Interaction Warnings
Amphetamine can be potentially dangerous in combination with other stimulants as it can increase one's heart rate and blood pressure to dangerous levels.
Amphetamine may increase the effects of tricyclic antidepressants to dangerous levels.
The neurotoxic effects of MDMA may be increased when combined with amphetamines.
This combination may increase strain on the heart.
Pharmacology
DrugBankDescription
Amphetamine, a compound discovered over 100 years ago, is one of the more restricted controlled drugs. It was previously used for a large variety of conditions and this changed until this point where its use is highly restricted. Amphetamine, with the chemical formula alpha-methylphenethylamine, was discovered in 1910 and first synthesized by 1927. After being proven to reduce drug-induced anesthesia and produce arousal and insomnia, amphetamine racemic mix was registered by Smith, Kline and French in 1935. Amphetamine structure presents one chiral center and it exists in the form of dextro- and levo-isomers. The first product of Smith, Kline and French was approved by the FDA on 1976. During World War II, amphetamine was used to promote wakefulness in the soldiers. This use derived into a large overproduction of amphetamine and all the surplus after the war finalized ended up in the black market, producing the initiation of the illicit abuse.
Mechanism of Action
It is important to consider that amphetamine has a very similar structure to the catecholamine neurotransmitters mainly on the presence of a long planar conformation, the presence of an aromatic ring and nitrogen in the aryl side chain. Amphetamine, as well as other catecholamines, is taken into presynaptic nerve terminals by the association with two sodium ions and one chloride ion. The complex of the amphetamine with the ions is actively transported by monoamine reuptake transporters. As amphetamine acts competitively with the endogenous monoamines, the greater the number of amphetamines the more internalized amphetamine will be found. Once inside the presynaptic terminal, amphetamine displaces other monoamines to be stored by VMAT2 which produces the pumping of the neurotransmitters into the synapse by a process called retro-transport. This process of release of neurotransmitters is approximately fourfold more potent in the d-isomer for the release of dopamine. The mechanism of action of amphetamine is complemented by the inhibition of the reuptake and of monoamine oxidase which acts synergistically to produce a significant increase the monoamine concentration. This activity is not done as an inhibitor per se but more as a competitive substrate and thus, amphetamine is known to be a weak dopamine reuptake inhibitor, moderate noradrenaline reuptake inhibitor and very weak serotonin reuptake inhibitor.
Pharmacodynamics
From its mechanism of action, it has been demonstrated that amphetamine augments the concentration of noradrenaline in the prefrontal cortex and dopamine in the striatum on a dose and time-dependent manner. The indistinct release of neurotransmitters which include adrenaline is known to produce cardiovascular side effects. There are old reports of a cognitive enhancement related to the administration of amphetamine in which improvements in intelligence test scores were reported. In ADHD, amphetamine has been largely showed to produce remarkable improvements in school performance, behavior, and demeanor. The effect was shown to be produced through both racemic forms and to this date, the use of racemic forms 3:1 (D:L) is very common. The therapeutic effect of amphetamine on serotonin does not seem to have a significant clinical effect on ADHD as observed on comparative studies with amphetamine and fenfluramine, a powerful serotonin releasing factor. However, the indirect effect on serotonin might have an effect on the depression and anxiety profile of ADHD. Studies regarding the illicit use of amphetamine in which heavy consumers were studied proved the generation of a paranoid state which flagged this drug as a psychiatric danger compound. This observation was supported by the continuous reports of misuse in patients under depression.
Metabolism
Amphetamine is known to be metabolized by the liver under the action of the CYP2D6. The metabolic pathway of amphetamine is mainly defined by aromatic hydroxylation, aliphatic hydroxylation, and n-dealkylation. The formed metabolites in this pathway are 4-hydroxyamphetamine, 4-hydroxynorephedrine, hippuric acid, benzoic acid, benzyl methyl ketone, and p-hydroxyamphetamine which is known to be a potent hallucinogen. However, a significant part of the original compound remains unchanged.
Absorption
Amphetamine is well absorbed in the gut and as it is a weak base hence the more basic the environment the more of the drug is found in a lipid-soluble form and the absorption through lipid-rich cell membranes is highly favored. The peak response of amphetamine occurs 1-3 hours after oral administration and approximately 15 minutes after injection and it presents a bioavailability of over 75%. Complete amphetamine absorption is usually done after 4-6 hours.
Toxicity
The mean lethal serum concentration is reported to be of 6.4 mg/l. Acute amphetamine overdose can lead to hyperthermia, respiratory depression, seizures, metabolic acidosis, renal failure, hepatic injury, and coma. Some of the neurologic effects have been shown to be agitation, aggressive behavior, irritability, headache, and hallucinations. In the cardiovascular site, there have been reports of arrhythmia, cardiomyopathy, myocardial infarction or ischemic stroke. Lastly, in the GI tract, there are reports if abdominal pain, vomiting, diarrhea, cramps, anorexia and GI hemorrhage. A dose of 1-2 g of amphetamine is known to cause severe intoxication but some chronic abusers can report usage of even 5-15 g per day. In animal studies, there is no evidence of carcinogenic potential, not clastogenic or to affect fertility or early embryonic development.
Indication
Amphetamine is indicated for the treatment of attention-deficit/hyperactivity disorders (ADHD) as well as for the treatment of central nervous system disorders such as narcolepsy. ADHD is a complex disorder associated with the substantial heterogeneity in etiology, clinical presentation, and treatment outcome. ADHD comes from a complex interplay between interdependent genetic and non-genetic factors which cause complex mental disorders in children and teenagers. On the other hand, narcolepsy is a chronic sleep disorder typically resenting during adolescence and characterized by excessive daytime sleepiness. Amphetamine is also being used nowadays off-label for the treatment of obesity, depression and chronic pain.
Half-life
The half-life of amphetamine highly depends on the isomer. For d-amphetamine, the reported half-life is of approximately 9-11 hours while for l-amphetamine the half-life is reported to be of 11-14 hours. The urine pH can modify this pharmacokinetic parameter which can vary from 7 hours in acid urine to 34 hours for alkaline urine.
Protein Binding
The reported protein binding of amphetamine is relatively low and register to be of 20%.
Elimination
The elimination of amphetamine is mainly via the urine from which about 40% of the excreted dose is found as unchanged amphetamine. About 90% of the administered amphetamine is eliminated 3 days after oral administration. The rate of elimination of amphetamine highly depends on the urine pH in which acidic pH will produce a higher excretion of amphetamine and basic pH produces a lower excretion.
Volume of Distribution
Amphetamine is reported to have a high volume of distribution of 4 L/kg.
Clearance
The reported normal clearance rate is of 0.7 L.h/kg. This clearance has been shown to get significantly reduced in patients with renal impairment reaching a value of 0.4 L.h/kg.
Receptor Profile
Receptor Actions
Receptor Binding
History & Culture
1887–1927
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 were not discovered until 1927, when American chemist Gordon Alles independently resynthesized the compound while searching for a replacement for ephedrine. Alles subsequently reported that the drug possessed significant sympathomimetic properties, marking the beginning of scientific interest in amphetamine's potential applications.
1932–1937
Following the discovery of its stimulant effects, amphetamine quickly moved toward commercial development. In 1932, the pharmaceutical company Smith, Kline & French introduced the Benzedrine inhaler, initially marketed as a nasal decongestant. By 1934, the company had expanded sales of the volatile salt form for this purpose. Medical applications broadened rapidly during this period. The first report describing amphetamine's therapeutic use for narcolepsy appeared in 1935, the same year Smith, Kline and French registered the racemic mixture. In 1937, researcher Charles Bradley published findings demonstrating that amphetamine could effectively treat behavioral problems in children, representing one of the earliest documented uses of stimulant medication for what would later be recognized as attention deficit disorders.
1939–1945
During World War II, amphetamine and methamphetamine saw widespread deployment among military forces on both sides of the conflict. Allied and Axis powers alike distributed these stimulants to soldiers to promote wakefulness, combat fatigue, and enhance performance during extended operations. The wartime demand led to massive overproduction of amphetamine. When hostilities concluded, the substantial surplus that had accumulated found its way into black markets, catalyzing the beginning of widespread illicit amphetamine abuse. As the addictive properties of the drug became increasingly apparent through this post-war period, governments around the world began implementing strict controls on its manufacture and sale.
1996–2002
Contemporary medical use of amphetamine centers largely on combination formulations developed for attention deficit hyperactivity disorder and narcolepsy. Adderall, a preparation containing dextroamphetamine and levoamphetamine in a 75% to 25% ratio, was introduced in 1996. A generic version of this formulation received approval in 2002, expanding accessibility to amphetamine-based treatment for these conditions.
Subjective Effect Notes
physical: The physical effects of amphetamine can be broken down into several components which progressively intensify proportional to dosage.
cognitive: 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.
Effect Profile
Curated + 625 ReportsStrong focus with moderate stimulation, mild euphoria and anxiety/jitters
User Experiences
Duration Timeline
BluelightEmpirical Duration
Erowid ReportsCommunity Effects
TripSitTolerance & Pharmacokinetics
drugs.wikiCross-Tolerances
Demographics
Gender Distribution
Age Distribution
Reports Over Time
Effect Analysis
Erowid + BluelightEffects aggregated from 595 experience reports (545 Erowid + 80 Bluelight)
Effect Sentiment Distribution
Confidence Distribution
Positive Effects 47
Adverse Effects 74
Dose-Response Correlation
How effect frequency changes across dose levels
Oral
View data table
| Effect | Common (n=79) | Strong (n=90) | Heavy (n=73) |
|---|---|---|---|
| Stimulation | 57.0% | 52.2% | 57.5% |
| Euphoria | 32.9% | 54.4% | 43.8% |
| Anxiety | 50.6% | 44.4% | 53.4% |
| Focus Enhancement | 39.2% | 43.3% | 28.8% |
| Sedation | 43.0% | 35.6% | 28.8% |
| Empathy | 19.0% | 33.3% | 26.0% |
| Music Enhancement | 26.6% | 28.9% | 30.1% |
| Confusion | 17.7% | 26.7% | 23.3% |
| Increased Heart Rate | 19.0% | 20.0% | 17.8% |
| Tactile Enhancement | 11.4% | 18.9% | 19.2% |
| Body High | 6.3% | 16.7% | 17.8% |
| Visual Distortions | 13.9% | 15.6% | 16.4% |
| Auditory Effects | 10.1% | 12.2% | 16.4% |
| Nausea | 12.7% | 8.9% | 13.7% |
| Hospital | 5.1% | 8.9% | 12.3% |
Insufflated
View data table
| Effect | Light (n=10) | Common (n=12) | Strong (n=13) | Heavy (n=11) |
|---|---|---|---|---|
| Euphoria | 70.0% | 50.0% | 53.8% | 36.4% |
| Stimulation | 50.0% | 58.3% | 61.5% | 63.6% |
| Focus Enhancement | 60.0% | 33.3% | 30.8% | 45.5% |
| Anxiety | 60.0% | 25.0% | 53.8% | 45.5% |
| Empathy | 20.0% | 16.7% | 30.8% | 54.5% |
| Music Enhancement | 40.0% | 25.0% | 46.2% | 45.5% |
| Auditory Effects | 40.0% | 0% | 0% | 0% |
| Sedation | 30.0% | 16.7% | 38.5% | 36.4% |
| Confusion | 0% | 16.7% | 30.8% | 36.4% |
| Tactile Enhancement | 0% | 0% | 0% | 36.4% |
| Body High | 20.0% | 0% | 15.4% | 27.3% |
| Increased Heart Rate | 20.0% | 25.0% | 23.1% | 18.2% |
| Jaw Clenching | 20.0% | 0% | 0% | 0% |
| Pupil Dilation | 20.0% | 0% | 0% | 0% |
| Visual Distortions | 20.0% | 16.7% | 0% | 18.2% |
Subjective Effect Ontology
Experience ReportsStructured effect tags extracted from 625 Erowid & Bluelight experience reports using a controlled vocabulary of 220+ canonical effects across 15 domains.
Auditory
Cognitive
Emotional
Motor
Dose–Effect Mapping
Experience ReportsHow reported effects shift across dose tiers, based on 545 experience reports.
| Effect | Light (n=10) | Common (n=12) | Strong (n=13) | Heavy (n=11) | |
|---|---|---|---|---|---|
| euphoria | ↓ | ||||
| stimulation | ↑ | ||||
| focus enhancement | ↓ | ||||
| anxiety | ↓ | ||||
| empathy | ↑ | ||||
| music enhancement | → | ||||
| auditory effects | — | — | — | → | |
| sedation | ↑ | ||||
| confusion | — | ↑ | |||
| tactile enhancement | — | — | — | → | |
| body high | — | ↑ | |||
| increased heart rate | → | ||||
| jaw clenching | — | — | — | → | |
| pupil dilation | — | — | — | → | |
| visual distortions | — | → | |||
| color enhancement | — | — | — | → | |
| memory suppression | — | — | → | ||
| creativity enhancement | — | — | — | → | |
| nausea | — | — | ↓ | ||
| introspection | — | — | — | → |
Showing top 20 of 23 effects
| Effect | Common (n=79) | Strong (n=90) | Heavy (n=73) | |
|---|---|---|---|---|
| stimulation | → | |||
| euphoria | ↑ | |||
| anxiety | → | |||
| focus enhancement | ↓ | |||
| sedation | ↓ | |||
| empathy | ↑ | |||
| music enhancement | → | |||
| confusion | ↑ | |||
| increased heart rate | → | |||
| tactile enhancement | ↑ | |||
| body high | ↑ | |||
| visual distortions | ↑ | |||
| auditory effects | ↑ | |||
| nausea | → | |||
| hospital | ↑ | |||
| memory suppression | ↓ | |||
| introspection | ↓ | |||
| color enhancement | ↓ | |||
| headache | ↓ | |||
| sweating | ↑ |
Showing top 20 of 34 effects
Risk Escalation
Sentiment AnalysisAverage frequency of positive vs adverse effects across dose tiers (Oral)
View effect breakdown
Adverse Effects
| Effect | Common (n=79) | Strong (n=90) | Heavy (n=73) | Change |
|---|---|---|---|---|
| Anxiety | 5% | |||
| Confusion | +31% | |||
| Increased Heart Rate | -6% | |||
| Nausea | 7% | |||
| Memory Suppression | -40% | |||
| Headache | -32% | |||
| Sweating | +88% | |||
| Psychosis | +152% | |||
| Jaw Clenching | — | +43% | ||
| Pupil Dilation | -23% | |||
| Appetite Suppression | -64% | |||
| Motor Impairment | -57% | |||
| Muscle Tension | +44% | |||
| Seizure | — | — | 0% |
Positive Effects
| Effect | Common (n=79) | Strong (n=90) | Heavy (n=73) | Change |
|---|---|---|---|---|
| Stimulation | 0% | |||
| Euphoria | +33% | |||
| Focus Enhancement | -26% | |||
| Empathy | +36% | |||
| Music Enhancement | +13% | |||
| Tactile Enhancement | +68% | |||
| Body High | +182% | |||
| Introspection | -15% | |||
| Color Enhancement | -40% | |||
| Creativity Enhancement | -28% | |||
| Pain Relief | — | — | 0% |
Risk Escalation
Sentiment AnalysisAverage frequency of positive vs adverse effects across dose tiers (Insufflated)
View effect breakdown
Adverse Effects
| Effect | Light (n=10) | Common (n=12) | Strong (n=13) | Heavy (n=11) | Change |
|---|---|---|---|---|---|
| Anxiety | -24% | ||||
| Confusion | — | +117% | |||
| Increased Heart Rate | -9% | ||||
| Jaw Clenching | — | — | — | 0% | |
| Pupil Dilation | — | — | — | 0% | |
| Memory Suppression | — | — | -9% | ||
| Nausea | — | — | -23% | ||
| Motor Impairment | — | — | — | 0% | |
| Muscle Tension | — | — | — | 0% |
Positive Effects
| Effect | Light (n=10) | Common (n=12) | Strong (n=13) | Heavy (n=11) | Change |
|---|---|---|---|---|---|
| Euphoria | -48% | ||||
| Stimulation | +27% | ||||
| Focus Enhancement | -24% | ||||
| Empathy | +172% | ||||
| Music Enhancement | +13% | ||||
| Tactile Enhancement | — | — | — | 0% | |
| Body High | — | +36% | |||
| Color Enhancement | — | — | — | 0% | |
| Creativity Enhancement | — | — | — | 0% | |
| Introspection | — | — | — | 0% |
Dosage Distribution
Dose distribution from experience reports
Oral
Insufflated
Real-World Dose Distribution
62K DosesFrom 935 individual dose entries
Oral (n=640)
Rectal (n=57)
Insufflated (n=145)
Smoked (n=5)
Common Combinations
Most co-occurring substances in experience reports
Form / Preparation
Most common forms and preparations reported
Body-Weight Dosing
Dose relative to body weight from reports with weight data
Oral
Insufflated
Unknown
Redose Patterns
Redosing behavior across 443 reports
Legal Status
| Country | Status | Notes |
|---|---|---|
| Australia | Schedule 8 | Controlled substance under national scheduling. Personal quantities under 1.5 grams were decriminalized in the Australian Capital Territory as of October 28, 2023. |
| Austria | Illegal (SMG) | Prohibited under the Suchtmittelgesetz (Narcotic Substances Act). Possession, production, and sale are illegal without authorization. |
| Brazil | Class A3 | Classified as a psychoactive substance requiring a prescription for purchase and a license to sell. |
| Canada | Schedule I (CDSA) | 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. |
| China | Prohibited | 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. |
| Finland | Prohibited | Controlled under the Finnish Narcotics Act. Possession, purchase, sale, and manufacture are illegal. |
| France | Stupéfiant | Scheduled as a recognized drug of abuse. Possession, purchase, sale, and manufacture are prohibited, and the substance is not available by prescription. |
| Germany | Anlage III BtMG | 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. |
| Israel | Prohibited | 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. |
| Japan | Prohibited | Amphetamine is banned even for medical use, making it unavailable for any therapeutic purpose within the country. |
| Luxembourg | Prohibited (recreational) | Recreational use is prohibited under national drug legislation. |
| Netherlands | List I (Opiumwet) | Controlled under the Opium Act as a List I substance. Possession, distribution, and production without authorization are illegal. |
| New Zealand | Class B1 | Reclassified from Class B2 to the more restrictive Class B1 controlled substance category on August 2, 2005. |
| Norway | Schedule II | Controlled substance under Norwegian drug legislation. Purchase and possession without a valid prescription are prohibited. |
| Poland | Group II-P | Listed in Appendix II-P of the Narcotic Drugs and Psychotropic Substances Law. Buying, selling, possessing, and using without authorization are criminal offenses. |
| Portugal | Decriminalized (personal use) | 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. |
| South Korea | Prohibited | Banned even for medical use in compliance with the United Nations Convention on Psychotropic Substances. |
| Sweden | Schedule II | Classified as a controlled drug and included in List II under Swedish law, corresponding to List P II of the 1971 Psychotropic Convention. |
| Switzerland | Verzeichnis A | Specifically named as a controlled substance under Schedule A of Swiss drug legislation. Medicinal use is permitted with appropriate authorization. |
| Thailand | Category 1 Narcotic | Classified under the Thai Narcotic Act of 2012. Category 1 represents the most restricted classification with severe penalties. |
| United Kingdom | Class B (Schedule 2) | 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. |
| United States | Schedule II | 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. |
Harm Reduction
drugs.wiki• Urinary pH strongly controls amphetamine clearance: acidic urine shortens the half‑life and alkaline urine can extend it into the 20–30+ hour range; antacids and bicarbonate can therefore increase exposure unpredictably. Avoid intentional pH manipulation for dosing. • Amphetamine is primarily metabolized by CYP2D6; potent CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine, ritonavir) can raise blood levels and side‑effects—dose cautiously and avoid stacking with such inhibitors. • Combining with MAOIs is dangerous (hypertensive crisis/serotonin toxicity); observe a minimum 14‑day washout. • Intranasal use damages nasal mucosa over time; to reduce harm, finely powder, use small, spaced lines, alternate nostrils, and rinse with sterile saline afterward. Persistent bleeding/crusting warrants a break. • Stimulant use increases heart rate, blood pressure, and body temperature; hot environments, intense exercise, or prolonged dancing further raise hyperthermia and rhabdomyolysis risk—take cool breaks, avoid overheating, and sip fluids regularly without overhydrating. • Redosing to chase euphoria rapidly elevates plasma levels due to the long half‑life, worsening anxiety, insomnia, and psychosis risk while providing diminishing returns; set a session cut‑off and prioritize sleep and nutrition. • Antihypertensives may work less effectively during stimulant use; those with cardiovascular disease or uncontrolled hypertension should avoid nonmedical use. • Test unknown powders and avoid mixed batches: street “speed” may contain other stimulants or contaminants; use drug‑checking services where available. • Mixing with DXM, tramadol, or triptans increases serotonin‑toxicity risk; know early symptoms (agitation, clonus, hyperthermia) and seek urgent care if they appear. • Sleep deprivation itself can precipitate stimulant psychosis; spacing use by weeks and keeping doses modest lowers this risk.
References
Data Sources
Cited References
Drugs.wiki References
- DrugBank: Amphetamine profile (mechanism, metabolism, renal pH effect, half‑life)
- Erowid health article (psychostimulant interactions; urinary alkalinisers; antihypertensives; seizure threshold)
- TripSit Wiki: Amphetamine & Methamphetamine timelines/interactions (community HR)
- Hi‑Ground: Amphetamine page (route‑specific durations and HR tips)
- Drugs‑Forum: Amphetamine information & MAOI warning; intranasal harms (community HR)