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Effects vary widely by individual, dose, and context.
The physical effects of amphetamine can be broken down into several components which progressively intensify proportional to dosage.
The cognitive effects of amphetamine can be broken down into several components which progressively intensify proportional to dosage. The general head space of amphetamine is described by many as one of extreme mental stimulation, increased focus, and powerful euphoria. It contains a large number of typical stimulant cognitive effects. Although negative side effects are usually mild at low to moderate dosages, they become increasingly likely to manifest themselves with higher amounts or extended usage. This particularly holds true during the offset of the experience.
Amphetamine exerts its primary pharmacological effects by promoting the release of dopamine and norepinephrine from presynaptic nerve terminals. It enters neurons via monoamine transporters (DAT, NET, and to a lesser extent SERT), where it acts as a competitive substrate that inhibits monoamine reuptake. Once inside the terminal, amphetamine displaces monoamines from vesicular storage by interacting with VMAT2, collapsing the vesicular pH gradient and expanding the cytosolic monoamine pool available for reverse transport. Amphetamine is also a potent full agonist at trace amine-associated receptor 1 (TAAR1), activation of which triggers intracellular kinase cascades (PKA, PKC, CaMKIIα) that phosphorylate monoamine transporters, further promoting neurotransmitter efflux into the synapse. At very high doses, amphetamine weakly inhibits monoamine oxidase. It also inhibits the neuronal glutamate transporter EAAT3 (SLC1A1), reducing glutamate clearance and potentiating excitatory neurotransmission. The only known post-synaptic receptor at which amphetamine binds in humans is the 5-HT1A receptor, where it acts as an agonist with low micromolar affinity.
Amphetamine is well absorbed from the gastrointestinal tract, with oral bioavailability typically around 90%. Absorption is favored in more basic intestinal environments, where the drug exists in a more lipid-soluble form. Peak plasma concentrations are reached approximately 1 to 3 hours after oral administration. Roughly 20% of circulating amphetamine is bound to plasma proteins, and the drug distributes readily into most tissues including brain and cerebrospinal fluid. Amphetamine is metabolized hepatically, primarily by CYP2D6, along with dopamine β-hydroxylase (DBH), flavin-containing monooxygenase 3 (FMO3), butyrate-CoA ligase (XM-ligase), and glycine N-acyltransferase (GLYAT). The major metabolic pathways include aromatic hydroxylation, aliphatic hydroxylation, and N-dealkylation, though a significant portion of the drug is excreted unchanged. Elimination half-life varies by enantiomer and is strongly influenced by urinary pH: at normal urine pH, the d-enantiomer has a half-life of approximately 9 to 11 hours and the l-enantiomer 11 to 14 hours, with highly acidic urine reducing these to around 7 hours and highly alkaline urine extending them up to 34 hours. Approximately 90% of an ingested dose is eliminated within 3 days.
These combinations are considered extremely harmful and should always be avoided. Reactions to these drugs taken in combination are highly unpredictable and have a potential to cause death.
There is considerable risk of physical harm when taking these combinations, they should be avoided where possible.
These combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.
Amphetamine has high abuse potential and can cause psychological dependence with chronic use. Addiction is a serious risk with heavy recreational use but is unlikely to arise from typical medical use at therapeutic doses. Cravings and withdrawal effects occur if use is suddenly discontinued.
Tolerance develops rapidly with recreational use, requiring increasingly larger doses. Withdrawal symptoms occur in roughly 88% of chronic high-dose users, persisting for 3-4 weeks with a marked crash phase during the first week. Symptoms include fatigue, depression, anxiety, irritability, intense hunger, disturbed sleep, and drug craving.
Human lethal dosage varies widely due to tolerance; toxic symptoms occasionally occur at doses as low as 2 mg as an idiosyncrasy, while doses of 400-500 mg are not necessarily fatal. A dose of 1-2 g causes severe intoxication, though chronic abusers may use 5-15 g per day. Mean lethal serum concentration reported at 6.4 mg/L. Fatal amphetamine poisoning usually involves convulsions and coma but is rarely fatal with appropriate care.
| Species | Route | Value |
|---|---|---|
| rat | oral | 96.8 mg/kg |
| rat | unspecified | 15-180 mg/kg range depending on study |
Cardiovascular effects including hypertension, tachycardia, and arrhythmias occur during intoxication; severe hypertensive crises, heart attacks, and circulatory collapse are primarily associated with high doses or pre-existing cardiovascular conditions.
No evidence of direct neurotoxicity in humans at typical doses; however, high-dose exposure may cause indirect neurotoxicity, particularly when hyperpyrexia occurs. Prolonged heavy use can lead to speech and thought disturbances.
Kidney damage is primarily associated with rhabdomyolysis from high-dose use, particularly when hyperthermia occurs; acute renal failure has been reported in overdose and fatality cases.
Hepatic injury has been reported in overdose contexts; liver damage and failure are possible with chronic high-dose use.
Long-term use is associated with dental caries, tooth loss, and gingivitis; jaw tension causes bruxism leading to permanent tooth wear and cracking.
Stimulant psychosis can occur with severe overdose or chronic heavy use, presenting with paranoia, hallucinations, delusions, and bizarre or violent behavior. Symptoms usually disappear within weeks after cessation, but approximately 5-15% of users fail to recover completely. Psychosis rarely arises from therapeutic use. Risk increases with multi-day use, sleep deprivation, and high doses.
Amphetamine reduces seizure threshold and convulsions can occur at high doses. Fatal poisoning is usually preceded by convulsions and coma. Seizures are rare at typical doses but represent a serious risk in overdose situations.
Amphetamine was first synthesized in 1887 by Romanian chemist Lazăr Edeleanu while working in Germany. Edeleanu originally named the compound phenylisopropylamine, though its central nervous system effects remained entirely unknown for the next four decades. The substance's stimulant properties…
United Nations Convention on Psychotropic Substances 1971 (Schedule II)
Controlled substance under national scheduling. Personal quantities under 1.5 grams were decriminalized in the Australian Capital Territory as of October 28, 2023.
Classified as a psychoactive substance requiring a prescription for purchase and a license to sell.
Disallowed as a prescription drug with limited exceptions for tourists carrying prescriptions from other countries. Chinese pharmacies do not stock amphetamine-based medicines. Long-term visitors may import prescriptions by mail with complex administrative approval.
Scheduled as a recognized drug of abuse. Possession, purchase, sale, and manufacture are prohibited, and the substance is not available by prescription.
Banned in July 2010 as part of legislation targeting amphetamines and their derivatives. The rules were designed to preemptively prohibit new substances before they reach the market.
Recreational use is prohibited under national drug legislation.
Reclassified from Class B2 to the more restrictive Class B1 controlled substance category on August 2, 2005.
Listed in Appendix II-P of the Narcotic Drugs and Psychotropic Substances Law. Buying, selling, possessing, and using without authorization are criminal offenses.
Banned even for medical use in compliance with the United Nations Convention on Psychotropic Substances.
Specifically named as a controlled substance under Schedule A of Swiss drug legislation. Medicinal use is permitted with appropriate authorization.
Controlled under the Misuse of Drugs Act 1971. Possession without prescription is illegal. Notably, UK law elevates any Class B drug to Class A status when prepared for injection, significantly increasing penalties.
Prohibited under the Suchtmittelgesetz (Narcotic Substances Act). Possession, production, and sale are illegal without authorization.
Controlled under the Controlled Drugs and Substances Act. Reclassified from Schedule III to Schedule I in 2012. Approved for ADHD treatment in children aged 6-12 and adults 18 and older.
Controlled under the Finnish Narcotics Act. Possession, purchase, sale, and manufacture are illegal.
Added to the Opiumgesetz (Opium Act) in 1941 and reformed under the Betäubungsmittelgesetz (Narcotics Act) in 1981. Can only be prescribed using a special narcotic prescription form.
Amphetamine is banned even for medical use, making it unavailable for any therapeutic purpose within the country.
Controlled under the Opium Act as a List I substance. Possession, distribution, and production without authorization are illegal.
Controlled substance under Norwegian drug legislation. Purchase and possession without a valid prescription are prohibited.
Personal use decriminalized under Law 30/2000, effective July 2001. Possession under 1 gram is not a criminal offense, though the substance may be seized and the individual referred to mandatory treatment. Sale and possession of larger quantities remain criminal offenses.
Classified as a controlled drug and included in List II under Swedish law, corresponding to List P II of the 1971 Psychotropic Convention.
Classified under the Thai Narcotic Act of 2012. Category 1 represents the most restricted classification with severe penalties.
Controlled under the Controlled Substances Act. Classified as having high abuse potential with accepted medical use. Illegal to sell without DEA licensure and illegal to possess without a valid prescription.
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