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Title: Psychoactive%20Plants


1
Psychoactive Plants Psychoactive plants produce
their effects by acting on the nervous system. In
general they mimic, block, or affect the normal
metabolism of neurotransmitters. They can be
classified as stimulants, depressants, or
hallucinogens. Stimulants excite portions of the
nervous system, promote alertness and activity,
reduce fatigue, and suppress appetite. Depressants
reduce physical activity and alertness.
Typically, the reduced awareness is seen as a
near-sleep, dreamlike state. Hallucinogens alter
perception, mood and thought patterns.
2
Most are alkaloids (but not the active ingredient
in marijuana). Some have legitimate medical uses
(including marijuana), but many are illegal,
recreational drugs. The use of these plants and
drugs is not new the use of opium poppy goes
back at least 6000 years in Sumerian records. We
typically think of these drugs collectively as
narcotics, but by definition the name only
applies to depressants. Modern usage adds to
depressants any other drugs that are addictive.
Addictive means that the drugs cause one or more
of psychological dependence, physiological
dependence, and tolerance.
3
Psychological dependence means that the
experience of the drug is so pleasurable that the
person has an irresistible need to re-experience
the sensations produced by taking the
drug. Physiological dependence means that the
body needs the drug to avoid painful withdrawal
symptoms. Tolerance means that it takes more and
more of the drug to obtain the same sensations or
responses to the chemical. Your text has a fine
description of the common neurological mode of
addictive drugs
4
The mesolimbic pathway links the ventral
tegmentum to the nucleus accumbens of the limbic
system. This pathway uses the neurotransmitter
dopamine, and is involved in both pleasure and
psychosis.
5
Dopamine is released at the nucleus accumbens by
axons of neurons of the ventral
tegmentum. Normally, those neurotransmitters are
recollected after a short time and returned to VT
neurons. Different drugs act in different ways to
prevent the normal cycle of controlled release
and recollection. The end result is accumulation
of dopamine at the nucleus accumbens neurons,
producing a euphoric sensation, whether in a
state of heightened or depressed
activity. Stimulant drugs like cocaine prevent
the recollection. Depressant drugs like heroin
shut down the control pathway that normally
reduces or stops the production and release of
dopamine.
6
Above is a cartoon depiction of the normal state
of the mesolimbic pathway. A complex dendritic
tree of a ventral tegmentum neuron gathers
stimulation. It connects to the nucleus accumbens
neuron at a synapse that releases dopamine. With
addiction, there are physical, as well as control
and chemical changes to the pathway. The
dendritic tree of the VT neuron simplifies.
Without a larger amount of drug, the NA cell is
starved for dopamine.
7
What was at first an increase in dopamine becomes
a reduced amount with tolerance. The basic
molecular biology of tolerance is now understood.
Chronically elevated dopamine in the nucleus
accumbens causes its neurons to produce cyclic
AMP. Cyclic AMP triggers a transcription factor
called CREB (cyclic AMP response element-binding
protein sorry!) that, when phosphorylated,
triggers genes that inhibit dopamine-producing
neurons in the VT. It takes more drug to
overwhelm this tolerance.
8
  • It is also important to recognize that neurons in
    our brains have opiate receptors. They respond to
    endorphins endogenous opiate-like molecules
    that enhance pleasure and reduce pain, but also
    to the various narcotics injected, inhaled,
    smoked, drunk or consumed.
  • What are those narcotics, and what plants produce
    them?
  • opium from the opium poppy (Papaver
    somniferum),
  • from which morphine, codeine, and heroin are
    derived.
  • marijuana from Cannabis sativa, which is also
    the
  • source for hasish (under its various names) and
    hash oil
  • cocaine from Erythroxylum coca

9
  • nicotine from Nicotiana tabacum
  • peyote from Lophophora williamsii
  • kava from Piper mysticum
  • caffeine from many sources
  • alcohol from many sources
  • Starting through this long list, we have already
    seen a lot about opium. There is more to add
    here
  • Opium
  • In the dried resin of the poppys pod are 20
    alkaloids. Both morphine and codeine are
    medically important. Both are phenanthrenes.
    There is another whole class of alkaloids
    present, in a group called benzylisoquinolines.

10
The leading producer of opium is Afganistan
(gt1000 metric tons, 70 of the worlds supply).
Other producers supplying the illegal drug trade
are Myanmar, Laos, Thailand, Pakistan, Iran, and
some countries of Central America and northern
South America. The leading producer of legal
opium poppies is India.
There have been many famous opium addicts
Elizabeth Barrett-Browning, Samuel Coleridge, and
Hector Berlioz. Berlioz got the ideas for his
Symphonie Fantastique under the influence in a
dream.
11
There have also been many famous heroin addicts.
During the 1950s and 1960s heroin addiction was
common among the leading jazz musicians Charlie
Yardbird Parker, Miles Davis, and Billie
Holiday among many others. Heroin is 6 times more
addictive than morphine. As well, withdrawal from
heroin addiction is much more severe than from
morphine. So much more severe that withdrawal
from heroin addiction is very difficult. Instead
of withdrawal cold turkey (the descriptive term
comes from the tendency to feel cold and get
goose bumps during withdrawal), medicine has
found that slow reduction in the dose of
methadone, a synthetic opiate that is less
addictive, can make withdrawal manageable.
12
Overdoses of either heroin or morphine can be
fatal. The opiates are central nervous system
depressants, and can, in overdose, completely
suppress the respiratory center in the
brain. Morphine as a prescription medicine is
still used to treat intense pain, for example
following surgery or in the case of severe burns,
for those in the pain of terminal cancer, and for
kidney stones. Both morphine and heroin were once
in commonly available, over-the-counter remedies,
like cough syrups, but the dangers were
recognized early in the 20th century, and those
products were no longer available by 1920.
13
Marijuana The species is a dioecious (separate
sexes) annual. The active ingredient is
?-9-tetrahydrocannabinol. It is present at low
concentrations even in the leaves of hemp grown
for rope, but is in much higher concentration in
the resin from unfertilized pistillate (female)
flowers and adjacent leaves. It takes about 5 mg
of THC to have a detectable psychological or
physiological effect.
14
THC is a phenolic molecule, in its own class
called cannabinoids.
There are two receptor types for cannabinol,
called CB1 and CB2 types. CB1 receptors are in
the brain, including the limbic system,
hippocampus (short term memory) and amygdala
(emotional memory), but are absent in the medulla
oblongata. CB2 receptors are in the immune system
(particularly the spleen), and are probably
responsible for anti-inflammatory response.
15
Much like endorphins, we produce endogenous
cannabinols. After discovering cannabinol
receptors in animal brains in 1988, endogenous
cannabinols were discovered in 1992. This is the
structure of the first one found
Its called anandamide, which comes from the
Sanskrit word for bliss, with the suffix for its
structure as an amide. It is approximately as
potent as THC and binds to both receptor types.
16
Cannabis has been used for at least 5,000 years
for its drug properties, beginning in China,
then India and among the Scythians of central
Asia. Use spread from there into Asia Minor (the
Arabic and Persian countries) and northern
Africa. It was used as a hallucinogen and in
religious ceremony. It is still used in religious
ceremony in India (it is one of the five sacred
plants), and is the preferred relaxant in
alcohol-free Muslim countries like Pakistan and
Bangladesh, smoked in hookahs. Estimates suggest
at least 20 of the populations of the U.S. and
Canada have used cannabis. Is that accurate? An
underestimate? An overestimate?
17
  • Symptoms and effects of marijuana
  • sporadic, uncontrollable laughter
  • often the (mistaken) impression their
  • conversation is witty and brilliant
  • limbs feel light....
  • decreased sperm count decreased Testosterone
    levels
  • the munchieshunger, usually for snack foods
  • an altered (distorted) sense of time and space
  • smoke may damage lungs as cigarette smoke
  • does

18
However, there are valuable medical uses for
marijuana. It is used to treat glaucoma a high
intraocular pressure that can be caused by
advancing age, diabetes, and other factors THC
reduces intraocular pressure.
It is used to treat the nausea, vomiting, and
loss of appetite brought on by cancer
chemotherapy. It is used to reduce or eliminate
spastic movements in patients with multiple
sclerosis and Parkinsons disease. It is used to
counteract the wasting syndrome that is part of
terminal AIDS.
19
In Canada marijuana is a schedule II drug,
meaning that it can be prescribed for approved
medical conditions when necessary. The medical
marijuana is all produced under contract to the
federal government by Prairie Plant Systems in
Manitoba and Saskatchewan. In the U.S. there is
no parallel federal approval system for medical
marijuana it is a schedule I drug (with heroin).
In a (conflicted) situation, some states have a
licensed mechanism to distribute medical
marijuana. The AMA is significantly more
liberal than government, and wants marijuana
reclassified as a schedule II drug.
20
Though they are controversial, there are local
regulations in some jurisdictions (e.g. Ann
Arbor, MI) that make possession of personal use
amounts of marijuana a civil offense like a
traffic ticket.
State laws concerning Cannabis Blue-medical
marijuana Red-decrimilization Purple-both
21
Even where marijuana is available for medical
use, smoking it, as noted with effects, can do
much the same damage as smoking tobacco (see
below). An inhaler for THC would be much better
medically, but has not become available. One last
point modern growth systems have increased the
THC content of marijuana in two ways one is
classical selection, the other is the production
of sinsemilla plants that are seedless hybrids of
C. sativa and C. indica. Artificial growth
systems clone pistillate plants of the hybrid
that are dwarfed in size, but have abundant
flowers and resin. One of the products of this
new growth method is a larger yield of hashish
(hash, hash oil, etc.)
22
The origin of the term Hashish is from
Hashishin, which is the Arabic word for
assassin or, possibly more likely, from the
Arabic for grass. The source for the term
assassin, and the reason for its association with
marijuana is the Hashshashin, the medieval Shia
sect of militants founded by Hassan-i-Sabah. They
were said to have been inspired to commit murder
under the influence of hashish Hashish normally
means the compressed trichomes from upper leaves
which are the source of the resin that is the
most concentrated source for THC. The current
product is a much stronger material today than
in the 1960s and 1970s the THC content has
increased by about 10x.
23
Cannabis trichomes
hashish
24
Cocaine coca leaves have been chewed by natives
in Peru and the pre-Columbian Andes for hundreds
of years. Cocaine has been used in western
culture for more than a century. Among famous
users (neglecting the many models (Kate Moss) and
musicians) have been Arthur Conan Doyle, Sigmund
Freud (where do you think those dreams for
analysis came from?), and Ulysses S. Grant. You
know that Coca-cola once contained cocaine, and
still contains a non-narcotic extractive of coca
leaves grown under government control in New
Jersey. Cocaine may be taken by injection,
consumption, smoking, or snorting (formally
insufflation). Effects occur fairly rapidly
(seconds to less than one hour).
25
Cocaine is a powerful stimulant, producing a
euphoria and a burst of energy and alertness.
However, after that short-term high there is a
period of depression and lethargy. All this
happens because cocaine blocks the transporter
protein involved in re-uptake of dopamine. Long
term users may suffer from a psychosis like
schizophrenia.
26
Cocaine is extracted from the coca leaves by
processing with sulfuric acid. Leaves are
macerated (stomped like grapes or otherwise
crushed), and mixed into the acidic solution.
After maceration, the water is evaporated,
leaving a brown mush that is dried into impure
cocaine sulfate. That product is sold in South
America. What is transported to North America is
much more concentrated cocaine hydrochloride.
This is the white powder sometimes called
snow. From this base cocaine, the many more
dangerous forms are made crack cocaine, freebase
cocaine, etc.
27
lines for insufflation
Cocaine hydrochloride
crack
28
Tobacco tobacco is a product of a New World
genus, and only two species are commonly used
Nicotiana tabacum and
N. rustica.
Both are tetraploid hybrids of closely related
Nicotiana species. As members of the nightshade
family, they have certain properties that are
particularly interesting (and another reason not
to smoke) for Canadians.
29
Members of the nightshade family accumulate soil
cadmium in their leaves (but not fruits).
Canadian soil (at least where tobacco was mostly
grown around Delhi, Ont.) is high in cadmium, a
toxin for kidneys (second only to Japan in Cd
concentration). We eat the fruits of other
Solanaceae e.g. tomatoes, green peppers,
potatoes, eggplants, but what we use of tobacco
is the leaves, the parts with high cadmium. The
use of tobacco isnt new it was used by native
Americans long before Europeans arrived. It was
smoked in large quantities as a hallucinogen by
shamans. It was also chewed, eaten, and drunk.
Missionaries saw the effects, and sent seeds back
to Europe, initially Spain.
30
From Spain use spread to France, then England. It
is argued that the desire for tobacco fueled the
European colonization of North America. John
Rolfe came to Jamestown in 1609, and became the
first person to successfully raise tobacco (N.
tabacum) as a crop, replacing the inferior N.
rustica. He later married Pocahontas. He became
rich on tobacco export to England, and continued
to improve the crop quality by selection. Tobacco
also drove the initial slave trade, bringing the
first slaves to Jamestown in 1619. King James I
disliked tobacco intensely, wrote a polemic about
that, and imposed a high tariff on imported
tobacco.
31
Here are those characters
John Rolfe with an imagined Pocahontas
King James I
Pocahontas as painted in England
32
Tobacco is an annual plant. It is grown from
seeds that are started in special beds. In the
U.S. these beds are fertilized with apatite, a
mineral that causes the plants to be partially
starved for nitrogen the object is taste. When
the seedlings reach sufficient size, they are
transplanted into fields and grown. To maximize
leaf area of tobacco plants, they are generally
not allowed to flower or to branch laterally.
Harvesting occurs by pulling mature leaves off
the plants, beginning at the bottom and working
upward over time as leaves mature. The leaves are
hand-picked. Alternatively, harvest can wait
until most leaves are mature, then the whole
plant is cut.
33
The cut leaves are then moved to barns to cure.
Curing is basically fermentation and drying.
This is the time when the flavors develop the
leaves turn from green to brown as the
chlorophylls break down and carotenoids
degrade. Tobacco leaves can be air-cured,
smoke-cured, or flue-cured (heated without
exposure to smoke).
34
The cured leaves are aged for weeks to years
before manufacturing the final product
(cigarettes, cigars, pipe tobacco, chewing
tobacco). Each product involves a mixture of
leaves of different cures as well as
additives. Cigarettes are the most recent of
these products, only having been marketed after
the Crimean War (1854-6) pitted Russia against an
alliance of France, England and the Ottoman
Empire. Mass marketing only followed the
development of machinery that could manufacture
cigarettes cheaply, beginning in 1881. Cigarette
consumption peaked in 1963 in the U.S., when 42
of the population were at least occasional
smokers. Today numbers have declined, but there
are still more than 1 billion smokers worldwide.
35
Why are we concerned about smoking? Because
tobacco contains the most widely used addictive
drug nicotine. All means of consuming tobacco
result in the absorption of nicotine in varying
amounts into the user's bloodstream, and over
time the development of tolerance and dependence,
i.e. addiction.
36
  • The addiction has significant health
    consequences. Among the statistics
  • 85 of lung cancer in men and 75 of lung cancer
    in women is caused by smoking
  • 30 of all cancer deaths can be linked to
    smoking
  • Male smokers die 13 years and women 14.5 years
    earlier on average than otherwise similar
    non-smokers.
  • Coronary heart disease and stroke, leading
    killers, are
  • caused by smoking. 120,000 deaths from
    coronary
  • artery disease are attributed to smoking
    annually.
  • Smokers having double the risk of dying.

37
  • Chronic obstructive pulmonary disease
    (bronchitis,
  • asthma, emphysema) is next on the list
    of leading
  • causes of death. 90 of these deaths
    are due to
  • smoking.
  • Second-hand smoke is now recognized as
    dangerous.
  • Exposed babies have higher risk of
    SIDS. Asthma,
  • emphysema and cancer risk is increased
    in exposed
  • children.

38
Public recognition of the danger took a long
time. In 1964 the US Surgeon Generals Office
reported links between smoking and lung cancer,
heart disease emphysema etc. In 1998 California
became the first state to ban smoking in bars. In
that same year settlements with the five major
cigarette manufacturers in the U.S. gave damages
to the states totaling 200 billion to recover
costs of medical treatments for smokers. Today
most states and Canada ban smoking in public
buildings. Bans are currently being extended more
broadly.
39
States in red are members of one or more of the
suits against tobacco manufacturers.
40
Nicotine is the addictive component, but not
necessarily the most dangerous compound in
tobacco. Table 20.1 in your text lists some of
the 2000 compounds in tobacco smoke. Check them
out. Many are carcinogens and/or toxic. Nicotine
comprises 0.3 5 of the dry weight of tobacco
leaves. It is a potent neurotoxin. You get about
1mg absorbed nicotine/cigarette (non-filtered).
41
Nicotine acts on acetylcholine receptors. In
small concentrations it increases their activity,
among other things leading to an increased flow
of adrenalin, a stimulating hormone. The release
of adrenaline causes an increase in heart rate,
blood pressure and respiration, as well as higher
glucose levels in the blood. However, in higher
doses, nicotine causes a blocking of
acetylcholine receptors, which is the reason for
its toxicity (higher than cocaine) and its
effectiveness as an insecticide. In addition,
nicotine increases dopamine levels in the reward
circuits of the brain. Studies have shown that
smoking tobacco inhibits monoamine oxidase, an
enzyme responsible for breaking down dopamine.
42
In this way, it generates feelings of pleasure,
similar to that caused by cocaine and heroin,
thus causing the addiction. The same dependence
and tolerance effects are observed. Breaking the
addiction, just as with the hard drugs, is
difficult. Transdermal nicotine patches are being
used successfully. They wean the person off
smoking by providing a steady, but slowly
decreasing supply of the alkaloid.
43
Peyote and Mescaline Peyote is the cactus
Lophophora wiliamsii that is native to
southwestern Texas and Mexico. It is a spineless
cactus.
44
It is slow growing, taking 10 30 years in the
wild to reach adult, flowering size. What is
harvested is the above ground button. It
contains a number of phenethylamine alkaloids,
the most important of which is mescaline.
Overharvesting has made Lophophora an endangered
species. The effective dose is 300 500 mg
mescaline, or about 5g of dried peyote. It is a
hallucinogen.
45
The hallucinogenic visions vary widely, from
LSD-like light shows to frightening visions of
snakes, demons and feelings as if trapped in a
cave. There are, additionally, many side effects,
including nausea, vomiting, and tremors. Those
effects typically precede the hallucinatory phase
of effects. In Canadian law, mescaline is a
prohibited (illegal) substance, but peyote is
exempt. In the U.S., after a protracted series of
legal challenges, use of peyote by a religious
group, the Native American Church, was permitted,
but the Supreme Court also upheld the rights of
individual states to outlaw peyote. The situation
might now be described as a morass, with
conflicting regulations in different states.
46
Kava - is a soporific derived from Piper
mysticum. The plant is native to the western
Pacific and was transported from island to island
by Polynesians. The name kava refers both to the
plant and the beverage made from it. The active
ingredients are lactones. There are 15 20
lactones in the leaves and roots, but only 6 are
pharmacologically active. Fresh roots contain
about 15 lactones, while leaves contain 5.
Exact proportions of different lactones differ
among the many sources across the South Pacific.
The effects vary similarly. Overharvesting of
roots has meant population decline and the
harvesting of younger and younger plants.
47
The most potent kava is produced by grinding or
pounding fresh roots, adding cold water, and
drinking the emulsion that results. It can also
be prepared by chewing, which is the traditional
Polynesian method.
48
The effects of consuming kava occur within an
hour or two of consumption. Initially blood
vessels of the lips and tongue constrict, some
numbness occurs there. Then there is a somewhat
euphoric period, and finally there is an
anxiolytic effect (reduced anxiousness, calming,
friendliness) and, typically, sleep. Stronger
beverages produce somnolence, then deep,
dreamless (??, there are also reports of vivid
dreams) sleep. Either mild or stronger effects
have the advantage that this drug is not
addictive, has no aftereffects, and, unlike
alcohol, does not affect reaction time. Use in
Europe and North America has been directed
towards reduction of anxiety and as a sleep aid.
However, there is conflicted evidence of liver
disease.
49
Kava has been the subject of an FDA alert, but
has not been banned. The difference between a
lack of liver disease in Polynesian users and
occurrence in Europe and North America is
suggested to be due to difference in
extraction/preparation methods. Commercial
preparation has used ethanol extraction of
lactones from roots versus the traditional method
that uses only water. However, there is tentative
evidence that methanol extracts of kava roots may
be useful in treating leukemia and ovarian cancer.
50
A few last pharmacoactive plants Other plants
from among the Solanaceae also produce alkaloids
that can be poisonous, but used are used
medically in small amounts. The plants are
deadly nightshade (Atropa belladonna) and
jimsonweed (Datura strumonium) Both species
contain atropine and scopolamine. Both chemicals
are hallucinogens and are dangerously toxic, but
also have medical applications. Symptoms of
atropine poisoning are tachycardia,
hallucinations, loss of balance, confusion, and
constipation. Atropine completely blocks
acetylcholine neurotransmission (and function of
the parasympathetic system).
51
Atropa belladonna
Datura strumonium
52
  • Atropine has valuable medical applications
  • when your optometrist or ophthalmologist puts
    drops
  • in your eyes to dilate your pupils, the active
    ingredient
  • was atropine, more recently replaced by
    synthetic agents
  • it is the antidote to poisoning by
    cholinesterase
  • inhibitors used in pesticides (Malathion,
    Parathion)
  • it acts much like pseudoephedrine, and is in
    some
  • over-the-counter cold and flu medicines
  • It takes only a few berries to reach a toxic
    dose. The atropine is most concentrated in the
    seeds within the berries.

53
So why do people fool around with jimsonweed?
The hallucinations, of course. The problem
before hallucinations a consumer will suffer the
anticholinergic effects, nausea, vomiting, etc.
The answer? Dont Salvia Salvia divinorum is a
hallucinogenic plant in the mint family. It is
native to the Sierra Mazateca mountains in the
state of Oaxaca, Mexico. It has long been used by
shamans of the Mazateca in rituals that are
Christian in origin. The active ingredient is a
diterpenoid called salvinorin. It seems not to
be toxic, unlike other hallucinogens that bind to
opiate and serotonin receptor sites.
Oaxaca
54
Salvinorin is also (by concentration) the most
potent naturally-occurring hallucinogen. Since it
appears to be non-toxic, has high potency, and is
readily available in the form of plants or dried
leaves, it is growing in popularity. Methods of
consumption include smoking (apparently higher
temperature (gt240?C) releases a much greater
proportion of the salvinorin in the leaves),
chewing (like using chewing tobacco), and using a
tincture. Intake method affects how rapidly and
how long-lasting effects are, but mostly they
last only a few minutes. Because Salvia is a
relatively recently adopted hallucingen, there is
still controversy about its safety, and there are
a global variety of laws and prohibitions.
55
Legality of Salvia divinorum  Banned by
law   Imports/sales prohibited   Sale to minors
prohibited
  • A list of the effects from a book about using
    Salvia includes
  • Uncontrollable laughter
  • Past memories, such as revisiting places from
    childhood memory
  • Sensations of motion, or being pulled or twisted
    by forces
  • Visions of membranes, films and various
    two-dimensional surfaces
  • Merging with or becoming objects

56
  • Overlapping realities, such as the perception of
    being in several locations at once

We wont talk about it here, but alcohol could
easily be classed with the other psychoactive
drugs. It is a CNS depressant, it is addictive
and shows tolerance development.
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