Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5515_Библиотеки_им_академика_М_И_Перельмана.pdf
of neural togetherness. In the 1950s Peter Witt first used stoned spiders to characterize
the possible neurological effects of drugs on spiderweb building. The idea is that if a
spider is fed something that affects the weaving of a web, then the substance that was
ingested more than likely affected the spider’s nervous system. Even venerable
institutions such as the National Aeronautics and Space Administration (NASA) have
used this assay to study the effects of substances on spider nervous systems (fig. 1.1).
Although it is obvious that certain substances (especially LSD and caffeine) affect the
architecture of spiderwebs, it is not clear how. Since it is not clear that cannabinoid
receptors exist in spiders, it cannot be determined whether the effect of marijuana
comes from the cannabinoids in the plant or from some other compound.
Most vertebrates do, however, have cannabinoid receptors, although cannabis
ingestion by vertebrate animals is somewhat rare. Rodents are known to nibble at
cannabis plants. There is an amusing anecdotal report of a mouse passing out from
eating marijuana leaves, replete with photographs of the mouse on its back, all four legs
sticking straight in the air; the only thing missing to make it a perfect Tom and Jerry
moment would be x’s over its eyes. Although this instance is amusing, the only
documentation for it are the photos—not valid documentation at all. There are also
reports of moles eating the roots of marijuana plants. Larger animals such as cattle,
goats, and sheep have been observed to nibble on cannabis plants, with some effects on
their motor skills (their walking patterns become erratic).
Figure 1.1. Drawings of webs woven by spiders under the influence of the indicated drugs. Adapted from
Noever, Cronise, and Relwani (1995).
Most of the concern about cannabis use by animals has revolved around
domesticated animals such as pet cats or dogs, for which there are many publications.
The National Capital Poison Control Center tracks intoxication events in pets. Ninetysix percent of reports concern dogs, and only 3 percent concern cats. (Without knowing
some biology, this skew would seem rather odd, but it really isn’t.)
One of the more common modes of ingestion is secondary intoxication via
marijuana smoke. Another route to ingestion would be surreptitious ingestion of edible
marijuana by one’s pet. As anyone with a pet knows, they are nosy and continually
hungry. They will sniff and eat anything they think they can get away with. But there is a
difference between cats and dogs regarding marijuana ingestion. Most of the edible
marijuana that people use is sweetened in some way. Cannabis-laced chocolate and
cannabis-infused brownies, gummies, and marijuana butter are all common ways in
which humans prep cannabis for eating. If you offer a cat a small bite of a candy bar,
more than likely it will turn its nose up. Do the same with a dog, and you will be lucky
to get away with your fingers. Cats cannot significantly taste sweet foods, whereas dogs
do. Sugar and salt have specific structures that our taste buds can detect because of
molecules we make called taste receptors (there are five kinds: salty, sweet, sour, bitter,
and umami). Cats have an inactive form of the sweet receptor; no cats, even big ones
such as lions and tigers, significantly taste sweetness. Dogs thus are attracted to
sweetened cannabis products while cats are not, leading to more cases of cannabis
poisoning in pet dogs.
Cats are known drug users, though, with catnip perhaps being their favorite. They
can attain a level of euphoria from catnip similar to what humans attain from cannabis
ingestion. The catnip plant Nepeta cataria is native to southern and eastern Europe, the
Middle East, central Asia, and parts of China, overlapping partially with the native
distribution of the Cannabis plant. Like cannabis, it has also been moved to most of the
rest of the planet by humans, so it currently overlaps broadly with Cannabis. Although
the psychoactivity of cannabis works through the cannabinoid receptors in the brain,
catnip—or more properly the oil called nepetalactone that is produced by the plant—
interacts with the brain’s olfactory lobe. This lobe lies just inside the nasal passage and
implements vertebrates’ capacity to smell. Once the nepetalactone oil is detected by the
olfactory system, signals are sent to the brain’s hypothalamus and amygdala regions.
The amygdala regulates emotional response in vertebrates such as cats, and the
hypothalamus controls instinctual behavior. Stimulation of the amygdala by catnip might
explain the euphoric behavior of cats on catnip. Stimulation of the hypothalamus might
also explain the aggressive behavior of some cats when they overdose on catnip.
Human behavior on catnip was first described by Basil Jackson and Alan Reed,
two medical doctors who encountered recreational human catnip use in the 1960s. Drug
experimentation in humans was peaking at this point, and Jackson and Reed felt obliged
to detail the phenomenon of catnip use by humans. Catnip prior to the 1960s had been
used to counter amenorrhea (the inability of females to menstruate in cycle), chlorosis
(a form of jaundice), and infant flatulent cholic (what it sounds like). It appears that the
use of catnip for medicinal purposes ceased around the middle of the twentieth century.
The four cases of recreational catnip use by humans described by Jackson and Reed
indicated that one can get high from catnip smoking, but it takes a lot more catnip than
cannabis to attain a similar high. In some of the cases there were adverse side effects,
including headaches and malaise. Jackson and Reed’s 1969 publication is rather famous
for another reason, however.
Note that the labels of the two plants in their study (fig. 1.2) were reversed. This
mislabeling in the prominent Journal of the American Medical Association (JAMA) led
to a flood of amusing correction letters from readers. One response from John T.
Petersik, MD, in particular piqued my interest, because in 1969 I was both a Boy Scout
and a farm boy: “Any farm boy or Boy Scout knows that Figure 1 in the article by Basil
Jackson, MD and Alan Reed, MD actually shows a catnip plant (Nepeta cataria) instead
of Cannabis sativa as labeled.” I did remember scouring our campsites for cannabis
plants at the behest of our scoutmaster, although we never knew what he was doing with
them. JAMA published twelve responses, almost all from medical doctors attempting to
correct the mislabeling, and it listed the names of another ten or so doctors who noticed
the mistake. Jokingly, the editors also reported that there were “856 irate and outraged
cats who noted the unusual phenomenon.” In a nod to the popularity of cannabis at the
time, they also lamented, “Let the journal carelessly move the spleen into the thorax or
lung into the pelvis, [and] a few mild restorative comments are received. But let us mix
up catnip with cannabis and …” While the animal ingestion examples above are
somewhat anecdotal, there are hundreds of scientific papers that have used animals as
experimental subjects in cannabis studies. These studies mostly involved using mice, as
they are easy to manipulate both physically and genetically.
Figure 1.2. Drawings of Cannabis sativa and Nepeta cataria from Jackson and Reed (1969). The labels are
as in the original publication.
No Stoned Monkeys
It is safe to say there is no stoned monkey hypothesis or even a stoned spider hypothesis
for cannabis. Animals in general do not forage on cannabis plants, especially
vertebrates and certainly not primates (except maybe for humans). Unlike alcohol,
where there is a connection between feeding on fruit and ingestion of alcohol, there is
no nutritive reason for primates to ingest cannabis. While cannabis seeds are a dietary
source for some animals, most are turned off by it because the plant’s generally nasty
smell and bitter taste probably evolved as an anti-herbivore tactic. The drunken monkey
hypothesis is, moreover, a roundabout explanation for alcohol consumption in humans.
According to the hypothesis, primates consume alcohol primarily because they want to
ingest ripe fruit; the altered consciousness from alcohol comes through the back door.
With drugs such as cannabis, the reliance on pleasure gained from altered consciousness
has to come from somewhere else, because the drive to ingest something nutritious
doesn’t open the front door. Rather, as Siegel argues, there is a drive to intoxication that
has evolved in organisms—which are often preadapted to using substances such as
alcohol and cannabis.
In some ways humans were preadapted to ingesting marijuana. Alcohol in general
is not a good thing to ingest for most animals. If there is too much of it in the body, the
toxic effects of alcohol on the brain and other organs can be lethal. For some organisms,
even a low level can be fatal. Animals have evolved enzyme systems to detoxify
ingested alcohol that involve several genes called alcohol dehydrogenases (ADHs),
numbered in the order of their discovery. These make proteins that can break down the
alcohol. All animals have the major ADH molecule, and in humans about 10 percent of
the total enzymes of the liver are these major ADH1 molecules. But it is another of the
ADH molecules that initially encounters alcohol coming into the body as it is introduced
in the tongue, esophagus, and stomach; this minor ADH (called ADH4) becomes an
important enzyme for understanding alcohol ingestion in animals.
We are primates, and to understand the history of drunkenness we need to start with
what our ancestors might have encountered. Several species of primates have been
compared for the distribution of ethanol-targeting ADH4 molecules in their tissues. The
species examined range from our rather distant relatives, the bush babies (galagos) of
Africa and the aye-ayes of Madagascar; to the Old and New World monkeys; to our
close chimpanzee relatives; and to our own species. The upshot of these comparisons is
that there was a dramatic switch of the capacity of the ancestral ADH4 protein to
process alcohol in the lineage that led to gorillas, chimps, and humans. This change led
to a whopping forty-fold increase in the body’s ability to metabolize ethanol, and thus to
neutralize it. We share the powerful capacity of this ancestral enzyme with those other
great apes.
In their book Alcohol and Humans: A Long and Social Affair, Kimberley J.
Hockings and Robin Dunbar propose that African apes’ new ability to deal with
naturally occurring alcohol might actually have saved them from extinction. They argue
that around 10 million years ago the apes (members of a formerly successful and
diverse forest-living group that was by then in decline) were coming under increasing
pressure from the flourishing cercopithecine monkeys. Specifically, those apes found
themselves in competition with the monkeys for the ripe fruit that composed the core of
their diets.
This explanation suggests that monkeys had the advantage in this competition,
because they were able to process fruits at nearly all stages of ripeness. But there was
one source of fruit for which the apes did not have to compete—the overripe fruit that
had fallen to the forest floor, gently fermenting, as rotting fruit will do once invaded by
wild yeasts. That fermentation produced alcohol—a new ingredient that, the argument
goes, placed this particular resource off-limits to the monkeys, lacking as they did the
enzyme needed to deal with it in any quantity. The newly alcohol-tolerant humanchimpanzee ancestors could therefore munch on those fermenting fruits as much as they
liked. Chimps and humans were therefore preadapted to drinking alcohol, and lots more
of it than your typical primate, prompting Robert Dudley to coin the term “drunken
monkey.” The question relative to marijuana then becomes, Were humans preadapted to
be susceptible to cannabis? The answer is yes, but not in the same way the drunken
monkeys prepared us for alcohol.
Because a broad range of animals have the capacity to react to the psychoactive
compounds made by the cannabis plant, the evolutionary event leading to this ability
must have happened long before our lineage diverged from other primate lineages. Cells
in the neural tissue of animals are peppered on their surfaces with small molecules
called receptors. The job of these receptors is to bind to specific small exogenous
molecules that are signals for the brain to process all kinds of information. In cannabis,
the small exogenous molecules in question are the cannabinoids previously referred to,
and the small brain molecules are the cannabinoid receptors.
Cannabinoid receptor activity appears to have arisen during the early evolution of
animals—or at least this is the most parsimonious explanation for their origin. Why?
Because, as suggested earlier, they are found in almost all animal lineages that have
brains. This means that most animals are programmed to react to cannabinoids, and that
in turn most animals can get stoned on cannabinoids (unless by some chance they have
lost the receptors, or the receptors have been altered in a way that renders them
nonfunctional, like the sweet receptors of cats). But a crucial conundrum arises here.
The genus Cannabis diverged from its closest living relative, the hops genus Humulus,
only around 20 million years ago (mya), making that the earliest time that animals could
psychoreact to marijuana cannabinoids. Animals arose at least twenty times that long
ago (400 mya), which brings up two related questions. The possibility exists that other
plants may have been making cannabinoids for much longer, meaning that it is possible
that a common ancestor of hops and cannabis could have produced cannabinoids. A
simpler explanation also exists: the lineage leading to Cannabis started making
cannabinoids in the last 20 million years. So the question becomes, Are there other
natural cannabinoids in other plants? And could other unrelated compounds in plants
mimic some aspect of cannabinoids, and hence interact with cannabinoid receptors?
Can molecules other than cannabinoids have cannabinoid receptors? The short answer
to all these questions is “more than likely.”
Regardless of the timing, we humans were preprogrammed to psychoreact to the
cannabinoids produced by cannabis in the same way we were preadapted to alcohol via
the drunken monkeys. Our species evolved with a brain fully capable of being impacted
by cannabinoids. The question is whether this capacity was originally possessed by a
stoned spider, a stoned sponge, a stoned starfish, or some more primitive stoned animal.
Knowing the evolutionary history of cannabinoids can answer this question, as
discussed in chapter 3.
2
Cannabis
A Short Cultural History
Cannabis has played key roles in human history, human culture, and the development of
human societies. Understanding its history and association with humans involves three
distinct endeavors: one that follows the medicinal usage of the plant, one that follows
its use as fiber, and one that follows its psychoactive use. Of course the first humans to
use cannabis may have used it in any of several combinations of the three. These three
potential uses require different methods for reconstructing past human behaviors within
cultures, and how the kinds of plants and animals they interacted with influenced past
behaviors. This complication limits the time frame we can use to around 20,000 years
ago. There could have been a rich history of cannabis use before this time, but it is
difficult to determine this without artifacts from archaeological sites of earlier ages
(which currently do not generally exist). The documentation of early use of cannabis by
humans thus has a ceiling that guides the arc of this chapter, and effectively what we
know most about cannabis use by early Neolithic humans starts at around 12,000 years
ago.
There are several ways in which scientists can implement the reconstruction of
human cultural events. The first concerns the discovery of preserved material from
paleontological or archaeological sites of known ages. This kind of evidence for
cannabis use usually consists of ancient pollen, seeds, or burnt resin. Sometimes other
artifacts, such as pipes or other ceremonial devices for cannabis smoking, have been
found. Since the older estimates for the movement of humans into large social groups
cluster around 12,000 years ago, the dating of the artifacts (both human-made and
natural, like cannabis seeds) is quite precise. This precision is possible because 12,000
years is a nearly perfect age range for radiocarbon dating. Another approach is to glean
information from ancient written texts; in other words, to note in which writings the
cannabis plant is mentioned, and in what contexts. This approach is also quite accurate,
as dates for most ancient texts are well established, but it is limited by the ages of the
earliest discovered texts: the oldest known decipherable writing is Sumerian, only a
little over 5,000 years old. Moreover, two things must fall into place if ancient writing
is to tell us about cannabis use when the accounts were written. First, the writing must
be decipherable; and second, it must contain something about cannabis use—and sadly,
while many ancient scripts exist, the vast majority of them make no reference to
cannabis. And there are some artifacts that contain what looks like writing but cannot be
deciphered. For instance, while what is thought to be the oldest example of abstract
representation can be found on the Blombos Cave plaques from South Africa originating
75,000 years ago, at this time we simply cannot interpret its meaning. Even if cannabis
is mentioned on such an artifact, we will likely never know what its context was.
More recent writing on clay tablets and papyrus are the main sources of
information for scholars attempting to reconstruct events in protohistoric times. These
artifacts come from the Middle East, Egypt, and China, and are no more than 5,000
years old. Oral tradition, while not as precise as fossils and texts, offers another source
of information in reconstructing past human cultural events. The oral tradition can be
complicated and is, of course, only as good as the accuracy of the storytellers.
Frequently evolutionary biologists use an approach called biogeography that can pin
down the past movements of organisms. This approach assesses the current location of
organisms (if fossils of an organism exist, all the better) to infer where the organism
originated and where it moved to. With the development of molecular biological
techniques that can extract and sequence DNA from ancient tissues (such as Cannabis
sativa seeds), yet another approach has been added to the arsenal of scholars interested
in reconstructing the past.
Fiber, Food (Fun), or Fitness First?
I examine several different kinds of historical events here: Where was the cannabis
plant naturally found? Which cultures used cannabis? Which cultures used it as a fiber?
Which cultures ingested it? Which cultures used it as a medicine? Each of these
questions can also be accompanied by another “and when did …” question. First of all,
any reader who wants the big picture fully fleshed out in all its glory should consult the
wonderful treatise on cannabis origins, evolution, and movement by Robert C. Clarke
and Mark D. Merlin, entitled Cannabis: Evolution and Ethnobotany. This amazing
book chronicles in scholarly detail some of what I consider in this chapter. I will
attempt to update and supplement the fascinating cannabis story that Clarke and Merlin
started.
Whereas the story of cannabis and culture in this chapter starts about 12,000 years
ago in Asia, we know that the plant has been around for a long time in both Asia and
Europe. The archaeological evidence of humans associating with cannabis goes back to
about 15,000 to 20,000 years ago. The question is, Were humans actually using it?
Suffice it to say that the cannabis plant connects with human culture at almost exactly the
same time that the first sedentary societies appeared. This means that cannabis had to be
near those early sedentary human populations as they formed larger groups than the
earlier hunter-gatherers had done. Since we will see that the original distribution of
cannabis (its so-called area of endemism) was largely limited to the Tibetan Plateau
(the general vicinity of Qinghai Lake), it makes sense to posit that early human groups
living there inaugurated the cultivation and spread of cannabis as a crop plant. But did
they?
To clearly establish the historical connection of cannabis to humans, there are
checks to consider: Was cannabis present when human cultures began? If cannabis was
present, was it being used as a fiber, being ingested (smoked or eaten), or being used
medicinally?
Archaeological sites and core slices provide the two most accurate sources of
information for exploring these checks. Because most plants spew their pollen and
seeds everywhere they can, the gametes that don’t participate in fertilization are
sometimes readily preserved in sediment samples. Thus there is a natural record of
plant pollen that can be obtained relatively easily. The record is extracted using core
slice sampling. A researcher takes a cylindrical core sample from a site, the core is laid
out and sliced across, and each slice is radiocarbon dated. After radiocarbon dating, the
contents of each slice are examined under a microscope, and different kinds of pollen
and seeds are identified. The shape and microstructures of both seeds and pollen are
fairly diagnostic of the kind of plant that produced them. If a particular plant’s seeds or
pollen are found in the slice, then it is assumed that the plant itself was at the locality at
the time the slice corresponds to. Upper and lower time ranges of a plant’s presence can
also be determined with this approach.