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Codeine (2)

None (5) · ''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) · (multiple, generic dominant) (1) · Aleve (OTC), Naprosyn (Rx), Anaprox (Rx), Naprelan (ER), EC-Naprosyn (enteric-coated), Vimovo (with esomeprazole) (1) · Bayer, Ecotrin, Bufferin, St. Joseph (low-dose 81 mg), Excedrin (with acetaminophen and caffeine) (1) · Darvon (1) · Deadly nightshade (1) · Demerol (1) · Dilaudid (1) · Dolophine (1) · Duragesic (1) · Henbane, black henbane (1) · Mandrake (1) · Nubain (1) · Nucynta (1) · Opana (1) · Reed canary grass (1) · Stadol (1) · Suboxone (1) · Talwin (1) · The ayahuasca vine, ''yagé'', ''caapi'', ''mariri'' (1) · Toradol (IV/IM, US brand discontinued), Sprix (nasal spray), Acular and Acuvail (ophthalmic) (1) · Vicodin (1) · Voltaren (IR oral, topical gel), Cataflam (potassium IR), Cambia (oral powder, migraine), Zorvolex (low-dose), Pennsaid (topical 2% solution), Flector (transdermal patch), Solaraze (3% gel for actinic keratosis) (1) · Wormwood, absinthe, la Fée Verte, the Green Muse (1)

None (4) · 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) · Kappa agonist; mu antagonist (1) · Kappa agonist; mu partial agonist (1) · Kappa agonist; mu partial agonist/antagonist (1) · Mu-opioid agonist; norepinephrine reuptake inhibitor (1) · Mu-opioid receptor agonist (4) · Mu-opioid receptor agonist; NMDA antagonist (1) · Mu-opioid receptor agonist; prodrug (metabolized to morphine) (1) · Mu-opioid receptor agonist; sodium channel blocker (1) · Mu/kappa/delta agonist; NMDA antagonist (1) · Partial mu-opioid agonist; kappa antagonist (1) · Phosphodiesterase inhibitor; calcium channel blocker (1) · Potent mu-opioid receptor agonist (3) · 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) · Prodrug; converted to [[Morphine|morphine]] by [[Enzyme:CYP2D6|CYP2D6]] for analgesic action. (1) · Root bark contains ~1% N,N-dimethyltryptamine (DMT) and related tryptamines. Oral activity requires MAOI co-administration. (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)

None (32) · 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) · Adult: 15–60 mg every 4 hours as needed. (1) · Antiplatelet: 81 mg PO once daily. Acute MI/stroke: 162-325 mg chewed. Analgesic: 325-650 mg PO every 4-6 hours as needed (1) · IM: 60 mg single dose or 30 mg every 6 hours. IV: 30 mg every 6 hours. Oral (continuation only): 10-20 mg every 4-6 hours. Sprix nasal: 31.5 mg every 6-8 hours. '''Maximum 5 days total combined use''' (1) · IR oral 50 mg PO TID or 75 mg BID. Voltaren 1% gel: apply 2-4 g to affected area QID. Pennsaid 2%: 40 drops to knee BID. Flector patch: every 12 hours (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) · OTC: 220 mg PO every 8-12 hours, max 660 mg/24h. Rx: 250-500 mg PO BID. Acute gout: 750 mg loading then 250 mg every 8 hours (1)

None (17) · 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 25, 50 mg; ER tablets 100 mg; Cataflam IR 50 mg; Zorvolex 18, 35 mg; Voltaren gel 1%; Pennsaid 2% topical solution; Flector transdermal patch; Solaraze 3% gel; Cambia oral powder 50 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) · OTC tablets 220 mg; Rx tablets 250, 375, 500 mg; ER tablets 375, 500, 750 mg (Naprelan); oral suspension 125 mg/5 mL; enteric-coated tablets (EC-Naprosyn) (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) · Tablet (15, 30, 60 mg); oral solution; combination products (with [[Acetaminophen|acetaminophen]] or ibuprofen). (1) · Tablets 10 mg; injection 15 mg/mL and 30 mg/mL; nasal spray 15.75 mg/spray (Sprix); ophthalmic solution 0.4%, 0.45%, 0.5% (1) · Tablets 81 (low-dose), 325, 500, 650 mg; chewable 81 mg; enteric-coated tablets; effervescent tablets; suppositories (1) · Toasted leaves and twigs decocted to a near-black concentrate (1)

None (36) · 120 mg/day (IV/IM); 40 mg/day (oral); '''5-day maximum total combined therapy''' to mitigate the GI bleeding, AKI, and platelet dysfunction risks (1) · 150 mg/day (oral); use lowest effective dose for shortest duration per FDA NSAID class guidance (1) · 1500 mg/day (Rx); 660 mg/24h (OTC, without provider direction) (1) · 360 mg/day (1) · 4000 mg/day (analgesic) (1)

None (33) · 15–30 min (2) · 30 minutes (IM); 30-60 minutes (oral) (1) · 30-60 minutes (1) · 30-60 minutes (oral); slower for topical (1) · 30–60 min (PO) (1) · Antiplatelet effect within 30-60 minutes; analgesic effect 30-60 minutes (1) · ~15–30 min (1)

None (33) · '''Antiplatelet effect lasts the platelet's lifetime (~7-10 days)''' due to irreversible COX-1 acetylation; analgesic 4-6 hours (1) · 2–4 h (1) · 3–4 h (1) · 3–5 h (subjective) (1) · 4-6 hours (1) · 4–6 hours (1) · 6-8 hours (IR oral); 12-24 hours (ER) (1) · 8-12 hours (the long-duration feature relative to ibuprofen) (1)

None (34) · 1-2 hours (parent compound)'"`UNIQ--ref-00000029-QINU`"' (1) · 12-17 hours'"`UNIQ--ref-00000029-QINU`"' (1) · 2.5–3 hours (1) · 5-6 hours'"`UNIQ--ref-00000020-QINU`"' (1) · Aspirin 15-30 minutes; salicylate metabolite 2-3 hours (concentration-dependent, saturable at high doses)'"`UNIQ--ref-00000027-QINU`"' (1) · ~5 h (caffeine) (2)

None (35) · ~100% (oral, but oral use is limited to continuation from parenteral)'"`UNIQ--ref-00000021-QINU`"' (1) · ~50% (oral; reduced by buffering and enteric coating but onset clinically similar)'"`UNIQ--ref-00000028-QINU`"' (1) · ~50% (variable, CYP2D6-dependent for analgesic effect). (1) · ~50-60% (oral; substantial first-pass metabolism)'"`UNIQ--ref-0000002A-QINU`"' (1) · ~95% (oral)'"`UNIQ--ref-0000002A-QINU`"' (1) · ~99% (caffeine) (1)

None (35) · Avoid from 20 weeks gestation onward per FDA's 2020 expanded NSAID warning (fetal renal dysfunction, oligohydramnios); contraindicated from 30 weeks (risk of premature ductus arteriosus closure)'"`UNIQ--ref-0000002B-QINU`"' (2) · Avoid from 20 weeks gestation onward per FDA's 2020 expanded NSAID warning; contraindicated from 30 weeks. Specifically contraindicated in labor and delivery due to inhibition of uterine contractions'"`UNIQ--ref-00000022-QINU`"' (1) · Avoid; risk of neonatal opioid withdrawal with chronic use; UM-mother breastfeeding contraindicated. (1) · Limit to <200 mg/d (~2 cups brewed) (1) · Low-dose (81 mg) safe and indicated for preeclampsia prophylaxis after 12 weeks in high-risk patients per USPSTF; high-dose aspirin avoid third trimester due to premature ductus arteriosus closure and bleeding risk (1)

None (31) · 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) · US Schedule II (single-entity); Schedule III–V (combination products by content). (1) · [[USLegal:Over-the-counter|OTC]] in US at all standard strengths (1) · [[USLegal:Over-the-counter|OTC]] in US at ≤220 mg/tablet and ≤660 mg/day; [[USLegal:Prescription only|Rx-only]] at higher strengths (1) · [[USLegal:Prescription only|Rx-only]] for oral and most topical formulations in US; Voltaren Arthritis Pain 1% gel switched to [[USLegal:Over-the-counter|OTC]] in 2020 (1) · [[USLegal:Prescription only|Rx-only]] in US (1)