The biology of addictive behavior
-Chapter 2-
Whenever we introduce a drug to the brain, we upset that balance.
The brain will seek to adapt to redress this imbalance, by minimizing the
effects of the drug.
Addictive behaviors that do not involve the administration of drugs still
involve the release of endogenous chemicals (neurotransmitters) in the
reward pathway.
All civilizations did experiment with drugs.
The primary reason for this is that drugs have a number of sought after effects
(enhance mood, alter consciousness, improve our performance on a task,
remove feelings of discomfort, and make us want them again.)
Drug= a chemical substance that produces a biological and psychological
effect when it’s administrated. They can be obtained from plants or animals.
They can be entirely synthetic or they may be result of genetic engineering.
To be a drug, it needs to be something that is administered to the body rather
than natural (endogenous) substance released by the body.
The drugs of abuse and dependence have their primary effects in the brain
and change our biological functions (heart rate, blood pressure and sweating),
how we feel and think (psychology) and how we act (behavior). Most drugs
will also have actions in other parts of the body, but drugs of dependence the
brain is the most important site of action.
All drugs of abuse produce a sought after or pleasurable effect. They are
rewarding to us in some way. Either by providing a sought-after positive effect
or removing some form of discomfort.
All drugs of dependence produce a positive emotional response by
releasing a neurotransmitter called dopamine in the reward pathway (the
part of our brain responsible for emotions).
If they reach our brain quickly and effectively, we become addicted to that
drug.
If we repeat the use, our brain will adapt to its presence and we are going to
feel “normal” when the drug is present.
We may feel that we need to use more and more of the drug to achieve the
sought-after effect, and we may experience depression, anxiety and a range of
unpleasant symptoms when we try to stop using the drug.
There are different routes of administration and there is a change not only as
far as how long it takes for us to feel the effect but also how intense those
effects will be and how long they will last.
How does the drug reach the brain: these phases we call absorption and
distribution.
How does the amount of drug in our body change over time?: the effects will
eventually wane; the body will break down the drug molecules and remove it-
these phases we call metabolism and excretion
The different effects produced by different drugs can be understood by
examining which structures of the brain are affected by the drug and how the
brain adapts to a drug’s continued presence.
Within the brain, drugs mostly work on proteins namely receptors, enzymes,
neurotransmitter carriers and ion channels.
, Receptors: protein molecules that recognize and respond to endogenous
chemical compounds called neurotransmitters, which send messages
between the cells in the brain.
Drugs bind only to certain receptors- Receptors only recognize certain classes
of drugs.
Drugs may either increase OR decrease the activity of structures and pathways
within the brain.
If we take a drug on a continuing basis, the body will adapt, leading to a
reduction in the effect of the drug. → this may possibly lead us to increase the
amount and frequency of the drug use.
Or we may feel that we need the use just to feel “normal”: these are issues of
tolerance and physical dependence.
How a drug enters the body, and how the body reacts to its presence?
Routes of administration:
1. oral (drinking liquid or taking a pill-slowest)
2. injection – (injecting a drug into a vein (intravenous), into a muscle
(intramuscular) or slightly under the skin (subcutaneous)-fastest)
3. inhalation (inhaling the heated vapors of a drug or smoking)
4. application to skin (applying an ointment, a method more common for
some therapeutic medicines rather than drugs)
5. through mucous membranes (sniffing a drug (intranasal) or holding a
liquid in your mouth-slower than injection)
The route of administration depends in part on the chemical characteristics of
the drug and in part by personal preferences.
The route can also be guided by the speed with which the person wants the
drug to act.
The slower the onset of drug action, the more gradual the buildup of the effect
and the longer it will seem to last.
The sooner an effect is experienced, the more reinforcing it is
Absorption:
Drugs to reach the brain and produce their effects they must journey from the
site of administration to the brain by travelling through the circulatory system.
The process by which a drug enters the blood stream after it has been
administered is called absorption.
The differences in the time it takes for a drug to produce an effect can be
explained in part by differences in the rates of absorption into the blood
stream.
Except the intravenous injection, all other routes of administration, the drug
needs to cross at least one barrier (cellular membrane- the walls of blood
vessels) to reach the bloodstream.
Cellular membranes, like hurdles over which the drug has to pass before it can
reach its site of action within the brain.
The drugs of abuse are quite good at passing these barriers.
Success characteristics of the drug:
1. The degree to which it is soluble in lipids (fats). Each cell membrane
consists mostly of lipids. So how easily a drug will move through depends on
the degree to which the drug will be dissolved in the membrane lipids.
, Highly lipid soluble drugs are easily passed in the cellular membranes.
2. The degree of ionization of the drug. An ionized molecule is one that has
had either a positive or negative particle removed or added to it. A certain
proportion of the drug molecules will ionize and become charged particles.
The ionized form of the drug is much less likely to cross the cellular
membrane than the deionized form.
The greater proportion of ionized molecules in the drug, the slower the rate of
movement of the drug across the membrane.
The proportion of ionized molecules is itself affected by the relationship
between the acidity or alkalinity of the fluids next to the membrane surface
and the acidity or alkalinity of the drug itself.
In general, alkaline drugs are most easily absorbed, and the drugs of abuse
tend to be alkaline
3. The size of the drug molecule will also affect the rate with which it is
absorbed into the bloodstream. Drugs that consist of relatively small
molecules will pass through the membrane faster than would be expected
purely by their degree of lipid solubility.
The vehicle in which the drug is administered can also be important.
4. The difference in concentration of the drug on the two sides of the
membrane. The greater the difference in drug concentration on each side
of a cellular membrane, the more rapid the movement – a process called
diffusion, which is the same process that occurs when a sugar cube dissolves
in a glass of water. Once a drug has entered the blood stream, it is immediately
carried away from the site of entry to others parts of the body. As a result,
there is always a difference in the drug concentration either side of the
membrane.
Drugs can enter the blood stream by crossing mucous membranes such as
those in the nose or mouth (snuff of cocaine)
Absorption via these routes (intramuscular – subcutaneous) can be fairly rapid
depending on the blood flow that is near the site of injection.
If a drug is injected very close to a blood vessel, such as into a muscle, then
only the wall of the blood vessel needs to be crossed for the drug to enter the
blood stream. However, id the drug is injected into body fat, then it may take
some time for the drug to move close to a blood vessel.
As we can see there are a number of factors that can affect the rate of
absorption of a drug into the blood stream, while, in turn, the rate of
absorption can affect the time it takes for a drug to produce an effect and the
size of the effect that is produced.
The delay in feeling a drug’s effect, and the intensity of the felt effects, can
affect how rewarding (or reinforcing) the drug is and the likelihood that it will
be taken again.
Distribution:
Once a drug has been absorbed into the blood stream, it then needs to travel
throughout the body to reach the brain. During its journey, some of the drug
may leave the blood stream and be stored in a body tissue, or it may be
metabolized, leaving less of the drug to reach the brain and have an effect.
, Eventually the remaining drug will reach the brain where it can finally have
the blood stream to connect with the brain and produce its effect. This process
of drug movement is called drug distribution.
As a drug travels throughout the body, it will come across a number of
barriers, slowing its movement and gradually removing some of the drug from
the blood stream.
Blood vessels are composed of cells that form various roadblocks for the drug,
slowing its entry into body tissues such as the brain.
These principles affect the rate of absorption and the degree and speed to
which a drug is distributed.
A drug that can cross a membrane rapidly and easily will eventually be
distributed throughout the entire body.
Drugs that cross membranes less easily are less evenly and widely distributed.
Essentially there is dilution, meaning that less of the drug reaches the brain
than was originally administered.
When it does finally reach the brain, it faces a further roadblock called the
blood-brain barrier.
This consist of the cellular lining of capillaries in the brain, and makes it
difficult for drug to enter the brain, it’s a defense against chemicals and other
foreign bodies
*Heroin is really just a way of packing morphine, so that more morphine can
cross the blood-brain barrier. In fact, heroin only lasts in the body for a minute
or two, and the effects that people experience are actually the effects of
morphine.
SUM UP:
The rate of absorption of a drug into the blood stream is affected by the route
of administration, the chemical properties of the drug, the conditions at the site
of administration and individual health factors.
Drugs, are distributed through the body by the blood stream and diffuse across
cell membranes (roadblocks between different parts of the body; protecting it
from what it may consider to be a foreign substance)
In case of drugs of abuse, the important barriers to cross include the lining of
the gastrointestinal tract and the blood-brain barrier.
To cross these barriers easily and quickly, drugs need to be lipid soluble,
deionized, and relatively small in molecular size.
How does the body remove the drug, and terminates its effects, via processes
called metabolism and excretion?
Drug elimination: metabolism and excretion
Metabolism: the way in which the body breaks down the drugs, making it
easier to remove, and involves a chemical reaction within the body to form a
product which is easily excreted.
The metabolites formed (that is, the chemicals produced when the drug is
metabolized) may themselves be active (that is, they can produce an effect in
the brain similar to the original drug) or they can be inactive (that is, they do
not produce a discernible effect)
Excretion: the elimination from the body of the drug and its metabolites
