|amphetamine aspartate monohydrate||(25%) stimulant|
|amphetamine sulfate||(25%) stimulant|
|dextroamphetamine saccharate||(25%) stimulant|
|dextroamphetamine sulfate||(25%) stimulant|
|Licence data||US FDA:|
|Routes||Oral, insufflation, rectal, sublingual|
|ATC code||N06 N06|
|(what is this?)|
Adderall[note 1] is a psychostimulant pharmaceutical drug of the phenethylamine class used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. Adderall is also used as a performance and cognitive enhancer, and recreationally as an aphrodisiac and euphoriant. The medication is a mixture of amphetamine stereoisomer salts and inactive ingredients. By salt content, the active ingredients are 75% dextroamphetamine salts (the dextrorotary or "right-handed" enantiomer) and 25% levoamphetamine salts (the levorotary or "left-handed" enantiomer).[note 2][sources 1]
Adderall works by increasing activity of certain neurotransmitters in the brain, namely norepinephrine and dopamine, which results from its interactions with trace amine associated receptor 1 (TAAR1) and vesicular monoamine transporter 2 (VMAT2). Adderall shares many chemical and pharmacological properties with the human trace amine neurotransmitters, especially phenethylamine and N-methylphenethylamine, the latter being an isomer of amphetamine that is produced within the human body.[sources 2]
Adderall is generally well-tolerated and effective in treating the symptoms of ADHD. The most common side effects are cardiovascular, such as irregular heartbeat (usually as a fast heartbeat), and psychological, such as euphoria or anxiety. Much larger doses of Adderall are likely to impair cognitive function and induce rapid muscle breakdown. Substance dependence (i.e., addiction) is a serious risk of Adderall abuse, but only rarely arises from medical use. Very high doses can result in a psychosis (e.g., delusions and paranoia) which rarely occurs at therapeutic doses even during long-term use. Recreational doses are generally much larger than prescribed therapeutic doses, and carry a far greater risk of serious side effects.[sources 3]
- 1 Uses
- 2 Contraindications
- 3 Side effects
- 4 Overdose
- 5 Interactions
- 6 Pharmacology
- 7 History, society, and culture
- 8 Notes
- 9 Reference notes
- 10 References
For kids like Oscar. Specifically gingers.
Amphetamine is used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy, and is sometimes prescribed off-label for its past medical indications, such as depression, obesity, and nasal congestion. Long-term amphetamine exposure in some animal species is known to produce abnormal dopamine system development or nerve damage, but, in humans with ADHD, amphetamines appear to improve brain development and nerve growth. Magnetic resonance imaging studies suggest that long-term treatment with amphetamine decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function in several parts of the brain, such as the right caudate nucleus.
Reviews of clinical stimulant research have established the safety and effectiveness of long-term amphetamine use for ADHD. Controlled trials spanning two years have demonstrated treatment effectiveness and safety. One review highlighted a nine-month randomized controlled trial in children with ADHD that found an average increase of 4.5 IQ points and continued improvements in attention, disruptive behaviors, and hyperactivity.
Current models of ADHD suggest that it is associated with functional impairments in some of the brain's neurotransmitter systems; these functional impairments involve impaired dopamine neurotransmission in the mesocorticolimbic projection and norepinephrine neurotransmission in the locus coeruleus and prefrontal cortex. Psychostimulants like methylphenidate and amphetamine are effective in treating ADHD because they increase neurotransmitter activity in these systems. Approximately 70% of those who use these stimulants see improvements in ADHD symptoms. Children with ADHD who use stimulant medications generally have better relationships with peers and family members, perform better in school, are less distractible and impulsive, and have longer attention spans. The Cochrane Collaboration's review[note 3] on the treatment of adult ADHD with amphetamines stated that while amphetamines improve short-term symptoms, they have higher discontinuation rates than non-stimulant medications due to their adverse side effects.
A Cochrane Collaboration review on the treatment of ADHD in children with tic disorders indicated that stimulants in general do not make tics worse, but high doses of dextroamphetamine in such people should be avoided. Other Cochrane reviews on the use of amphetamine following stroke or acute brain injury indicated that it may improve recovery, but further research is needed to confirm this.
Dosing and administration
Adderall is available as immediate release tablets or extended-release capsules. The extended release capsule is generally used in the morning. The extended release formulation available under the brand Adderall XR is designed to provide therapeutic effect and plasma concentrations identical to taking two doses 4 hours apart.
Therapeutic doses of amphetamine improve cortical network efficiency, resulting in higher performance on working memory tests in all individuals. Amphetamine and other ADHD stimulants also improve task saliency (motivation to perform a task) and increase arousal (wakefulness), in turn promoting goal-directed behavior. Stimulants such as amphetamine can improve performance on difficult and boring tasks, and are used by some students as a study and test-taking aid. Based upon studies of self-reported illicit stimulant use, performance-enhancing use, rather than abuse as a recreational drug, is the primary reason that students use stimulants. However, high amphetamine doses that are above the therapeutic range can interfere with working memory and cognitive control.
Amphetamine is used by some athletes for its psychological and performance-enhancing effects, such as increased stamina and alertness; however, its use is prohibited at sporting events regulated by collegiate, national, and international anti-doping agencies. In healthy people at oral therapeutic doses, amphetamine has been shown to increase physical strength, acceleration, stamina, and endurance, while reducing reaction time. Like the psychostimulants methylphenidate and bupropion, amphetamine increases stamina and endurance in humans primarily through reuptake inhibition and effluxion of dopamine in the central nervous system. At therapeutic doses, the adverse effects of amphetamine do not impede athletic performance; however, at much higher doses, amphetamine can induce effects that severely impair performance, such as rapid muscle breakdown and elevated body temperature.
Adderall has been banned in the National Football League (NFL), Major League Baseball (MLB), National Basketball Association (NBA), and the National Collegiate Athletics Association (NCAA). In leagues such as the NFL, there is a very rigorous process required to obtain an exemption to this rule even when the athlete has been medically prescribed the drug by his physician.
Adderall is considered to have a high potential for misuse. Adderall tablets can be crushed and snorted, or dissolved in water and injected. Injection into the bloodstream can be dangerous because insoluble fillers within the tablets can block small blood vessels.
According to the International Programme on Chemical Safety (IPCS) and United States Food and Drug Administration (USFDA),[note 4] amphetamine is contraindicated in people with a history of drug abuse, heart disease, severe agitation, or severe anxiety. It is also contraindicated in people currently experiencing arteriosclerosis (hardening of the arteries), glaucoma (an eye condition), hyperthyroidism (excessive production of thyroid hormone), or severely elevated blood pressure. People who have experienced allergic reactions to other stimulants in the past or are taking monoamine oxidase inhibitors (MAOIs) are advised not to take amphetamine. These agencies also state that anyone with anorexia nervosa, bipolar disorder, depression, elevated blood pressure, liver or kidney problems, mania, psychosis, Raynaud's phenomenon, seizures, thyroid problems, tics, or Tourette syndrome should monitor their symptoms while taking amphetamine. Evidence from human studies indicates that therapeutic amphetamine use does not cause developmental abnormalities in the fetus or newborns (i.e., it is not a human teratogen), but amphetamine abuse does pose risks to the fetus. Amphetamine has also been shown to pass into breast milk, so the IPCS and USFDA advise mothers to avoid breastfeeding when using it. Due to the potential for reversible growth impairments,[note 5] the USFDA advises monitoring the height and weight of children and adolescents prescribed amphetamines.
The side effects of Adderall are many and varied, but the amount of substance consumed is the primary factor in determining the likelihood and severity of side effects. Adderall is currently approved for long-term therapeutic use by the USFDA. Recreational use of Adderall generally involves far larger doses and is therefore significantly more dangerous, involving a much greater risk of serious side effects.
At normal therapeutic doses, the physical side effects of amphetamine vary widely by age and from person to person. Cardiovascular side effects can include irregular heartbeat (usually an increased heart rate), hypertension (high blood pressure) or hypotension (low blood pressure) from a vasovagal response, and Raynaud's phenomenon (reduced blood flow to extremities). Sexual side effects in males may include erectile dysfunction, frequent erections, or prolonged erections. Abdominal side effects may include stomach pain, loss of appetite, nausea, and weight loss. Other potential side effects include dry mouth, excessive grinding of the teeth, acne, profuse sweating, blurred vision, reduced seizure threshold, and tics (a type of movement disorder). Dangerous physical side effects are rare at typical pharmaceutical doses.
Amphetamine stimulates the medullary respiratory centers, producing faster and deeper breaths. In a normal person at therapeutic doses, this effect is usually not noticeable, but when respiration is already compromised, it may be evident. Amphetamine also induces contraction in the urinary bladder sphincter, the muscle which controls urination, which can result in difficulty urinating. This effect can be useful in treating bed wetting and loss of bladder control. The effects of amphetamine on the gastrointestinal tract are unpredictable. If intestinal activity is high, amphetamine may reduce gastrointestinal motility (the rate at which content moves through the digestive system); however, amphetamine may increase motility when the smooth muscle of the tract is relaxed. Amphetamine also has a slight analgesic effect and can enhance the pain relieving effects of opiates.
USFDA commissioned studies from 2011 indicate that in children, young adults, and adults there is no association between serious adverse cardiovascular events (sudden death, heart attack, and stroke) and the medical use of amphetamine or other ADHD stimulants.[sources 4]
Common psychological effects of therapeutic doses can include increased alertness, apprehension, concentration, decreased sense of fatigue, mood swings (elated mood followed by mildly depressed mood), increased initiative, insomnia or wakefulness, self-confidence, and sociability. Less common side effects include anxiety, change in libido, grandiosity, irritability, repetitive or obsessive behaviors, and restlessness;[sources 5] these effects depend on the user's personality and current mental state. Amphetamine psychosis (e.g., delusions and paranoia) can occur in heavy users. Although very rare, this psychosis can also occur at therapeutic doses during long-term therapy. According to the USFDA, "there is no systematic evidence" that stimulants can produce aggressive behavior or hostility.
An amphetamine overdose can lead to many different symptoms, but is rarely fatal with appropriate care. The severity of overdose symptoms vary positively with dosage and inversely with drug tolerance to amphetamine. Tolerant individuals have been known to take as much as 5 grams of amphetamine, roughly 100 times the maximum daily therapeutic dose, in a day. Symptoms of a moderate and extremely large overdose are listed below; fatal amphetamine poisoning usually also involves convulsions and coma. Chronic overdose of amphetamine poses a high risk of developing an addiction, since high doses result in increased expression of the addiction gene ΔFosB. Consistent aerobic exercise appears to magnitude-dependently reduce this risk.
|System||Minor or moderate overdose||Severe overdose[sources 6]|
Addiction is a serious risk with heavy recreational amphetamine use, but is unlikely to arise from typical medical use at therapeutic doses. Tolerance develops rapidly in amphetamine abuse, so periods of extended use require increasingly larger doses of the drug in order to achieve the same effect.
Current models of addiction from chronic drug use involve alterations in gene expression in certain parts of the brain, particularly the nucleus accumbens. The most important transcription factors[note 6] that produce these alterations are ΔFosB, cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), and nuclear factor kappa B (NFκB). ΔFosB is the most significant factor in drug addiction, since its overexpression in the nucleus accumbens is necessary and sufficient for many of the associated neural adaptations that occur; it has been implicated in addictions to alcohol, cannabinoids, cocaine, nicotine, opiates, phenylcyclidine, and substituted amphetamines. ΔJunD is the transcription factor which directly opposes ΔFosB. Increases in nucleus accumbens ΔJunD expression using viral vectors can reduce or, with a large increase, even block many of the neural and behavioral alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFosB). ΔFosB also plays an important role in regulating behavioral responses to natural rewards, such as palatable food, sex, and exercise. Since natural rewards induce expression of ΔFosB just like drugs of abuse do, chronic acquisition of these rewards can result in a similar pathological state of addiction. Consequently, ΔFosB is the key transcription factor involved in amphetamine addiction and amphetamine-induced sex addictions, a phenomenon observed in some patients taking dopaminergic medications.
The effects of amphetamine on gene regulation are both dose- and route-dependent. Most of the research on gene regulation and addiction is based upon animal studies with intravenous amphetamine administration at very high doses. The few studies that have used equivalent (weight-adjusted) human therapeutic doses and oral administration show that these changes, if they occur, are relatively minor.
A Cochrane Collaboration review on amphetamine and methamphetamine addiction and abuse indicates that the current evidence on effective treatments is extremely limited. The review indicated that fluoxetine[note 7] and imipramine[note 8] have some limited benefits in treating abuse and addiction, but concluded that there is currently no effective pharmacological treatment for amphetamine addiction or abuse. A corroborating review indicated that amphetamine addiction is mediated through increased activation of dopamine receptors and co-localized NMDA receptors in the mesolimbic dopamine pathway (a pathway in the brain that connects the ventral tegmental area to the nucleus accumbens). This review also noted that magnesium ions and serotonin inhibit NMDA receptors and that the magnesium ions do so by blocking the receptor's calcium channels. It also suggested that, based upon animal testing, pathological (addiction-inducing) amphetamine use significantly reduces the level of intracellular magnesium throughout the brain. Supplemental magnesium,[note 9] like fluoxetine treatment, has been shown to reduce amphetamine self-administration (doses given to oneself) in both humans and lab animals.
Cognitive behavioral therapy is currently the most effective clinical treatment for psychostimulant addiction. Additionally, research on the neurobiological effects of physical exercise suggests that consistent aerobic exercise, especially endurance exercise (e.g., marathon running), prevents the development of drug addiction and is an effective adjunct (supplemental) treatment for amphetamine addiction. Exercise leads to better treatment outcomes when used as an adjunct treatment, particularly for psychostimulant addictions. In particular, aerobic exercise decreases psychostimulant self-administration, reduces the reinstatement (i.e., relapse) of drug-seeking, and induces opposite effects on striatal dopamine receptor D2 (DRD2) signaling (increased DRD2 density) to those induced by pathological stimulant use (decreased DRD2 density).
According to another Cochrane Collaboration review on withdrawal in highly addicted amphetamine and methamphetamine abusers, "when chronic heavy users abruptly discontinue amphetamine use, many report a time-limited withdrawal syndrome that occurs within 24 hours of their last dose." This review noted that withdrawal symptoms in chronic, high-dose users are frequent, occurring in up to 87.6% of cases, and persist for three to four weeks with a marked "crash" phase occurring during the first week. Amphetamine withdrawal symptoms can include anxiety, drug craving, depressed mood, fatigue, increased appetite, increased movement or decreased movement, lack of motivation, sleeplessness or sleepiness, and lucid dreams. The review indicated that withdrawal symptoms are associated with the degree of dependence, suggesting that therapeutic use would result in far milder discontinuation symptoms. Manufacturer prescribing information does not indicate the presence of withdrawal symptoms following discontinuation of amphetamine use after an extended period at therapeutic doses.
Abuse of amphetamine can result in a stimulant psychosis that may present with a variety of symptoms (e.g., paranoia and delusions). A Cochrane Collaboration review on treatment for amphetamine, dextroamphetamine, and methamphetamine abuse-induced psychosis states that about 5–15% of users fail to recover completely. According to the same review, there is at least one trial that shows antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis. Psychosis very rarely arises from therapeutic use.
In rodents and primates, sufficiently high doses of amphetamine cause dopaminergic neurotoxicity, or damage to dopamine neurons, which is characterized as reduced transporter and receptor function. There is no evidence that amphetamine is directly neurotoxic in humans. High-dose amphetamine can cause indirect neurotoxicity as a result of increased oxidative stress from reactive oxygen species and autoxidation of dopamine.
- Monoamine oxidase inhibitors (MAOIs) taken with Adderall may result in a hypertensive crisis if taken within two weeks after last use of an MAOI type drug.
- Inhibitors of enzymes that directly metabolize amphetamine (particularly FMO3 and CYP2D6) will prolong the elimination of amphetamine.
- Stimulants and antidepressants (sedatives and depressants) may increase (decrease) the drug effects of Adderall, and vice versa.
- Dietary pH affects the absorption and elimination half-life of Adderall; an alkaline diet increases the rate of absorption and decreases the rate of excretion, while acidic diets decrease absorption and increase excretion rates.
Pharmacodynamics of amphetamine enantiomers in a dopamine neuron
Mechanism of action
Amphetamine, the active ingredient of Adderall, works primarily by increasing the activity of the neurotransmitters dopamine and norepinephrine in the brain and more specifically, in the nucleus accumbens, prefrontal cortex, and locus coeruleus regions. It also triggers the release of several other neurotransmitters (e.g., serotonin, histamine, and epinephrine, among others) from neurons and also the synthesis of neuropeptides (e.g., cocaine and amphetamine regulated transcript (CART) peptides). Both active ingredients of Adderall, dextroamphetamine and levoamphetamine, bind to the same biological targets, but their binding affinities (that is potency) differ somewhat. Dextroamphetamine and levoamphetamine are both potent full agonists (activating compounds) of trace amine-associated receptor 1 (TAAR1) and interact with vesicular monoamine transporter 2 (VMAT2), with dextroamphetamine being the more potent agonist of TAAR1. Consequently, dextroamphetamine produces roughly two times more CNS stimulation than levoamphetamine; however, levoamphetamine has slightly greater cardiovascular and peripheral effects. Levoamphetamine provides Adderall with a quicker onset and longer-lasting effects than dextroamphetamine alone. It has been reported that certain children have a better clinical response to levoamphetamine.
In the absence of amphetamine, VMAT2 will normally move monoamines (e.g., dopamine, histamine, serotonin, norepinephrine, etc.) from the intracellular fluid of a monoamine neuron into its synaptic vesicles, which are essentially chemical storage units inside a neuron. When amphetamine enters a neuron and interacts with VMAT2, the transporter reverses its direction of transport, thereby releasing stored monoamines inside synaptic vesicles back into the neuron's intracellular fluid. Meanwhile, when amphetamine activates TAAR1, the receptor causes the neuron's cell membrane-bound monoamine transporters (i.e., the dopamine transporter, norepinephrine transporter, or serotonin transporter) to either stop transporting molecules altogether (via internalization) or even transport them in reverse; in other words, the reversed membrane transporter will push dopamine, norepinephrine, and serotonin out of the neuron's intracellular fluid and into the synaptic cleft. In summary, by interacting with both VMAT2 and TAAR1, amphetamine releases neurotransmitters from synaptic vesicles (the effect from VMAT2) into the intracellular fluid where they subsequently exit the neuron through the membrane-bound, reversed monoamine transporters (the effect from TAAR1).
Related endogenous compounds
Amphetamine has a very similar structure and function to the endogenous trace amines, which are naturally occurring neurotransmitter molecules produced in the human body and brain. Among this group, the most closely related compounds are phenethylamine, the parent compound of amphetamine, and N-methylphenethylamine, an isomer of amphetamine (i.e., it has an identical molecular formula). In humans, phenethylamine is produced directly from L-phenylalanine by the aromatic amino acid decarboxylase (AADC) enzyme, which converts L-DOPA into dopamine as well. In turn, N‑methylphenethylamine is metabolized from phenethylamine by phenylethanolamine N-methyltransferase, the same enzyme that metabolizes norepinephrine into epinephrine. Like amphetamine, both phenethylamine and N‑methylphenethylamine regulate monoamine neurotransmission via TAAR1; unlike amphetamine, both of these substances are broken down by monoamine oxidase B, and therefore have a shorter half-life than amphetamine.
History, society, and culture
Richwood Pharmaceuticals, which later merged with Shire plc, introduced the current Adderall brand in 1996 as an instant-release tablet. In 2006, Shire agreed to sell rights to the Adderall name for this instant-release medication to Duramed Pharmaceuticals DuraMed Pharmaceuticals was acquired by Teva Pharmaceuticals in 2008 when during their acquisition of Barr Pharmaceuticals, including Barr's Duramed division.
The first generic version of Adderall IR was introduced to market in 2002. Later on, Barr and Shire reached a settlement agreement permitting Barr to offer a generic form of the drug beginning in April 2009.
Rexar, a pharmaceutical company, reformulated another drug, branded as Obetrol, and continued to sell this new formulation under the same brand name. This new unapproved formulation was later rebranded and sold as Adderall by Richwood after it acquired Rexar resulting in FDA warning in 1994. Richwood submitted this formulation as NDA 11-522 and Adderall gained FDA approval for the treatment of attention-deficit/hyperactivity disorder therapy on 13 February 1996.
Chemically, Adderall is a mixture of several amphetamine salts; specifically, it is composed of equal parts (by mass) of amphetamine aspartate monohydrate, amphetamine sulfate, dextroamphetamine sulfate, and dextroamphetamine saccharate. This drug mixture has slightly stronger CNS effects than racemic amphetamine due to the higher proportion of dextroamphetamine. Adderall is produced as both an immediate release (IR) and extended release (XR) formulation. As of December 2013[update], ten different companies have produced generic Adderall IR at one point, while Teva Pharmaceutical Industries, Actavis, and Barr Pharmaceuticals currently manufacture generic Adderall XR. Shire plc, the company that held the original patent for Adderall and Adderall XR, still manufactures brand name Adderall XR, but not Adderall IR.
- In Canada, amphetamines are in Schedule I of the Controlled Drugs and Substances Act, and can only be obtained by prescription.
- In Japan, the use, production, and import of any medicine containing amphetamine are prohibited.
- In South Korea, amphetamines are prohibited.
- In Thailand, Amphetamines are classified as Type 1 Narcotics.
- In the United Kingdom, amphetamines are regarded as Class B drugs. The maximum penalty for unauthorized possession is 5 years in prison and an unlimited fine. The maximum penalty for illegal supply is 14 years in prison and an unlimited fine.
- In the United States, amphetamine is a Schedule II prescription drug, classified as a CNS stimulant.
- Internationally (United Nations), amphetamine is in Schedule II of the Convention on Psychotropic Substances.
- The US nonproprietary name of Adderall is dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine sulfate and amphetamine aspartate. It is sometimes referred to as amphetamine mixed salts and other variants thereof.
- Enantiomers are molecules that are "mirror images" of one another; they are structurally identical but of the opposite orientation, like left and right hands. The compound "amphetamine" (racemic amphetamine) refers to equal parts of the enantiomers, i.e. 50% levoamphetamine and 50% dextroamphetamine.
- Cochrane Collaboration reviews are high quality meta-analytic systematic reviews of randomized controlled trials.
- The statements supported by the USFDA come from prescribing information, which is the copyrighted intellectual property of the manufacturer and approved by the USFDA.
- In individuals who experience sub-normal height and weight gains, a rebound to normal levels is expected to occur if stimulant therapy is briefly interrupted. The average reduction in final adult height from continuous stimulant therapy over a 3 year period is 2 cm.
- Transcription factors are proteins that increase or decrease the expression of specific genes.
- During short-term treatment, fluoxetine may decrease drug craving.
- During "medium-term treatment," imipramine may extend the duration of adherence to addiction treatment.
- The review indicated that magnesium L-aspartate and magnesium chloride produce significant changes in addictive behavior; other forms of magnesium were not mentioned.
- Heal DJ, Smith SL, Gosden J, Nutt DJ (June 2013). "Amphetamine, past and present – a pharmacological and clinical perspective". J. Psychopharmacol. 27 (6): 479–496. doi:10.1177/0269881113482532. PMC 3666194. PMID 23539642. "Mixed enantiomers/mixed salts amphetamine (3:1 d:l isomers)"
- "National Drug Code Amphetamine Search Results". National Drug Code Directory. United States Food and Drug Administration. Archived from the original on 7 February 2014. Retrieved 16 December 2013.
- Montgomery KA (June 2008). "Sexual desire disorders". Psychiatry (Edgmont) 5 (6): 50–55. PMC 2695750. PMID 19727285.
- Wilens TE, Adler LA, Adams J, Sgambati S, Rotrosen J, Sawtelle R, Utzinger L, Fusillo S (January 2008). "Misuse and diversion of stimulants prescribed for ADHD: a systematic review of the literature". J. Am. Acad. Child Adolesc. Psychiatry 47 (1): 21–31. doi:10.1097/chi.0b013e31815a56f1. PMID 18174822. "Stimulant misuse appears to occur both for performance enhancement and their euphorogenic effects, the latter being related to the intrinsic properties of the stimulants (e.g., IR versus ER profile) ...
Although useful in the treatment of ADHD, stimulants are controlled II substances with a history of preclinical and human studies showing potential abuse liability."
- Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 154–157. ISBN 9780071481274.
- Miller GM (January 2011). "The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity". J. Neurochem. 116 (2): 164–76. doi:10.1111/j.1471-4159.2010.07109.x. PMC 3005101. PMID 21073468.
- Eiden LE, Weihe E (January 2011). "VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse". Ann. N. Y. Acad. Sci. 1216: 86–98. doi:10.1111/j.1749-6632.2010.05906.x. PMID 21272013. "VMAT2 is the CNS vesicular transporter for not only the biogenic amines DA, NE, EPI, 5-HT, and HIS, but likely also for the trace amines TYR, PEA, and thyronamine (THYR) ... [Trace aminergic] neurons in mammalian CNS would be identiﬁable as neurons expressing VMAT2 for storage, and the biosynthetic enzyme aromatic amino acid decarboxylase (AADC)."
- Broadley KJ (March 2010). "The vascular effects of trace amines and amphetamines". Pharmacol. Ther. 125 (3): 363–375. doi:10.1016/j.pharmthera.2009.11.005. PMID 19948186. "Fig. 2. Synthetic and metabolic pathways for endogenous and exogenously administered trace amines and sympathomimetic amines ...
Trace amines are metabolized in the mammalian body via monoamine oxidase (MAO; EC 188.8.131.52) (Berry, 2004) (Fig. 2) ... It deaminates primary and secondary amines that are free in the neuronal cytoplasm but not those bound in storage vesicles of the sympathetic neurone ...
Thus, MAO inhibitors potentiate the peripheral effects of indirectly acting sympathomimetic amines ... this potentiation occurs irrespective of whether the amine is a substrate for MAO. An α-methyl group on the side chain, as in amphetamine and ephedrine, renders the amine immune to deamination so that they are not metabolized in the gut. Similarly, β-PEA would not be deaminated in the gut as it is a selective substrate for MAO-B which is not found in the gut ...
Brain levels of endogenous trace amines are several hundred-fold below those for the classical neurotransmitters noradrenaline, dopamine and serotonin but their rates of synthesis are equivalent to those of noradrenaline and dopamine and they have a very rapid turnover rate (Berry, 2004). Endogenous extracellular tissue levels of trace amines measured in the brain are in the low nanomolar range. These low concentrations arise because of their very short half-life ..."
- "Adderall XR Prescribing Information". United States Food and Drug Administration. December 2013. p. 11. Retrieved 30 December 2013.
- "Adderall XR Prescribing Information". United States Food and Drug Administration. December 2013. pp. 4–8. Retrieved 30 December 2013.
- Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 13: Higher Cognitive Function and Behavioral Control". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 318. ISBN 9780071481274. "Therapeutic (relatively low) doses of psychostimulants, such as methylphenidate and amphetamine, improve performance on working memory tasks both in in normal subjects and those with ADHD. Positron emission tomography (PET) demonstrates that methylphenidate decreases regional cerebral blood flow in the doroslateral prefrontal cortex and posterior parietal cortex while improving performance of a spacial working memory task. This suggests that cortical networks that normally process spatial working memory become more efficient in response to the drug. ... [It] is now believed that dopamine and norepinephrine, but not serotonin, produce the beneficial effects of stimulants on working memory. At abused (relatively high) doses, stimulants can interfere with working memory and cognitive control ... stimulants act not only on working memory function, but also on general levels of arousal and, within the nucleus accumbens, improve the saliency of tasks. Thus, stimulants improve performance on effortful but tedious tasks ... through indirect stimulation of dopamine and norepinephrine receptors."
- Shoptaw SJ, Kao U, Ling W (2009). Shoptaw SJ, Ali R, ed. "Treatment for amphetamine psychosis". Cochrane Database Syst. Rev. (1): CD003026. doi:10.1002/14651858.CD003026.pub3. PMID 19160215. "A minority of individuals who use amphetamines develop full-blown psychosis requiring care at emergency departments or psychiatric hospitals. In such cases, symptoms of amphetamine psychosis commonly include paranoid and persecutory delusions as well as auditory and visual hallucinations in the presence of extreme agitation. More common (about 18%) is for frequent amphetamine users to report psychotic symptoms that are sub-clinical and that do not require high-intensity intervention ...
About 5–15% of the users who develop an amphetamine psychosis fail to recover completely (Hofmann 1983) ...
Findings from one trial indicate use of antipsychotic medications effectively resolves symptoms of acute amphetamine psychosis."
- Greydanus D. "Stimulant Misuse: Strategies to Manage a Growing Problem". American College Health Association (Review Article). ACHA Professional Development Program. p. 20. Retrieved 2 November 2013.
- Stolerman IP (2010). Stolerman IP, ed. Encyclopedia of Psychopharmacology. Berlin; London: Springer. p. 78. ISBN 9783540686989.
- Westfall DP, Westfall TC (2010). "Miscellaneous Sympathomimetic Agonists". In Brunton LL, Chabner BA, Knollmann BC. Goodman & Gilman's Pharmacological Basis of Therapeutics (12th ed.). New York: McGraw-Hill. ISBN 9780071624428.
- Cooper, WO; Habel, LA; Sox, CM; Chan, KA; Arbogast, PG; Cheetham, TC; Murray, KT; Quinn, VP; Stein, CM; Callahan, ST; Fireman, BH; Fish, FA; Kirshner, HS; O'Duffy, A; Connell, FA; Ray, WA (17 November 2011). "ADHD drugs and serious cardiovascular events in children and young adults.". The New England Journal of Medicine 365 (20): 1896–904. doi:10.1056/NEJMoa1110212. PMID 22043968.
- "Adderall IR Prescribing Information". United States Food and Drug Administration. Barr Laboratories, Inc. March 2007. pp. 4–5. Retrieved 2 November 2013.
- Heal DJ, Smith SL, Gosden J, Nutt DJ (June 2013). "Amphetamine, past and present – a pharmacological and clinical perspective". J. Psychopharmacol. 27 (6): 479–496. doi:10.1177/0269881113482532. PMC 3666194. PMID 23539642.
- Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remião F, Carvalho F, Bastos Mde L (August 2012). "Toxicity of amphetamines: an update". Arch. Toxicol. 86 (8): 1167–1231. doi:10.1007/s00204-012-0815-5. PMID 22392347.
- Berman S, O'Neill J, Fears S, Bartzokis G, London ED (2008). "Abuse of amphetamines and structural abnormalities in the brain". Ann. N. Y. Acad. Sci. 1141: 195–220. doi:10.1196/annals.1441.031. PMC 2769923. PMID 18991959.
- Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K (February 2013). "Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects". JAMA Psychiatry 70 (2): 185–198. doi:10.1001/jamapsychiatry.2013.277. PMID 23247506.
- Spencer TJ, Brown A, Seidman LJ, Valera EM, Makris N, Lomedico A, Faraone SV, Biederman J (September 2013). "Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies". J. Clin. Psychiatry 74 (9): 902–917. doi:10.4088/JCP.12r08287. PMC 3801446. PMID 24107764.
- Frodl T, Skokauskas N (February 2012). "Meta-analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects.". Acta psychiatrica Scand. 125 (2): 114–126. doi:10.1111/j.1600-0447.2011.01786.x. PMID 22118249. "Basal ganglia regions like the right globus pallidus, the right putamen, and the nucleus caudatus are structurally affected in children with ADHD. These changes and alterations in limbic regions like ACC and amygdala are more pronounced in non-treated populations and seem to diminish over time from child to adulthood. Treatment seems to have positive effects on brain structure."
- Millichap JG (2010). "Chapter 3: Medications for ADHD". In Millichap JG. Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD (2nd ed.). New York: Springer. pp. 111–113. ISBN 9781441913968.
- Huang YS, Tsai MH (July 2011). "Long-term outcomes with medications for attention-deficit hyperactivity disorder: current status of knowledge". CNS Drugs 25 (7): 539–554. doi:10.2165/11589380-000000000-00000. PMID 21699268.
- Millichap JG (2010). "Chapter 3: Medications for ADHD". In Millichap JG. Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD (2nd ed.). New York: Springer. pp. 121–123, 125–127. ISBN 9781441913968.
- Bidwell LC, McClernon FJ, Kollins SH (August 2011). "Cognitive enhancers for the treatment of ADHD". Pharmacol. Biochem. Behav. 99 (2): 262–274. doi:10.1016/j.pbb.2011.05.002. PMC 3353150. PMID 21596055.
- "Stimulants for Attention Deficit Hyperactivity Disorder". WebMD. Healthwise. 12 April 2010. Retrieved 12 November 2013.
- Greenhill LL, Pliszka S, Dulcan MK, Bernet W, Arnold V, Beitchman J, Benson RS, Bukstein O, Kinlan J, McClellan J, Rue D, Shaw JA, Stock S (February 2002). "Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults". J. Am. Acad. Child Adolesc. Psychiatry 41 (2 Suppl): 26S–49S. doi:10.1097/00004583-200202001-00003. PMID 11833633.
- Scholten RJ, Clarke M, Hetherington J (August 2005). "The Cochrane Collaboration". Eur. J. Clin. Nutr. 59 Suppl 1: S147–S149; discussion S195–S196. doi:10.1038/sj.ejcn.1602188. PMID 16052183.
- Castells X, Ramos-Quiroga JA, Bosch R, Nogueira M, Casas M (2011). Castells X, ed. "Amphetamines for Attention Deficit Hyperactivity Disorder (ADHD) in adults". Cochrane Database Syst. Rev. (6): CD007813. doi:10.1002/14651858.CD007813.pub2. PMID 21678370.
- Pringsheim T, Steeves T (April 2011). Pringsheim T, ed. "Pharmacological treatment for Attention Deficit Hyperactivity Disorder (ADHD) in children with comorbid tic disorders". Cochrane Database Syst. Rev. (4): CD007990. doi:10.1002/14651858.CD007990.pub2. PMID 21491404.
- Martinsson L, Hårdemark H, Eksborg S (January 2007). Martinsson L, ed. "Amphetamines for improving recovery after stroke". Cochrane Database Syst. Rev. (1): CD002090. doi:10.1002/14651858.CD002090.pub2. PMID 17253474.
- Forsyth RJ, Jayamoni B, Paine TC (October 2006). Forsyth RJ, ed. "Monoaminergic agonists for acute traumatic brain injury". Cochrane Database Syst. Rev. (4): CD003984. doi:10.1002/14651858.CD003984.pub2. PMID 17054192.
- Harbeck-Seu A, Brunk I, Platz T, Vajkoczy P, Endres M, Spies C (April 2011). "A speedy recovery: amphetamines and other therapeutics that might impact the recovery from brain injury". Curr. Opin. Anaesthesiol. 24 (2): 144–153. doi:10.1097/ACO.0b013e328344587f. PMID 21386667.
- "Prescription Drugs". National Institute on Drug Abuse. Archived from the original on 4 April 2014. Retrieved 23 May 2014.
- "ADDERALL (CII)" (PDF). Food and Drug Administration. February 2007. Retrieved 23 June 2009.
- "Amphetamine/Dextroamphetamine (by mouth)". Micromedex consumer medication information. Truven Health Analytics. Retrieved 20 June 2013.
- "Medication Guide Adderall XR". US Food and Drug Administration (FDA). Retrieved 19 May 2013.
- Devous MD, Trivedi MH, Rush AJ (April 2001). "Regional cerebral blood flow response to oral amphetamine challenge in healthy volunteers". J. Nucl. Med. 42 (4): 535–42. PMID 11337538.
- Wood S, Sage JR, Shuman T, Anagnostaras SG (January 2014). "Psychostimulants and cognition: a continuum of behavioral and cognitive activation". Pharmacol. Rev. 66 (1): 193–221. doi:10.1124/pr.112.007054. PMID 24344115.
- Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 10: Neural and Neuroendocrine Control of the Internal Milieu". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 266. ISBN 9780071481274. "Dopamine acts in the nucleus accumbens to attach motivational significance to stimuli associated with reward."
- Twohey M (26 March 2006). "Pills become an addictive study aid". JS Online. Archived from the original on 15 August 2007. Retrieved 2 December 2007.
- Teter CJ, McCabe SE, LaGrange K, Cranford JA, Boyd CJ (October 2006). "Illicit use of specific prescription stimulants among college students: prevalence, motives, and routes of administration". Pharmacotherapy 26 (10): 1501–1510. doi:10.1592/phco.26.10.1501. PMC 1794223. PMID 16999660.
- Liddle DG, Connor DJ (June 2013). "Nutritional supplements and ergogenic AIDS". Prim. Care 40 (2): 487–505. doi:10.1016/j.pop.2013.02.009. PMID 23668655. "Amphetamines and caffeine are stimulants that increase alertness, improve focus, decrease reaction time, and delay fatigue, allowing for an increased intensity and duration of training ...
Physiologic and performance effects
• Amphetamines increase dopamine/norepinephrine release and inhibit their reuptake, leading to central nervous system (CNS) stimulation
• Amphetamines seem to enhance athletic performance in anaerobic conditions 39 40
• Improved reaction time
• Increased muscle strength and delayed muscle fatigue
• Increased acceleration
• Increased alertness and attention to task"
- Bracken NM (January 2012). "National Study of Substance Use Trends Among NCAA College Student-Athletes". NCAA Publications. National Collegiate Athletic Association. Retrieved 8 October 2013.
- Docherty JR (June 2008). "Pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA)". Br. J. Pharmacol. 154 (3): 606–622. doi:10.1038/bjp.2008.124. PMC 2439527. PMID 18500382.
- Parr JW (July 2011). "Attention-deficit hyperactivity disorder and the athlete: new advances and understanding". Clin. Sports Med. 30 (3): 591–610. doi:10.1016/j.csm.2011.03.007. PMID 21658550.
- Roelands B, de Koning J, Foster C, Hettinga F, Meeusen R (May 2013). "Neurophysiological determinants of theoretical concepts and mechanisms involved in pacing". Sports Med. 43 (5): 301–311. doi:10.1007/s40279-013-0030-4. PMID 23456493.
- Leon Moore, David. "Do pro sports leagues have an Adderall problem?". USA TODAY. Retrieved 4 May 2014.
- "Commonly Abused Prescription Drugs Chart". National Institute on Drug Abuse. Retrieved 7 May 2012.
- "Stimulant ADHD Medications – Methylphenidate and Amphetamines". National Institute on Drug Abuse,. Retrieved 7 May 2012.
- "National Institute on Drug Abuse. 2009. Stimulant ADHD Medications – Methylphenidate and Amphetamines". National Institute on Drug Abuse. Retrieved 27 February 2013.
- "Adderall XR Prescribing Information". United States Food and Drug Administration. Shire US Inc. December 2013. pp. 4–6. Retrieved 30 December 2013.
- Heedes G; Ailakis J. "Amphetamine (PIM 934)". INCHEM. International Programme on Chemical Safety. Retrieved 24 June 2014.
- Vitiello B (April 2008). "Understanding the risk of using medications for attention deficit hyperactivity disorder with respect to physical growth and cardiovascular function". Child Adolesc. Psychiatr. Clin. N. Am. 17 (2): 459–474. doi:10.1016/j.chc.2007.11.010. PMC 2408826. PMID 18295156.
- "FDA Drug Safety Communication: Safety Review Update of Medications used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in children and young adults". United States Food and Drug Administration. 20 December 2011. Retrieved 4 November 2013.
- Cooper WO, Habel LA, Sox CM, Chan KA, Arbogast PG, Cheetham TC, Murray KT, Quinn VP, Stein CM, Callahan ST, Fireman BH, Fish FA, Kirshner HS, O'Duffy A, Connell FA, Ray WA (November 2011). "ADHD drugs and serious cardiovascular events in children and young adults". N. Engl. J. Med. 365 (20): 1896–1904. doi:10.1056/NEJMoa1110212. PMID 22043968.
- "FDA Drug Safety Communication: Safety Review Update of Medications used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in adults". United States Food and Drug Administration. 15 December 2011. Retrieved 4 November 2013.
- Habel LA, Cooper WO, Sox CM, Chan KA, Fireman BH, Arbogast PG, Cheetham TC, Quinn VP, Dublin S, Boudreau DM, Andrade SE, Pawloski PA, Raebel MA, Smith DH, Achacoso N, Uratsu C, Go AS, Sidney S, Nguyen-Huynh MN, Ray WA, Selby JV (December 2011). "ADHD medications and risk of serious cardiovascular events in young and middle-aged adults". JAMA 306 (24): 2673–2683. doi:10.1001/jama.2011.1830. PMC 3350308. PMID 22161946.
- O'Connor PG (February 2012). "Amphetamines". Merck Manual for Health Care Professionals. Merck. Retrieved 8 May 2012.
- Spiller HA, Hays HL, Aleguas A (June 2013). "Overdose of drugs for attention-deficit hyperactivity disorder: clinical presentation, mechanisms of toxicity, and management". CNS Drugs 27 (7): 531–543. doi:10.1007/s40263-013-0084-8. PMID 23757186. "Amphetamine, dextroamphetamine, and methylphenidate act as substrates for the cellular monoamine transporter, especially the dopamine transporter (DAT) and less so the norepinephrine (NET) and serotonin transporter. The mechanism of toxicity is primarily related to excessive extracellular dopamine, norepinephrine, and serotonin."
- Lynch WJ, Peterson AB, Sanchez V, Abel J, Smith MA (September 2013). "Exercise as a novel treatment for drug addiction: a neurobiological and stage-dependent hypothesis". Neurosci Biobehav Rev 37 (8): 1622–44. doi:10.1016/j.neubiorev.2013.06.011. PMC 3788047. PMID 23806439. "these data show that exercise can affect dopaminergic signaling at many different levels, which may underlie its ability to modify vulnerability during drug use initiation. ... chronic moderate levels of forced treadmill running blocks not only subsequent methamphetamine-induced conditioned place preference, but also stimulant-induced increases in dopamine release in the NAc (Chen et al., 2008) and striatum (Marques et al., 2008). ... [These] findings indicate the efficacy of exercise at reducing drug intake in drug-dependent individuals ... Smith et al. (2011) examined the effects of chronic voluntary wheel running on cocaine self-administration under extended access conditions and found that exercising rats self-administered less cocaine and showed less escalation of intake over time as compared to sedentary rats. Similar effects of wheel running have also been reported for methamphetamine self-administration under extended access conditions (Engelmann et al., 2013) ... These findings suggest that exercise may "magnitude"-dependently prevent the development of an addicted phenotype possibly by blocking/reversing behavioral and neuro-adaptive changes that develop during and following extended access to the drug. ... Exercise also produces neuroadaptations that may influence an individual's vulnerability to initiate drug use. Consistent with this idea, chronic moderate levels of forced treadmill running blocks not only subsequent methamphetamine-induced conditioned place preference, but also stimulant-induced increases in dopamine release in the NAc (Chen et al., 2008) and striatum (Marques et al., 2008). ... Exercise has been proposed as a treatment for drug addiction that may reduce drug craving and risk of relapse. Although few clinical studies have investigated the efficacy of exercise for preventing relapse, the few studies that have been conducted generally report a reduction in drug craving and better treatment outcomes (see Table 4). ... Taken together, these data suggest that the potential benefits of exercise during relapse, particularly for relapse to psychostimulants, may be mediated via chromatin remodeling and possibly lead to greater treatment outcomes. [emphasis added]"
- Greene SL, Kerr F, Braitberg G (October 2008). "Review article: amphetamines and related drugs of abuse". Emerg. Med. Australas 20 (5): 391–402. doi:10.1111/j.1742-6723.2008.01114.x. PMID 18973636.
- Albertson TE (2011). "Amphetamines". In Olson KR, Anderson IB, Benowitz NL, Blanc PD, Kearney TE, Kim-Katz SY, Wu AHB. Poisoning & Drug Overdose (6th ed.). New York: McGraw-Hill Medical. pp. 77–79. ISBN 9780071668330.
- "Amphetamines: Drug Use and Abuse". Merck Manual Home Edition. Merck. February 2003. Archived from the original on 17 February 2007. Retrieved 28 February 2007.
- Pérez-Mañá C, Castells X, Torrens M, Capellà D, Farre M (2013). Pérez-Mañá C, ed. "Efficacy of psychostimulant drugs for amphetamine abuse or dependence". Cochrane Database Syst. Rev. 9: CD009695. doi:10.1002/14651858.CD009695.pub2. PMID 23996457.
- Hyman SE, Malenka RC, Nestler EJ (2006). "Neural mechanisms of addiction: the role of reward-related learning and memory". Annu. Rev. Neurosci. 29: 565–598. doi:10.1146/annurev.neuro.29.051605.113009. PMID 16776597.
- Robison AJ, Nestler EJ (November 2011). "Transcriptional and epigenetic mechanisms of addiction". Nat. Rev. Neurosci. 12 (11): 623–637. doi:10.1038/nrn3111. PMC 3272277. PMID 21989194. "ΔFosB has been linked directly to several addiction-related behaviors ... Importantly, genetic or viral overexpression of ΔJunD, a dominant negative mutant of JunD which antagonizes ΔFosB- and other AP-1-mediated transcriptional activity, in the NAc or OFC blocks these key effects of drug exposure14,22–24. This indicates that ΔFosB is both necessary and sufficient for many of the changes wrought in the brain by chronic drug exposure. ΔFosB is also induced in D1-type NAc MSNs by chronic consumption of several natural rewards, including sucrose, high fat food, sex, wheel running, where it promotes that consumption14,26–30. This implicates ΔFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive-like states."
- Steiner H, Van Waes V (January 2013). "Addiction-related gene regulation: risks of exposure to cognitive enhancers vs. other psychostimulants". Prog. Neurobiol. 100: 60–80. doi:10.1016/j.pneurobio.2012.10.001. PMC 3525776. PMID 23085425.
- Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 4: Signal Transduction in the Brain". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 94. ISBN 9780071481274. "All living cells depend on the regulation of gene expression by extracellular signals for their development, homeostasis, and adaptation to the environment. Indeed, many signal transduction pathways function primarily to modify transcription factors that alter the expression of specific genes. Thus, neurotransmitters, growth factors, and drugs change patterns of gene expression in cells and in turn affect many aspects of nervous system functioning, including the formation of long-term memories. Many drugs that require prolonged administration, such as antidepressants and antipsychotics, trigger changes in gene expression that are thought to be therapeutic adaptations to the initial action of the drug."
- Olsen CM (December 2011). "Natural rewards, neuroplasticity, and non-drug addictions". Neuropharmacology 61 (7): 1109–1122. doi:10.1016/j.neuropharm.2011.03.010. PMC 3139704. PMID 21459101. "Similar to environmental enrichment, studies have found that exercise reduces self-administration and relapse to drugs of abuse (Cosgrove et al., 2002; Zlebnik et al., 2010). There is also some evidence that these preclinical findings translate to human populations, as exercise reduces withdrawal symptoms and relapse in abstinent smokers (Daniel et al., 2006; Prochaska et al., 2008), and one drug recovery program has seen success in participants that train for and compete in a marathon as part of the program (Butler, 2005). ... In humans, the role of dopamine signaling in incentive-sensitization processes has recently been highlighted by the observation of a dopamine dysregulation syndrome in some patients taking dopaminergic drugs. This syndrome is characterized by a medication-induced increase in (or compulsive) engagement in non-drug rewards such as gambling, shopping, or sex (Evans et al., 2006; Aiken, 2007; Lader, 2008)."
- Kanehisa Laboratories (2 August 2013). "Alcoholism – Homo sapiens (human)". KEGG Pathway. Retrieved 10 April 2014.
- Blum K, Werner T, Carnes S, Carnes P, Bowirrat A, Giordano J, Oscar-Berman M, Gold M (2012). "Sex, drugs, and rock 'n' roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms". J. Psychoactive Drugs 44 (1): 38–55. doi:10.1080/02791072.2012.662112. PMC 4040958. PMID 22641964. "It has been found that deltaFosB gene in the NAc is critical for reinforcing effects of sexual reward. Pitchers and colleagues (2010) reported that sexual experience was shown to cause DeltaFosB accumulation in several limbic brain regions including the NAc, medial pre-frontal cortex, VTA, caudate, and putamen, but not the medial preoptic nucleus. ... these findings support a critical role for DeltaFosB expression in the NAc in the reinforcing effects of sexual behavior and sexual experience-induced facilitation of sexual performance. ... both drug addiction and sexual addiction represent pathological forms of neuroplasticity along with the emergence of aberrant behaviors involving a cascade of neurochemical changes mainly in the brain's rewarding circuitry."
- Pitchers KK, Vialou V, Nestler EJ, Laviolette SR, Lehman MN, Coolen LM (February 2013). "Natural and drug rewards act on common neural plasticity mechanisms with ΔFosB as a key mediator". J. Neurosci. 33 (8): 3434–3442. doi:10.1523/JNEUROSCI.4881-12.2013. PMC 3865508. PMID 23426671. "Drugs of abuse induce neuroplasticity in the natural reward pathway, specifically the nucleus accumbens (NAc), thereby causing development and expression of addictive behavior. ... Together, these findings demonstrate that drugs of abuse and natural reward behaviors act on common molecular and cellular mechanisms of plasticity that control vulnerability to drug addiction, and that this increased vulnerability is mediated by ΔFosB and its downstream transcriptional targets. ... Sexual behavior is highly rewarding (Tenk et al., 2009), and sexual experience causes sensitized drug-related behaviors, including cross-sensitization to amphetamine (Amph)-induced locomotor activity (Bradley and Meisel, 2001; Pitchers et al., 2010a) and enhanced Amph reward (Pitchers et al., 2010a). Moreover, sexual experience induces neural plasticity in the NAc similar to that induced by psychostimulant exposure, including increased dendritic spine density (Meisel and Mullins, 2006; Pitchers et al., 2010a), altered glutamate receptor trafficking, and decreased synaptic strength in prefrontal cortex-responding NAc shell neurons (Pitchers et al., 2012). Finally, periods of abstinence from sexual experience were found to be critical for enhanced Amph reward, NAc spinogenesis (Pitchers et al., 2010a), and glutamate receptor trafficking (Pitchers et al., 2012). These findings suggest that natural and drug reward experiences share common mechanisms of neural plasticity"
- Srisurapanont M, Jarusuraisin N, Kittirattanapaiboon P (2001). Srisurapanont M, ed. "Treatment for amphetamine dependence and abuse". Cochrane Database Syst. Rev. (4): CD003022. doi:10.1002/14651858.CD003022. PMID 11687171. "Although there are a variety of amphetamines and amphetamine derivatives, the word "amphetamines" in this review stands for amphetamine, dextroamphetamine and methamphetamine only."
- Nechifor M (March 2008). "Magnesium in drug dependences". Magnes. Res. 21 (1): 5–15. PMID 18557129.
- Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 386. ISBN 9780071481274. "Currently, cognitive–behavioral therapies are the most successful treatment available for preventing the relapse of psychostimulant use."
- Shoptaw SJ, Kao U, Heinzerling K, Ling W (2009). Shoptaw SJ, ed. "Treatment for amphetamine withdrawal". Cochrane Database Syst. Rev. (2): CD003021. doi:10.1002/14651858.CD003021.pub2. PMID 19370579. "The prevalence of this withdrawal syndrome is extremely common (Cantwell 1998; Gossop 1982) with 87.6% of 647 individuals with amphetamine dependence reporting six or more signs of amphetamine withdrawal listed in the DSM when the drug is not available (Schuckit 1999) ... The severity of withdrawal symptoms is greater in amphetamine dependent individuals who are older and who have more extensive amphetamine use disorders (McGregor 2005). Withdrawal symptoms typically present within 24 hours of the last use of amphetamine, with a withdrawal syndrome involving two general phases that can last 3 weeks or more. The first phase of this syndrome is the initial "crash" that resolves within about a week (Gossop 1982;McGregor 2005) ..."
- "Adderall IR Prescribing Information". United States Food and Drug Administration. Barr Laboratories, Inc. March 2007. Retrieved 4 November 2013.
- "Dexedrine Medication Guide". United States Food and Drug Administration. Amedra Pharmaceuticals LLC. May 2013. Retrieved 4 November 2013.
- "Adderall XR Prescribing Information". United States Food and Drug Administration. Shire US Inc. December 2013. Retrieved 30 December 2013.
- Hofmann FG (1983). A Handbook on Drug and Alcohol Abuse: The Biomedical Aspects (2nd ed.). New York: Oxford University Press. p. 329. ISBN 9780195030570.
- Advokat C (2007). "Update on amphetamine neurotoxicity and its relevance to the treatment of ADHD". J. Atten. Disord. 11 (1): 8–16. doi:10.1177/1087054706295605. PMID 17606768.
- "Amphetamine". Hazardous Substances Data Bank. National Library of Medicine. Retrieved 26 February 2014. "Direct toxic damage to vessels seems unlikely because of the dilution that occurs before the drug reaches the cerebral circulation."
- Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and addictive disorders". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 370. ISBN 9780071481274. "Unlike cocaine and amphetamine, methamphetamine is directly toxic to midbrain dopamine neurons."
- Sulzer D, Zecca L (February 2000). "Intraneuronal dopamine-quinone synthesis: a review". Neurotox. Res. 1 (3): 181–195. doi:10.1007/BF03033289. PMID 12835101.
- Miyazaki I, Asanuma M (June 2008). "Dopaminergic neuron-specific oxidative stress caused by dopamine itself". Acta Med. Okayama 62 (3): 141–150. PMID 18596830.
- "Adderall XR Prescribing Information". United States Food and Drug Administration. December 2013. pp. 8–10. Retrieved 30 December 2013.
- Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018.
- "Biomolecular Interactions and Pathways". "Amphetamine". PubChem Compound. National Center for Biotechnology Information. Retrieved 13 October 2013.
- Lewin AH, Miller GM, Gilmour B (December 2011). "Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class". Bioorg. Med. Chem. 19 (23): 7044–7048. doi:10.1016/j.bmc.2011.10.007. PMC 3236098. PMID 22037049.
- Smith R C, Davis J M (June 1977). "Comparative effects of d-amphetamine, l-amphetamine, and methylphenidate on mood in man". Psychopharmacology 53 (1): 1–12. doi:10.1007/bf00426687. PMID 407607.
- Glaser PE, Thomas TC, Joyce BM, Castellanos FX, Gerhardt GA (March 2005). "Differential effects of amphetamine isomers on dopamine release in the rat striatum and nucleus accumbens core". Psychopharmacology (Berl.) 178 (2–3): 250–8. doi:10.1007/s00213-004-2012-6. PMID 15719230.
- Arnold LE (2000). "Methyiphenidate vs. Amphetamine: Comparative review". Journal of Attention Disorders 3 (4): 200–11. doi:10.1177/108705470000300403.
- Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends Pharmacol. Sci. 26 (5): 274–281. doi:10.1016/j.tips.2005.03.007. PMID 15860375. "In addition to the main metabolic pathway, TAs can also be converted by nonspecific N-methyltransferase (NMT)  and phenylethanolamine N-methyltransferase (PNMT)  to the corresponding secondary amines (e.g. synephrine , N-methylphenylethylamine and N-methyltyramine ), which display similar activities on TAAR1 (TA1) as their primary amine precursors."
- "APPROVAL LETTER". United States Food and Drug Administration. Retrieved 30 December 2013.
- "Barr and Shire Sign Three Agreements". "August 2006 News Archives". GenericsWeb. Retrieved 30 December 2013. "WOODCLIFF LAKE, N.J., Aug. 14 /PRNewswire-FirstCall/ – Barr Pharmaceuticals, Inc. today announced that its subsidiary Duramed Pharmaceuticals, Inc. and Shire plc have signed a Product Acquisition Agreement for ADDERALL(R) (immediate-release mixed amphetamine salts) tablets and a Product Development Agreement for six proprietary products, and that its subsidiary Barr Laboratories, Inc. (Barr) has signed a Settlement and License Agreement relating to the resolution of two pending patent cases involving Shire's ADDERALL XR(R) ..."
- "Teva Completes Acquisition of Barr". Drugs.com. Retrieved 31 October 2011.
- "Teva sells 1st generic of Adderall XL in US". Forbes Magazine. Associated Press. 2 April 2009. Archived from the original on 9 April 2009. Retrieved 22 April 2009.
- "REGULATORY NEWS: Richwood's Adderall". Health News Daily. 22 February 1996. Retrieved 29 May 2013.
- "Dexedrine Medication Guide". United States Food and Drug Administration. May 2013. Retrieved 4 November 2013.
- The Minister and Attorney General. "Controlled Drugs and Substances Act". Justice Laws Website. Government of Canada.
- "Importing or Bringing Medication into Japan for Personal Use". Japan Ministry of Health, Labour and Welfare.
- "Thailand Law". Government of Thailand. Retrieved 23 May 2013.
- "Class A, B and C drugs". Home Office, Government of the United Kingdom. Archived from the original on 4 August 2007. Retrieved 23 July 2007.
- Substance Abuse and Mental Health Services Administration. "Trends in Methamphetamine/Amphetamine Admissions to Treatment: 1993–2003". The Drug and Alcohol Services Information System (DASIS) Report. United States Department of Health and Human Services. Retrieved 28 February 2007.
- United Nations Office on Drugs and Crime (2007). Preventing Amphetamine-type Stimulant Use Among Young People: A Policy and Programming Guide. New York: United Nations. ISBN 92-1-148223-2.
- International Narcotics Control Board. "List of psychotropic substances under international control" (PDF). Vienna: United Nations. Archived from the original on 5 December 2005. Retrieved 19 November 2005.