2-FA

Uncontrolled hypertension, Recent myocardial infarction, Structural heart disease, Significant cardiac arrhythmia

Uncontrolled hypertension, recent myocardial infarction, structural heart disease, or significant arrhythmia. 2-FA's presumed catecholaminergic mechanism imposes sympathomimetic cardiovascular stress that is dangerous in the presence of pre-existing cardiovascular compromise. No 2-FA-specific cardiovascular adverse event data exist, but the amphetamine class mechanism is well-established.

Epilepsy, History of seizures, Lowered seizure threshold

Epilepsy or conditions with lowered seizure threshold. Amphetamine-class stimulants can reduce seizure threshold, with risk increasing at higher doses and with concurrent sleep deprivation. No 2-FA-specific seizure data exist; this is a class-level contraindication.

Panic disorder, Generalized anxiety disorder

Panic disorder, generalized anxiety disorder (GAD), and related conditions. NET-mediated norepinephrine release drives sympathetic arousal that can precipitate panic attacks or worsen baseline anxiety. Article prose notes that doses above common range shift the effect profile toward anxiety and overstimulation.

Schizophrenia, Schizoaffective disorder, History of psychosis

Schizophrenia, schizoaffective disorder, or history of psychosis. Mesolimbic dopamine elevation from DAT reverse transport can trigger or worsen psychotic symptoms. Stimulant psychosis is a well-established class-level risk for all amphetamine-type compounds, with risk amplified by high doses and sleep deprivation.

Significant liver disease, Severe hepatic impairment

Significant liver disease. If 2-FA undergoes hepatic metabolism via CYP2D6/CYP2C19 as predicted from structural analogy with related substituted phenethylamines, impaired hepatic function could reduce clearance and increase plasma exposure. Additionally, Luethi et al. (2019) showed para-halogenated amphetamines exhibit hepatocellular toxicity (HepG2 ATP depletion), though ortho-halogenation has not been tested. No hepatotoxicity data specific to 2-FA exist.

Active hyperthyroidism

Active hyperthyroidism produces a baseline state of sympathetic hyperactivation. Adding a catecholamine-releasing agent such as 2-FA creates additive cardiovascular and metabolic stress. This is a standard class-level contraindication for all sympathomimetic stimulants.

Pregnancy, Breastfeeding

Pregnancy. Amphetamine-class compounds cause vasoconstriction that may compromise placental blood flow. The amphetamine class carries FDA Category C designation. No reproductive or teratogenicity data exist for 2-FA. Breastfeeding safety is unknown.

Irreversible MAOI therapy, Reversible MAOI therapy, Dietary MAOI consumption

Concurrent use of monoamine oxidase inhibitors (MAOIs) — including irreversible MAOIs (phenelzine, tranylcypromine), reversible MAOIs (moclobemide), and dietary MAOIs (harmaline, harmine in ayahuasca) — with any monoamine releasing agent is contraindicated due to risk of hypertensive crisis and serotonin syndrome. This applies universally to the amphetamine class without exception. No 2-FA-specific case report exists, but the mechanism is established at the class level.

Concurrent tramadol use

Tramadol is a mu-opioid agonist, serotonin-norepinephrine reuptake inhibitor, and weak MAO inhibitor. Combined with a norepinephrine-releasing agent such as 2-FA, massively elevated synaptic monoamine concentrations create conditions for serotonin syndrome. Tramadol independently lowers the seizure threshold, and stimulants may compound this risk. Designated 'lethal' in community interaction databases. No 2-FA + tramadol case report has been published; the designation reflects class-level mechanism.