Bupropion

Wellbutrin, Zyban, Amfebutamone

Psychoactive Class

Antidepressant Stimulant (mild)Nootropic

Chemical Class

Cathinone (substituted)Phenethylamine (substituted)

Bupropion is an atypical antidepressant belonging to the substituted cathinone¹ and phenethylamine classes.² First marketed under the brand name Wellbutrin, it functions as a norepinephrine-dopamine reuptake inhibitor (NDRI) and is prescribed for major depressive disorder, seasonal affective disorder, and smoking cessation.² Unlike typical antidepressants, bupropion is less associated with sexual dysfunction and weight gain.³ It carries an elevated seizure risk, particularly in predisposed individuals, and should not be combined with other drugs without caution.²

Dosage & Duration

Dosage

Moderate400-400 mg

Bioavailability

5-20%

Duration

Onset15-90 minutes

After Effects1-6 hours

Half-life

12-30 hours (mean ~21-24 hours with chronic use)

Subjective Effects

Bupropion is a prescription antidepressant whose subjective profile is dominated by mild stimulation rather than any pronounced alteration of consciousness. Reported effects include increased energy, elevated mood, and improved focus, though many people describe the experience as unpleasant rather than desirable, with jitteriness, anxiety, and tremor often outweighing any positive elements. Non-oral use has been described as resembling a very weak, short-lived cocaine-like effect lasting only seconds to around thirty minutes, and users have characterized it as roughly a fifth as intense as cocaine. At high doses and in overdose the profile shifts sharply toward agitation, confusion, hallucinations, paranoid ideation, and seizures.

Physical

Physical effects centre on stimulation with tachycardia, tremor, dry mouth, and insomnia; some describe a jittery, overstimulated bodily discomfort that is a common reason to discontinue the drug. Nausea, sweating, and appetite reduction are also reported.

Autonomic

Excessive sweating

Cardiovascular

Coordination

Stimulation

Uncomfortable

Constipation

Cognitive

The mental state is characterized by increased energy, interest, and concentration, sometimes accompanied by reduced anxiety but just as often by heightened anxiety, agitation, and paranoia. Confusion, disorientation, and frank delusional thinking have been documented at toxic doses.

Emotional

Enhancements

Impairment

Visual

Visual hallucinations are confined to overdose and excessive dosing, often described as seeing figures walking around.

Auditory

Auditory hallucinations appear only in overdose, generally as voices.

Reagent Testing

Loading reagent data

Expected colorimetric results are being prepared.

Pharmacology

Pharmacodynamics

Bupropion is a norepinephrine-dopamine reuptake inhibitor (NDRI) that weakly inhibits the reuptake of norepinephrine and dopamine by binding to the norepinephrine transporter (NET) and dopamine transporter (DAT), prolonging their action in the synaptic cleft.⁴ It also acts as a negative allosteric modulator of nicotinic acetylcholine receptors, with activity at α3β2, α4β2, and α7 subtypes, being most potent at α3β2 and least potent at α7. This nicotinic antagonism is thought to contribute to its efficacy as a smoking cessation aid by blunting the effects of nicotine and affecting receptor subtypes associated with dopamine and norepinephrine release. Bupropion is essentially inactive at the serotonin transporter and has no meaningful direct activity at adrenergic, dopamine, serotonin, histamine, or muscarinic acetylcholine receptors.⁵ PET studies show that bupropion at therapeutic doses occupies only approximately 20% of dopamine transporters in the human brain, considerably lower than other NDRIs like methylphenidate, raising questions about the relative contribution of dopamine reuptake inhibition to its clinical effects.⁶ Due to the higher plasma concentrations of its metabolite hydroxybupropion, which has greater affinity for NET than DAT, the overall pharmacological profile in humans may be more consistent with noradrenergic than dopaminergic activity. Bupropion and its primary metabolite hydroxybupropion have also been found to block serotonin 5-HT3A receptors.⁷

Pharmacokinetics

Bupropion is rapidly and completely absorbed after oral administration, but absolute bioavailability is presumed to be low (5-20%) due to extensive first-pass metabolism. It is extensively metabolized via multiple pathways, with CYP2B6 being the principal enzyme responsible for formation of the major active metabolite hydroxybupropion⁴, while CYP2C19 contributes to a lesser degree. Additional reductive pathways involving 11β-hydroxysteroid dehydrogenase type 1 in the liver⁸ and AKR7A2/AKR7A3 in the intestine produce threohydrobupropion and erythrohydrobupropion. Metabolism is highly variable between individuals, with effective doses differing by as much as 5.5-fold for bupropion and 7.5-fold for hydroxybupropion. The half-life is approximately 21-24 hours with chronic use, while metabolites have half-lives of 20-30 hours or greater and accumulate with repeated dosing.⁴ Hydroxybupropion reaches steady-state concentrations 7-10 times higher than the parent compound. Bupropion is 84% bound to plasma proteins.⁴ Following oral administration, 87% of the dose is recovered in urine and 10% in feces, with only 0.5% excreted unchanged.⁴ Bupropion also inhibits CYP2D6, which can lead to clinically significant drug interactions.⁴

Interactions

Caution

Use caution

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.

1,2-BenzodiazepineAbacavirAbametapirAbataceptAbrocitinib

TripSit

Tolerance

Tolerance not written up yet

Harm Potential

Addiction & Dependence

Psychological

Low

Bupropion has been identified as having mild abuse potential with amphetamine-like activity, particularly when insufflated or injected. At oral doses around 400 mg, patients with substance abuse history may experience mild amphetamine-like effects.⁹ Some recreational use has been reported, though the substance is usually not very pleasant.

Physical

Extremely Low

A handful of case reports suggest that abrupt discontinuation may cause antidepressant discontinuation syndrome, but significant physical dependence is not a prominent feature of bupropion use.

Toxicity

Hepatic

Cases of liver toxicity leading to death or liver transplantation have been reported¹⁰; bupropion is considered one of several antidepressants with greater hepatotoxicity risk, with documented cases developing within the first 6 months of treatment.

Cardiovascular

Bupropion has been shown to increase blood pressure and may exacerbate unmanaged or pre-existing hypertension⁹; QT prolongation has been associated with overdose but not therapeutic doses.¹¹

Dermatologic

Bupropion has rarely been associated with Stevens-Johnson syndrome.⁹

Ocular

Bupropion may trigger angle-closure glaucoma attacks in susceptible individuals.⁹

Psychosis Risk

Bupropion-induced psychosis may develop in rare cases¹², typically associated with higher than recommended doses. Symptoms include visual hallucinations such as figures walking around, auditory hallucinations including voices, severe agitation, and disorientation to time. Hallucinations are fairly often seen with significant overdoses. At least one report described hallucinated voices suggesting self-harm.¹³

Seizure Risk

Seizures are the primary severe medical concern with bupropion and are strongly dose-dependent.⁹ At therapeutic doses of 300-450 mg daily, seizure incidence is approximately 0.4%, but this climbs almost ten-fold at 600 mg.⁹ The median seizure dose in overdose is 1-2 grams, with one analysis finding seizures in 11% of intentional overdoses overall, increasing to 41% in cases with other clinical effects. An Australian review found 37% of overdoses resulted in seizure.¹⁴ Bupropion lowers the seizure threshold even at doses of 150-450 mg, which poses risk for susceptible individuals.¹¹ The drug has a narrow safety range given this seizure risk, and the FDA initially withdrew it from the market due to seizure concerns before reintroducing it with adjusted dosing.

History & Culture

Discovery and Early Development

Bupropion was synthesized in 1969 by Nariman Mehta, a chemist working at Burroughs Wellcome (now GlaxoSmithKline), during efforts to develop a new antidepressant compound. The US patent was granted in 1974.¹⁵ Testing proceeded through the 1970s, with researchers reporting in…

Legality

International

Not scheduled under the Single Convention on Narcotic Drugs (1961).

Not scheduled under the Convention on Psychotropic Substances (1971).

Not scheduled under the United Nations Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances (1988).

By Country

United StatesUnscheduled (Prescription only)Citation needed

Not a controlled substance under the Controlled Substances Act, but available only with a prescription. The FDA approved it for depression in 1985, withdrew it briefly due to seizure concerns, then reapproved it in 1989. Approved for smoking cessation in 1997 under the brand name Zyban. Despite being unscheduled, bupropion has been identified as having abuse potential due to its stimulant effects and structural similarity to the controlled substance cathinone, with mild amphetamine-like activity particularly when inhaled or injected.

By state

Iowa

Prescription onlyNot state-scheduled

Michigan

Prescription onlyNot state-scheduled

Minnesota

Prescription onlyExcluded from cathinone schedule

Missouri

Prescription onlyNot state-scheduled

Montana

Prescription onlyExcluded from cathinone schedule

Nebraska

Prescription onlyExcluded from state schedule

South Dakota

Prescription onlynoncontrolled-prescription-drug

Wisconsin

Prescription onlynoncontrolled-prescription-drug

Wyoming

Prescription onlynoncontrolled-prescription-drug

CanadaPrescription onlyPRESCRIPTION

Food and Drugs Act / Drug Product Database²⁸²⁹³⁰

Health Canada's Drug Product Database lists bupropion hydrochloride products with the schedule designation PRESCRIPTION. Bupropion is therefore supplied in Canada as a prescription drug product.

GermanyPrescription onlyverschreibungspflichtig

Arzneimittelverschreibungsverordnung³³

BfArM identifies the AMVV as the legal basis for prescription status. Its published material expressly describes bupropion-containing medicines as all prescription-only. The evidence addresses medicines containing bupropion rather than a narcotics scheduling entry.

SingaporePrescription onlyPRESCRIPTION ONLY MEDICINES

Health Products Act 2007 therapeutic-product framework; Singapore National Drug Formulary product registration SIN10983P^37383940

Singapore's official National Drug Formulary identifies WELLBUTRIN SR TABLETS 150 MG (SIN10983P) as bupropion HCl 150 mg and gives its forensic classification as PRESCRIPTION ONLY MEDICINES. Separately, the Poisons Act Schedule lists ‘Bupropion; its salts’; the 2000 amendment notification inserted that entry effective 1 March 2000. HSA cautions that, from 18 December 2023, active ingredients are regulated under the Health Products Act and its regulations, and the Poisons Act/Rules no longer apply to active ingredients; this entry therefore relies on the current registered-product POM classification for supply status, not on the poison-list entry alone.

SwedenPrescription onlyRecept krävs

Läkemedelslag (2015:315), 4 kap. 20 §⁴²⁴³

The Swedish FASS professional product record for Voxra 150 mg identifies bupropion as the active substance and states ‘Recept krävs’ (prescription required). Sweden’s Medicines Act requires the Medical Products Agency, when granting marketing authorisation, to classify a medicine as prescription-only or non-prescription; the official product classification therefore supports prescription-only status for authorised bupropion products. This finding concerns medicinal-product supply and does not assert narcotics scheduling.

BrazilPrescription onlyLista C1

Portaria SVS/MS nº 344/1998, Anexo I, Lista C1²⁶²⁷

Bupropion is listed as “Bupropiona” in Brazil’s Lista C1 of other substances subject to special control. Medicines containing Lista C1 substances require a two-copy special-control prescription, with one copy retained by the dispensing pharmacy or drugstore.

DenmarkPrescription onlyreceptpligtigt lægemiddel

Danish Medicines Agency Medicinpriser dispensing classification³¹³²

The Danish Medicines Agency's Medicinpriser database lists Zyban 150 mg prolonged-release tablets under the active substance bupropion. The database explains that an asterisk denotes a medicine that may be bought without prescription; the listed Zyban packs carry no asterisk, supporting prescription-only supply. This is a medicine-dispensing classification, not a narcotics or analogue scheduling finding.

NorwayPrescription onlyReseptgruppe C

Legemiddelforskriften § 7-3³⁴³⁵³⁶

The Norwegian Directorate of Medical Products' Legemiddelsøk entry for Bupropion hydrochloride Teva identifies the active substance as bupropion hydrochloride and assigns the product to prescription group C. Legemiddelforskriften § 7-3 provides that prescription medicines are placed in groups A, B, or C; this supports classification as prescription-only rather than narcotic control. DMP describes the narcotics list as part of the Narkotikaforskriften, including both named substances and 12 generic groups; no bupropion listing was located in the inspected official list.

SpainPrescription onlymedical prescription

AEMPS bupropion safety notice⁴¹

AEMPS expressly calls bupropion a prescription medicine requiring medical supervision. Its accompanying official product information concerns bupropion hydrochloride for smoking cessation. The source supports prescription status rather than a controlled-substance listing.

SwitzerlandPrescription onlycategory B

Swissmedic dispensing category B⁴⁴

Swissmedic Journal lists Bupropion Accord XR in dispensing category B. Swissmedic describes its authorisation process as assigning the method of sale, including prescription-only supply. The classification is pharmaceutical dispensing regulation.

References

Source Pages

Citations

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Bupropion

Wellbutrin, Zyban, Amfebutamone

Psychoactive Class

Antidepressant Stimulant (mild)Nootropic

Chemical Class

Cathinone (substituted)Phenethylamine (substituted)