A remarkable chemical compound born over a century ago in a lab, amphetamine’s potent but controversial journey from medicine to widespread abuse reveals a molecule of complex duality.
Key Takeaways
- Amphetamine was first synthesized in 1887 by Romanian chemist Lazăr Edeleanu.
- The chemical formula of amphetamine is C9H13N.
- Amphetamine has a molecular weight of 135.21 g/mol.
- Amphetamine is used to treat ADHD in children over 3 years old.
- Adderall (mixed amphetamine salts) is approved for narcolepsy.
- Dextroamphetamine (Dexedrine) treats ADHD at doses 5-40 mg/day.
- In 2021, 16 million US adults reported lifetime amphetamine misuse.
- Past-year amphetamine use disorder affected 1.3 million US people in 2021.
- Among US high school seniors, 3.9% used amphetamines nonmedically in 2022.
- Chronic high-dose amphetamine use causes dopamine transporter downregulation by 20-30%.
- Amphetamine overdose can cause hyperthermia up to 42°C.
- Cardiovascular risks include tachycardia; HR increases 20-50 bpm.
- Amphetamine is Schedule II under US Controlled Substances Act.
- Amphetamine possession illegal without prescription in most countries.
- DEA production quotas for amphetamine: 25,000 kg in 2023.
Amphetamines are prescribed for ADHD but also widely misused with significant risks.
Adverse Effects
- Chronic high-dose amphetamine use causes dopamine transporter downregulation by 20-30%.
- Amphetamine overdose can cause hyperthermia up to 42°C.
- Cardiovascular risks include tachycardia; HR increases 20-50 bpm.
- Amphetamines associated with 2-4 fold increased stroke risk.
- Psychosis incidence in chronic users: 20-40%.
- Amphetamine withdrawal features depression in 60-80% of users.
- Long-term use leads to dental decay ("meth mouth") in 30-50% of heavy users.
- Amphetamines increase myocardial infarction risk by 3-fold acutely.
- Neurotoxicity: amphetamine reduces striatal dopamine by 20-50% in primates.
- Anxiety disorders in 25% of amphetamine-dependent individuals.
- Skin picking and ulceration common; 40% of chronic users affected.
- Amphetamine-induced cardiomyopathy in 10-15% of heavy users.
- Cognitive deficits persist 1 year post-abstinence in 30% of users.
- Hepatotoxicity risk elevated 2-fold with chronic use.
- Amphetamines linked to rhabdomyolysis in overdose cases (5-10%).
- Insomnia duration averages 3-5 days in binge use.
- Amphetamines cause serotonin syndrome risk with SSRIs (rare, <1%).
- Chronic use associated with Parkinson's-like symptoms in 10%.
- Appetite suppression leads to 10-20% body weight loss in 6 months.
- Psychotic symptoms resolve in 80% within 1 week abstinence.
- Amphetamine elevates blood pressure by 10-20 mmHg systolic.
- Seizure risk 2-5% in overdose.
- Memory impairment: 15-25% deficit in chronic users.
- Amphetamine vasoconstriction causes peripheral ischemia.
- Renal failure in 5% of severe overdoses.
- Aggression and violence 3-fold increased in users.
- Amphetamine tolerance develops within weeks to dopamine effects.
- Pulmonary hypertension risk with IV use (rare).
- Sexual dysfunction: priapism in males (0.1-1%).
Adverse Effects Interpretation
Amphetamines offer a comprehensive and aggressively efficient demolition of the human body, systematically dismantling everything from your brain's pleasure centers and cardiovascular stability to your teeth, skin, and sanity, all while convincing you it's a good idea.
Epidemiology/Prevalence
- In 2021, 16 million US adults reported lifetime amphetamine misuse.
- Past-year amphetamine use disorder affected 1.3 million US people in 2021.
- Among US high school seniors, 3.9% used amphetamines nonmedically in 2022.
- Lifetime prevalence of amphetamine use in US college students is 11.5%.
- In Australia, 7.2% of population aged 14+ used amphetamines lifetime in 2019.
- US emergency department visits for amphetamines rose 103% from 2011-2019.
- 2.7% of US 12th graders reported past-year Adderall misuse in 2022.
- Global amphetamine-type stimulant seizures reached 200 tons in 2020.
- In Europe, 1.3% of adults used amphetamines in past year (2022).
- US prescription stimulant misuse among adults 18-25: 6.2% past year (2021).
- Amphetamine use disorder prevalence in US military veterans: 5-10%.
- Past-month nonmedical amphetamine use in US: 0.2% overall population (2021).
- In Canada, 1.5% of students grade 7-12 used amphetamines nonmedically (2019).
- Amphetamine overdose deaths in US: 3,452 in 2021.
- 75% of amphetamine users report polysubstance use.
- In US, ADHD medication diversion rate: 16% of prescriptions.
- Amphetamines in 25% of US ADHD treatment prescriptions.
- Past-year misuse among US young adults 18-25: 10.1% (2021 NSDUH).
- Amphetamine-related hospitalizations in US: 110,000 annually pre-COVID.
- In New Zealand, 2.5% lifetime amphetamine use (2019).
- 50% of US college students obtain stimulants illicitly for studying.
- Amphetamine use among US homeless: 15-20%.
- Global ATS users: 36 million (2022 UNODC).
- In Sweden, amphetamine most common illicit stimulant (1.2% past year).
- US 8th graders nonmedical amphetamine use: 1.5% (2022).
- Female amphetamine use rising faster than males in US (20% increase).
- Amphetamine positive urine tests in workplace: 0.5% (2022).
- Amphetamine cessation rates with behavioral therapy: 20-30% at 1 year.
Epidemiology/Prevalence Interpretation
It's a grim irony that we've manufactured both a rampant stimulant crisis and the urgent need for stimulants to keep pace with it, with millions caught in the middle, self-medicating a burnout they can't outrun.
Legal/Regulation
- Amphetamine is Schedule II under US Controlled Substances Act.
- Amphetamine possession illegal without prescription in most countries.
- DEA production quotas for amphetamine: 25,000 kg in 2023.
- Amphetamine trafficking penalties: up to 40 years US federal prison.
- In UK, amphetamine is Class B drug; max 14 years possession.
- Amphetamine precursors like phenylacetone regulated under UN conventions.
- FDA requires REMS for amphetamine ADHD products due to abuse potential.
- Amphetamine prescription limited to 30-day supply in some US states.
- In Australia, amphetamine Schedule 8 (controlled drug).
- Canada classifies amphetamine as Schedule I narcotic.
- Amphetamine analoges like MDMA also scheduled internationally.
- US state laws vary; some require database checks for amphetamine Rx.
- Global amphetamine production estimated 500 tons illicit annually.
- Amphetamine prescription fraud cases: 5,000 annually US.
- EU Early Warning System monitors 50+ amphetamine NPS.
- Amphetamine manufacturing labs seized: 1,200 in US 2022.
- In Japan, amphetamine (shabu) is strictly prohibited; death penalty possible.
- Prescription amphetamine sales US: $5 billion in 2022.
- UN 1988 Convention schedules amphetamine precursors.
- Amphetamine theft from pharmacies: 500 incidents/year US.
- In Mexico, amphetamine production fuels 20% of cartel revenue.
- US amphetamine import quotas tightly controlled by DEA.
- Amphetamine analog scheduling under US Analog Act.
Legal/Regulation Interpretation
Despite its legitimate medical use as a potent Schedule II prescription for ADHD, the global statistics paint amphetamine as a high-stakes molecule living a perilous double life, fueling a $5 billion pharmaceutical industry while simultaneously generating an estimated 500 tons of illicit production that bankrolls cartels, floods markets with dangerous analogs, and keeps law enforcement from Tokyo to Texas working overtime with severe penalties, strict quotas, and international conventions all struggling to contain its powerful and deeply abused potential.
Medical Uses
- Amphetamine is used to treat ADHD in children over 3 years old.
- Adderall (mixed amphetamine salts) is approved for narcolepsy.
- Dextroamphetamine (Dexedrine) treats ADHD at doses 5-40 mg/day.
- Amphetamines improve attention and reduce hyperactivity in 70-80% of ADHD patients.
- Lisdexamfetamine (Vyvanse) is a prodrug of dextroamphetamine for ADHD.
- Amphetamine doses for obesity treatment were historically 5-30 mg/day.
- Evekeo (amphetamine sulfate) approved for ADHD and exogenous obesity.
- Amphetamines increase wakefulness in narcolepsy patients by 4-6 hours.
- In treatment-resistant depression, amphetamines show 50% response rate adjunctively.
- Amphetamine promotes weight loss of 0.5-1 kg/week in short-term obesity therapy.
- Mydayis (extended-release amphetamines) for ADHD in ages 13+ up to 50 mg/day.
- Amphetamines used off-label for treatment-emergent sexual dysfunction in SSRI users.
- Amphetamine used in veterinary medicine for lethargy.
- Amphetamines effective in 75% of narcolepsy cataplexy cases adjunctively.
- Zenzedi (dextroamphetamine) for ADHD starting 2.5 mg.
- ProCentra (liquid dextroamphetamine) for ADHD ages 6+.
- Amphetamine reduces fatigue in multiple sclerosis patients (off-label).
- In Parkinson's, amphetamines improve bradykinesia temporarily.
- Historical use for asthma; bronchodilation via beta-2 agonism.
- Amphetamine paste used in some dental applications historically.
- Adzenys XR-ODT (amphetamine) for ADHD ages 6+.
Medical Uses Interpretation
This whirlwind tour of amphetamine’s medical resume reveals a stimulant that, when properly prescribed, is a remarkably versatile Swiss Army knife for the nervous system—treating everything from attention deficits and sleep attacks to stubborn depression and even veterinary lethargy, all while sternly reminding us it’s a powerful tool, not a toy.
Pharmacology
- Amphetamine was first synthesized in 1887 by Romanian chemist Lazăr Edeleanu.
- The chemical formula of amphetamine is C9H13N.
- Amphetamine has a molecular weight of 135.21 g/mol.
- Amphetamine is a chiral molecule with dextroamphetamine being the more potent enantiomer.
- Amphetamine acts primarily by releasing monoamines like dopamine, norepinephrine, and serotonin.
- Oral bioavailability of amphetamine is approximately 70-90%.
- Half-life of amphetamine in adults is 9-11 hours.
- Amphetamine increases synaptic dopamine by inhibiting reuptake and promoting release.
- Peak plasma concentration of amphetamine occurs 3 hours after oral dose.
- Amphetamine pKa is 9.9, making it a weak base.
- Dextroamphetamine has 3-5 times the potency of levoamphetamine on CNS.
- Amphetamine is metabolized primarily by CYP2D6 in the liver.
- Volume of distribution for amphetamine is 3-4 L/kg.
- Amphetamine crosses the blood-brain barrier rapidly due to lipophilicity.
- Therapeutic plasma levels of amphetamine range 20-50 ng/mL.
- Amphetamine sulfate is the most common pharmaceutical form.
- LogP (octanol-water partition coefficient) of amphetamine is 1.76.
- Amphetamine melting point is 102-104°C.
- Amphetamine is excreted 30-40% unchanged in urine.
- Urinary pH affects amphetamine excretion; acidic urine increases elimination.
- Amphetamine was used in WWII by militaries for alertness.
- Amphetamine elevates extracellular dopamine by 1000% at high doses.
- Norepinephrine release by amphetamine is 10-fold baseline.
- Amphetamine VMAT2 inhibition leads to cytoplasmic monoamine accumulation.
- Levoamphetamine contributes more to peripheral effects.
- Protein binding of amphetamine is <20%.
Pharmacology Interpretation
Born in 1887 as a humble weak base with a pKa of 9.9, amphetamine has since perfected the art of overachievement, hijacking our monoamine systems to flood synapses with a tenfold surge of norepinephrine and, at its most ambitious, a thousand percent dopamine deluge, all while expertly navigating the body's pH to prolong its own dramatic performance.
Sources & References
- Reference 1ENen.wikipedia.orgVisit source
- Reference 2PUBCHEMpubchem.ncbi.nlm.nih.govVisit source
- Reference 3NCBIncbi.nlm.nih.govVisit source
- Reference 4NATUREnature.comVisit source
- Reference 5PUBMEDpubmed.ncbi.nlm.nih.govVisit source
- Reference 6DRUGSdrugs.comVisit source
- Reference 7FDAfda.govVisit source
- Reference 8ACCESSDATAaccessdata.fda.govVisit source
- Reference 9NIDAnida.nih.govVisit source
- Reference 10SAMHSAsamhsa.govVisit source
- Reference 11MONITORINGTHEFUTUREmonitoringthefuture.orgVisit source
- Reference 12AIHWaihw.gov.auVisit source
- Reference 13CDCcdc.govVisit source
- Reference 14UNODCunodc.orgVisit source
- Reference 15EMCDDAemcdda.europa.euVisit source
- Reference 16CCSAccsa.caVisit source
- Reference 17DEAdea.govVisit source
- Reference 18FEDERALREGISTERfederalregister.govVisit source
- Reference 19GOVgov.ukVisit source
- Reference 20TGAtga.gov.auVisit source
- Reference 21CANADAcanada.caVisit source
- Reference 22DEADIVERSIONdeadiversion.usdoj.govVisit source
- Reference 23HPAhpa.org.nzVisit source
- Reference 24QUESTDIAGNOSTICSquestdiagnostics.comVisit source
- Reference 25IQVIAiqvia.comVisit source