The chemicals in these products of nature are not a sideshow—they are the main event, and we've unwittingly stolen them from a war raging all around us. We use these toxic chemicals to greet our days (caffeine), titillate our tongues (capsaicin), recover from our surgeries (morphine), cure our infections (penicillin), mend our hearts (digoxin), bend our minds (psilocybin), calm our nerves (cannabinol), spice up our food and drink (myristicin), and enhance our social lives (ethanol).#5829•
Chapter 6
The danger of using extracts of toad glands to trip might be why, despite the lore associated with toad venom, there is scant historical evidence of Indigenous peoples of the Americas using it. However, some Indigenous communities there have now incorporated toad venom into their practices, particularly as a treatment for methamphetamine and other drug use disorders.
In fact, the practice of smoking toad venom was unheard-of until 1983, when Ken Nelson, then an artist from Denton, Texas, milked the skin of a Sonoran Desert toad because he had read that chemists discovered bufotenine in that species. Nelson then wrote a pamphlet titled "Bufo alvaris: The Psychedelic Toad of the Sonoran Desert" under the pseudonym Albert Most.#5868•
DMTs bind to our brain's serotonin receptors, or 5-HT receptors, so called because serotonin is an endogenous tryptamine alkaloid, 5-hydroxytryptamine, or 5-HT. They have an affinity for a specific type of 5-HT receptor called 5-HTA, which I'll later show may be related to alcohol cravings.#5872•
DMT is also the principal psychedelic in ayahuasca—a Quechua term for "vine of the gods." This chemical is used as a medicinal and in shamanistic rituals of a diverse group of Indigenous cultures of the Amazon and the Andes. Ayahuasca is prepared in countless ways, but the principal ingredients often include tissues from two sets of plants.
One set of plants produces DMTs and includes species of Psychotria from the coffee family or Diplopterys from the Malpighiaceae family.
A different set of plants produces alkaloids called beta-carbolines, or harmine alkaloids, and includes plants in the genus Banisteriopsis, which also belong to the Malpighiaceae.#5845•
When beta-carbolines are included in the mixture, the DMT is then free to travel through the gut and into the blood, where it eventually makes its way to the brain, binds to the serotonin receptors, and works its magic. In contrast, when toad venom is smoked, its DMTs slip past the MAOs in the gut because it reaches the brain through the lungs.#5830•
For magic mushrooms and psilocybin, one clue to how they evolved to produce psychedelics comes from their blue color. Magic mushrooms turn blue when wounded, and psilocybin is responsible for this change of color. When the mushroom is wounded, two enzymes chemically transform psilocybin into a chain of psilocin molecules that become bonded to one another.
When formed, these chains of psilocin molecules act much like tannins, which also turn blue when oxidized.
These blue chemicals probably produce gut-damaging free-radical oxygen molecules when the insects eat the fungi.#5861•
Some scientists have proposed that because ergot-infected grasses are quite colorful, the fungi may be warning animals to stay away. In other words, ergot might have evolved a similar overall strategy like that of the monarch butterfly, whose bright colors warn predators of the toxins within.#5854•
Corroborating this idea are experiments with rhesus monkeys. Animals that were housed in a dark box with self-administered lettuce cigarettes (originally designed as a nicotine-free cigarette for people wanting to quit smoking) containing DMT. If the animals were not held in complete darkness, they avoided the DMT cigarettes.
The scientists who ran these experiments think that the DMT caused the light-deprived monkeys to experience an "internal hallucinatory light," which itself became a reward.#5856•
Even more astounding than monkeys smoking DMT-laced lettuce cigarettes, brains of mammals, including rats and humans, produce DMT, too, in small amounts. I've already discussed how the human body makes salicylic acid and cardiac glycosides or molecules that mimic their effects. So, maybe the presence of endogenous DMT in our brains isn't much of a surprise.
Still, the lesson is remarkable: plants, fungi, and bacteria have repeatedly evolved to deploy molecular mimics of our neurotransmitters and hormones or to produce chemicals that disrupt their production and movement in our bodies.#5883•
A small placebo-controlled trial using ayahuasca (containing DMT) to treat treatment-resistant depression was reported in 2018. The participants receiving the ayahuasca reported significantly reduced depression severity within one day of the treatment compared with people taking the placebo. The effect persisted through the one-week study period.
LSD showed great promise in treating AUD in the mid-twentieth century, but backlash against the counterculture that used it for other purposes snuffed out progress by the 1980s. However, between 1966 and 1970, six randomized, controlled studies using LSD were conducted on people with AUD. Early on, after one to three months, there was near-complete abstinence from alcohol use among those who received the single dose of LSD in the trial.
After three to six months of the participants' receiving a single dose of LSD, there was a twofold reduction in risk of alcohol misuse.#5876•
Chapter 7
I made the switch to making only filtered coffee after reading a 2020 study of more than half a million people in Norway that found the adults who consumed unfiltered coffee had a significantly higher chance of dying over twenty years than did those who drank filtered coffee or no coffee. The increased mortality risk is probably associated with drinking unfiltered coffee, at least partly due to the presence of two coffee terpenoids that are largely removed during filtration.
Both are associated with increased cardiovascular and heart disease because they raise cholesterol levels.#5877•
But the devil is in the details. A slightly reduced risk of dying was found for those who drank up to 2.5 drinks per day compared to those who didn't drink coffee. The people drinking 2.5 to 4.5 coffee drinks per day were 29 percent less likely to die during the study than were people who drank no coffee.
Above 4.5 drinks per day, and the risk of dying during the study was the same as those who consumed up to 2.5 drinks per day.#5840•
In the Norwegian study on unfiltered coffee, the higher mortality rates among unfiltered-coffee drinkers (compared with the filtered-coffee drinkers and nondrinkers) may be caused by the LDL-raising effects of the terpenoids cafestol and kahweol. On the other hand, the lower death rates among filtered-coffee drinkers compared with the nondrinkers may be caused by the polyphenols, including chlorogenic acids.
So, coffee contains toxins that are associated with both positive and negative effects on human health.#5874•
On October 7, 1984, a breakthrough was announced in the New York Times: "Caffeine Is Natural Insecticide, Scientist Says." As the headline suggests, biologist James Nathanson had just demonstrated that caffeine is indeed a potent natural insecticide. Nathanson discovered this by incorporating powdered tea leaves and coffee beans into artificial caterpillar food, which he then gave to newly hatched tobacco hornworm caterpillars, which don't feed on plants containing caffeine in the wild.
The hornworm adult is also called a hawk moth.
What Nathanson found shocked the world (although, by now, probably not you): "At concentrations from 0.3 to 10 percent (by weight) for coffee and from 0.1 to 3 percent for tea, there was a dose-dependent inhibition of feeding associated with hyperactivity, tremors, and stunted growth. At concentrations greater than 10 percent for coffee or 3 percent for tea larvae were killed within 24 hours."
Further experimentation revealed that the level of caffeine naturally found in undried tea leaves (0.68 to 2.1 percent) or undried coffee beans (0.8 to 1.8 percent) was sufficient to kill all of the caterpillars. Nathanson found the same insecticidal effects of caffeine on mosquitoes, beetles, butterflies, and true bugs, including at concentrations found in nature.#5858•
These dark lessons teach us that plants don't make caffeine for our benefit. They make it as a defense against being eaten. However, we've learned to use caffeine to improve our own lives because, unlike the tiny bodies of insects, our own big bodies can handle fairly large doses of this alkaloid and because our brains seem prewired to interact with it.#5832•
In a large study within the United Kingdom, geneticists found a telling relationship between an individual's coffee consumption and how intensely they perceive three substances: caffeine, a bitter chemical called propylthiouracil, and quinine. Those who were more sensitive to the bitterness of propylthiouracil and quinine consumed less coffee, and vice versa.#5852•
Before we get to the bottom of this sweet subterfuge, we must first understand how honeybees gather nectar for honey production. Honeybees have evolved to be among the most sophisticated social animals because they are able to do something you or I could never do. A single honeybee forager can communicate to her sisters the exact location of a new flower patch she has found by doing a unique waggle dance in the darkness of the hive.
The other bees then use this information to fly to the patch without ever having been to it before.#5875•
The speed with which our bodies remove nicotine from the bloodstream is also a key piece of the puzzle. A study of thousands of smokers in Finland found that the ability to metabolize nicotine into cotinine was highly heritable. In other words, if the parents were fast metabolizers, the children tended to be, and vice versa for slow nicotine metabolizers.
The genomes of the study's participants were scanned to determine which, if any, genetic differences between people might be correlated with different rates of nicotine metabolism. The single biggest difference was in a gene encoding the liver enzyme CYPA, which detoxifies nicotine. One version of this enzyme causes faster metabolism of nicotine, and other versions cause slower metabolism, much as different forms of the CYPA determine our ability to detoxify caffeine.#5882•