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''Areca catechu'' (the nut); ''Piper betle'' (the leaf) (1) · ''Brugmansia'' spp., Angel's trumpet, ''borrachero'', ''toé'' (1) · ''Camellia sinensis'' (formerly ''Thea sinensis'') (1) · ''Catha edulis''. Chat, qat, the Flower of Paradise (1) · ''Coffea arabica'', ''Coffea canephora'' (robusta) (1) · ''Cola nitida'', ''Cola acuminata'' (1) · ''Erythroxylum coca'', ''E. novogranatense'' (1) · ''Ilex paraguariensis'' (1) · ''Ilex vomitoria'' (1) · ''Mimosa tenuiflora''. Jurema preta, tepescohuite (1) · ''Paullinia cupana'' (1) · ''Sophora secundiflora''. Texas mountain laurel, frijolillo (1) · ''Theobroma cacao'' (1) · Ativan (oral, injectable), Loreev XR (1) · Buspar (US brand discontinued; generic widely available) (1) · Deadly nightshade (1) · Effexor XR, Effexor IR (discontinued in US, generic widely available) (1) · Henbane, black henbane (1) · Klonopin (1) · Lexapro (1) · Luvox (US brand discontinued; generic widely available), Luvox CR, Faverin (other markets) (1) · Mandrake (1) · Paxil (IR), Paxil CR (controlled-release), Brisdelle (low-dose for menopausal vasomotor symptoms), Pexeva (paroxetine mesylate) (1) · Prozac (1) · Reed canary grass (1) · The ayahuasca vine, ''yagé'', ''caapi'', ''mariri'' (1) · Valium (oral, IV/IM, rectal), Diastat (rectal gel for breakthrough seizures), Valtoco (nasal spray for breakthrough seizures), Libervant (buccal film) (1) · Vistaril (pamoate), Atarax (HCl, discontinued in US as brand) (1) · Wormwood, absinthe, la Fée Verte, the Green Muse (1)

None (7) · Active alkaloid is cytisine, a nicotinic acetylcholine receptor agonist. NOT a classical 5-HT2A psychedelic. (1) · Active principle is thujone, a GABA-A antagonist (the opposite of most CNS depressants). Also present in cooking sage (''Salvia officinalis''), tansy, and ''Thuja'' cedars. (1) · Caffeine (1.5–2%) + theobromine + kolanin (a glycoside). (1) · Caffeine (highest of the ''Ilex'' genus) plus saponins that produce ritual vomiting at high doses. (1) · Caffeine (sometimes called 'mateine' historically, though chemically identical), theobromine, theophylline, plus polyphenols. (1) · Caffeine + theophylline + L-theanine. L-theanine (an amino acid unique to tea) modulates glutamate and produces an 'alpha-wave' calming overlay on caffeine's stimulation, hence tea's reputation as a 'cleaner' stimulant than coffee. (1) · Caffeine is a non-selective adenosine A1/A2A receptor antagonist; also weak PDE inhibition. Beans contain theobromine (3,7-DMX) and theophylline (1,3-DMX) in smaller amounts. (1) · Contains the β-carboline alkaloids harmine, harmaline, and tetrahydroharmine, reversible monoamine oxidase inhibitors (RIMAs) that allow oral DMT to reach the brain. (1) · Contains varying amounts of DMT, 5-MeO-DMT, bufotenine, and gramine depending on strain and growing conditions. (1) · Highest natural caffeine content of any plant (2–7% by dry weight, ~2–4× coffee). Caffeine is bound to tannins, producing a slower release than pure coffee caffeine. (1) · Primary alkaloid is (S)-(-)-cathinone, a phenylpropanolamine close kin to amphetamine. Releases dopamine and norepinephrine. Also contains cathine (=norpseudoephedrine) and norephedrine. (1) · Primary alkaloid is arecoline, a muscarinic agonist (M1, M2, M3, M4) and partial agonist at nicotinic receptors. Produces alertness, salivation, sweating, mild euphoria. (1) · Primary alkaloid is cocaine, a tropane that blocks reuptake of dopamine and norepinephrine (and serotonin). At low oral doses from leaf chewing, the slow release favors NE-mediated alertness over DA-mediated euphoria. (1) · Primary alkaloid is theobromine (3,7-dimethylxanthine), with minor caffeine. Also contains phenethylamine, anandamide (an endogenous cannabinoid), tryptophan (serotonin precursor), and flavanols. The combined effect is mild stimulation + mood elevation. (1) · Root bark contains ~1% N,N-dimethyltryptamine (DMT) and related tryptamines. Oral activity requires MAOI co-administration. (1) · TrkB/BDNF'"`UNIQ--ref-00000040-QINU`"' '"`UNIQ--vote-00000041-QINU`"' (1) · Tropane alkaloids: hyoscyamine (dominant; the racemic form is atropine), scopolamine. Competitive muscarinic antagonism. (1) · Tropane alkaloids: hyoscyamine, scopolamine, atropine, apoatropine. (1) · Tropane alkaloids: hyoscyamine, scopolamine, in higher seed concentrations than belladonna or datura. (1) · Tropane alkaloids: scopolamine (dominant), hyoscyamine, atropine. Competitive antagonism at muscarinic acetylcholine receptors. (1) · '"`UNIQ--vote-0000001D-QINU`"' '''QT prolongation''' risk at high doses prompted the FDA's 2015 caution against use in patients with prolonged QT or with concurrent QT-prolonging medicines'"`UNIQ--ref-0000001E-QINU`"'. (1) · '"`UNIQ--vote-0000001D-QINU`"' CYP2C19 + CYP3A4 metabolism, with CPIC PGx guidance: poor CYP2C19 metabolizers have ~3-fold higher exposure and benefit from a lower starting dose; ultrarapid metabolizers may have inadequate response'"`UNIQ--ref-0000001E-QINU`"'. (1)

None (15) · 10 mg (1) · 10 mg PO once daily; titrate to 20 mg/day after 1-2 weeks if needed (1) · 5 mg PO TID or 7.5 mg PO BID; titrate by 5 mg every 2-3 days to clinical effect, commonly 30-60 mg/day divided BID-TID (1) · 50 mg PO at bedtime; titrate by 50 mg every 4-7 days to clinical effect. Total daily doses >100 mg divided BID. Luvox CR: 100 mg PO once daily, may titrate to 300 mg/day (1) · A ''marduuf'' bundle (~50 g fresh leaves) chewed over a couple of hours (1) · A measured pour of absinthe diluted 5:1 with cold water over sugar (the louche ritual) (1) · Anxiety: 0.25 mg PO BID, titrate by 0.125-0.25 mg every 3 days to target 1-4 mg/day divided. Seizures: 1.5 mg/day divided TID, titrate by 0.5-1 mg every 3 days (1) · Anxiety: 0.5-1 mg PO BID-TID. Insomnia: 1-2 mg PO at bedtime. Status epilepticus: 4 mg IV (adult), repeat after 5-10 minutes if needed. Acute agitation: 1-2 mg IM (1) · Anxiety: 2-10 mg PO 2-4 times daily. Alcohol withdrawal: 10-20 mg PO/IV every 4-6 hours, symptom-triggered. Status epilepticus: 5-10 mg IV. Breakthrough seizures: Diastat rectal 0.2-0.5 mg/kg or Valtoco intranasal 5-20 mg (1) · Anxiety: 25-50 mg PO QID. Pruritus: 25 mg PO TID-QID. Insomnia: 25-50 mg PO at bedtime. Pediatric: 50-100 mg/day divided (1) · MDD/GAD: 20 mg PO once daily. Panic disorder: 10 mg titrating to 40 mg. OCD: 20 mg titrating to 40-60 mg. CR: 25 mg/day. Brisdelle: 7.5 mg at bedtime for hot flashes (1) · One cup (~40–60 mg caffeine; about half of brewed coffee) (1) · One cup (~80–145 mg caffeine for brewed; 60–100 mg for instant) (1) · XR 37.5 mg PO once daily for 4-7 days, then 75 mg/day; titrate by 75 mg every ≥4 days to clinical effect. IR 25-37.5 mg BID-TID (1)

10 mg, 20 mg, 40 mg caps (1) · A ''betel quid'': areca nut slice + betel leaf + slaked lime (calcium hydroxide) ± tobacco ± spices, chewed (1) · Acid/base extraction of fresh young grass for tryptamines; combined with an MAOI (1) · Bark/woody stem decocted with a DMT-source plant (''Psychotria viridis'', ''Diplopterys cabrerana'') to make ayahuasca (1) · Bright red seeds, traditionally ingested or smoked. Highly toxic, narrow margin between active and lethal (1) · Dried leaves and twigs, infused in a gourd (''mate'') and drunk through a metal straw (''bombilla'') (1) · Dried leaves, infused. Six major processings: white, green, yellow, oolong, black, pu-erh (1) · Dried leaves; absinthe liqueur (120–160 proof, with hyssop, lemon balm, fennel, anise, sometimes Acorus calamus) (1) · Fermented and roasted seeds, ground. Mexican tradition: drunk with chili, cornmeal, achiote. European tradition: with sugar and milk (1) · Flowers or leaves infused or smoked. Highly variable potency; narrow toxic margin (1) · Fresh leaves and tender twigs chewed; degrades on drying (1) · Fresh nuts chewed; also dried and powdered (1) · IR tablets 10, 20, 30, 40 mg; CR tablets 12.5, 25, 37.5 mg; oral suspension 10 mg/5 mL; Brisdelle capsules 7.5 mg (1) · IR tablets 25, 37.5, 50, 75, 100 mg; XR capsules 37.5, 75, 150, 225 mg (1) · IR tablets 25, 50, 100 mg; Luvox CR capsules 100, 150 mg (1) · Leaves and seeds, traditionally smoked or infused. Possibly the original Pythia oracle plant (1) · Leaves chewed with a pinch of slaked lime (the lime converts cocaine HCl to freebase for buccal absorption); also drunk as tea (''mate de coca'') (1) · Leaves, berries, root. Historically: belladonna cigarettes ("Asthmador") OTC in US until the 1970s (1) · Roasted beans, ground; brewed (drip, French press, espresso, cold brew, percolated) (1) · Roasted seeds ground to powder, mixed with water; commercial syrups and energy drinks (1) · Root bark acid/base-extracted for DMT; or as the resurrected ''jurema preta'' brew (decocted with an MAOI such as ''Peganum harmala'') (1) · Root, traditionally carved into ''mannikens'' or infused into wine (1) · Tablets 0.5, 1, 2 mg; oral concentrate 2 mg/mL; injection 2 mg/mL and 4 mg/mL; Loreev XR capsules 1, 2, 3 mg (1) · Tablets 0.5, 1, 2 mg; orally disintegrating tablets 0.125, 0.25, 0.5, 1, 2 mg (1) · Tablets 10, 25, 50 mg (HCl); capsules 25, 50, 100 mg (pamoate); oral suspension 25 mg/5 mL; injection 25, 50 mg/mL (IM only, never IV) (1) · Tablets 2, 5, 10 mg; oral solution 1, 5 mg/mL; injection 5 mg/mL; Diastat rectal gel 2.5, 5, 10, 20 mg; Valtoco nasal spray 5, 7.5, 10 mg/dose; Libervant buccal film (1) · Tablets 5, 10, 20 mg; oral solution 1 mg/mL (1) · Tablets 5, 7.5, 10, 15, 30 mg (the 15 and 30 mg tablets are scored for halving and quartering) (1) · Toasted leaves and twigs decocted to a near-black concentrate (1)

None (19) · 10 mg/day (anxiety, oral) (1) · 20 mg/day (adult); 10 mg/day in elderly and in hepatic impairment (1) · 20 mg/day (seizures); commonly limited to 4 mg/day for anxiety in current practice (1) · 225 mg/day outpatient (XR); 375 mg/day inpatient (IR divided TID); 75 mg/day in moderate hepatic impairment (1) · 300 mg/day (IR or CR) (1) · 40 mg/d (1) · 40 mg/day (oral, anxiety) (1) · 400 mg/day theoretical; in practice rarely exceeds 200 mg/day (1) · 50 mg/day (IR); 62.5 mg/day (CR); 60 mg/day (OCD) (1) · 60 mg/day (1)

buccal (1) · buccal); refined cocaine has its own profile (1) · IM (1) · inhalation (2) · intramuscular (2) · intranasal (1) · intravenous (1) · IV (1) · Oral (24) · Oral (buccal absorption) (1) · Oral (buccal) (1) · Oral (leaf (1) · Oral (with MAOI) (2) · rectal (1) · smoked (extracted DMT) (1) · topical (1)

None (17) · '''Anxiolytic effect emerges over 2-4 weeks'''; buspirone does NOT work for acute anxiety, which is the central teaching point and the most common cause of treatment failure (1) · 15-30 minutes (oral) (1) · 15-60 minutes (oral); 1-5 minutes (IV); 4-10 minutes (rectal or intranasal) (1) · 15–30 min (2) · 20-60 minutes (1) · 30-60 minutes (oral); 5 minutes (IV); 15-30 minutes (IM) (1) · Antidepressant effect emerges over 1-2 weeks (1) · Antidepressant effect emerges over 1-2 weeks; full clinical effect 4-6 weeks (1) · Antidepressant effect over 1-2 weeks; anxiolytic effect over 4-6 weeks (1) · OCD effect over 1-2 weeks initial, with full effect typically 6-12 weeks; among the slowest SSRIs for OCD response (1) · ~15–30 min (1)

None (16) · 24 hours (once-daily dosing) (2) · 24 hours (XR); 12 hours (IR) (1) · 2–4 h (1) · 3–4 h (1) · 3–5 h (subjective) (1) · 4-6 hours (1) · 6-12 hours (long-acting among benzodiazepines) (1) · 6-24 hours (parent); much longer when accounting for the long-lived active metabolites (1) · 6-8 hours (1) · BID at higher doses (IR); once-daily (CR) (1) · Very long (1) · ~8 hours (TID dosing) (1)

None (17) · 12-15 hours (intermediate); '''no active metabolites''' (key clinical feature)'"`UNIQ--ref-00000023-QINU`"' (1) · 14-25 hours (longer in elderly and hepatic impairment)'"`UNIQ--ref-00000026-QINU`"' (1) · 1–4 days (7–15 days for norfluoxetine) (1) · 27-32 hours'"`UNIQ--ref-00000026-QINU`"' (1) · 30-40 hours (long; accumulates with chronic dosing)'"`UNIQ--ref-00000026-QINU`"' (1) · Buspirone 2-3 hours; 1-PP active metabolite 4-6 hours'"`UNIQ--ref-0000001D-QINU`"' (1) · Diazepam 20-50 hours; '''N-desmethyldiazepam (nordazepam) 30-200 hours''' is the major active metabolite and accumulates substantially with chronic dosing'"`UNIQ--ref-00000026-QINU`"' (1) · Venlafaxine 5 hours; desvenlafaxine active metabolite 11 hours'"`UNIQ--ref-00000026-QINU`"' (1) · ~15 hours (IR)'"`UNIQ--ref-00000023-QINU`"' (1) · ~21 hours (with nonlinear pharmacokinetics from CYP2D6 autoinhibition)'"`UNIQ--ref-0000002B-QINU`"' (1) · ~5 h (caffeine) (2)

None (18) · 70–90% (oral) (1) · Highly variable due to saturable first-pass metabolism'"`UNIQ--ref-0000002C-QINU`"' (1) · ~4% (extensive first-pass metabolism)'"`UNIQ--ref-0000001E-QINU`"' (1) · ~45%'"`UNIQ--ref-00000027-QINU`"' (1) · ~53% (oral)'"`UNIQ--ref-00000024-QINU`"' (1) · ~80% (oral)'"`UNIQ--ref-00000027-QINU`"' (2) · ~90% (oral)'"`UNIQ--ref-00000024-QINU`"' (1) · ~90% (oral)'"`UNIQ--ref-00000027-QINU`"' (1) · ~93% (oral); ~90% (rectal)'"`UNIQ--ref-00000027-QINU`"' (1) · ~99% (caffeine) (1)

None (19) · '''Among the least preferred SSRIs in pregnancy.''' Observational signal for cardiac malformations (atrial and ventricular septal defects) with first-trimester exposure, and the most severe neonatal adaptation syndrome of any SSRI with third-trimester exposure'"`UNIQ--ref-0000002D-QINU`"' (1) · Category C'"`UNIQ--ref-00000045-QINU`"' (1) · Limit to <200 mg/d (~2 cups brewed) (1) · Limited human data; older agent with substantial use experience and no clear teratogenic signal.[[[Pharmacopedia:Citation needed|citation needed]]] (1) · Limited human data; older agent with substantial use experience; some signal for first-trimester exposure but not conclusive.[[[Pharmacopedia:Citation needed|citation needed]]] (1) · Limited human data; some signal for cleft palate with first-trimester exposure (debated); neonatal sedation and withdrawal with third-trimester exposure.[[[Pharmacopedia:Citation needed|citation needed]]] (1) · Observational signal for neonatal adaptation syndrome with late-pregnancy exposure; weigh against the risks of untreated maternal depression.[[[Pharmacopedia:Citation needed|citation needed]]] (1) · Observational signal for neonatal adaptation syndrome with third-trimester exposure (SSRI class effect).[[[Pharmacopedia:Citation needed|citation needed]]] (1) · Some signal for cleft lip/palate with first-trimester exposure (debated); neonatal sedation and withdrawal with third-trimester exposure.[[[Pharmacopedia:Citation needed|citation needed]]] (1) · Some signal for cleft palate with first-trimester exposure (debated); neonatal sedation and withdrawal with third-trimester exposure.[[[Pharmacopedia:Citation needed|citation needed]]] (1)

None (14) · Currently legal in most jurisdictions with thujone limits (1) · Leaves legal in Bolivia, Peru, Colombia; cocaine internationally controlled (1) · Plant unrestricted; pharmaceutical atropine Rx-only (1) · Schedule I in US since 1993 (despite traditional use elsewhere); legal in Ethiopia, Kenya, Yemen, Somalia, Djibouti (1) · Unrestricted (food) (1) · [[USLegal:Prescription only|Rx-only]] in US (1) · [[USLegal:Prescription only|Rx-only]] in US. Carries the antidepressant '''Boxed Warning''' for suicidality in children, adolescents, and young adults'"`UNIQ--ref-00000025-QINU`"' (1) · [[USLegal:Prescription only|Rx-only]] in US. Carries the antidepressant '''Boxed Warning''' for suicidality in children, adolescents, and young adults'"`UNIQ--ref-00000028-QINU`"' (2) · [[USLegal:Prescription only|Rx-only]] in US. Carries the antidepressant '''Boxed Warning''' for suicidality in children, adolescents, and young adults'"`UNIQ--ref-0000002E-QINU`"' (1) · [[USLegal:Prescription only|Rx-only]] in US. Not a controlled substance, which is a meaningful clinical advantage over benzodiazepine alternatives for chronic anxiety'"`UNIQ--ref-0000001F-QINU`"' (1) · [[USLegal:Prescription only|Rx-only]] in US. Not a controlled substance, which is a meaningful clinical advantage over the benzodiazepine alternatives for short-term anxiety'"`UNIQ--ref-00000028-QINU`"' (1) · [[USLegal:Schedule IV|Schedule IV controlled substance]] in US. Carries the benzodiazepine class '''Boxed Warning''' for risk of fatal respiratory depression, coma, and death when combined with opioids'"`UNIQ--ref-00000025-QINU`"' (1) · [[USLegal:Schedule IV|Schedule IV controlled substance]] in US. Carries the benzodiazepine class '''Boxed Warning''' for risk of fatal respiratory depression, coma, and death when combined with opioids'"`UNIQ--ref-00000028-QINU`"' (2)