Background
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
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
Clinical
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
- 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
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
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
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
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
Keywords
insomnia, anorexia, controlled substances, stimulant toxicity, 3, 4-methylenedioxy-methamphetamine, 3, 4-methylenedioxymethamphetamine, MDMA, ecstasy, illicit drugs, drug abuse, illegal drugs, controlled substances, aminorex, methyl-aminorex, ice, methcathinone, cathinone, khat, amphetamines, dextroamphetamine, methamphetamine, phenmetrazine, dexfenfluramine, sibutramine, phentermine, fenfluramine, mazindol, diethylpropion, fenproporex, clortermine, pemoline, sibutramine, Meridia, ma-huang, phenylpropanolamine, PPA, ephedrine, norephedrine, pseudoephedrine, cocaine
More on Stimulants |
| References |
References
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].
Jasinski DR. An evaluation of the abuse potential of modafinil using methylphenidate as a reference. J Psychopharmacol. Mar 2000;14(1):53-60. [Medline].
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].
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].
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].
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].
McElhatton PR, Bateman DN, Evans C, et al. Congenital anomalies after prenatal ecstasy exposure. Lancet. Oct 23 1999;354(9188):1441-2. [Medline].
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].
Chait LD, Uhlenhuth EH, Johanson CE. Phenylpropanolamine: reinforcing and subjective effects in normal human volunteers. Psychopharmacology (Berl). 1988;96(2):212-7. [Medline].
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].
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].
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].
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].
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].
Hardman JG, Limbird LE, Gilman AG, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill; 2001.
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].
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].
Jacobs KM, Hirsch KA. Psychiatric complications of Ma-huang. Psychosomatics. Jan-Feb 2000;41(1):58-62. [Medline].
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].
Lieberman HR. The effects of ginseng, ephedrine, and caffeine on cognitive performance, mood and energy. Nutr Rev. Apr 2001;59(4):91-102. [Medline].
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].
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].
Parrott AC. Chronic tolerance to recreational MDMA (3,4-methylenedioxymethamphetamine) or Ecstasy. J Psychopharmacology. 2005;19 (1):71-83. [Medline].
Pham JV, Puzantian T. Ecstasy: dangers and controversies. Pharmacotherapy. Dec 2001;21(12):1561-5. [Medline].
Shannon M. Methylenedioxymethamphetamine (MDMA, "Ecstasy"). Pediatr Emerg Care. Oct 2000;16(5):377-80. [Medline].
Teter CJ, Guthrie SK. A comprehensive review of MDMA and GHB: two common club drugs. Pharmacotherapy. Dec 2001;21(12):1486-513. [Medline].
Tinsley JA. The hazards of psychotropic herbs. Minn Med. May 1999;82(5):29-31. [Medline].
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].
Further Reading
Keywords
insomnia, anorexia, controlled substances, stimulant toxicity, 3, 4-methylenedioxy-methamphetamine, 3, 4-methylenedioxymethamphetamine, MDMA, ecstasy, illicit drugs, drug abuse, illegal drugs, controlled substances, aminorex, methyl-aminorex, ice, methcathinone, cathinone, khat, amphetamines, dextroamphetamine, methamphetamine, phenmetrazine, dexfenfluramine, sibutramine, phentermine, fenfluramine, mazindol, diethylpropion, fenproporex, clortermine, pemoline, sibutramine, Meridia, ma-huang, phenylpropanolamine, PPA, ephedrine, norephedrine, pseudoephedrine, cocaine
