The curious garden

• Tobacco Nicotiana rustica, N. tabacum, 12,300 years ago: nicotine → nicotinic acetylcholine receptors. Big, sticky leaves, a candelabra of pink trumpet flowers. Nicotine concentrates in the leaves, up to a few percent by weight in N. rustica, the wild, strong species the first Americans used. The leaves are picked, hung and cured, which is where the smell comes from. Tobacco kills about eight million people a year, more than every other plant in this garden combined. Nicotine itself is the hook; the smoke is what kills. Nothing here is a reason to start.
• Coca Erythroxylum coca, 8,000 years ago: cocaine → the dopamine transporter (and norepinephrine, serotonin transporters; sodium channels). A modest bush with glossy oval leaves, each holding roughly half a percent cocaine, plus a dozen related alkaloids. The leaf is the point: it is picked three or four times a year and dried in the sun. The leaf and the drug are the same molecule at different speeds. Cocaine raises heart rate and blood pressure and can cause strokes and arrhythmias at any dose; there is no safe amount of the purified form.
• Opium poppy Papaver somniferum, 7,600 years ago: morphine → the μ-opioid receptor. A papery flower, four petals, often a dark blotch at the base, that lasts about two days. When the petals drop, the pod swells. Scored with a blade while still green, it bleeds latex that dries brown overnight: opium, about ten percent morphine. Opioids are the best treatment for severe pain and the leading cause of overdose death. Both are true. Breathing stops before anything else does; naloxone reverses it.
• Peyote Lophophora williamsii, 5,700 years ago: mescaline → the serotonin 2A receptor. A blue-green button with soft ribs and tufts of white wool where spines would be, and once a year, a pink flower the size of a coin. Mescaline, about one to six percent of the dry weight, sits in the green crown. Peyote is a protected plant and a sacrament; the Native American Church’s use is legal, and the wild population is in decline. Mescaline is physically gentle but raises heart rate and blood pressure, and the experience is long and can be frightening.
• Kava Piper methysticum, 3,000 years ago: kavain (one of six main kavalactones) → GABA-A receptors (positive modulation), sodium and calcium channels. A shrub of jointed green stems and heart-shaped leaves, two or three metres tall, that looks like nothing special, above ground. Below it is a dense, knobbly rootstock, and that is where the kavalactones are, a third of its dry weight in good cultivars. Kava has randomised-trial evidence for anxiety and a safety concern: a cluster of liver injuries in Europe around 2000 led to bans, later eased; traditional water extracts of the root appear safer than the extracts involved. Don’t mix it with alcohol or sedatives.
• Psilocybe (the honorary plant) Psilocybe mexicana, P. cubensis, 3,000 years ago: psilocybin, which the body converts to psilocin → the serotonin 2A receptor. Little brown mushrooms, a cap with a nipple on top, a stem that bruises blue where it is handled, which is the psilocin oxidising. The Mazatec of Oaxaca ate them in night ceremonies that outsiders first witnessed in 1955. Psilocybin is physically very safe and psychologically powerful: the risk is the hours themselves, in the wrong setting or the wrong person. Trials screen out psychosis and bipolar disorder and use trained support. Not legal in most places.
• Cannabis Cannabis sativa, 2,500 years ago: Δ⁹-tetrahydrocannabinol (THC) → the cannabinoid CB1 receptor. Tiny glass-like glands on the flowers, trichomes, make the resin. THC is there as THCA, an acid that does nothing until heat knocks off a carboxyl group, which is why the plant has to be smoked, vaporised or baked. About one user in ten develops dependence, higher among teenagers; high-potency cannabis raises the risk of psychosis in the vulnerable; and the adolescent brain is the one that should wait. Cannabis is also medicine for a short, specific list of things.
• Tea Camellia sinensis, 2,150 years ago: caffeine, with L-theanine → adenosine A1 and A2A receptors. Glossy, toothed leaves and small white flowers with a yellow heart. Caffeine is the plant’s pesticide; theanine, an amino acid found almost nowhere else in nature, is made in the roots and travels up to the leaves in the shade. Tea is safe at ordinary doses. Its one real trick is sleep: caffeine’s half-life is about five hours, so an afternoon cup is still a third present at bedtime.
• Ayahuasca Banisteriopsis caapi with Psychotria viridis, 1,000 years ago: N,N-dimethyltryptamine (DMT), made orally active by harmine → the serotonin 2A receptor; harmine inhibits the enzyme MAO-A. Caapi holds harmine and harmaline, beta-carbolines that block an enzyme in your gut. Chacruna leaves hold DMT, a molecule your own body makes in trace amounts. Swallow DMT alone and that enzyme destroys it before it reaches your blood. Swallow it with the vine, and it gets through. Ayahuasca is a drug interaction by design. The harmine makes many medicines dangerous with it, antidepressants above all (serotonin syndrome), and the setting matters as much as the brew. Trial evidence for depression is early and promising.
• Coffee Coffea arabica, the 1400s: caffeine → adenosine A1 and A2A receptors. A glossy evergreen shrub of the Ethiopian forest understory, kept to picking height on farms. The cherry is sweet and thin; the two green seeds inside are what the world wants, about one percent caffeine by weight. Coffee is safe for most adults at a few cups a day and even looks mildly protective in large cohorts. Its one reliable harm is to sleep, and sleep is where most of mental health lives.
• Morning glory Turbina corymbosa, Ipomoea tricolor, the 1570s: ergine (lysergic acid amide) → the serotonin 2A receptor. Trumpet flowers that open at dawn and close by afternoon, white in Turbina, blue in Ipomoea tricolor, the “Heavenly Blue” sold in every garden centre. The seeds, not the flowers, carry the chemistry. Commercial seeds are often treated with fungicides and other chemicals, and the plant’s own glycosides cause vomiting. The history here is interesting; the practice is not recommended.
• Sacred datura Datura wrightii, about 400 years ago: scopolamine, with hyoscyamine (atropine) → muscarinic acetylcholine receptors, blocked. Enormous white trumpets, sometimes tinged violet, that open at dusk, smell sweet, and are pollinated by hawkmoths. By midmorning they have wilted. The Chumash called the plant momoy and the drink toloache, and gave it to adolescents once, as a passage. Datura is the one plant in this garden with no safe recreational dose. Poisonings send people to emergency rooms every year and some die; the antidote, physostigmine, exists, and the treatment is a hospital. Admire the flower.
• Iboga Tabernanthe iboga, the 1860s: ibogaine → many at once: NMDA, κ-opioid, serotonin transporter, nicotinic and sigma receptors. Inconspicuous, chest-high, with the fruit hanging in twos. The bark is scraped from the roots, dried, and taken in large amounts only once, at a Bwiti initiation that lasts through a night and a day. Ibogaine can stop a heart. Any use needs cardiac monitoring, and the evidence for addiction treatment, while striking in case series and an early open-label veterans study, is not yet from controlled trials. Not legal in the US.
• Salvia divinorum Salvia divinorum, 1939: salvinorin A → the κ-opioid receptor. Large soft leaves with scalloped edges and, when it flowers, a spike of white blooms in purple cups. Salvinorin A is on the leaf surface, in glands, and it is the most potent naturally occurring hallucinogen known: active at a fraction of a milligram. Salvia is physically benign and psychologically abrupt; the danger is falling, and doing it alone. Legal status varies by state. It has given pharmacology a new class of κ-opioid tools, which may matter more than the plant ever did.