question: Why do people with ADHD feel "normal" on Adderall?
comment: Psychology PhD here. ADHD is not my specialty, but here's the gist of it in as close to ELI5 as I can get it. & #x200B; There are parts of the brain that keep the brain on task (they are near the front part of the brain for the most part). These parts need to be active in order to do their thing. In the brain of someone with ADHD, these brain parts are less active. So they can have difficulty focusing. Drugs like Adderall work because they make those parts of the brain more active (as well as other parts of the brain - they are stimulants, but that's not a word a 5 year old would know, so anyway). So, if you have ADHD, adderall and other stimulants can help by giving those brain parts the activation they need to keep you on task.
passages: Although ADHD has most often been treated with medication, medications do not cure ADHD. They are used solely to treat the symptoms associated with this disorder and the symptoms will come back once the medication stops.
  
  Section::::Treatment.:Medication.
  
  Stimulants are typically formulated in fast and slow-acting as well as short and long-acting formulations. The fast-acting amphetamine mixed salts (Adderall) and its derivatives, with short and long-acting formulations bind to the trace amine associated receptor and triggers the release of dopamine into the synaptic cleft. They may have a better cardiovascular disease profile than methylphenidate and potentially better tolerated.
   Section::::History, society, and culture.:Commercial formulation.
   Hales has talked about how he was diagnosed with A.D.D. many times and released a documentary video about Adderall on August 8, 2016. He mentioned he was prescribed Adderall about 6 months before he started his channel and said he has never seen the doctor who diagnosed him with ADD again. He also said that Adderall is the reason behind all his videos, but mentioned he doesn't want to talk about the subject because he doesn't take treatment any more.
   Adderall is generally well-tolerated and effective in treating the symptoms of ADHD and narcolepsy. At therapeutic doses, Adderall causes emotional and cognitive effects such as euphoria, change in desire for sex, increased wakefulness, and improved cognitive control. At these doses, it induces physical effects such as a faster reaction time, fatigue resistance, and increased muscle strength. In contrast, much larger doses of Adderall can impair cognitive control, cause rapid muscle breakdown, or induce a psychosis (e.g., delusions and paranoia). The side effects of Adderall vary widely among individuals, but most commonly include insomnia, dry mouth, and loss of appetite. The risk of developing an addiction is insignificant when Adderall is used as prescribed at fairly low daily doses, such as those used for treating ADHD; however, the routine use of Adderall in larger daily doses poses a significant risk of addiction due to the pronounced reinforcing effects that are present at high doses. Recreational doses of Adderall are generally much larger than prescribed therapeutic doses, and carry a far greater risk of serious adverse effects.
   BULLET::::- Proton-pump inhibitors (PPIs) modify the absorption of Adderall XR and Mydayis.
  
  BULLET::::- Zinc supplementation may reduce the minimum effective dose of amphetamine when it is used for the treatment of ADHD.
  
  Section::::Pharmacology.
  
  Section::::Pharmacology.:Mechanism of action.
   Section::::Uses.
  
  Section::::Uses.:Medical.
  
  Adderall is used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy (a sleep disorder).
  
  Section::::Uses.:Medical.:Available forms.
   Adderall is available as immediate-release tablets or two different extended-release formulations. The extended-release capsules are generally used in the morning. A shorter, 12-hour extended-release formulation is available under the brand Adderall XR and is designed to provide a therapeutic effect and plasma concentrations identical to taking two doses 4 hours apart. The longer extended-release formulation, approved for 16 hours, is available under the brand Mydayis. In the United States, the immediate and extended release (XR) formulations of Adderall are both available as generic drugs, while Mydayis is available only as a brand-name drug.
  
  Section::::Uses.:Enhancing performance.
   Danny Brown's album "XXX" contains many references to Adderall, such as the song "Adderall Admiral".
  
  Section::::Society and culture.:In film.
  
  Producer David O. Selznick, an amphetamine user, would often dictate long and rambling memos to his directors under the influence of amphetamine. The documentary "Shadowing The Third Man" relates that Selznick introduced "The Third Man" director Carol Reed to the use of amphetamine, which allowed Reed to bring the picture in below budget and on schedule by filming nearly 22 hours at a time.
   Amphetamine and its derivatives, prototype stimulants, are likewise available in immediate and long-acting formulations. Amphetamines act by multiple mechanisms including reuptake inhibition, displacement of transmitters from vesicles, reversal of uptake transporters and reversible MAO inhibition. Thus amphetamines actively increases the release of these neurotransmitters into the synaptic cleft. They may have a better side-effect profile than methylphenidate cardiovascularly and potentially better tolerated.
   BULLET::::- Amphetamine systematic reviews and meta-analyses report that low-dose amphetamine improve cognitive functions (e.g., inhibitory control, episodic memory, working memory, and aspects of attention) in healthy people and in individuals with ADHD. A 2014 systematic review noted that low doses of amphetamine also improve memory consolidation, in turn leading to improved recall of information in non-ADHD youth. It also improves task saliency (motivation to perform a task) and performance on tedious tasks that required a high degree of effort.
   Some parents and professionals have raised questions about the side effects of drugs and their long-term use. Magnetic resonance imaging studies suggest that long-term treatment with amphetamine or methylphenidate decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function of 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 continuous treatment effectiveness and safety. One review highlighted a 9-month randomized controlled trial of amphetamine in children that found an average increase of 4.5 IQ points and continued improvements in attention, disruptive behaviors, and hyperactivity.
  
  Section::::Medications.:Concerns regarding stimulants.:Withdrawal and rebound.
   Various drug classes, most especially stimulants and to a lesser degree opioids and sedatives, are subject to comedowns. A milder analogous mood cycle can happen even with blood sugar levels (thus sugar highs and sugar lows), which is especially relevant to people with diabetes mellitus and to parents and teachers managing children's behavior, as well as in adults with ADHD. Stimulant comedowns are unique in that they often appear very abruptly after a period of focus or high, and are typically the more intensely dysphoric phase of withdrawal than that following complete elimination from the bloodstream. Besides general dysphoria, this phase can be marked by frustration, anger, anhedonia, social withdrawal, and other symptoms characteristic to a milder mixed episode in bipolar disorder. Alertness and other general stimulant effects are still present.
   Methamphetamine was formerly in widespread use by truck drivers to combat symptoms of somnolence and to increase their concentration during driving, especially in the decades prior to the signing by former president Ronald Reagan of Executive Order 12564, which initiated mandatory random drug testing of all truck drivers and employees of other DOT-regulated industries.
  
  Up to a quarter of college students use Adderall to help them focus on their studies instead of its intended purpose of helping people with ADHD. This use sometimes continues after the student graduates college due to its addictive properties.
   Many postsecondary students have reported using Adderall for study purposes in different parts of the developed world. Among these students, some of the risk factors for misusing ADHD stimulants recreationally include: possessing deviant personality characteristics (i.e., exhibiting delinquent or deviant behavior), inadequate accommodation of special needs, basing one's self-worth on external validation, low self-efficacy, earning poor grades, and suffering from an untreated mental health disorder.
  
  Section::::Adverse effects.
   According to a Cochrane review on withdrawal in individuals who compulsively use amphetamine and methamphetamine, "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 roughly 88% of cases, and persist for  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 the severity of withdrawal symptoms is positively correlated with the age of the individual and the extent of their dependence. Mild withdrawal symptoms from the discontinuation of amphetamine treatment at therapeutic doses can be avoided by tapering the dose.
   Section::::Contraindications.
   In the absence of amphetamine, will normally move monoamines (e.g., dopamine, histamine, serotonin, norepinephrine, etc.) from the intracellular fluid of a monoamine neuron into its synaptic vesicles, which store neurotransmitters for later release (via exocytosis) into the synaptic cleft. 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 , 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 monoamines altogether (via transporter internalization) or transport monoamines out of the neuron; 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).
   Section::::History, society, and culture.:Comparison to other formulations.
  
  Adderall is one of several formulations of pharmaceutical amphetamine, including singular or mixed enantiomers and as an enantiomer prodrug. The table below compares these medications (based on US approved forms):
  
  Section::::History, society, and culture.:History.
   The two amphetamine enantiomers that compose Adderall (i.e., levoamphetamine and dextroamphetamine) alleviate the symptoms of ADHD and narcolepsy by increasing the activity of the neurotransmitters norepinephrine and dopamine in the brain, which results in part from their interactions with human trace amine-associated receptor 1 (hTAAR1) and vesicular monoamine transporter 2 (VMAT2) in neurons. Dextroamphetamine is a more potent stimulant than levoamphetamine, but levoamphetamine has slightly stronger cardiovascular and peripheral effects and a longer elimination half-life (i.e., it remains in the body longer) than dextroamphetamine. The levoamphetamine component of Adderall has been reported to improve the treatment response in some individuals relative to dextroamphetamine alone. Adderall's active ingredient, amphetamine, shares many chemical and pharmacological properties with the human trace amines, particularly phenethylamine and , the latter of which is a positional isomer of amphetamine. In 2016, it was the 45th most prescribed medication in the United States, with more than 17 million prescriptions.
   The slow and long-acting nonstimulant atomoxetine (Strattera), is primarily a norepinephrine reuptake inhibitor and, to a lesser extent, a dopamine reuptake inhibitor. It may be more effective for those with predominantly inattentive concentration. It is sometimes prescribed in adults who do not get enough vigilant concentration response from mixed amphetamine salts (Adderall) or get too many side effects. It is also approved for ADHD by the US Food and Drug Administration.
   Reviews of clinical stimulant research have established the safety and effectiveness of long-term amphetamine use for ADHD. An evidence review noted the findings of a randomized controlled trial of amphetamine treatment for ADHD in Swedish children following 9 months of amphetamine use. During treatment, the children experienced improvements in attention, disruptive behaviors, and hyperactivity, and an average change of +4.5 in IQ. It noted that the population in the study had a high rate of comorbid disorders associated with ADHD and suggested that other long-term amphetamine trials in people with less associated disorders could find greater functional improvements.
   Stimulants are the most commonly prescribed medications for ADHD. The stimulant medications indicated to treat ADHD are methylphenidate (Ritalin, Concerta), dexmethylphenidate (Focalin), mixed amphetamine salts (Adderall), dextroamphetamine (Dexedrine), lisdexamfetamine (Vyvanse), and in rare cases methamphetamine (Desoxyn). Controlled-release pharmaceuticals may allow once daily administration of medication in the morning. This is especially helpful for children who do not like taking their medication in the middle of the school day. Several controlled-release methods are used.
   The adverse 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 adverse drug effects than dosages used for therapeutic purposes.
  
  Section::::Interactions.
  
  BULLET::::- Monoamine oxidase inhibitors (MAOIs) taken with amphetamine may result in a hypertensive crisis if taken within two weeks after last use of an MAOI type drug.
   Five different amphetamine-based pharmaceuticals are currently used in ADHD treatment: racemic amphetamine, dextroamphetamine, lisdexamfetamine, and two mixed enantiomer products (Adderall and Dyanavel XR). Lisdexamfetamine is an inactive prodrug of dextroamphetamine (i.e., lisdexamfetamine itself doesn't do anything in the body, but it metabolizes into dextroamphetamine). Adderall is a proprietary mixture of (75%) dextroamphetamine and (25%) levoamphetamine salts, which results in very mild differences between their effects. Dyanavel XR contains a similar mixture. Adderall begins to work before dextroamphetamine because of levoamphetamine. Levoamphetamine also provides Adderall with a longer clinical effect than dextroamphetamine. Some children with ADHD and comorbid disorders respond well to levoamphetamine.
  