Adderall and Mydayis
At therapeutic doses, Adderall causes emotional and cognitive effects such as euphoria, change in Libido, 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 Rhabdomyolysis, provoke , or induce psychosis (e.g., paranoia, , ). The side effects vary widely among individuals but most commonly include insomnia, dry mouth, loss of appetite and weight loss. The risk of developing an addiction or dependence is insignificant when Adderall is used as prescribed and at fairly low daily doses, such as those used for treating ADHD.
The two amphetamine enantiomers that compose Adderall, such as Adderall tablets/capsules (levoamphetamine and dextroamphetamine), alleviate the symptoms of ADHD and narcolepsy by increasing the activity of the norepinephrine and dopamine in the human brain, which results in part from their interactions with human trace amine-associated receptor 1 (hTAAR1) and vesicular monoamine transporter 2 (VMAT2) in . Dextroamphetamine is a more potent CNS stimulant than levoamphetamine, but levoamphetamine has slightly stronger cardiovascular and peripheral effects and a longer elimination half-life than dextroamphetamine. The active ingredient in Adderall, amphetamine, shares many chemical and pharmacological properties with the human , particularly phenethylamine and , the latter of which is a positional isomer of amphetamine. In 2022, Adderall was the fourteenth most commonly prescribed medication in the United States, with more than 34million prescriptions.
Uses
Medical
Adderall is commonly used to treat attention deficit hyperactivity disorder (ADHD) and
narcolepsy.
ADHD
Narcolepsy
Available forms
Adderall is available as immediate-release (IR) tablets and
extended-release (XR) capsules.
Mydayis is only available as an extended-release formulation.
Adderall XR is approved to treat ADHD for up to 12 hours in individuals 6 years and older and uses a double-bead formulation. The capsule can be swallowed like a tablet, or it can be opened and the beads sprinkled over applesauce for comparable absorption.
Upon ingestion, half of the beads provide immediate administration of medication, while the other half are enveloped in a coating that must dissolve, delaying absorption of its contents. It is designed to provide a therapeutic effect and plasma concentrations identical to taking two doses of Adderall IR four hours apart.
Mydayis uses a longer-lasting triple-bead formulation and is approved to treat ADHD for up to 16 hours in individuals 13 years and older.
In the
United States, the immediate and extended-release formulations of Adderall are both available as
.
Generic formulations of Mydayis became available in the US in October 2023.
Enhancing performance
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 their physician.
Recreational
Adderall has a high potential for misuse as a recreational drug.
Adderall tablets can either be swallowed, crushed and snorted, or dissolved in water and injected.
Injection into the bloodstream can be dangerous because
Excipient can block small blood vessels.
Many postsecondary students have reported using Adderall for study purposes in different parts of the developed world.
Contraindications
Adverse effects
The
adverse 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.
Overdose
Interactions
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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.
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Enzyme inhibitor that directly metabolize amphetamine (particularly CYP2D6 and FMO3) will prolong the elimination of amphetamine and increase drug effects.
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Serotonin drugs (such as most antidepressants) co-administered with amphetamine increases the risk of serotonin syndrome.
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Stimulants and antidepressants ( and ) may increase (decrease) the drug effects of amphetamine, and vice versa.
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Gastrointestinal and urinary pH affect the absorption and elimination of amphetamine, respectively. Gastrointestinal alkalinizing agents increase the absorption of amphetamine. Urinary alkalinizing agents increase the concentration of non-ionized species, decreasing urinary excretion.
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Proton-pump inhibitors (PPIs) modify the absorption of Adderall XR and Mydayis.
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Zinc supplementation may reduce the minimum effective dose of amphetamine when it is used for the treatment of ADHD.
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Norepinephrine reuptake inhibitors (NRIs) like atomoxetine prevent norepinephrine release induced by amphetamines and have been found to reduce the stimulant, euphoriant, and sympathomimetic effects of dextroamphetamine in humans.
Pharmacology
Mechanism of action
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Notes: The smaller the value, the more strongly the drug releases the neurotransmitter. See also Monoamine releasing agent ยง Activity profiles for a larger table with more compounds. Refs: |
Amphetamine, the active ingredient of Adderall, works primarily by increasing the activity of the dopamine and norepinephrine in the brain.
In the absence of amphetamine, will normally move (e.g., dopamine, histamine, serotonin, norepinephrine, etc.) from the intracellular fluid of a monoamine neuron into its , which store neurotransmitters for later release (via exocytosis) into the synaptic cleft.
Pharmacokinetics
Pharmacomicrobiomics
Related endogenous compounds
History
The pharmaceutical company Rexar reformulated their popular weight loss drug
Obetrol following its mandatory withdrawal from the market in 1973 under the Kefauver Harris Amendment to the Federal Food, Drug, and Cosmetic Act due to the results of the Drug Efficacy Study Implementation (DESI) program (which indicated a lack of efficacy). The new formulation simply replaced the two methamphetamine components with dextroamphetamine and amphetamine components of the same weight (the other two original dextroamphetamine and amphetamine components were preserved), preserved the Obetrol branding, and despite it lacking FDA approval, it still made it onto the market and was marketed and sold by Rexar for many years.
In 1994, Richwood Pharmaceuticals acquired Rexar and began promoting Obetrol as a treatment for ADHD (and later narcolepsy as well), now marketed under the new brand name of Adderall, a contraction of the phrase "A.D.D. for All" intended to convey that "it was meant to be kind of an inclusive thing" for marketing purposes.
Richwood Pharmaceuticals, which later merged with Shire plc, introduced the current Adderall brand in 1996 as an instant-release tablet.
The first generic version of Adderall IR was introduced to the market in 2002.
Commercial formulation
Chemically, Adderall is a mixture of four amphetamine salts; specifically, it is composed of equal parts (by
mass) of amphetamine
aspartic acid, amphetamine
sulfate, dextroamphetamine sulfate, and dextroamphetamine
saccharic acid.
This drug mixture has slightly stronger 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.
, ten different companies produced generic Adderall IR, while Teva Pharmaceutical Industries,
Actavis, and Barr Pharmaceuticals manufactured generic Adderall XR.
,
Shire plc, the company that held the original patent for Adderall and Adderall XR, still manufactured brand name Adderall XR, but not Adderall IR.
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 U.S.-approved forms):
Society and culture
Legal status
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In Canada, amphetamines are in Schedule I of the Controlled Drugs and Substances Act, and can only be obtained by prescription.
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In Japan, the use, production, and import of any medicine containing amphetamines is prohibited.
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In South Korea, amphetamines are prohibited.
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In Taiwan, amphetamines including Adderall are Schedule 2 drugs with a minimum five-year prison term for possession.
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In Thailand, amphetamines are classified as Type 1 Narcotics.
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In the United Kingdom, amphetamines are regarded as Class B drugs. The maximum penalty for unauthorized possession is five years in prison and an unlimited fine. The maximum penalty for illegal supply is 14 years in prison and an unlimited fine.
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In the United States, amphetamine is a Schedule II prescription drug, classified as a central nervous system (CNS) stimulant.
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Internationally, amphetamine is in Schedule II of the Convention on Psychotropic Substances.
Shortages
In February 2023, news organizations began reporting on shortages of Adderall in the United States that have lasted for over five months.
The Food and Drug Administration first reported the shortage in October 2022.
In May 2023, seven months into the shortage, the Food and Drug Administration commissioner
Robert Califf stated that "a number of generic drugs are in shortage at any given time because there's not enough profit". He points out that Adderall is a special case because it is a controlled substance and the amount available for prescription is controlled by the Drug Enforcement Administration. He also faults a "tremendous increase in prescribing" due to virtual prescribing and general overprescribing and overdiagnosing, adding that "if only the people that needed these drugs got them, there probably wouldn't be a stimulant shortage".
The shortage has continued into 2024.
It has led to the creation and expansion of businesses that outsource the search for Adderall. One company charges $50 per U.S. customer to hire workers in the Philippines or another country to make phone calls to all the pharmacies located near the customer and check whether they have any Adderall. Celebrity endorsements have contributed to the increased demand for Adderall.
Notes
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Reference notes
External links
