The vast majority of amphetamine addicts experience symptoms of AW. According to a study conducted several years ago in the United Kingdom, 86% of 50 current or past amphetamine dependent clients reported irritability, musculoskeletal pain, dysphoric moods or depression and impaired social functioning [1]. Less frequently, fatigue, exhaustion, chills, night sweats, sleeping disorders, nausea and vomiting, headaches and an increased appetite were noted. Here, AW symptoms lasted up to a few weeks.

These observations have been confirmed in other studies [8]. Most severe symptoms occur within a few days after initiation of detoxification and some symptoms may persist for a few weeks. In rare cases, complete resolution of AW complaints could only be achieved within several months.

Because amphetamines act as psychotropic stimulants, cessation of administration may uncover underlying mood disorders and depression. Dysphoric moods are one of the main triggers of relapse. If amphetamines are not available, dependent patients may switch to other drugs. Abuse of cannabis, alcohol and benzodiazepines are very common among patients undergoing AW.

Amphetamines cause erectile dysfunction but generally augment the sexual drive. It is therefore not uncommon to detect symptoms of sexually transmitted diseases in AW patients [9].

• Fatigue

  […] the drug, fatigue may set in Excessive sleeping - Along with the fatigue will come long periods of sleep as the body attempts to repaid some of the damage done by no sleep when taking amphetamines Increased appetite - To offset the loss of hunger while [gomentor.com]

  But while lethargy, fatigue and increased appetite were relieved by administration of amineptine, craving for amphetamines and risk of relapse could not be decreased. [symptoma.com]

  After taking bupropion, his withdrawal symptoms i.e. dysphoric mood, fatigue, somnolence, and psychomotor retardation gradually disappeared within two to three days. Moreover, his craving for amphetamines was absent. [ncbi.nlm.nih.gov]

  Amphetamine withdrawal effects include depression, fatigue, irritability, anxiety, trouble concentrating, and increased appetite. In a worst-case scenario, a person may become suicidal or profoundly depressed. [withdrawal.net]

  The worst onset of symptoms (fatigue, depression and disorientation) often occurs directly after withdrawal or coming off of Adderall. Many people report that the most common reaction to acute Adderall withdrawal is that of fatigue and oversleeping. [prescription-drug.addictionblog.org]

• Increased Energy

  In order to increase energy, alertness, concentration, self-confidence and sociability, many individuals will begin taking Amphetamines. [mtregis.com]

  At first, it may take only a small amount of the drug to produce the increased energy and alertness, but as tolerance develops and grows, the user will find that more amphetamine is required in order for the effects of the drug to be reproduced on the [drugfree.com]

  Signs and Symptoms of Amphetamine Abuse include: Increased body temperature Euphoria Increased blood pressure Dry mouth Faster breathing Dilated pupils Increased energy and alertness Decreased fatigue Decreased appetite Before amphetamine’s addictive [narconon.org]

• Chills

  Two (or more) of the following signs or symptoms, developing during, or shortly after, stimulant use: Tachycardia or bradycardia Pupillary dilatation Elevated or lowered blood pressure Perspiration or chills Nausea or vomiting Evidence of weight loss [emedicine.medscape.com]

  Other signs and symptoms of intoxication are increased heartrate, dilation of the pupils, elevated or lowered blood pressure, perspiration or chills, nausea or vomiting, weight loss, cardiac irregularities and, eventually, confusion, seizures, coma, or [minddisorders.com]

  Less frequently, fatigue, exhaustion, chills, night sweats, sleeping disorders, nausea and vomiting, headaches and an increased appetite were noted. Here, AW symptoms lasted up to a few weeks. These observations have been confirmed in other studies. [symptoma.com]

  Children Children under 13 who quit taking Adderall may experience: a loss of appetite sleep problems including insomnia and oversleeping stomach cramps, diarrhea, pains nausea & vomiting fever & chills anxiety, nervousness, jittery behavior Teenagers [adderalladdictionsupport.com]

• Camping

  At the cellular level, opioid tolerance and withdrawal is modulated by alterations in kinase cascades, which modulate the production and effects of second messengers such as cyclic adenosine monophosphate (cAMP). [emedicine.medscape.com]

  It sits on the fence politically, legally, socially and even in terms of addictions, with camps of ardent supporters on either side of the issue. [drugaddictionhelponline.com]

• Gangrene

  Difficulties swallowing, voice problems, gastrointestinal bleeding, bowel gangrene, nosebleeds and loss of weight, appetite, and the sense of smell also occur as a result of using cocaine. [livestrong.com]

• Overeating

  In spite of these limited benefits, amineptine is not available for use due to concerns over abuse liability when using the drug. [ncbi.nlm.nih.gov]

  Over the last 4-5 years(used ephedrine for over a year, previously), I've had some serious side-effects, totally life altering side-effects. Hello people. [healthquestions.medhelp.org]

  Come back often and play the songs over and over again. You won't be sorry. God will teach you many things you need to know. A Communication From God : A meditation tape that will give you long communications from God. [robertperkinson.com]

• Increased Appetite

  But while lethargy, fatigue and increased appetite were relieved by administration of amineptine, craving for amphetamines and risk of relapse could not be decreased. [symptoma.com]

  The week-1 and week-2 intention-to-treat analyses showed that the mean AWQ reversed vegetative scores (combined scores of decreased energy, increased appetite and craving for sleep items) of the amineptine group were significantly lower than those of [ncbi.nlm.nih.gov]

  Read More Some of the common amphetamine withdrawal signs and symptoms include: 4 Fatigue and increased need for sleep. Increased appetite. Bodily movements and twitches. Slowed reaction and movement. Aches and pains. Irritability and/or agitation. [withdrawal.net]

  Dysphoric mood and two (or more) of the following physiological changes, developing within a few hours to several days after Criterion A: (1) fatigue (2) vivid, unpleasant dreams (3) Insomnia or Hypersomnia (4) increased appetite (5) psychomotor retardation [behavenet.com]

  The analysis revealed that in order of ranking, craving for sleep, increased appetite, decreased energy, dysphoric mood, slowing of movement and loss of interest or pleasure attracted the highest mean scores. [health.gov.au]

• Diarrhea

  Intravenous (IV) fluids are sometimes needed if the baby becomes dehydrated or has severe vomiting or diarrhea. [stanfordchildrens.org]

  Children Children under 13 who quit taking Adderall may experience: a loss of appetite sleep problems including insomnia and oversleeping stomach cramps, diarrhea, pains nausea & vomiting fever & chills anxiety, nervousness, jittery behavior Teenagers [adderalladdictionsupport.com]

  […] reported at very high doses of modafinil include the following symptoms: Excitation, anxiety, or agitation Insomnia, Slight or moderate elevations in hemodynamic parameters (e.g., blood pressure or heart rate changes such as heart palpitations) Tremor Diarrhea [americanaddictioncenters.org]

  In addition to the caloric expenditure caused by increased activity, crying, and decreased sleep, calories may be lost through vomiting, drooling, and diarrhea. [pediatrics.aappublications.org]

• Dyspepsia

  When controlled studies have listed the side effects of modafinil that occur with normal use compared to placebo control groups, the most common reported side effects appear to be: High blood pressure Rash Headache Nausea Nervousness Anxiety Dizziness Dyspepsia [americanaddictioncenters.org]

• Muscle Cramp

  Following amphetamine intoxication, a "crash" occurs with symptoms of anxiety, shakiness, depressed mood, lethargy, fatigue, nightmares, headache, perspiring, muscle cramps, stomach cramps, and increased appetite. [minddisorders.com]

  Long-acting benzodiazepines can be added to control insomnia and muscle cramps. Stimulant-withdrawal syndrome is treated by observation alone and does not require any specific medications. See Treatment and Medication for more detail. [emedicine.medscape.com]

• Myalgia

  The syndrome is characterized by rhinorrhea, sneezing, yawning, lacrimation, abdominal cramping, leg cramping, piloerection (gooseflesh), nausea, vomiting, diarrhea, mydriasis, myalgias and arthalgias. [emedicine.medscape.com]

• Dysphoric Mood

  They usually comprise: Dysphoric moods, depression Fatigue Sleeping disorders Irritability Increased appetite Vivid, unpleasant dreams Musculoskeletal pain Diagnosis AW may be diagnosed if a patient presents dysphoric mood and at least two additional [symptoma.com]

  After taking bupropion, his withdrawal symptoms i.e. dysphoric mood, fatigue, somnolence, and psychomotor retardation gradually disappeared within two to three days. Moreover, his craving for amphetamines was absent. [ncbi.nlm.nih.gov]

  Dysphoric mood and two (or more) of the following physiological changes, developing within a few hours to several days after Criterion A: (1) fatigue (2) vivid, unpleasant dreams (3) Insomnia or Hypersomnia (4) increased appetite (5) psychomotor retardation [behavenet.com]

  The analysis revealed that in order of ranking, craving for sleep, increased appetite, decreased energy, dysphoric mood, slowing of movement and loss of interest or pleasure attracted the highest mean scores. [health.gov.au]

  Dysphoric mood and two (or more) of the following physiologic changes developing within a few hours to several days after Criterion A: Fatigue Vivid, unpleasant dreams Insomnia or hypersomnia Increased appetite Psychomotor retardation or agitation The [emedicine.medscape.com]

• Psychomotor Retardation

  After taking bupropion, his withdrawal symptoms i.e. dysphoric mood, fatigue, somnolence, and psychomotor retardation gradually disappeared within two to three days. Moreover, his craving for amphetamines was absent. [ncbi.nlm.nih.gov]

  Dysphoric mood and two (or more) of the following physiological changes, developing within a few hours to several days after Criterion A: (1) fatigue (2) vivid, unpleasant dreams (3) Insomnia or Hypersomnia (4) increased appetite (5) psychomotor retardation [behavenet.com]

  Dysphoric mood and two (or more) of the following physiologic changes developing within a few hours to several days after Criterion A: Fatigue Vivid, unpleasant dreams Insomnia or hypersomnia Increased appetite Psychomotor retardation or agitation The [emedicine.medscape.com]

  Psychomotor retardation or agitation. The stimulant (or closely related substance) is taken to relieve or avoid withdrawal symptoms. [mentalhealth.com]

• Anger

  Clinically significant problematic behavioral or psychological changes (e.g., euphoria or affective blunting; changes in sociability; hypervigilance; interpersonal sensitivity; anxiety, tension, or anger; stereotyped behaviors; impaired judgment) that [emedicine.medscape.com]

  Other symptoms include anxiety, tension, grandiosity, repetitive behavior, anger, fighting, and impaired judgment. [minddisorders.com]

  The most common symptoms experienced include: skin & acne problems lack of sleep OR over-sleeping fatigue OR hyperactive behavior irritability, anger anxiety and panic attacks personality changes that your friends and family will notice psychosis or psychotic [adderalladdictionsupport.com]

  […] impairment Economic problems caused by squandering money or drug-related unemployment Works poorly with others Wisdom vs Irrationality : Impaired cognitive functioning Eccentricity, delusions, hallucinations Courage vs Negative Emotion : Depression, anger [mentalhealth.com]

• Compulsive Behavior

  Obsessive-compulsive behavior Helping Others vs Detachment : Suspiciousness, social withdrawal Self-Control vs Disinhibition : Impulsivity, dangerous risk taking, intoxicated behavior Justice vs Antagonism: Irresponsibility, prostitution or drug-dealing [mentalhealth.com]

  That said, addiction remains characterized by uncontrollable or compulsive behavior to the detriment of the individual’s health. Because each case is unique, no single approach can be taken towards the treatment of drug addiction. [drugaddictionhelponline.com]

• Stroke

  Heart attacks often occur as do strokes. Strokes are a result of blood pressure becoming so high that the vessels in the brain begin to burst. Amphetamines as a group include drugs such as crystal, MDMA, Ecstasy, speed and Meth (methamphetamine). [addictionhope.com]

  Detoxing from amphetamine is not always dangerous, but for some, the risk of heart attack, stroke, coma or death is eminent when a drug such as an amphetamine is abruptly removed or eliminated from regular use. [drugfree.com]

  (Image: lolostock/iStock/Getty Images) Physical side effects include seizures, trembling, loss of balance, strokes, nerve damage, headaches, coma, nausea, stomach pain and major heart problems, including heart attacks. [livestrong.com]

• Poor Coordination

  Common symptoms and dangers of amphetamine withdrawal include: Excessive Sleeping Depression Nagging Hunger That Won't Stop Arrhythmia Cardiac Arrest Tachycardia Poor Coordination Upset Stomach Tremors and Increased Risk of Seizure Hallucinations Misperception [drugfree.com]

• Difficulty Concentrating

  Common symptoms include fatigue, depression and difficulty concentrating. What Is Adderall Withdrawal? People who take large doses of Adderall for prolonged periods of time run the risk of becoming physically dependent on the drug. [addictioncenter.com]

According to the current version of the Diagnostic and Statistical Manual of Mental Disorders, diagnosis of AW is based on the patient's medical history, clinical and psychological examination:

• Anamnesis should reveal prolonged use of amphetamines and recent reduction or cessation of administration.
• AW patients feel a strong desire to use amphetamines again.
• Dysphoric moods are an exclusion criterion for AW.
• Furthermore, the patient claims at least two of the following symptoms: fatigue, insomnia or hypersomnia, psychomotor agitation or retardation, increased appetite, vivid dreams.
• These symptoms interfere with day-to-day activities and social functioning and may not be explained by any other pathological condition, substance abuse or withdrawal.

Drug abuse and drug dependence are no longer distinguished clinically and the above given definition holds true for both conditions.

Several compounds have been tested for their effectivity in AW, but there is no approved drug for treatment of this condition nor sufficient scientific evidence that would justify such an approval [8].

Amineptine, a tricyclic antidepressant, has been proven to alleviate symptoms resulting from autonomous dysfunction [3]. But while lethargy, fatigue and increased appetite were relieved by administration of amineptine, craving for amphetamines and risk of relapse could not be decreased. Reboxetine, an antidepressant that inhibits reuptake of norepinephrine, has also been proposed as a possible therapeutic approach to AW. This recommendation is based on a small clinical study comprising eleven patients. In ten out of eleven patients, "some beneficial effects withdrawing from amphetamine" were observed [4]. Finally, AW has been treated with mirtazapine, a noradrenergic and serotonergic antidepressant [10]. This compound has initially been found to reduce agitation and anxiety, but not depression. However, a following study could not confirm these results [11].

Psychological therapy may be of greater use than any medication. Both individual therapy, group or family sessions may be helpful. Methods like cognitive behavioral therapy and contingency management may be applied [5].

Prolonged use of amphetamines induces physical and psychological dependence. The former results from reversible receptor desensitization and is self-limiting if patients don't have relapses. However, cognitive function may be partially permanent [7]. Psychological support as well as changes to the patient's social environment may be required to overcome the latter because the desire to feel amphetamine-mediated euphoria may persist even after neurotransmitter balance is regained.

Amphetamines is a rather broad term and may refer to any of the following illegal drugs:

• Amphetamine ("Speed")
• Methylenedioxyamphetamine ("Sally", "Sass")
• Metamphetamine ("Crystal", "Crystal Meth")
• 3,4-Methylenedioxymethamphetamine ("Ecstasy")
• Other derivatives of amphetamine

While addiction and AW are generally associated with use of illicit drugs, application of certain amphetamines and derivatives is approved in Europe and the United States for treatment of attention deficit and hyperactivity disorder (ADHD). This applies to dextroamphetamine, for instance.

It has been suggested that both an individual predisposition and environmental factors play key roles in developing drug dependence. Although these are general assumptions, they are most likely applicable to amphetamine abuse. In this context, a family history of drug addiction may be considered a risk factor for amphetamine dependence. However, it is unclear whether this fact results from inherited gene variants or from persisting social surroundings that facilitate access to legal and illegal drugs. While the latter may seem more plausible, inherited alterations of central nervous system signaling cascades may in fact render a person more susceptible to the effects of amphetamines and other drugs.

Psychological disorders are generally considered to increase the risk of drug dependence.

Abuse and subsequent dependence on amphetamines constitutes a public health concern of increasing importance. While there are regional differences in incidence and prevalence of amphetamine abuse, alarmingly high figures are reported from all continents. According to a survey conducted in the United States in 2006, more than 1% of all respondents had consumed amphetamine, metamphetamine or related drugs during the previous month. In Australia and New Zealand, numbers of amphetamine addicts exceed those of cocaine addicts by far, while the opposite seems to be the case in Africa [5]. Independent of their geographical location, the vast majority of patients that reduce or cease amphetamine administration experience symptoms of AW.

Amphetamines are indirect sympathomimetics that bind to distinct receptors expressed in the central nervous system. They alter extracellular concentrations of monoamines, i.e., of dopamine, norepinephrine, serotonin and other neurotransmitters by impeding re-uptake and increasing release.

Different molecular mechanisms have been identified:

• Amphetamines and dopamine. Under physiological conditions, dopamine is cleared from the synaptic cleft by reuptake into presynaptic neurons. Reuptake is mediated by dopamine transporter DAT. Now, amphetamines serve as substrates for this transporter and therefore act as competitive inhibitors of DAT. It has also been proposed that amphetamines induce reverse dopamine transport through DAT independent of neurotransmitter release triggered by an action potential [6].
• Amphetamines and norepinephrine. Presumably, inhibition of reuptake and induction of reverse transport also account for prolonged action of norepinephrine.

Pharmacodynamic tolerance is induced by desensitization of amphetamine receptors. Consequently, equal amounts of amphetamines (or endogenous ligands) are insufficient to trigger neurotransmitter release and higher doses are necessary. After reduction or cessation of amphetamine use, desensitization persists for a few days. Limited excitability of these neurons causes symptoms of AW and since they are part of the reward pathway, AW patients experience dysphoric moods, depression and irritability.

Of note, pharmacodynamic tolerance should not be confused with tachyphylaxis. The latter consists in decreased effectivity of amphetamines administered within short periods of time after those drugs had been used for the last time. Here, neurotransmitter stores are not yet replenished and even though receptors are not yet desensitized, amphetamines will not cause significant increases of extracellular monoamine levels.

Distinct amphetamines may present different affinities to determined molecular targets. Also, desensitization varies with receptors and with ligands. And although symptoms associated with AW result from physical and psychological dependence, the individual experience of withdrawal largely depends on the patient, on the drug they used and on consumption habits.

Education is the key to prevent all kinds of drug abuse. There are no specific measures regarding amphetamine dependence unless information about detrimental effects, possible permanent impairment of cognitive function and symptoms associated with AW.

Most amphetamine addicts use other legal and illicit drugs before first administration of amphetamine or related substances. Frequently, drugs are sold and consumed in secondary schools, high schools and colleges. Social pressure may be particularly high in these institutions. Thus, the above mentioned education programs should primarily be addressed to adolescents and young adults. They should be comprehensive and not restricted to amphetamines.

Amphetamine addicts should have the possibility to seek psychological counseling in order to resolve their problems.

Amphetamines pertain to the large group of psychoactive drugs, more precisely to those mediating central nervous system stimulation. From a pharmacological point of view, amphetamines act as central sympathomimetics. They bind to distinct receptors and increase extracellular concentrations of the neurotransmitters dopamine, norepinephrine and serotonin in various brain regions. Elevated levels of these neurotransmitters are associated with alertness, agitation, euphoria, hallucinations, reduction of appetite and hypertension.

Alertness and above all euphoria cause psychological dependence on amphetamines. Additionally, prolonged intake of amphetamines induces pharmacodynamic tolerance, i.e., doses need to be constantly increased in order to trigger the desired effect. Pharmacodynamic tolerance is mainly mediated by desensitization of receptors and subsequent decrease of neurotransmitter release. Reduction of receptor density may also play an important role. Pharmacodynamic tolerance is related to physical dependence on these drugs.

Therefore, any reduction of amphetamine doses or cessation of intake causes symptoms of amphetamine withdrawal (AW) [1]. Symptom onset usually occurs within one day after significant dose reduction or discontinuation of amphetamine use. In order to overcome AW, the patient needs to resist the desire to consume amphetamines and has to endure dysphoric moods, irritability, depression, fatigue, sleep disorders and possibly pain. These complaints interfere with life quality and often cause relapses or administration of other drugs to compensate for the lack of amphetamines [2].

According to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V), in order to be diagnosed with AW, a patient needs to present at least two of the above mentioned symptoms. Symptoms have to be observed in a close temporal connection with reduction or cessation of amphetamine use and cannot be explained by any other pathological condition.

No drugs are approved for AW treatment, and few studies yielded promising results [3] [4].

Amphetamine is the name of an illicit drug; it is also the name of a group of substances that comprises amphetamine itself ("Speed"), Methylenedioxyamphetamine ("Sally", "Sass"), Metamphetamine ("Crystal", "Crystal Meth") 3,4-Methylenedioxymethamphetamine ("Ecstasy") and other compounds. Prolonged use of these drugs causes physical and psychological dependence and therefore, symptoms corresponding to amphetamine withdrawal (AW) are experienced if doses are drastically reduced or administration of amphetamines is ceased altogether.

Causes

From a pharmacological point of view, amphetamines are psychotropic stimulants that bind to distinct receptors in the central nervous system. Here, they mediate an increase in extracellular concentrations of neurotransmitters like dopamine, norepinephrine and serotonin. These effects cause alertness, agitation, euphoria, hallucinations, reduction of appetite and hypertension.

Over time, amphetamine receptors "get used" to the administrated drug and higher doses become necessary to induce the same effect. This phenomenon is deemed tolerance. If amphetamine use is suddenly stopped, these receptors remain sensitized for a few days or weeks and symptoms of physical dependence manifest.

The above mentioned effect of euphoria is what triggers psychological dependence. Amphetamine addicts crave to experience that effect again and desire to readminister the drug.

Symptoms

Symptoms are most severe within the first few days after initiation of detoxification. They usually comprise:

• Dysphoric moods, depression
• Fatigue
• Sleeping disorders
• Irritability
• Increased appetite
• Vivid, unpleasant dreams
• Musculoskeletal pain

Diagnosis

AW may be diagnosed if a patient presents dysphoric mood and at least two additional symptoms included in the list given above. These complaints show a close temporal connection to cessation of drug use and can't be explained by other pathological conditions, substance abuse or withdrawal.

Treatment

There is no medical treatment for AW. A few compounds have been tested for their effectivity in this condition, but evidence supporting beneficial effects is scarce. Recommendations are merely based on observations made in very small test groups and therefore, no compound has been approved for AW therapy so far. However, psychological treatment - in form of individual, group or family sessions - may be of great help to overcome amphetamine dependence.

Recognition of amphetamine dependence is the first step in the right direction. Nobody should hesitate to seek professional help.

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