Amphetamine
Amphetamine[note 2] (contracted from alpha-methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. Amphetamine was discovered as a chemical in 1887 by Lazăr Edeleanu, and then as a drug in the late 1920s.[26] It exists as two enantiomers:[note 3] levoamphetamine and dextroamphetamine. Amphetamine properly refers to a specific chemical, the racemic free base, which is equal parts of the two enantiomers in their pure amine forms. The term is frequently used informally to refer to any combination of the enantiomers, or to either of them alone. Historically, it has been used to treat nasal congestion and depression. Amphetamine is also used as an athletic performance enhancer and cognitive enhancer, and recreationally as an aphrodisiac and euphoriant. It is a prescription drug in many countries, and unauthorized possession and distribution of amphetamine are often tightly controlled due to the significant health risks associated with recreational use.[sources 1]
This article is about mixtures of levoamphetamine and dextroamphetamine. For other uses, see Amphetamine (disambiguation).Clinical data
α-methylphenethylamine
- US DailyMed: Amphetamine
Physical: Low Psychological: Moderate[1]
High (varying with dosage and route of administration)[2]
Medical: oral, intravenous[3]
Recreational: oral, insufflation, rectal, intravenous, intramuscular
- AU: S8 (Controlled drug)
- BR: Class A3 (Psychoactive drugs)[10]
- CA: Schedule I
- DE: Anlage III (Special prescription form required)
- NZ: Class B
- UK: Class B
- US: WARNING[9]Schedule II
- UN: Psychotropic Schedule II
Oral: ~90%[11]
20%[12]
C9H13N
135.210 g·mol−1
.936 g/cm3 at 25 °C[21]
146 °C (295 °F) [22]
The first amphetamine pharmaceutical was Benzedrine, a brand which was used to treat a variety of conditions. Currently, pharmaceutical amphetamine is prescribed as racemic amphetamine, Adderall,[note 4] dextroamphetamine, or the inactive prodrug lisdexamfetamine. Amphetamine increases monoamine and excitatory neurotransmission in the brain, with its most pronounced effects targeting the norepinephrine and dopamine neurotransmitter systems.[sources 2]
At therapeutic doses, amphetamine causes emotional and cognitive effects such as euphoria, change in desire for sex, increased wakefulness, and improved cognitive control. It induces physical effects such as improved reaction time, fatigue resistance, and increased muscle strength. Larger doses of amphetamine may impair cognitive function and induce rapid muscle breakdown. Addiction is a serious risk with heavy recreational amphetamine use, but is unlikely to occur from long-term medical use at therapeutic doses. Very high doses can result in 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]
Amphetamine belongs to the phenethylamine class. It is also the parent compound of its own structural class, the substituted amphetamines,[note 5] which includes prominent substances such as bupropion, cathinone, MDMA, and methamphetamine. As a member of the phenethylamine class, amphetamine is also chemically related to the naturally occurring trace amine neuromodulators, specifically phenethylamine and N-methylphenethylamine, both of which are produced within the human body. Phenethylamine is the parent compound of amphetamine, while N-methylphenethylamine is a positional isomer of amphetamine that differs only in the placement of the methyl group.[sources 4]
Uses
Medical
Amphetamine is used to treat attention deficit hyperactivity disorder (ADHD), narcolepsy (a sleep disorder), and obesity, and is sometimes prescribed off-label for its past medical indications, particularly for depression and chronic pain.[1][37][51]
Long-term amphetamine exposure at sufficiently high doses in some animal species is known to produce abnormal dopamine system development or nerve damage,[52][53] but, in humans with ADHD, long-term use of pharmaceutical amphetamines at therapeutic doses appears to improve brain development and nerve growth.[54][55][56] Reviews of magnetic resonance imaging (MRI) 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 of the basal ganglia.[54][55][56]
Reviews of clinical stimulant research have established the safety and effectiveness of long-term continuous amphetamine use for the treatment of ADHD.[45][57][58] Randomized controlled trials of continuous stimulant therapy for the treatment of ADHD spanning 2 years have demonstrated treatment effectiveness and safety.[45][57] Two reviews have indicated that long-term continuous stimulant therapy for ADHD is effective for reducing the core symptoms of ADHD (i.e., hyperactivity, inattention, and impulsivity), enhancing quality of life and academic achievement, and producing improvements in a large number of functional outcomes[note 6] across 9 categories of outcomes related to academics, antisocial behavior, driving, non-medicinal drug use, obesity, occupation, self-esteem, service use (i.e., academic, occupational, health, financial, and legal services), and social function.[45][58] One review highlighted a nine-month randomized controlled trial of amphetamine treatment for ADHD in children that found an average increase of 4.5 IQ points, continued increases in attention, and continued decreases in disruptive behaviors and hyperactivity.[57] Another review indicated that, based upon the longest follow-up studies conducted to date, lifetime stimulant therapy that begins during childhood is continuously effective for controlling ADHD symptoms and reduces the risk of developing a substance use disorder as an adult.[45]
Current models of ADHD suggest that it is associated with functional impairments in some of the brain's neurotransmitter systems;[59] these functional impairments involve impaired dopamine neurotransmission in the mesocorticolimbic projection and norepinephrine neurotransmission in the noradrenergic projections from the locus coeruleus to the prefrontal cortex.[59] Psychostimulants like methylphenidate and amphetamine are effective in treating ADHD because they increase neurotransmitter activity in these systems.[28][59][60] Approximately 80% of those who use these stimulants see improvements in ADHD symptoms.[61] 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.[62][63] The Cochrane reviews[note 7] on the treatment of ADHD in children, adolescents, and adults with pharmaceutical amphetamines stated that short-term studies have demonstrated that these drugs decrease the severity of symptoms, but they have higher discontinuation rates than non-stimulant medications due to their adverse side effects.[65][66] A Cochrane review on the treatment of ADHD in children with tic disorders such as Tourette syndrome indicated that stimulants in general do not make tics worse, but high doses of dextroamphetamine could exacerbate tics in some individuals.[67]