Amphetamine side effects include neurotoxicity and neuronal damage.
Amphetamines in FOCUS
Are short-term benefits worth long-term effects?
Updated January 8, 2019
These powerful stimulants do more than increase alertness, concentration and mental productivity, amphetamines decrease fatigue and produce a short-term mood elevation, even in those who are not depressed. Like steroids for the brain, amphetamines appear to make people feel like they perform better at whatever they do—until the effects wear off. The next day without the drug, amphetamine users often complain that they feel tired, “stupid,” or depressed.
Like steroids for the brain, amphetamines appear to make people feel like they perform better at whatever they do—until the effects wear off.
The real trouble begins when the user doesn't stop taking the drug.
Amphetamine Side Effects
Amphetamines damage brain cells needed for cognitive speed and function.
A clinical study funded by the National Institutes of Health compared persons who had previously used amphetamines with non-users. The former drug users were found to have significantly lower levels of N-acetylasparatate (a neuronal marker indicating neurotoxicity and damage) in two key areas of their brains, the basal ganglia and frontal white matter.
Researchers found amphetamine users develop the same neuronal damage as found in dementia and Alzheimer's disease. The lead scientist, Dr. Thomas Ernst, stated: “Many brain diseases associated with brain cell or neuronal damage or loss, such as Alzheimer's disease and other dementia, epilepsy, multiple sclerosis, brain tumors, stroke and HIV brain diseases, consistently have shown decreased N-acetylaspartate. This, in the drug users' brains, suggests neuronal loss or damage as a result of long-term methamphetamine use.”
Researchers found amphetamine users develop the same neuronal damage as found in dementia and Alzheimer's disease.
The areas of greatest damage are responsible for communication within the brain. Basal ganglia is in the deepest inner region of the brain and acts as a major switching station for thinking ability, problem solving, task flexibility, motor function and emotion. Frontal white matter provides communication pathways for cognitive speed and cognitive function.
Ernst T, et al. Evidence for long-term neurotoxicity associated with methamphetamine abuse A 1H MRS study. Neurology 2000;54(6):1344-1349.
DEA Schedule II Control Substance means this drug has a “high potential for abuse” that “may lead to severe psychological or physical dependence,” and the federal government sets limits on the amount that may be manufactured each year.
How Do Amphetamines Work?
Amphetamines work by by initiating the acute stress response (“fight or flight” response). The central nervous system prepares the body for physical action by creating physiological changes as if it were stressed or under threat. These changes include:
The release of adrenaline, raises cortisol levels and other stress hormones
Increased heart rate and blood pressure
Redirected blood flow into the muscles and away from the brain
Small doses of amphetamines can banish tiredness and make the user feel alert and refreshed. However, the burst of energy comes at a price. A “speed crash” always follows the high and typically leaves the user feeling nauseous, irritable, depressed and extremely exhausted.
“The effects of amphetamines and methamphetamine are similar to cocaine, but their onset is slower and their duration is longer.”
ABOVE:Drug Enforcement Administration (DEA), US Department of Justice (DOJ). “Drug Fact Sheet: Amphetamines,” undated, retrieved 1/5/2013: www.justice.gov/dea/druginfo/drug_data_sheets/Amphetamines.pdf
Do Not Use If
You have not tried other psychotherapy, have high blood pressure or any form of heart disease, are very nervous or have severe insomnia, have a history of addiction to drugs or alcohol, or have Tourette syndrome. Do not combine with monoamine oxidase inhibitors.
Nervousness including agitation, anxiety and irritability
Addiction
Less Common Side Effects of Amphetamines
High blood pressure
Rapid pulse rate
Tolerance (constant need to raise the dose)
Feelings of suspicion and paranoia
Visual hallucinations (seeing things that are not there)
Depression
Cocaine craving
Dermatoses (infected or diseased skin)
Urinary tract infection
Infection or viral infection
Elevated ALT enzyme levels in the blood (signaling liver damage)
Overdose Side Effects of Amphetamines
Amphetamines have been extensively abused. Extreme psychological dependence and severe social disability have resulted. Abuse of amphetamines may cause a sudden heart attack even in those with no signs of heart disease. Symptoms of overdose that require immediate medical assistance include:
Restlessness
Tremor
Aggression
Hallucinations
Panic states
Hyperreflexia (overactive reflexes, which can include twitching or spasms)
Personality changes
Symptoms of depression
Seizures or abnormal EEGs
High blood pressure
Rapid heart beat
Swelling of hands/feet/ankles (for example, numbing of the fingertips)
Delusions
Sweating
Vomiting
Dehydration
Unexplained muscle pain
Lower abdominal pain
Rhabdomyolysis and kidney damage
Chronic abuse can manifest itself as psychosis, often indistinguishable from schizophrenia
Amphetamine-Induced Anxiety Disorder
The onset of amphetamine-induced anxiety disorder can occur during amphetamine use or withdrawal, according to the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders as cited in the best-selling psychiatry text, Kaplan and Sadock's Synopsis of Psychiatry.
“Amphetamine, as with cocaine, can induce symptoms similar to those seen in obsessive disorder, panic disorder, and phobic disorders,” states Synopsis of Psychiatry.
Amphetamine-Induced Psychosis
Induction of schizophrenic-like states in children on prescribed doses of stimulant medications, including Adderall (amphetamines), have been observed, though not as well documented as with amphetamine abusers, according to The Journal of the American Board of Family Medicine in an article entitled, “Adderall-Induced Psychosis in an Adolescent.”
Amphetamine-Induced Sexual Dysfunction
The American Psychiatric Association’s Manual of Mental Disorders, Synopsis of Psychiatry states: “High doses and long-term use of amphetamines are associated with erectile disorder and other sexual dysfunctions.”
FDA: Links Between ADHD Drugs and Priapism and Sexual Dysfunction
In a 2013 drug-safety announcement, the FDA announced that drugs containing methylphenidate must including warnings about the risk of priapism. It's a serious problem. Priapism is a persistent, usually painful, erection that lasts for more than four hours and occurs without sexual stimulation. If the condition is not treated immediately, it can lead to scarring and permanent erectile dysfunction.
The safety warning also raised concerns about links between priapism and amphetamine drugs, which include Adderall.
ABOVE: U.S. FDA Drug Safety Communication, “FDA warns of rare risk of long-lasting erections in males taking methylphenidate ADHD medications and has approved label changes.” (12/17/2013).
It is possible to build up a tolerance to amphetamines, which means the person using the drug needs to take larger doses to achieve the same effect. Over time, the body might come to depend on amphetamines just to function normally. The person craves the drug and their psychological dependence makes them panic if access is denied, even temporarily.
Withdrawal symptoms can include tiredness, panic attacks, crankiness, extreme hunger, depression and nightmares. Some people experience a pattern of “binge crash” characterized by using continuously for several days without sleep, followed by a period of heavy sleeping.
If It Doesn't Work
The drug should be stopped gradually. Withdrawal symptoms are psychological and stopping suddenly can cause extreme fatigue and severe, even suicidal, depression in adult patients.
Abrupt cessation of Adderall and Adderall XR can cause extreme fatigue and severe, even suicidal, depression in adult patients.
ABOVE: The Essential Guide to Psychiatric Drugs—Rev. and updated (2007).
If It Does Work
“In the treatment of ADHD for children and young adults, Adderall XR is now prescribed frequently, often as a first-line drug. This is, in my opinion, a very serious mistake,” states Jack M. Gorman, M.D., professor of psychiatry at Columbia University and deputy director of the New York State Psychiatric Institute. “Adderall is now abused throughout college campuses, where it is bought, sold, stolen, borrowed, snorted and injected. It is a very powerful drug that undoubtedly works for ADHD, but there are alternatives with less abuse potential that should be tried first.”
Amphetamines produce gross reductions in blood flow to the brain.
Decreased blood flow to the brain plays a major role in cognitive impairment, dementia and Alzheimer's.
ABOVE: Abreu BE, et al. Influence of amphetamine sulfate on cerebral metabolism and blood flow in man. J Pharm Sci, 1949;38:186–188. Mazza M, et al. Primary cerebral blood flow deficiency and Alzheimer's disease: shadows and lights. Journal of Alzheimer's Disease 2011;23(3):375-89.
What are the differences between the various Amphetamines?
“All amphetamines have essentially the same chemical properties and their actions are so alike that even experienced users may not feel a difference between them.”
ABOVE: Drug Enforcement Administration (DEA), US Department of Justice (US DOJ). “Amphetamines,” Drugs of Abuse Publication. National Drug Intelligence Center, 2005 ed.
In small doses amphetamines can banish tiredness and make the user feel alert and refreshed. However, the burst of energy comes at a price. A "speed crash" always follows the high and may leave the person feeling nauseous, irritable, depressed and extremely exhausted. [More]
Many think methylphenidate (Ritalin) is safe, or mild, because so many children use it. However, the government classifies the psychoactive drug with cocaine and morphine because it's highly addictive. [More]
Although Vyvanse is referred to as “pro-drug” of dextroamphetamine, it's still an amphetamine, meaning that it's easily abused and can cause insomnia, agitation, anxiety and sometimes psychotic symptoms like seeing things or becoming paranoid. [More]
Most people may not know that Strattera (atomoxetine) appears to cause unsatisfactory sexual function (decreased libido, ejaculatory problems and impotence). [More]
Drug Enforcement Administration, US Department of Justice. “Amphetamines,” Drugs of Abuse Publication. National Drug Intelligence Center, 2005 ed.
Drug Enforcement Administration, US Department of Justice. “Drug Fact Sheet: Amphetamines,” undated, retrieved January 5, 2013: justice .gov/dea/ druginfo/ drug_data_sheets/ Amphetamines.pdf.
National Institute of Mental Health. Medications. Bethesda, MD: National Institute of Mental Health,
National Institutes of Health, US Department of Health and Human Services; NIH Publication No. 02-3929, 2007 ed.
Australian Drug Foundation, Victorian Minister for Health. “Amphetamines Fact Sheet,” 2007 ed.: betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf /pages/Amphetamines.
Johns Hopkins Medicine, Health Alerts, “Heart Attack: Symptoms and Remedies”: johnshopkinshealthalerts.com/symptoms_remedies/ heart_attack/83-1.html#3 (2008).
U.S. Food and Drug Association, Center for Drug Evaluation and Research. “Public Health Advisory for Adderall and Adderall XR,” 02/09/2005.
Adderall XR Medication Guide, Rev. 03/2009.
Sadock, B.J., et al. Kaplan and Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry (Synopsis of Psychiatry), 10th ed. Philadelphia, PA; Lippincott Williams & Wilkins, 2007.
American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC, 2000, as cited above.
S., L.K., et al. “Adderall-Induced Psychosis in an Adolescent,” The Journal of the American Board of Family Medicine. Vol. 15 No. 6, Nov-Dec 02.
Gorman, Jack M. The Essential Guide to Psychiatric Drugs—Rev. and updated, 4th ed. New York, NY: St. Martin's Press, 2007.
Westover AN, Nakonezny PA. “Aortic dissection in young adults who abuse amphetamines.” Am Heart J 2010; 160:315-321.
Seppa N. “Amphetamine abusers face blood vessel risk,” Science News, Web ed. Aug. 23, 2010: sciencenews .org.
National Institutes of Health. “Aortic dissection: Aortic aneurysm - dissecting” PubMed Health, produced by the National Center for Biotechnology Information, a division of the National Library of Medicine at the National Institutes of Health, dated 5/4/2010: ncbi.nlm.nih.gov/pubmedhealth/ PMH0001233/
Isselbacher, EM; Eagle KA, Zipes DP, et al. “Diseases of the aorta”. In Braunwald. Heart disease: a textbook of cardiovascular medicine (5th ed.). Philadelphia: WB Saunders, pp. 1546:81, 1997.
Abreu BE, et al. Influence of amphetamine sulfate on cerebral metabolism and blood flow in man. J Pharm Sci, 1949;38:186–188.
Lombard J, et al. The Brain Wellness Plan; Kensington Pub. Corp., 1998.
Mazza M, et al. Primary cerebral blood flow deficiency and Alzheimer's disease: shadows and lights. Journal of Alzheimer's Disease 2011;23(3):375-89.
