kg (1.5-2.25 g/70 kg); prolonged deep sleep 75-100 mg/kg (5-7 g/70 kg); and anesthetic induction greater than 100 mg/kg (> 7 g/70 kg). Illicit manufacture often introduces impurities and wide variations in potency. Recreational use of GHB often involves doses well in excess of one teaspoon (~2.5 g, or 35 mg/kg in a 70 kg adult) of the powder dissolved in water/alcohol, or one capful of liquid GHB, GBL, or 1,4-BD; such doses far exceed therapeutic doses. Chronic use can consist of dosing every few hours, around the clock, for months to years. Up to 100 g GHB has been reportedly used by an individual in one day. GHB and its precursor drugs are often used in combination with alcohol, MDMA, marijuana, methamphetamine, and cocaine.

Route of Administration: Oral, intravenous.

Pharmacodynamics: GHB is a naturally occurring compound present in both mammalian CNS and peripheral tissue. It is also a minor metabolite and precursor of the major inhibitory neurotransmitter GABA. GHB is also the pharmacologically active form of both GBL and 1,4-BD. GHB has weak agonist activity at GABA B receptors and there appears to be a distinct GHB receptor site in the brain. GHB dose-dependently alters dopaminergic activity; at sub-anesthetic doses there is an initial excitation of dopamine neurons producing elevated levels of synaptic dopamine; at anesthetic doses GHB blocks impulse flow from dopamine neurons resulting in a build-up of dopamine in the nerve terminals. GHB mimics natural physiological sleep, enhances REM sleep, and increases stage 3 and 4 of slow-wave sleep. GHB decreases alcohol consumption and intensity of withdrawals. Beyond the CNS effects, GHB has significant cardiovascular pharmacology, causing bradycardia and dysregulation of blood pressure (hyper- and hypotension). Interestingly, GHB causes a detectable increase in growth hormone and prolactin concentrations with doses as small as 3 g, and this is the basis for its use in body building despite there being no evidence of an actual increase in body mass.

Pharmacokinetics: Oral doses are rapidly absorbed from the gastrointestinal tract and exhibit first pass metabolism. Absorption is capacity limited (an increase in dose results in increased time to peak concentration). There is an increased rate of absorption of GHB on an empty stomach leading to a decreased time to peak concentration and an increased concentration. Accumulation is not known to occur following repeated doses. GHB readily crosses the blood-brain barrier and placental barrier, and is distributed in the brain, cerebrospinal fluid, vitreous, liver, and kidney. The dose-response curve is steep, and a large between and within subject variability is noted. GHB is rapidly eliminated and has a half-life of 27 minutes (range 20-53 minutes) which appears to increase with higher doses, a sign of zero order or saturation kinetics. GHB is metabolized to succinic semialdehyde (SSA) via GHB-dehydrogenase, then to succinic acid via SSA-dehydrogenase. GBL is metabolized to GHB via lactonase; while 1,4-BD is first metabolized to g-hydroxybutyraldehyde via alcohol dehydrogenase, then to GHB via aldehyde dehydrogenase.

Molecular Interactions / Receptor Chemistry: Metabolism via cytochrome P450 isoenzymes has not been described.

Blood to Plasma Concentration Ratio: 1.2 (N=1)

Interpretation of Blood Concentrations:Peak plasma concentrations are observed at 20-45 minutes. Due to rapid elimination, GHB is undetectable in plasma or blood after

6-8 hours. Following single oral doses of 25 mg/kg GHB in 10 alcoholic dependant patients, mean peak plasma GHB concentrations were 54 mg/L (24-88 mg/L). Single oral doses of 12.5, 25, and 50 mg/kg in 8 healthy subjects produced mean peak plasma GHB concentrations of 23, 46 and 80 mg/L, respectively. Single oral doses of 26-52 mg/kg in 6 narcoleptic patients resulted in mean peak plasma GHB concentrations of 63 mg/L (30-102 mg/L). The same doses were administered to the same subjects 4 hours later, and the mean peak GHB concentrations obtained were 91 mg/L (47-125 mg/L). An intravenous dose of 50 mg/kg in an adult produced a peak blood GHB concentration of approximately 170 mg/L within 15 minutes. Patients presenting to an emergency department with GHB overdose/intoxication, had blood GHB concentrations ranging from 29-432 mg/L (mean 118 mg/L; N = 54).

Although GHB is naturally present in the human body, endogenous blood GHB concentrations are typically well below 1 mg/L in living subjects. In contrast, endogenous postmortem production of GHB can occur, and concentrations of up to 170 mg/L GHB have been reported in non-GHB using subjects. In postmortem analysis the analysis of multiple specimens such as vitreous and urine is recommended.

Interpretation of Urine Test Results:Peak urine concentrations are observed within 4 hours of administration and GHB is undetectable in urine after 10-12 hours. Endogenous concentrations of up to ~7 mg/L GHB have been detected in urine of non-GHB using subjects. It is suggested that a cut-off for urinary GHB be set at 10 mg/L. Similarly, in postmortem urine specimens from non-GHB using subjects, urine concentrations of GHB are typically below 10 mg/L.


Psychological: At low doses, effects are similar to those seen with alcohol. Effects include relaxation, reduced inhibitions, euphoria, confusion, dizziness, drowsiness, sedation, inebriation, agitation, combativeness, and hallucinations.

Physiological: Nausea, vomiting, profuse sweating, somnolence, visual disturbances, nystagmus, loss of peripheral vision, short-term amnesia, uncontrolled shaking or seizures, bradycardia, hypothermia, suppression of gag reflex, respiratory depression, and transient or unarousable unconsciousness.

Side Effect Profile: Disorientation, sweating, vomiting, incontinence, apnea, severe ataxia, sinus bradycardia, twitching, seizure-like activity and hypothermia. In overdose, symptoms may include severe respiratory depression, mild acute respiratory acidosis, sinus bradycardia or sinus tachycardia, suppression of gag reflex, acute delirium, combativeness, unarousable unconsciousness, coma, and patients often need to be intubated. Deaths have been reported following overdose from GHB, GBL and 1,4-BD alone, and in combination with other drugs.

Duration of Effects: Onset of effects occurs within 10-20 minutes, peak plasma concentrations are achieved within 20-45 minutes, and effects generally last 2-5 hours. Complete recovery from GHB overdose can occur within 3-6 hours. Sleep induction time is shortest with GBL and longest with 1,4-BD, as GBL is more lipophilic and is absorbed faster. There is a longer duration of effect following 1,4-BD ingestion as it metabolizes more slowly to GHB than does GBL.

Tolerance, Dependence and Withdrawal Effects:Tolerance can develop to GHB with chronic abuse and even following chronic treatment. Subjects do not become tolerant to all the effects (e.g. tolerance does not develop to the enhanced sleep that GHB produces). Cross-tolerance exists between GHB and ethanol. Severe physical and psychological addiction occurs with chronic abuse. Clinical presentation of withdrawal may include mild clinical anxiety, confusion, agitation, tremor, muscular cramps, insomnia, combativeness, delirium, delusions, paranoia with hallucinations (auditory, tactile and visual), tachycardia, hypotension, and an occasional schizophrenic-like state. The withdrawal syndrome can start as early as 1-2 hours after the last dose in addicted individuals.

Drug Interactions: Potential additive effects between GHB and other sedating CNS depressants, including alcohol, antidepressants, antipsychotics, antihistamines and muscle relaxants. In rats, ethanol has significant synergistic effects on the sedative, behavioral and toxic effects of GHB, GBL and 1,4-BD. Ethanol also delays the conversion of 1,4-BD to GHB, because both 1,4-BD and ethanol utilize alcohol-dehydrogenase in their metabolic pathways. Several drugs have been shown to inhibit GHB-dehydrogenase and it is not known clinically what effects these drugs would have if administered concurrently. These drugs include valproate, ethosuximide, salicylate, amobarbital, phenytoin, disulfiram and cyanide.

Performance Effects: Oral GHB doses of 1-2 g have been shown not to deteriorate reactive, attentive and co-ordination skills related to driving, nor increase the effects of low dose alcohol. Similarly, oral doses of 12.5-25 mg/kg GHB had no effect on attention, vigilance, alertness, short-term memory or psychomotor coordination; although dizziness or dullness were experienced in 50-66% of subjects. It is important to note, however, that doses used in laboratory studies to date have been well below both recreational and abused doses of GHB.

Effects on Driving: Signs of behavioural effects and impaired performance have been reported in several driving case reports. In 13 driving under the influence cases where GHB was detected, the reported symptoms were generally those of a CNS depressant. The subjects were typically stopped because of erratic driving, such as weaving, ignoring road signs, and near-collisions. Common signs of impairment included confusion and disorientation, incoherent speech, short-term memory loss, dilated pupils, lack of balance and unsteady gait, poor coordination, poor performance of field sobriety tests, copious vomiting, unresponsiveness, somnolence, and loss of consciousness. GHB concentrations in blood specimens collected between 1-3.5 hours of the arrest ranged from 26-155 mg/L (median 95 mg/L). In another 11 cases of driving under the influence of GHB, concentrations of GHB in blood and urine specimens ranged from 81-360 mg/L and 780-2380 mg/L, respectively. Circumstances of their arrest, observed driving behavior and signs of impairment were similar to the previous study. Other reported symptoms have included dizziness, drowsiness, agitation, loss of peripheral vision, slow responses, slow and slurred speech, and transient unconsciousness.

DEC Category: CNS depressant

DEC Profile: Horizontal gaze nystagmus present; vertical gaze nystagmus present in high doses; lack of convergence present; pupil size generally dilated; reaction to light slow; pulse rate normal; blood pressure normal; body temperature generally down. Other characteristic indicators include vomiting, sweating, slurred speech, somnolence or transient unconsciousness, poor balance and coordination, and poor performance on field sobriety tests. Note that while pulse rate and blood pressure may decrease after GHB ingestion, both parameters may be elevated during drug withdrawal.

Panel’s Assessment of Driving Risks: Given the ability of GHB to induce sleep and unconsciousness, recreational use of GHB or its precursor drugs have the potential to produce moderate to severe driving impairment.

References and Recommended Reading:

Baselt RC. Drug effects on psychomotor performance. Biomedical Publications, Foster City, CA; pp 179-80;2001.

Chin RL, Sporer KA, Cullison B, Dyer JE, Wu TD. Clinical course of gamma-hydroxybutyrate overdose. Ann Emerg Med 1998;31(6):716-22.

Couper FJ, Marinetti L. g-Hydroxybutyrate (GHB) - Effects on Human Performance and Behavior. Forens Sci Rev 2002;14(1/2):101-21.

Couper FJ, Logan BK. GHB and driving impairment. J Forens Sci 2001;46(4):919-23.

Dyer JE. g-Hydroxybutyrate: A health-food product producing coma and seizurelike activity. Am J Emerg Med 1991;9:321-4.

Dyer JE, Roth B, Hyma BA. Gamma-hydroxybutyrate withdrawal syndrome. Ann Emerg Med 2001;37(2):147-53.

Ferrara SD, Zotti S, Tedeschi G, et al. Pharmacokinetics of gamma-hydroxybutyric acid in alcohol dependent patients after single and repeated oral doses. Br J Clin Pharmacol 1992;34(3):231-5.

Hoes MJAJM, Vree TB and Guelen PJM, Gamma-hydroxybutyric acid as hypnotic. L’Encephale 6:93-99,1980.

Palatini P, Tedeschi G, Frison R, et al. Dose-dependent absorption and elimination of gamma-hydroxybutyric acid in healthy volunteers. Eur J Clin Pharmacol 1993;45:353-6.

Scharf MB, Lai AA, Branigan B, et al. Pharmacokinetics of gammahydroxybutyrate (GHB) in narcoleptic patients. Sleep 1998;21(5):507-14.

Stephens BG, Baselt RC. Driving under the influence of GHB? J Anal Toxicol 1994;18:357-8.