AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Background
• Drug Enforcement Agency Classification System
• Stimulants
• Clinical
• Differential Diagnoses
• Workup
• Treatment
• Consultations
• Patient and Family Education
• References

BACKGROUND

Section 2 of 11  

• Authors and Editors
• Background
• Drug Enforcement Agency Classification System
• Stimulants
• Clinical
• Differential Diagnoses
• Workup
• Treatment
• Consultations
• Patient and Family Education
• References

Stimulants are substances that induce a number of characteristic symptoms. CNS effects include alertness with increased vigilance and a sense of well-being and euphoria. Many users experience insomnia and anorexia, and some may develop psychotic symptoms. Stimulants have peripheral cardiovascular activity, elevating blood pressure and increasing the heart rate. They encompass a broad category of substances, including those prescribed for medical conditions; those manufactured for illicit substance abuse; and those found in over-the-counter (OTC) decongestants, herbal extracts, caffeinated beverages, and cigarettes.

A number of stimulants are classified by the US Drug Enforcement Agency (DEA) as controlled substances. The initial section of this article reviews the different stimulants classified by the DEA. Several of these stimulants have not been significantly prescribed, abused, or investigated in the United States; consequently, limited data are available. Stimulants that have been studied and classified by the DEA and several OTC drugs and herbal medications with active stimulant ingredients are discussed. The mechanism of action of these stimulants, when known, is mentioned. Typical signs and symptoms of stimulant toxicity, along with appropriate pharmacologic and nonpharmacologic treatment, are also reviewed.

Caffeine, cocaine, amphetamines, and nicotine are not discussed in this article. See Cocaine-Related Psychiatric Disorders, Amphetamine-Related Psychiatric Disorders, Caffeine-Related Psychiatric Disorders, and Nicotine Addiction for further information regarding these substances.

For excellent patient education resources, visit eMedicine's Substance Abuse Center. Also, see eMedicine's patient education articles Club Drugs, Cocaine Abuse, Drug Dependence and Abuse, Narcotic Abuse, and Substance Abuse.

DRUG ENFORCEMENT AGENCY CLASSIFICATION SYSTEM

Section 3 of 11  

• Authors and Editors
• Background
• Drug Enforcement Agency Classification System
• Stimulants
• Clinical
• Differential Diagnoses
• Workup
• Treatment
• Consultations
• Patient and Family Education
• References

The following is the DEA classification of controlled substances.

Schedule I

These substances have no accepted medical use in the United States and have a high abuse potential. They cannot be prescribed.

• Schedule I stimulants
• • Aminoxaphen - Aminorex
  • Cathinone
  • Fenethylline
  • Methcathinone
  • Methylaminorex
  • Amphetamine variants (eg, 3,4-methylenedioxymethamphetamine [MDMA], N-ethylamphetamine, N,N-dimethylamphetamine)

Schedule II

These substances have a high abuse potential with severe psychic or physical dependence liability. Schedule II controlled substances consist of certain narcotic, stimulant, and depressant drugs. Prescriptions must be written in ink or typewritten and must be signed by the practitioner except in a genuine emergency, in which case the practitioner is required to supply written confirmation of the verbal order within 72 hours. No renewals may be prescribed.

• Schedule II stimulants
• • Cocaine
  • Dextroamphetamine - Dexedrine
  • Lisdexamfetamine dimesylate - Vyvanse
  • Methamphetamine - Desoxyn
  • Methylphenidate - Ritalin
  • Phenmetrazine - Preludin
  • Biphetamine

Schedule III

These substances have an abuse potential less than those in schedules I and II, including compounds containing limited quantities of certain narcotic and nonnarcotic drugs. Prescriptions may be oral or written, and up to 5 renewals are permitted within 6 months.

• Schedule III stimulants
• • Benzphetamine - Didrex
  • Chlorphentermine
  • Clortermine
  • Phendimetrazine tartrate - Plegine, Prelu 2

Schedule IV

These substances have an abuse potential less than those in schedule III. Prescriptions may be oral or written, and up to 5 renewals are permitted within 6 months.

• Schedule IV stimulants
  
  
  
  • Armodafinil - Nuvigil
  • Diethylpropion hydrochloride - Tenuate
  • Fencamfamin
  • Fenproporex
  • Mazindol - Sanorex, Mazanor
  • Mefenorex
  • Modafinil - Provigil
  • Norpseudoephedrine
  • Pemoline - Cylert (No longer available in United States)
  • Phentermine - Fastin, Ionamin, Adipex
  • Pipradrol
  • Sibutramine - Meridia

Schedule V

These substances have an abuse potential less than those in schedule IV. Schedule V controlled substances consist of preparations containing limited quantities of certain narcotic drugs and are generally for antitussive and antidiarrheal purposes. These drugs are subject to state and local regulation, and a prescription may not be required.

• Schedule V stimulants – Pyrovalerone

STIMULANTS

Section 4 of 11  

• Authors and Editors
• Background
• Drug Enforcement Agency Classification System
• Stimulants
• Clinical
• Differential Diagnoses
• Workup
• Treatment
• Consultations
• Patient and Family Education
• References

Schedule I drugs

The stimulants listed on schedule I are more potent than cocaine and have no established medical use. Based on animal studies, aminorex, methyl-aminorex, methcathinone, and cathinone are more potent relative to cocaine.

• Aminorex is a stimulant synthesized in the early 1960s. It diminishes appetite and stimulates motor activity in animals. Aminorex and methyl-aminorex increase available catecholamines at the neural synapse, thereby acting as indirect sympathomimetic agents. Aminorex was removed from the market 30 years ago because of reports of chronic pulmonary hypertension.
• Methyl-aminorex is a derivative of aminorex and has also been abused. The street term "ice" is usually indicative of methamphetamine. However, in Philadelphia and Florida, 4-methyl-aminorex has been identified in the street drug sold as ice.
• Methcathinone, isolated in 1957, was initially produced for use as an appetite suppressant.
• • It is structurally related to amphetamine and cathinone, a stimulant found in nature.
  • Methcathinone was not marketed because of the recognized addictive potential, but it emerged as a common drug of abuse in the former Soviet Union during the 1970s.
  • It was illegally synthesized by oxidation of ephedrine and first appeared in the United States in rural Michigan in 1989. Methcathinone was made a schedule I drug in 1992, and its use has not spread widely in the United States beyond the northern Midwest region.
• Cathinone is the active chemical in a shrub commonly known as khat (Catha edulis) and has been abused for centuries.
• MDMA is derived from methamphetamine by the addition of another methyl group. This additional methyl group confers increased lipophilicity to MDMA, leading to its rapid entry into the brain.
• • MDMA was synthesized in 1910 and patented 4 years later by Merck. Initial plans for the drug were to market it as an appetite suppressant. Although soldiers used it during World War I, the drug did not see widespread use until the 1970s.
  • MDMA was used as an adjunct to psychotherapy in the 1970s and 1980s for its ability to induce feelings of empathy and to enhance communication.
  • Illicit use under the street name "ecstasy" was initially limited to all-night dance parties (ie, raves).
  • Because of concerns regarding addiction and potential toxicity, MDMA was labeled as a schedule I hallucinogen in 1985.
  • Use of this illicit drug has been increasing in prevalence. A study of 50,000 high school students found that the prevalence in high school seniors increased from 6% to 11% between 1996 and 2000. A study by Strote et al surveying more than 14,000 US college students estimated that the prevalence of MDMA use increased from 2.8% to 4.7% between 1997 and 1999.¹
  • MDMA acts as an indirect sympathomimetic, stimulating release and inhibiting reuptake of epinephrine, norepinephrine, and dopamine.
  • Although structurally similar to amphetamines, it is psychoactively complex. Unlike amphetamines, it directly stimulates 5HT2 1A autoreceptors. It also stimulates the release of serotonin and inhibits its reuptake.
  • MDMA directly affects other neurotransmitters including histamine, GABA, acetylcholine, and dopamine receptors and binds to the norepinephrine transporter protein. In addition, it has several pharmacokinetic effects. It inhibits tryptophan hydroxylase (the rate-limiting step of serotonin synthesis) along with MAO A and B activity. It inactivates the cytochrome P450 2D6 enzyme for several days after MDMA ingestion.
  • Similar to other stimulants, it may cause tachycardia, elevated blood pressure, increased energy, anorexia, and increased concentration.
  • Doses of MDMA are typically in the range of 50-250 mg.
  • It is a drug that rapidly induces tolerance and diminishing responsiveness via a unique mechanism, destruction of serotonergic axon terminals.
  • Regular users often need to increase their doses, and heavy users may snort or inject MDMA to obtain desired effects.
  • Although MDMA may cause alterations in color perception, patients do not usually develop frank hallucinations.
  • Undesirable adverse effects may include nausea, diaphoresis, anorexia, tremor, myoclonus, tics, paresthesias, nystagmus, hyperreflexia, hypertension, urinary retention, and ataxia.

Schedule II drugs

See Cocaine-Related Psychiatric Disorders and Amphetamine-Related Psychiatric Disorders for a detailed discussion of those schedule II stimulants.

Amphetamines include dextroamphetamine and methamphetamine. Amphetamines act as stimulants by releasing presynaptic dopamine, in contrast to cocaine, which inhibits reuptake of dopamine.

Amphetamines were initially used in inhalers for nasal congestion in the 1930s. The use of amphetamines, which were not controlled substances, spread to athletes, truck drivers, and the general population to promote alertness. Amphetamines are currently used to treat narcolepsy and attention deficit hyperactivity disorder (ADHD). They have been used and abused for weight control in individuals with eating disorders or obesity.

Methylphenidate is a piperidine that acts in a similar pharmacologic manner but is not structurally an amphetamine. It also has more prominent CNS versus peripheral stimulant activity.

• Methamphetamine can be created from ephedrine by drug dealers in home laboratories. Methamphetamine effects are more pronounced in the CNS, with relatively diminished peripheral activity.
• Dextroamphetamine was used by soldiers to increase alertness and stamina during World War II. It has more prominent CNS activity relative to peripheral stimulant activity.
• Phenmetrazine is a stimulant that was widely prescribed for treatment of obesity in the United States in the 1950s and 1960s and in several European countries such as Sweden and Germany. It became an extremely popular drug of abuse. A study of drug use among criminals found that for many methamphetamine addicts, phenmetrazine became their drug of choice. In 1971, phenmetrazine was placed into the schedule II category. Abuse of this drug has ended because phenmetrazine was never illicitly manufactured and is no longer prescribed.
• Newer classes of stimulants have similar properties to amphetamines; however, they are less likely to lead to dependence and abuse.

The appetite-suppressant effect of stimulants has been apparent for many decades. In more recent years, stimulant medications with a lower risk of abuse (often related to decreased potency of the agents) have been developed for the treatment of obesity. Because of this lower risk, the newer anorectic agents were placed in schedule III and schedule IV. These drugs include dexfenfluramine, sibutramine, phentermine, fenfluramine, mazindol, diethylpropion, and fenproporex. Phentermine, mazindol, and diethylpropion affect noradrenergic systems, whereas fenfluramine modulates serotonergic activity. The efficacy of these agents in weight reduction is limited in part due to tolerance that develops with long-term treatment.

Schedule III drugs

A number of stimulants listed by the DEA are not widely used or abused. Limited information is available for the class III stimulants. Clortermine, a class III agent, has been available for many years and has been found in several trials to be more effective than placebo in obesity treatment. It has not been used to any significant degree.

Schedule IV drugs

• Diethylpropion has been available since 1960. Several studies have proven diethylpropion to be efficacious for the short-term treatment of obesity. It reportedly has a low abuse potential.
• • The mechanism of action of diethylpropion is similar to that of dextroamphetamine, although at a tenth of the potency.
  • At the usual prescribed dose of 25-75 mg, it increases blood pressure and body temperature and reduces energy intake and sleep.
  • In animal studies, diethylpropion was able to serve as a substitute for cocaine in food-deprived rats.
  • Initial open-labeled studies of patients with cocaine dependency suggested that diethylpropion might be an effective treatment to maintain abstinence. These findings were not confirmed by a placebo-controlled double-blind study.
• Fenproporex, although initially marketed as a nonstimulant anorectic agent, is metabolized to several active amphetamines.
• Phentermine and fenfluramine are the active ingredients of the infamous Phen-Fen anorectic agent, which has been associated with cardiac valvular disease.
• • Fenfluramine has been removed from the market, but phentermine remains available as a treatment for obesity. Various formulations with doses of 15-37.5 mg are available.
  • Cardiac valvular disease does not appear to be a risk with the use of phentermine alone.
• Mazindol inhibits norepinephrine reuptake and is structurally related to tricyclic antidepressants.
• • Mazindol reduces appetite with fewer stimulant properties and less potential for abuse than amphetamine.
  • Mazindol appeared effective in the treatment of obesity in open-labeled studies; however, patients have developed atrial fibrillation and syncope, thus discouraging widespread use of this medication.
• Modafinil is an atypical stimulant that has lower abuse potential than most other stimulants.
• • Modafinil affects the hypocretin/orexin neuropeptide in the hypothalamus. This chemical has a role in the stimulation of appetite and in alertness in the canine version of narcolepsy. Modafinil is currently indicated for the treatment of human narcolepsy. It does not act on noradrenergic, serotonergic, or dopaminergic systems.
  • While both amphetamines and modafinil increase wakefulness, only amphetamines increase activity in regions of the brain such as the basal ganglia and nucleus accumbens. Considered a CNS reward center, the nucleus accumbens has been associated with positive reinforcement and implicated in cocaine abuse.
  • One study by Jasinski compared modafinil to methylphenidate and found significant differences between the two.² Doses were 200-800 mg for modafinil and 45-90 mg for methylphenidate. The Amphetamine Scale, which is used to identify stimulants by their subjective effects, was used to identify amphetaminelike qualities of these drugs. Modafinil did not produce elevations in the Amphetamine Scale, suggesting that the subjective effects of this drug are qualitatively different from traditional stimulants.
  • Certain chemical properties of modafinil reduce its potential for abuse. Modafinil is insoluble in water and thus cannot be readily injected. Also, it degrades with heating, preventing a pharmacologic effect if smoked. Modafinil has a long half-life, which would further minimize its abuse potential.
  • In fact, Dackis et al investigated modafinil as a potential treatment for cocaine dependence.³ His group conducted a double-blind, placebo-controlled 8-week trial with 62 patients dependent on cocaine. They found that modafinil improved cocaine abstinence.
• Armodafinil is the R-enantiomer of modafinil. The R-enantiomer has a longer half life (10-14 h) than the S-enantiomer (3-4 h). A study comparing the 2 drugs at doses of 200 mg found that modafinil had an earlier peak plasma concentration and armodafinil had higher plasma concentrations at 6-14 hours. These characteristics of armodafinil have been suggested to offer the advantage of once daily dosing and longer duration of wakefulness than modafinil. Armodafinil has been studied in the treatment of sleep disorders, including obstructive sleep apnea and narcolepsy. 
• Pemoline is a stimulant with similar pharmacologic activity to methylphenidate that has been used to treat ADHD. It has a potential for serious hepatotoxicity; therefore, stimulants with safer adverse effect profiles may be preferable clinically. The United States Food and Drug Administration (FDA) concluded that the overall risk of liver toxicity from pemoline outweighs the benefits. In May 2005, Abbott chose to stop sales and marketing of their brand of pemoline (Cylert) in the United States. In October 2005, all companies that produced generic versions of pemoline also agreed to stop sales and marketing of pemoline.
• Sibutramine is a combination serotonin and norepinephrine and dopamine reuptake inhibitor whose appetite-suppressive effects appear to be related to its noradrenergic action. When its noradrenergic activity is blocked, the appetite suppression is lost. Selective serotonin reuptake inhibitors cause initial transient anorexia without causing long-term weight loss. Sibutramine is marketed as Meridia and is available in doses of 10-15 mg/d.

Schedule V stimulants

Pyrovalerone is the only class V stimulant listed by the DEA. This drug is used in Europe, but no information is available in English-language medical journals.

Other stimulants

• Phenylpropanolamine (PPA) is closely related to ephedrine and has been recognized as having anorectic properties without significant risk of dependence.
• • In fact, a controlled study of healthy volunteers found PPA to be mildly aversive, with a greater proportion of patients preferring placebo to 75 mg of PPA. In the same study, dextroamphetamine was confirmed as having strong reinforcing behaviors.
  • A number of case reports suggest an association between intracranial hemorrhage and the use of PPA. A study designed to investigate this risk found that the use of PPA in appetite suppressants was an independent risk factor for hemorrhagic strokes in women. As a result, the US Food and Drug Administration (FDA) issued a warning, and PPA was removed from the market in October 2000.
• Ephedrine, norephedrine, and pseudoephedrine can be found in numerous OTC medications. For many years, ephedrine has been used in numerous OTC drugs as a nasal decongestant and appetite suppressant.
• • Alternative medicines, including herbal supplements, have gained widespread popularity and are currently a multibillion-dollar business. Hundreds of these supplements contain stimulants as active ingredients.
  • In 1994, the Dietary Supplement Health and Education Act essentially exempted dietary supplements from FDA regulation. This allows stimulants to be sold as food supplements, thereby avoiding governmental regulation. Although these drugs have no proven efficacy in the treatment of any medical conditions, they are marketed as solutions to common problems such as low energy and obesity.
  • Without regulation, the actual content of active agents is often unreliable. In several cases, significant quantities of schedule IV controlled substances, such as norpseudoephedrine, were isolated from these products. The herb ma-huang, which consists of the dried stems of the Ephedra equisetina plant, contains ephedrine, norephedrine, pseudoephedrine, and norpseudoephedrine. It has been used for centuries in China.
  • Ephedrine was first isolated in 1885 and, shortly after, was used to treat asthma. Many OTC medications contain ephedrine and pseudoephedrine for treating asthma and allergic rhinitis. Herbs with ephedrine are sold as food and exercise supplements. Previously used by physicians as treatments for asthma, hypotension, and depression, these medications have been replaced by safer, more selective agents.
  • Ephedrine is also structurally related to amphetamines and acts as a sympathomimetic that has nonspecific alpha- and beta-adrenergic agonist activity. Ephedrine acts as a direct sympathomimetic agent and also acts via increasing catecholamine levels in the brain and cardiovascular system.
  • Ephedrine has a half-life of 5 hours and is excreted primarily unchanged in the urine. Common effects include bronchodilation, tachycardia, vasoconstriction, transient hypertension, nervousness, insomnia, appetite suppression, and headache.
  • These drugs are not safe and may cause serious toxicity. Long-term use at doses recommended by some manufacturers has been found to be a cause of fatal cardiomyopathy in an otherwise healthy 23-year-old man.⁴
  • Additionally, use of ephedrine-containing compounds appears to be a potential cause of nephrolithiasis. A study by Powell et al found an association between ephedrine usage and kidney stone formation.⁵ However, the most serious complications arise from its adverse cardiovascular and neurologic effects. It has been linked to 34 deaths and 800 cited serious complications, including hypertension, arrhythmias, cardiomyopathy, myocardial infarction, hemorrhagic stroke, seizures, nephrolithiasis, and psychosis.
  • These products often contain both ephedrine and caffeine. The combination of these agents can be synergistic, increasing blood pressure and the risk of stroke. Owing to public health risks, the FDA initially proposed placing limitations on the use of these drugs.
  • In February 2004, the FDA prohibited the sale of dietary supplements containing ephedrine citing that they constitute an unreasonable risk due to their potential health risks and questionable health benefits. Most ephedra-containing dietary supplements have been removed from the market.

CLINICAL

Section 5 of 11  

• Authors and Editors
• Background
• Drug Enforcement Agency Classification System
• Stimulants
• Clinical
• Differential Diagnoses
• Workup
• Treatment
• Consultations
• Patient and Family Education
• References

History

A thorough history of recent and past use of illicit drugs, herbal medications, food supplements, caffeine, alcohol, and prescribed medications is critical. Elevated mood, increased alertness, increased energy, insomnia, and anorexia are all common symptoms associated with stimulant use. Chest pain, tachypnea, nausea, abdominal pain, and headaches may also be associated with such use. Long-term stimulant use may result in tolerance, weight loss, and potential adverse psychiatric symptoms such as irritability, aggression, impulsivity, hallucinations, and delusions.

Use of MDMA is distinguished from stimulant intoxication by the propensity for calmness and empathy. Common adverse effects may include restlessness, anxiety, trismus, fever, and impaired memory.

Physical

Cardiovascular signs are often found with the use of stimulants. Increases in blood pressure, heart rate, and pupillary dilation are common. Hyperthermia, hyponatremia, arrhythmias, myocardial infarction, and hemorrhagic stroke are also potential results of stimulant use.

With regard to MDMA, short-term effects include dehydration, hyperthermia, and heat stroke. Overdoses can simulate methamphetamine overdose. Rhabdomyolysis and acute renal failure have also been reported.

Mental Status Examination (during stimulant intoxication)

• Attitude - Tense
• Psychomotor activity - Agitated and often restless
• Mood/affect - Good or euphoric, labile
• Speech - Talkative
• Thought processes or content - Flight of ideas; paranoia; auditory, visual, and tactile (formication) hallucinations; grandiosity; hypersexuality; homicidal ideation
• Insight or judgment - Impaired
• Orientation - Confusion, delirium
• Memory - Although small doses of stimulants may improve alertness and task performance, the heavy use associated with stimulant abuse would be detrimental to memory and could lead to a coma.

Mental status examination (during stimulant withdrawal)

• Behavior - Sedated
• Psychomotor activity - Retarded
• Mood or affect - Depressed or irritable
• Speech - Nonspontaneous
• Thought processes or content - Linear at times with suicidal ideation and drug craving. Please note homicidal potential during withdrawal as well as paranoia, which is often observed.
• Insight or judgment - Variable
• Orientation - May be normal or close to normal
• Memory - Likely to be impaired due to sleep deprivation, associated fatigue, decreased attention and irritability

Mortality and morbidity

Adverse effects of the more common stimulants are discussed in other articles on cocaine and methamphetamine abuse. See Cocaine-Related Psychiatric Disorders and Amphetamine-Related Psychiatric Disorders for a detailed discussion.

Toxicity related to MDMA use differs from other stimulants. In animals, single high-dose or multiple lower doses cause loss of 5-HT axon terminals. Similar findings have been noted in humans who abuse MDMA. Clinically, memory deficits along with mood and anxiety symptoms are strongly correlated to cumulative use of MDMA.

Tolerance develops with MDMA due to a gradual destruction of serotonergic neuronal axon terminals.

A review of the literature in 2003 by Patel et al noted 86 fatalities associated with MDMA use.⁶

In 1999, McElhatton et al noted an increased incidence of congenital anomalies associated with MDMA abuse, including musculoskeletal and cardiac abnormalities.⁷

DIFFERENTIAL DIAGNOSES

Section 6 of 11  

• Authors and Editors
• Background
• Drug Enforcement Agency Classification System
• Stimulants
• Clinical
• Differential Diagnoses
• Workup
• Treatment
• Consultations
• Patient and Family Education
• References

• Delirium (toxic-metabolic, infectious)
• Hyperthyroidism
• Acute intermittent porphyria
• Lysergic acid diethylamide (LSD) intoxication
• Phencyclidine (PCP) intoxication
• Caffeine overuse
• Neuroleptic malignant syndrome
• Alcohol, benzodiazepine, or barbiturate withdrawal
• Anticholinergic overdose
• Schizophrenia
• Bipolar disorders
• Anxiety disorders

WORKUP

Section 7 of 11  

• Authors and Editors
• Background
• Drug Enforcement Agency Classification System
• Stimulants
• Clinical
• Differential Diagnoses
• Workup
• Treatment
• Consultations
• Patient and Family Education
• References

Drug screens for amphetamines lack specificity for MDMA. If testing is not performed within several hours of cocaine use, findings are often negative for the parent compound. However, cocaine metabolites can be identified for several days after ingestion. Urine drug screens may be useful for excluding other substances (eg, PCP, cannabis) that may mimic stimulant intoxication.

Routine evaluations should include an ECG and electrolyte evaluation. Users of MDMA have a risk of dehydration. Cases of hyponatremia due to excessive hypotonic fluid intake have been reported with MDMA abuse. Any patient with an altered mental status should receive consideration for immediate cranial neuroimaging with a CT scan to help exclude acute intracranial pathology.

TREATMENT

Section 8 of 11  

• Authors and Editors
• Background
• Drug Enforcement Agency Classification System
• Stimulants
• Clinical
• Differential Diagnoses
• Workup
• Treatment
• Consultations
• Patient and Family Education
• References

A specific antidote does not exist for acute stimulant intoxication. Treatment can target specific signs and symptoms such as hypertension, agitation, and hyperthermia. In the study of fatalities related to MDMA ingestion by Patel et al, a significant delay occurred between onset of symptoms and health care treatment in the cases reviewed.⁶ Rapid supportive treatment may reduce mortality.

Supportive therapy

• Establish and maintain ABCs.
• Monitor vital signs and hydrate with intravenous fluids.
• Provide symptomatic treatment of agitation or psychosis with benzodiazepines or neuroleptics. Physical restraints may be required in certain cases.
• Decontamination with gastric lavage may be appropriate in cases of recent ingestion.

Withdrawal from stimulants may cause non–life-threatening symptoms such as dysphoria, hypersomnia, hyperphagia, and irritability.

Stimulant dependence

Studies have investigated the use of newer stimulants with lesser potential for abuse as transitional replacements to cocaine. Over time, cravings for stimulants such as cocaine appear to dissipate regardless of placebo administration or alternative stimulant treatment. The relatively small, double-blind, placebo-controlled study by Dackis et al suggested that modafinil may have use in the treatment of cocaine dependence.³

Outpatient and inpatient nonpharmacologic treatment of stimulant dependence has been shown to be beneficial. However, relapse after treatment is common. Educating patients and their families about substance dependence and abuse is important. See Patient and Family Education.

CONSULTATIONS

Section 9 of 11  

• Authors and Editors
• Background
• Drug Enforcement Agency Classification System
• Stimulants
• Clinical
• Differential Diagnoses
• Workup
• Treatment
• Consultations
• Patient and Family Education
• References

Consultation with a psychiatrist may be indicated for patients with a history of mental illness, current psychosis, evidence of self-harm, or violent behavior. Brief psychiatric observation and treatment of acute agitation with referral to a treatment program may suffice for some patients. However, persistent paranoia, homicidal ideation, or severe dysphoria with suicidal ideation during stimulant withdrawal may necessitate psychiatric hospitalization. Comorbid psychiatric disorders, including depression, psychotic disorders, and personality disorders (eg, antisocial and borderline personalities), should be identified, and appropriate treatment should be initiated.

PATIENT AND FAMILY EDUCATION

Section 10 of 11  

• Authors and Editors
• Background
• Drug Enforcement Agency Classification System
• Stimulants
• Clinical
• Differential Diagnoses
• Workup
• Treatment
• Consultations
• Patient and Family Education
• References

Educating patients and their families about substance dependence and abuse is important. Potential medical complications of stimulant abuse should be discussed with patients. Those who abuse stimulants need to identify triggers for relapse, often with the assistance of substance abuse counselors. Recognizing behaviors of family members that allow substance abuse to occur can help patients achieve abstinence. See Cocaine-Related Psychiatric Disorders for further information.

Patients can find online information on stimulant abuse and support groups at the following Web sites.

• National Institute on Drug Abuse
• Division of Alcohol and Drug Abuse
• The Anti-Meth Site
• Help for Drug Problems
• Narcotics Anonymous

REFERENCES

Section 11 of 11

• Authors and Editors
• Background
• Drug Enforcement Agency Classification System
• Stimulants
• Clinical
• Differential Diagnoses
• Workup
• Treatment
• Consultations
• Patient and Family Education
• References

1. Strote J, Lee JE, Wechsler H. Increasing MDMA use among college students: results of a national survey. J Adolesc Health. Jan 2002;30(1):64-72. [Medline].
2. Jasinski DR. An evaluation of the abuse potential of modafinil using methylphenidate as a reference. J Psychopharmacol. Mar 2000;14(1):53-60. [Medline].
3. Dackis CA, Kampman KM, Lynch KG, et al. A double-blind, placebo-controlled trial of modafinil for cocaine dependence. Neuropsychopharmacology. Jan 2005;30(1):205-11. [Medline].
4. Theoharides TC. Sudden death of a healthy college student related to ephedrine toxicity from a ma huang-containing drink. J Clin Psychopharmacol. Oct 1997;17(5):437-9. [Medline].
5. Powell T, Hsu FF, Turk J, Hruska K. Ma-huang strikes again: ephedrine nephrolithiasis. Am J Kidney Dis. Jul 1998;32(1):153-9. [Medline].
6. Patel MM, Wright DW, Ratcliff JJ, Miller MA. Shedding new light on the "safe" club drug: methylenedioxymethamphetamine (ecstasy)-related fatalities. Acad Emerg Med. Feb 2004;11(2):208-10. [Medline].
7. McElhatton PR, Bateman DN, Evans C, et al. Congenital anomalies after prenatal ecstasy exposure. Lancet. Oct 23 1999;354(9188):1441-2. [Medline].
8. Alim TN, Rosse RB, Vocci FJ Jr, et al. Diethylpropion pharmacotherapeutic adjuvant therapy for inpatient treatment of cocaine dependence: a test of the cocaine-agonist hypothesis. Clin Neuropharmacol. Apr 1995;18(2):183-95. [Medline].
9. Chait LD, Uhlenhuth EH, Johanson CE. Phenylpropanolamine: reinforcing and subjective effects in normal human volunteers. Psychopharmacology (Berl). 1988;96(2):212-7. [Medline].
10. Cody JT, Valtier S, Stillman S. Amphetamine and fenproporex levels following multidose administration of fenproporex. J Anal Toxicol. May-Jun 1999;23(3):187-94. [Medline].
11. Dinges DF, Arora S, Darwish M, Niebler GE. Pharmacodynamic effects on alertness of single doses of armodafinil in healthy subjects during a nocturnal period of acute sleep loss. Current Medical Research and Opinion. January 2006;22 (No.1):159-167. [Medline].
12. Glazer G. Long-term pharmacotherapy of obesity 2000: a review of efficacy and safety. Arch Intern Med. Aug 13-27 2001;161(15):1814-24. [Medline].
13. Gurley BJ, Gardner SF, Hubbard MA. Content versus label claims in ephedra-containing dietary supplements. Am J Health Syst Pharm. May 15 2000;57(10):963-9. [Medline].
14. Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med. Dec 21 2000;343(25):1833-8. [Medline].
15. Hardman JG, Limbird LE, Gilman AG, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 10^th ed. New York, NY: McGraw-Hill; 2001.
16. Harsh JR, Hayduk R, Rosenberg R, et al. The efficacy and safety of armodafinil as treatment for adults with excessive sleepiness associated with narcolepsy. Current Medical Research and Opinion. April 2006;22 (No. 4):761-764. [Medline].
17. Hirshkowitz M, Black JE, Wesnes K, Niebler G, Arora S, Roth T. Adjunct armodafinil improves wakefulness and memory in obstructive sleep apnea/hypopnea syndrome. Respiratory Medicine. March 2007;101 (3):616-627. [Medline].
18. Jacobs KM, Hirsch KA. Psychiatric complications of Ma-huang. Psychosomatics. Jan-Feb 2000;41(1):58-62. [Medline].
19. Kernan WN, Viscoli CM, Brass LM, et al. Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med. Dec 21 2000;343(25):1826-32. [Medline].
20. Lieberman HR. The effects of ginseng, ephedrine, and caffeine on cognitive performance, mood and energy. Nutr Rev. Apr 2001;59(4):91-102. [Medline].
21. Martin WR, Sloan JW, Sapira JD, Jasinski DR. Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man. Clin Pharmacol Ther. Mar-Apr 1971;12(2):245-58. [Medline].
22. McCann UD, Mertl M, Eligulashvili V, Ricaurte GA. Cognitive performance in (+/-) 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") users: a controlled study. Psychopharmacology (Berl). Apr 1999;143(4):417-25. [Medline].
23. Parrott AC. Chronic tolerance to recreational MDMA (3,4-methylenedioxymethamphetamine) or Ecstasy. J Psychopharmacology. 2005;19 (1):71-83. [Medline].
24. Pham JV, Puzantian T. Ecstasy: dangers and controversies. Pharmacotherapy. Dec 2001;21(12):1561-5. [Medline].
25. Shannon M. Methylenedioxymethamphetamine (MDMA, "Ecstasy"). Pediatr Emerg Care. Oct 2000;16(5):377-80. [Medline].
26. Teter CJ, Guthrie SK. A comprehensive review of MDMA and GHB: two common club drugs. Pharmacotherapy. Dec 2001;21(12):1486-513. [Medline].
27. Tinsley JA. The hazards of psychotropic herbs. Minn Med. May 1999;82(5):29-31. [Medline].
28. Yacoubian GS. Tracking ecstasy trends in the United States with data from three national drug surveillance systems. J Drug Educ. 2003;33(3):245-58. [Medline].

Article Last Updated: Jan 29, 2008