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Phentermine
Phentermine is a stimulant and appetite suppressant of the substituted amphetamine class.1 It is used medically for short-term weight management in people with obesity,2 alongside dietary changes, exercise, and behavioral changes.2 Its chemical structure differs from amphetamine by an additional methyl group at the alpha carbon.3 Common adverse effects include a fast heartbeat, high blood pressure, insomnia, dizziness, and restlessness.1 It also has potential for abuse.2
Dosage & Duration
Dosage
Doses are population estimates that vary widely between individuals.
Threshold~15 mg
Light15-20 mg
Moderate20-40 mg
Strong40-70 mg
Heavy70+ mg
Duration
Onset4-6 hours
After Effects1-10 hours
Subjective Effects
Subjective Effects not written up yet
Pharmacology
Pharmacodynamics
Phentermine acts mainly as a monoamine transporter substrate that promotes norepinephrine release, with less potent dopamine release and only weak effects on serotonin.4 It is described as a weak substrate or uptake inhibitor of the serotonin transporter.5 Norepinephrine release in the lateral hypothalamus indirectly stimulates β2-adrenergic receptors and contributes to appetite suppression; dopamine release may be weak or negligible in humans at typical clinical doses, although this remains uncertain. Reported inhibition of neuropeptide Y signaling, a possible increase in leptin, and increased resting energy expenditure may also contribute to its appetite and weight effects. Phentermine activates rat and human TAAR1, with weak partial agonism at the human receptor, which may constrain its monoamine effects. Findings at 5-HT2C differ between studies, with inactivity reported in some and weak partial agonism in another; phentermine is inactive at VMAT2, and its very weak monoamine oxidase inhibition in vitro has uncertain significance in humans, with no neurochemical evidence of this action in rodents in vivo.
Pharmacokinetics
Phentermine is rapidly absorbed from the gastrointestinal tract after oral administration, with its weakly basic properties facilitating absorption in the small intestine. Its pharmacokinetics are dose-dependent, and continuous administration has produced steady-state plasma concentrations around 200 ng/mL. Phentermine is 17.5% bound to plasma proteins8; distribution into fatty tissues may contribute to its persistence. Metabolism accounts for only about 6% of an administered dose and involves para-hydroxylation, N-oxidation, and N-hydroxylation followed by conjugation, with N-oxidized and N-hydroxylated products accounting for about 5% of the dose. Phentermine is listed as a CYP3A4 substrate8 and is not known to significantly induce or inhibit CYP450 enzymes; most pharmacological activity is attributed to the parent compound. Elimination is mainly urinary, with reported unchanged excretion of 70-80% in one source8 and 62-85% in another. The mean terminal half-life is reported as approximately 20 hours,8 with an elimination half-life range of 20-25 hours also reported; acidic urine below pH 5 shortens it to 7-8 hours. Population pharmacokinetic analysis estimates phentermine's oral clearance (CL/F) at 8.79 L/h.8
Interactions
Interactions not written up yet
An unlisted combination is an unknown one, not a safe one. Check a dedicated combination chart before mixing.
Tolerance
Tolerance timelines are rules of thumb, not exact schedules, and vary widely between individuals and use patterns.
Tolerance usually develops with phentermine use, although rapid tolerance (tachyphylaxis) has not been reported. The time required for full tolerance to develop is unspecified.
Harm Potential
Addiction & Dependence
Toxicity
Psychosis Risk
Psychotic episodes and hallucinations are reported very rarely with phentermine. Acute overdose can cause hallucinations,11 while severe chronic overdosage can produce schizophrenia-like psychosis.12
History & Culture
Phentermine first received approval from the United States Food and Drug Administration (FDA) as an appetite suppressant in 195913 and became widely used in 1960. Hydrochloride salt and resin formulations subsequently became available. Its name was derived from…
Legality
International
Phentermine has approved, illicit, and investigational regulatory groupings.
By Country
Illegal1
United StatesIllegalPhentermine is listed by exact name as a Schedule IV stimulant at 21 C.F.R. § 1308.14(f)(9), effective July 6, 1973. The listing covers any quantity of phentermine, including its salts, isomers, and salts of isomers, unless specifically excepted or listed in another schedule. Federal law prohibits unauthorized possession, manufacture, distribution, dispensing, and possession with intent to manufacture, distribute, or dispense; possession obtained directly or under a valid prescription or practitioner order, and other authorized possession, is permitted. A current phentermine hydrochloride tablet is a Schedule IV prescription drug approved for short-term use as an adjunct in a weight-reduction regimen for specified patients with exogenous obesity.
References
Citations
Article Status
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