Excerpted from Sex, Drugs, and Rock ‘N’ Roll: The Science of Hedonism and the Hedonism of Science by Zoe Cormier (footnotes omitted), © 2015, and reprinted by permission of Da Capo Press. All rights reserved. No part of this excerpt may be reprinted, reproduced, posted on another website or distributed by any means without the written permission of the publisher.
For an exploration of the history of drugs and science, we ought to start somewhere colourful. We are downright spoiled for choice. The history of the human love affair ranges from a president of the Royal Society’s addiction to laughing gas, the world’s first acid trip commencing in the mind of a biochemist riding a bicycle on a mountaintop in Switzerland, the shack a rogue chemist set up in his garden where he churned out ecstasy and hundreds of new psychoactive drugs, spiders on speed and monkeys dosed with DMT and locked in dark boxes. Or perhaps, most eccentrically, the hippos that now run rampant in the rainforests of Colombia thanks to infamous drugs baron Pablo Escobar, who imported the aggressive amphibious African beasts for his private zoo.
The history of human drug use is colourful, complex and confusing. Where to begin? Let’s start with the simplest question.
What, exactly, is a drug? Definitions vary, and the implications are important.
Some classify a drug as an illegal compound that produces psychological or emotional effects. But all of our favourite legal drugs — tobacco, alcohol and coffee — have at one time or another been prohibited. Today we remember that alcohol spent much of the 1920s as a banned substance in America (bootlegged booze was in fact the source of much of the fortune of the Kennedys; being Irish Catholics, we can assume abstinence from alcohol would have been unconscionable), but we have largely forgotten that the caffeine contained in the fruiting bodies of the plant Coffea arabica was once deemed so detrimental to the moral fibre of human beings that coffee houses were outlawed in sixteenth century Turkey.
21. Poster for the propaganda film Reefer Madness (1937), which has
become a cinematic classic adored by potheads everywhere. You
literally have to scrape the resin off the seats after a screening.
Smoking to absorb the nicotine produced by the leaves of Nicotiana tobaccum through the lining of our lungs widely garnered public floggings in Renaissance Europe — or worse. Being caught with a cigarette in your hand would earn you a slit nose in parts of Russia in the seventeenth century. The legal status of Cannabis sativa is changing so rapidly worldwide there is no point in trying to keep up to date with the pace of change in the pages of a book. Yet only half a century ago it was portrayed as a corrupting poison that would lead to murder, theft and interracial sex (heaven forfend).
Suffice it to say that the legality of a substance has little to do with whether or not it is a ‘drug’. So what designates a chemical as narcotic?
If you were a plant instead of a politician, you would think of a drug as this:
‘Something I use to make animals do what I want.’
Many drugs evolved in their plant producers as a means to manipulate the behaviour of predators, mainly by tasting foul to deter insects — or outright poisoning the pests and removing them from the environment. The caffeine in coffee and tea, nicotine in tobacco, and crystalline tropanes in the coca plant all developed in their plant hosts as a means to repel insect invaders. We have inherited this neural hardware from hundreds of millions of years of evolution, so botanical chemicals can tickle our nervous systems by hijacking the same basic circuitry.
22. Counter-intuitively, nerve cells do not neatly fit together
like electrical wires but are separated by spaces called
synapses. Chemical messages must traverse this space
before information can be relayed via electrical signals.
So if these astringent chemicals are designed to repel, why are we drawn to them? In doses designed for most predators of plants, these chemicals are poisonous: nicotine, for example, is lethal to nearly all animals except primates. Birds are highly sensitive to it, and death by tobacco butt is a frequent cause of avian expiration in modern cities. We are just less overwhelmed by the effects. As Paracelsus (Philippus Aureolus Theophrastus Bombastus von Hohenheim, to be precise, 1493–1541) the founder of toxicology put it half a millennium ago: the dose makes the poison. A bit of something bad can feel mighty good.
Paracelsus made his astute observation without our modern understanding of the mechanics of the nervous system. Had he known then what we do now — that information travels via electrical sparks that zip down the highways of the nervous system, triggering the release of globular chemical messengers that neatly fit into docking bays at the gates of the next highway, in turn triggering the firing of yet more electrical zaps — he would be mighty impressed.
All the nerves in our bodies (if found in the brain, termed ‘neurons’) are like tiny wires. Akin to electrical cables wrapped in rubber, they are cloaked in an insulating membrane of fat that allows electrical signals to twitter down them at maximum speed. The velocity is impressive: it allows the sight of this word to be transmitted to the patch of your brain that decodes signals from the eyes almost instantaneously. Where nerves connect to each other, a space exists between the nerve cells, dubbed a ‘synaptic gap’.
Instead of transmitting this electricity through a continuous string of wires (which might make more sense), nerves have to pass signals to each other by means of globs of chemicals. These have to travel through the synaptic space between two cells like cargo chucked between two ships.
The cargo in these packages are known as ‘neurotransmitters’: they comprise the chemical language of the nervous system. The docking bays on cells that receive them are called ‘receptors’. It is these neurotransmitter messengers that allow electrical signals to be converted into chemical signals and then back into electrical signals.
You’ve heard the names of the most famous neurotransmitters before: serotonin, dopamine, endorphins and adrenaline are all well known. But there are many thousands more floating around your body that play important roles. The complexity of the circuitry and the intricacy of the chemical lexicon is staggering.
Many drugs work by mimicking our body’s native neurotransmitters. For example, the opiate painkiller morphine produced by the poppy Papaver somniferum is a better fit for our body’s ‘μ-opioid’ endorphin receptors than our own endorphins are. LSD is a more ardent match for our serotonin receptors than serotonin itself. Ditto for psilocybin, the active component in magic mushrooms. Serotonin receptors latch on to it with a fervent passion, leaving native serotonin without a receptor to call home. It’s an impressive feat of biochemical insurrection.
We in fact identified many of our most powerful neurotransmitters and elucidated their structure in the very first place thanks to our relationship with narcotic drugs.
The thought process of scientists in the nineteenth and twentieth centuries went something like this: how can foreign chemicals produce effects in our body? What could be the mechanism at play? Chemists identified the structure of most of our favourite botanical drugs in the nineteenth century — including opium, cocaine, caffeine and nicotine — but how exactly these substances hacked our neural hardware remained mysterious.
Scientists achieved the very first discovery of a neurotransmitter receptor thanks to our predisposition to smoke: biologists at the beginning of the twentieth century were puzzled by the fact that nicotine, derived from a plant, can affect the way an animal feels. Nicotine had first been isolated in 1843, and its chemical structure revealed in 1893. But how this molecule actually produced effects in our bodies was unknown. In 1905 Cambridge professor John Langley proposed that animal tissues must contain ‘a substance that combines with nicotine… [and] receives the stimulus and transmits it.’ He called this hypothetical keyhole a ‘receptive substance’.
The idea proved insightful and inspirational. It took many decades of biochemical detective work by scientists across disciplines and around the world, but the receptor was finally located by French scientists in the 1970s, who cleverly combined snake toxins with the reactive tissues of an electric eel. The receptor normally binds to our native neurotransmitter acetylcholine, but nicotine can masquerade as an indigenous chemical messenger. The receptor was respectfully named after our relationship with tobacco, and christened the ‘nicotinic acetylcholine receptor’. Its sibling receptor, the ‘muscarinic acetylcholine receptor’, which also normally binds to acetylcholine, is named after fly agaric mushrooms, Amanita muscaria. Psychedelic chemicals in this horrifically hallucinogenic fungus bind to the receptors for acetylcholine in a similar act of biological break and entry.
23. The ancient ‘hagfish’ deserves its jacket description.
The bottom-feeding scavenger not only smells remarkably
foul, it exudes putrid slime from every pore.
According to pharmacologist Professor Richard Miller of Northwestern University in Chicago, the discovery of the nicotinic acetylcholine receptor was the ‘initial breakthrough in our understanding of the molecular properties of receptors.’ Tobacco, the cause of death for untold millions, led to a watershed moment in our understanding of the brain.
Similarly, neuroscientists identified our native neurotransmitter painkillers, the endorphins, thanks to the search for the cellular cradle into which invading opiate molecules fit. Though opium was a favoured tonic of the ancients, and the chemical structure of morphine mapped in 1805, it was not until 1973 that the receptor for opium was located by American neuroscientist Sol Snyder. He demonstrated that the keyholes for opiates exist not only in human tissue but also in ancient animals such as the hagfish, a phenomenally ugly and slimy eel-like marine creature. Lacking both a spine and a jaw, the primeval hagfish — known as a ‘living fossil’ — evolutionarily predates fish, frogs, birds, and, indeed, all vertebrates. It is a formidable and rather foul relic.
That receptors for morphine — a comparatively modern molecule, produced by terrestrial plants — could exist in such an ancient animal inspired a ground-breaking idea. Could opiates operate by hijacking the receptors for naturally occurring heroinlike molecules that animals themselves produce? Do our bodies create their own painkillers?
In 1975 they were found: we know them today as endorphins. We may never have found them were it not for our fondness for junk — or the poppy’s unrivalled capacity to medicate the human condition. Try as we might, all the laboratory manpower combined with pharmaceutical finance has never produced a painkiller as effective as morphine. Plants are still the victors in the battle between the leaf and the brain.
Moreover, not only did morphine lead us to discover our inborn endorphins, this landmark discovery paved the way for Snyder to also discover the receptors for dopamine — the ‘pleasure chemical’, one of the world’s most famous neurotransmitters — and GABA, one of the most ubiquitous and important neurotransmitters.
In this same vein, the active ingredient in marijuana, the endocannabinoids, is nothing more than a chemical mimic of our body’s own painkillers, which are thusly named thanks to our pre-existing knowledge of and relationship with marijuana. The chemical investigation followed the same framework: One, identify the chemical structure of a narcotic drug. Two, locate the receptor that embraces the illicit invader. Three, find the ‘endogenous’ chemical — native to our own body — that latches on to the same receptor. Voila: chemists identified delta-9-THC as the active treat in weed in 1964, located the receptor in 1990, and tracked down our own ‘endocannabinoids’ shortly thereafter. We understood the chemistry of marijuana before we discovered our body’s homegrown anaesthetics.
From the perspective of C. sativa, evolving the capacity to produce delta-9-tetrahydrocannabinol, or THC, was the best thing that ever happened to it. Compare the global distribution, population and living conditions of C. sativa and its cousin C. indica with their non-THC-containing relatives. Behold a stark contrast between scruff y scrubs confined to a few remote corners of central Asia and a widely worshipped weed whose seed has spread to every corner of the earth.* Animal emissaries may have unwittingly aided in transporting C. sativa and C. indica seeds on their hooves, wings and fur, but no animal has done more to spread the progeny of this plant than Homo sapiens. So who exactly is domesticating whom?
Evolution has more tricks up its sleeve designed to addle our minds and manipulate our behaviour. Again, plants are the best lockpickers of your genome.
Caffeine produced by coffee, tea and chocolate played a key role in helping scientists unravel the structure of the chemical coinage we use to transmit energy: adenosine triphosphate, or ATP. Known as the ‘molecular unit of currency’, ATP is a nimble chemical package that all living things use to store and transport energy.
This handy storage battery of a molecule is constantly on the move, swirling round our cell’s metabolic circuits. It is continually broken down to release energy to fuel chemical reactions and then recreated to store the energy produced by other molecular transformations in the assembly lines of our microscopic chemical factories.
A mobile and multifunctional molecule, ATP is biological bullion. Universally employed by all forms of life on earth, it is the gold standard of evolution. It never depreciates in value. ATP was officially discovered in 1929 — but the structure of its chemical saboteur, caffeine, was first revealed in 1881, garnering Emil Fischer the Nobel Prize in 1902.
Again, we identified the botanical trickster before becoming familiar with our own friendly biochemical natives.
Intriguingly, caffeine — remember, embedded in the leaves of tea and coffee plants as a means to deter pests — could actually be used by some plants as an alluring attractant, not a revulsive repellent. Dr Geraldine Wright of Newcastle University trained bees to associate a scent with a sugary reward. She found that lacing sugary water with caffeine enhanced the memories of her bees: those fed from caffeine-tainted dispensers were twice as likely to remember the scent (measured by whether or not they stuck out their tongues in anticipation of a sweet reward) than those fed without caffeine. The neurons responsible for memory formation seem to be behind this mechanism: caffeine blocks the receptors for the neurotransmitter adenosine.
This hints at an interesting proposition: can an insect become addicted to a drug? Because caffeine is found in the nectar of more than 100 plant species, Dr Wright thinks it’s plausible that plants are dosing their pollinators to coax them into revisiting their flowers and thus spreading their seeds. There are intriguing implications for how caffeine may affect the ability to form new memories in humans, as the scientific evidence for whether or not caffeine is a memory aid is mixed.
At the core of the debate lies this single question: Is caffeine a drug?
You probably know that Coca-Cola originally contained hefty doses of cocaine before the company was forced to remove it.
In fact, the ‘secret’ recipe today is still made with decocainised coca leaf (which might explain why it tastes better than Pepsi). But few of us remember that long before the company became embroiled in scandals in the developing world over public water supplies, the all-American drinks company endured a lengthy court battle to prove that caffeine is not a dangerous drug.
The battle between plants and insects continues to produce new drugs, but now straight from the laboratory rather than extracted from the leaf. We have unwittingly produced new narcotics as a by-product of our indirect efforts to aid plants in their war with insects. The synthetic drug 4-methylmethcathinone (4-MMC), also known as mephedrone, ‘miaow miaow’, and M-CAT, was first synthesised in 192914 but mostly forgotten for 70 years. Only when Israeli scientists investigated the potential to use it as an insecticide in the early 2000s were its neurotoxic and (in the opinion of some) pleasurable properties discovered when their fingers accidentally became tainted with the chemical’s residue. Hence the drug’s other nickname: ‘plant food’. M-CAT, like Viagra, demonstrates that new and powerful drugs are often discovered by accident rather than deliberate chemical intent.
In the running battle between the nervous systems of animals and the chemical production factories of plants, animals have learned to convert aversions into affections. Reports of wildlife consuming psychotropic, hallucinogenic, stimulating or sedating plants for purposes that seem designed for pleasure alone are rife in the scientific literature.
24. The red toadstool, Amanita muscaria, or ‘fly agaric’. Unlike
other ‘magic’ mushrooms, this fungus creates hallucinations
not through psilocybin but a cocktail of chemicals.
Botanists and zoologists have extensively documented animals deliberately intoxicating themselves. Ducklings too busy feeding on narcotic plants to respond to their mother’s calls. Hawkmoths gorging on the nectar of Datura flowers. Pumas gnawing at the bark of the Cinchona tree are especially noteworthy because indigenous populations in Peru who noticed the behaviour mimicked it themselves. Centuries later, quinine was isolated from the bark in 1820 and deployed in the battle with the parasitic plasmodium viruses responsible for malaria.
Housecats are notorious fiends for the plant Nepeta cataria, also known as catnip. Interestingly, wild tomcats are less fond of the herb, and pumas, lions, and other wild species belonging to the group of animals known as Felis (cats) are positively averse to it. A captive tiger once ‘leaped several feet into the air, urinated, and ran head-first into the wall of his cage upon simply sniffing the leaves’.
The tales are endless. Wild bighorn sheep scamper along treacherous mountain ledges in pursuit of psychotropic lichen. Reindeer are drawn like clockwork to Amanita muscaria — also known as fly agaric mushrooms, or red toadstools — seasonally gorging on the fungi and wandering erratically from their migratory paths.
Their ardent attraction to the metabolites of the white-spotted fungus is so strong they will smother themselves in urine left by the people of the Arctic circle who have themselves snacked on fly agarics — even willing to do battle over access to the urine-stained snow. And of course there is the Sclerocarya birrea tree, known more popularly by the butterscotchy liqueur Amarula created from it. The fermented fruit draws African land mammals — most famously elephants (hence the bottle’s label) — to it in aggressive, rowdy hordes.
Animals in the wild habitually consume intoxicating, hallucinogenic and sedating chemicals. But it is at the intersection between animals, humans, and our own drugs that the story starts to become more interesting. And more questionable.
Take the popular alkaloid nicotine (alkaloids being a broad class of chemicals that includes cocaine, caffeine, morphine, and many other of our favourite drugs). The product of the leaves of N. tobaccum is lethal, as noted, to almost all animals. Except primates. The tiniest doses of the chemical will kill insects, frogs and birds. Yet monkeys and apes are somehow impervious to nicotine’s lethal properties.
You’ve probably seen old film footage from the 1920s of circus chimps smoking cigars (perhaps while roller skating).
Chimps have not only been coaxed into smoking — they have become genuinely addicted. Zookeepers worldwide have struggled to get captive animals to kick the habit, most famously Charlie22 of the Mangaung Zoo, in Bloemfontein, South Africa, who first became hooked when visitors tossed him lit cigarettes.
25. Tobacco companies notoriously hijacked the ideals
of Suffragette movements with ad campaigns that
framed the right to smoke as a feminist cause.
Enticing captive apes to smoke is an old and cliched trick. Chimpanzees have been put on show smoking for centuries. The first recorded instance in Europe took place in The Hague in 1635. It was around this time that the dosing of animals took on a scientific, systematic dimension as medical doctors, chemists and other enterprising experimentalists of the burgeoning scientific disciplines began to immerse, inject, feed and cloak animals in a variety of psychoactive chemicals, from alcohol to ether, morphine to mescaline.
For better or for worse, the use of animals to investigate the properties of drugs resulted in a number of medical milestones. The first needle (which eventually evolved into the heroin friendly hypodermic form) was produced by Sir Christopher Wren (1632–1723), who paired goose quills with animal bladders to inject dogs with opium in 1656. Another breakthrough came with the French medic Pierre-Alexandre Charvet (1799–1879), who in 1826 published Action comparée de l’opium et de ses principes constituans sur l’économie animale, a detailed account of his work administering opium to animals, including paramecia, crayfish, snails, fish, salamanders, frogs, birds, rabbits, dogs, cats — and himself. This is regarded by many as the first book in the field we now know as ‘experimental pharmacology’.
26. Monkey see monkey do. Chimps — indeed all
other apes and monkeys — are just as susceptible to
the seductive qualities of tobacco as we are.
LSD has frequently been given to animals. Guppies dosed with acid swim into the walls of their tanks. Siamese fighting fish display their fighting stance to unoccupied water. Worms work their way upwards through soil. Snails fall from the sides of trees.
Perhaps the most famous experiments on animals with LSD involved spiders, who were dosed with a variety of narcotics in experiments funded by space agency NASA.
Why arachnids? In addition to being cheap and easily sourced, the influence of a drug on the arrangement of a spider’s web seemed to provide a rough indicator of a chemical’s toxicity.
27. Even spiders can get high. Studies funded by NASA tested a
variety of drugs, from quotidian caffeine to other worldly mescaline,
by examining the impacts of each narcotic on web geometry.
The geometric array is illuminating: webs made on caffeine are erratic and nonfunctional. Chloral hydrate, also known as the sleeping aid Hydrate, produces a sparse arrangement of threads. Marijuana results in a fairly competent web, but it appears as if the spider abandoned its task halfway through. The LSD web resembles a normal one proportionally, but it is definitively broader. Make of this what you will.
Aside from sheer spectacle, what is the utility in experimenting on animals with drugs? Non-human models cannot make for a perfect replica of the brain of Homo sapiens, but according to many biologists, they serve as a decent proxy.
Psychiatrist Dr Ronald Siegel of the Department of Psychiatry and Biobehavioral Sciences at the University of California Los Angeles, spent the better part of 30 years studying the impacts of narcotics on animals. He believed that understanding the biological basis of addiction would aid his treatment of patients suffering the ravages of chemical dependencies. Siegel worked daily as a clinician treating addicts: he saw with his own eyes how drugs destroy lives.
His aims were undoubtedly compassionate and his methods undeniably colourful. He trekked to the mountains of the Andes to understand the ancient use of the coca leaf. He darted a captive colony of chimpanzees off the coast of California with cocaine both at the low concentrations found in the leaf and with the high concentrations found on the street. Result: coca leaf levels rendered the animals social and cheerful. Miami-style doses led to aggression and disrupted social dynamics. Odd as this may sound, it was not until Siegel’s experiments that cocaine was accepted by the scientific establishment and the general public as ‘addictive’. Until then, it was merely thought to be habit-forming.
28. Geographically widespread and found worldwide in
high population numbers, rhesus monkeys have been
used to develop vaccines for rabies and smallpox, drugs
for HIV, and – in less orthodox settings – to study the
effects of the world’s most powerful hallucinogens.
His experiments with the hallucinogen N,N-dimethyltryptamine (DMT) on rhesus monkeys are described with such striking detail that, rather than paraphrasing, they are best quoted verbatim:
Darkness, solitude and the silence of night are the most common times for humans to use hallucinogens. All primitive societies prefer these drugs under conditions when there is little else to see or hear in the environment… In dark and isolated settings, monkeys also find exploring visual stimuli exciting and rewarding. In a classic demonstration of this motivation to explore, rhesus monkeys were confined one at a time to a dimly lighted wire cage that was covered with an opaque box. Because monkeys need visual stimulation as much as we do, I was certain they would accept an enlightening hallucinogen rather than darkness. Initially, each monkey was given the opportunity to live alone in the dark chamber for ten consecutive days and nights. The smoking machine was filled with cigarettes made from ordinary garden lettuce… and the cigarettes were laced with DMT… by Day 8 [Claude] had worked up to smoking almost two whole cigarettes each day… Lucy has been smoking almost two DMT cigarettes each day. She has become extremely proficient at catching whatever she has been chasing: she now brings ‘it’ to her mouth, chews and lip-smacks with delight.
His conclusion: if deprived of light, stimulation, company and comfort, monkeys will smoke an overwhelmingly strong psychedelic. He says this has profound implications for our own species. ‘Under the right conditions [DMT] was as useful to a monkey as it is to a human. We share the same motivation to light up our lives with chemical glimpses of another world.’ One is tempted to suggest that had Dr Siegel ever tried hallucinogens himself (he maintains that he would never, never, take any of these substances), he wouldn’t have locked a monkey in a dark box to reach this deduction.
Among his peers, opinions are mixed.
‘He’s not exactly very popular,’ says Rick Doblin, PhD, founder of the Multidisciplinary Association for Psychedelic Studies (MAPS), who has endeavoured to demonstrate the potential to treat human ailments with psychotropic drugs since the 1970s. ‘He did tremendously important work, but not everyone is a fan of his methods.’
‘I genuinely think of him as a hero,’ says medical doctor Dr George Koob, Chairman of the Committee on the Neurobiology of Addictive Disorders at the Scripps Institute in California, who has spent his career trying to understand what predisposes some but not others towards addiction. ‘He really was the first person to chart the case histories of cocaine addiction when nobody thought of it as a “addictive drug”.’