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Bupropion Stats & Data

Stimulant Nootropic

Zyban Wellbutrin Amfebutamone Wellbutrin xl

NPS DataHub

MW239.74

FormulaC13H18ClNO

CAS34911-55-2

IUPAC2-(tert-butylamino)-1-(3-chlorophenyl)propan-1-one

SMILESClc1cccc(c1)C(=O)C(C)NC(C)(C)C

InChIKeySNPPWIUOZRMYNY-UHFFFAOYSA-N

Phenethylamines; Cathinones; 2020/1. Von 2-Phenethylamin abgeleitete Verbindungen; 2021/1. Von 2-Phenethylamin abgeleitete Verbindungen; 2022/1. Von 2-Phenethylamin abgeleitete Verbindungen

Chemical Class Cathinone

Psychoactive Class Stimulant

Pharmacology

DrugBank

Half-life 24 hours State Solid

Description

Bupropion (also known as the brand name product Wellbutrin®) is a norepinephrine/dopamine-reuptake inhibitor (NDRI) used most commonly for the management of Major Depressive Disorder (MDD), Seasonal Affective Disorder (SAD), and as an aid for smoking cessation. Bupropion exerts its pharmacological effects by weakly inhibiting the enzymes involved in the uptake of the neurotransmitters norepinephrine and dopamine from the synaptic cleft, therefore prolonging their duration of action within the neuronal synapse and the downstream effects of these neurotransmitters. More specifically, bupropion binds to the norepinephrine transporter (NET) and the dopamine transporter (DAT). Bupropion was originally classified as an "atypical" antidepressant because it does not exert the same effects as the classical antidepressants such as Monoamine Oxidase Inhibitors (MAOIs), Tricyclic Antidepressants (TCAs), or Selective Serotonin Reuptake Inhibitors (SSRIs). While it has comparable effectiveness to typical first-line options for the treatment of depression such as SSRIs, bupropion is a unique option for the treatment of MDD as it lacks any clinically relevant serotonergic effects, typical of other mood medications, or any effects on histamine or adrenaline receptors.

Mechanism of Action

Bupropion is a norepinephrine/dopamine-reuptake inhibitor (NDRI) that exerts its pharmacological effects by weakly inhibiting the enzymes involved in the uptake of the neurotransmitters norepinephrine and dopamine from the synaptic cleft, therefore prolonging their duration of action within the neuronal synapse and the downstream effects of these neurotransmitters. More specifically, bupropion binds to the norepinephrine transporter (NET) and the dopamine transporter (DAT). Bupropion was originally classified as an "atypical" antidepressant because it does not exert the same effects as the classical antidepressants such as Monoamine Oxidase Inhibitors (MAOIs), Tricyclic Antidepressants (TCAs), or Selective Serotonin Reuptake Inhibitors (SSRIs). While it has comparable effectiveness to typical first-line options for the treatment of depression such as SSRIs, bupropion is a unique option for the treatment of MDD as it lacks any clinically relevant serotonergic effects, typical of other mood medications, or any effects on histamine or adrenaline receptors. Lack of activity at these receptors results in a more tolerable side effect profile; bupropion is less likely to cause sexual side effects, sedation, or weight gain as compared to SSRIs or TCAs, for example.

Pharmacodynamics

Bupropion is chemically unrelated to tricyclic, tetracyclic, selective serotonin re-uptake inhibitors, or other known antidepressant agents. Compared to classical tricyclic antidepressants, Bupropion is a relatively weak inhibitor of the neuronal uptake of norepinephrine and dopamine. In addition, Bupropion does not inhibit monoamine oxidase. Bupropion has been found to be essentially inactive at the serotonin transporter (SERT)(IC50 >10 000 nM), however both bupropion and its primary metabolite hydroxybupropion have been found to block the function of cation-selective serotonin type 3A receptors (5-HT3ARs). Bupropion produces dose-related central nervous system (CNS) stimulant effects in animals, as evidenced by increased locomotor activity, increased rates of responding in various schedule-controlled operant behaviour tasks, and, at high doses, induction of mild stereotyped behaviour . Due to these stimulant effects and selective activity at dopamine and norepinephrine receptors, bupropion has been identified as having an abuse potential.FDA Label,A178846 Bupropion has a similar structure to the controlled substance DB01560, and has been identified as having mild amphetamine-like activity, particularly when inhaled or injected. Bupropion is also known to lower the seizure threshold, making any pre-existing seizure conditions a contraindication to its use.

Metabolism

Bupropion is extensively metabolized in humans. Three metabolites are active: hydroxybupropion, which is formed via hydroxylation of the tert-butyl group of bupropion, and the amino-alcohol isomers, threohydrobupropion and erythrohydrobupropion, which are formed via reduction of the carbonyl group. In vitro findings suggest that CYP2B6 is the principal isoenzyme involved in the formation of hydroxybupropion, while cytochrome P450 enzymes are not involved in the formation of threohydrobupropion. Hydroxybupropion has been shown to have the same affinity as bupropion for the norepinephrine transporter (NET) but approximately 50% of its antidepressant activity despite reaching concentrations of ~10-fold higher than that of the parent drug. Oxidation of the bupropion side chain results in the formation of a glycine conjugate of meta-chlorobenzoic acid, which is then excreted as the major urinary metabolite. The potency and toxicity of the metabolites relative to bupropion have not been fully characterized. However, it has been demonstrated in an antidepressant screening test in mice that hydroxybupropion is one-half as potent as bupropion, while threohydrobupropion and erythrohydrobupropion are 5-fold less potent than bupropion. This may be of clinical importance because the plasma concentrations of the metabolites are as high as or higher than those of bupropion.

Absorption

Bupropion is currently available in 3 distinct, but bioequivalent formulations: immediate release (IR), sustained-release (SR), and extended-release (XL). **Immediate Release Formulation** In humans, following oral administration of bupropion hydrochloride tablets, peak plasma bupropion concentrations are usually achieved within 2 hours. IR formulations provide a short duration of action and are therefore generally dosed three times per day. **Sustained Release Formulation** In humans, following oral administration of bupropion hydrochloride sustained-release tablets (SR), peak plasma concentration (Cmax) of bupropion is usually achieved within 3 hours. SR formulations provide a 12-hour extended release of medication and are therefore generally dosed twice per day. **Extended Release Formulation** Following single oral administration of bupropion hydrochloride extended-release tablets (XL) to healthy volunteers, the median time to peak plasma concentrations for bupropion was approximately 5 hours. The presence of food did not affect the peak concentration or area under the curve of bupropion.

Toxicity

Symptoms of overdose include seizures, hallucinations, loss of consciousness, tachycardia, and cardiac arrest.

Indication

Bupropion is indicated for the treatment of major depressive disorder (MDD), seasonal affective disorder (SAD), and as an aid to smoking cessation. When used in combination with naltrexone as the marketed product ContraveⓇ, bupropion is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of: 30 kg/m^2 or greater (obese) or 27 kg/m^2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia). Bupropion is also used off-label as a first-line treatment in patients with ADHD and comorbid bipolar disorder when used as an adjunct to mood stabilizers.

Protein Binding

In vitro tests show that bupropion is 84% bound to human plasma proteins at concentrations up to 200 mcg per mL. The extent of protein binding of the hydroxybupropion metabolite is similar to that for bupropion, whereas the extent of protein binding of the threohydrobupropion metabolite is about half that seen with bupropion.

Elimination

Bupropion is extensively metabolized in humans. Oxidation of the bupropion side chain results in the formation of a glycine conjugate of metachlorobenzoic acid, which is then excreted as the major urinary metabolite. Following oral administration of 200 mg of 14C-bupropion in humans, 87% and 10% of the radioactive dose were recovered in the urine and feces, respectively. However, the fraction of the oral dose of bupropion excreted unchanged was only 0.5%, a finding consistent with the extensive metabolism of bupropion.

Receptor Profile

Receptor Actions

Antagonists

Nicotinic acetylcholine receptor antagonist (noncompetitive

Inhibitors

Dopamine-norepinephrine reuptake inhibitor (NDRI)

Other

α3β2, α4β2, α7 nAChRs)

Receptor Binding

Sodium-dependent dopamine transporter inhibitor

Sodium-dependent noradrenaline transporter inhibitor

Sodium-dependent serotonin transporter inhibitor

Neuronal acetylcholine receptor subunit alpha-3 antagonist

5-hydroxytryptamine receptor 3A negative modulator

Effect Profile

Curated + 178 Reports

Stimulant 6.4

Strong anxiety/jitters and stimulation with moderate euphoria and focus

Stimulation / Energy×3

97.2

Euphoria / Mood Lift×2

64.6

Focus / Productivity×2

63.1

Anxiety / Jitters×1

1010

Catalog Erowid

Based on reports from:

Erowid Experience Reports PsychonautWiki Bupropion

Tolerance & Pharmacokinetics

drugs.wiki

Tolerance Decay

Full tolerance 1h Half tolerance 4d Baseline ~5d

Experience Report Analysis

Erowid

178 Reports

1994–2024 Date Range

69 With Age Data

33 Effects Detected

Demographics

Gender Distribution

Age Distribution

Reports Over Time

Effect Analysis

Erowid

Effects aggregated from 178 experience reports (178 Erowid)

178 Reports

33 Effects Detected

11 Positive

13 Adverse

9 Neutral

Effect Sentiment Distribution

Confidence Distribution

Positive Effects 11

Stimulation 41.6% 70%

Euphoria 30.9% 70%

Tactile Enhancement 20.2% 70%

Music Enhancement 19.1% 70%

Color Enhancement 19.1% 70%

Focus Enhancement 15.7% 70%

Empathy 11.8% 70%

Body High 9.0% 70%

Introspection 7.3% 70%

Pain Relief 5.1% 70%

Creativity Enhancement 3.4% 70%

Adverse Effects 13

Anxiety 43.3% 70%

Nausea 16.9% 70%

Confusion 15.2% 70%

Seizure 14.0% 70%

Memory Suppression 11.2% 70%

Increased Heart Rate 11.2% 70%

Headache 9.0% 70%

Pupil Dilation 7.9% 70%

Motor Impairment 6.7% 70%

Muscle Tension 6.2% 70%

Psychosis 6.2% 70%

Jaw Clenching 5.1% 70%

Sweating 5.1% 70%

Dose-Response Correlation

How effect frequency changes across dose levels

View data table

Effect	Threshold (n=12)	Common (n=41)	Strong (n=39)	Heavy (n=27)
Anxiety	41.7%	53.7%	46.2%	55.6%
Stimulation	41.7%	48.8%	53.8%	40.7%
Euphoria	33.3%	48.8%	33.3%	25.9%
Visual Distortions	16.7%	19.5%	35.9%	25.9%
Color Enhancement	33.3%	26.8%	20.5%	29.6%
Nausea	0%	12.2%	20.5%	33.3%
Sedation	25.0%	19.5%	17.9%	29.6%
Hospital	0%	14.6%	17.9%	29.6%
Tactile Enhancement	25.0%	19.5%	23.1%	25.9%
Auditory Effects	25.0%	17.1%	12.8%	25.9%
Music Enhancement	25.0%	19.5%	25.6%	14.8%
Seizure	25.0%	9.8%	5.1%	22.2%
Headache	0%	7.3%	23.1%	0%
Focus Enhancement	16.7%	22.0%	12.8%	11.1%
Empathy	0%	22.0%	15.4%	7.4%

Dose–Effect Mapping

Experience Reports

How reported effects shift across dose tiers, based on 178 experience reports.

Oral dose range: 150.0–400.0 mg (median 300.0 mg)

Effect	Threshold (n=12)	Common (n=41)	Strong (n=39)	Heavy (n=27)
anxiety	42%	54%	46%	56%	↑
stimulation	42%	49%	54%	41%	→
euphoria	33%	49%	33%	26%	↓
visual distortions	17%	20%	36%	26%	↑
color enhancement	33%	27%	20%	30%	→
nausea	—	12%	20%	33%	↑
sedation	25%	20%	18%	30%	↑
hospital	—	15%	18%	30%	↑
tactile enhancement	25%	20%	23%	26%	→
auditory effects	25%	17%	13%	26%	→
music enhancement	25%	20%	26%	15%	↓
seizure	25%	10%	5%	22%	→
headache	—	7%	23%	—	↑
focus enhancement	17%	22%	13%	11%	↓
empathy	—	22%	15%	7%	↓
confusion	—	17%	13%	18%	→
open-eye visuals	—	—	10%	18%	↑
memory suppression	—	—	8%	18%	↑
increased heart rate	—	12%	18%	15%	↑
pupil dilation	17%	5%	10%	11%	↓

Showing top 20 of 32 effects

Risk Escalation

Sentiment Analysis

Average frequency of positive vs adverse effects across dose tiers

Threshold n=12

6 positive 29.2% 3 adverse 27.8%

Common n=41

11 positive 21.5% 11 adverse 12.9%

Strong n=39

9 positive 23.1% 13 adverse 15.0%

Heavy n=27

8 positive 21.3% 9 adverse 21.8%

View effect breakdown

Adverse Effects

Effect	Threshold (n=12)	Common (n=41)	Strong (n=39)	Heavy (n=27)	Change
Anxiety	42%	54%	46%	56%	+33%
Nausea	—	12%	20%	33%	+172%
Seizure	25%	10%	5%	22%	-11%
Headache	—	7%	23%	—	+216%
Confusion	—	17%	13%	18%	8%
Memory Suppression	—	—	8%	18%	+140%
Increased Heart Rate	—	12%	18%	15%	+21%
Pupil Dilation	17%	5%	10%	11%	-33%
Sweating	—	—	15%	—	0%
Muscle Tension	—	7%	13%	—	+75%
Psychosis	—	7%	5%	11%	+52%
Motor Impairment	—	5%	8%	11%	+126%
Jaw Clenching	—	5%	10%	—	+110%

Positive Effects

Effect	Threshold (n=12)	Common (n=41)	Strong (n=39)	Heavy (n=27)	Change
Stimulation	42%	49%	54%	41%	-2%
Euphoria	33%	49%	33%	26%	-22%
Color Enhancement	33%	27%	20%	30%	-11%
Tactile Enhancement	25%	20%	23%	26%	3%
Music Enhancement	25%	20%	26%	15%	-40%
Focus Enhancement	17%	22%	13%	11%	-33%
Empathy	—	22%	15%	7%	-66%
Introspection	—	5%	10%	15%	+202%
Body High	—	12%	13%	—	4%
Creativity Enhancement	—	7%	—	—	0%
Pain Relief	—	5%	—	—	0%

Dosage Distribution

Dose distribution from experience reports

Insufflated

Median: 150.0 mg IQR: 100.0–200.0 mg n=26

Oral

Median: 300.0 mg IQR: 150.0–400.0 mg n=100

Real-World Dose Distribution

62K Doses

From 321 individual dose entries

Oral (n=247)

Median: 300.0mg 25th: 150.0mg 75th: 300.0mg 90th: 500.0mg

mg/kg median: 3.779 mg/kg 75th: 5.597

Insufflated (n=38)

Median: 150.0mg 25th: 75.0mg 75th: 150.0mg 90th: 236.1mg

mg/kg median: 1.934 mg/kg 75th: 2.45

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

Insufflated

Median: 1.933 mg/kg IQR: 1.259–2.574 mg/kg n=24

Oral

Median: 3.891 mg/kg IQR: 2.451–6.012 mg/kg n=100

Redose Patterns

Redosing behavior across 160 reports

15.0% Redosed

1.2 Avg Doses

60m Median Interval

Read full reports on Erowid →

Legal Status

Country	Status	Notes
Russia	banned as a narcotic drug, due to it being a derivative of methcathinone
United States	Unscheduled, though it’s only available with a prescription.

References

Data Sources

Cited References

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