How Drugs Affect The Brain
- Routes of Administration
- The Importance Of Synapses
- The Neurotransmitters
- How Drugs Work (In General)
- Mechanisms Of Specific Drug Activity:
Routes of Administration
In order for a drug to have an effect on someone, it must first be taken into that person's body and bloodstream so that it can then interact with that persons' brain. Drugs that get into the bloodstream faster tend to have faster, more intense effects.
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How you take a drug has a lot to do with how quickly it will effect you, and how long its effects will last. The more directly a person is able to get their drug of choice into their bloodstream, the faster and more intense the drug effect tends to be. Thus, all other things being equal, Intravenous (IV) injection of a drug will produce a greater rush than an oral dose of that same drug because the IV administered drug is immediately available to the brain, and does not have to be absorbed or otherwise processed.
In addition to the route of administration, the amount of drug that can enter the blood stream at a time is an important factor as well. Drinking alcohol on an empty stomach will result in the alcohol entering the bloodstream faster than if the same drinks were had with a full stomach. The contents of the stomach act as a sort of sponge or buffer, limiting the amount of alcohol that can be absorbed into the blood stream and sent to the brain at any given moment.
|Direct IV injection into the blood||Fast, intense onset of drug effect|
|Inhalation (drug gets into the bloodstream via the lungs or nasal membranes)|
|Eating (drug enters the bloodstream through the normal process of digestion via the stomach and intestine)||Longer more gentle onset of drug effect|
Once the drug is in the blood it has almost immediate access to the brain. There is a blood-brain barrier that keeps many substances out of the brain, but the drugs we are concerned with here are able to go through that barrier with little difficulty.
(^) The Importance Of Synapses
In order to understand how drugs work on the brain, we must first have some understanding of how the brain is constructed. The brain is a very complicated collection of cells known as neurons or (more informally) nerves. Whenever you think about something, sense something or do something, what is happening at the level of the brain is that various neurons are sending information to one another concerning what you are thinking, sensing or doing. It is at the level of this inter-neuron communication that most drugs have their effects.
A given neuron is a long skinny cell. It has three prominent parts: the dendrites, the nucleus, and the axon. Information flows through neurons starting in the dendrites and ending at the terminal part of the axon (known as the button). Neurons receive information through branch-like structures called dendrites. As neurons grow, their dendrites reach out and make contact with the axons of adjacent neurons. The input parts of a given neuron, then, makes contact with the output parts of many other neurons. Signals coming from many axons converge on the dendrites of another neuron. Some of these incoming signals (excitatory signals) tell the neuron to activate itself, while others (inhibitory signals) tell the neuron to remain passive. When the number of excitatory signals gets larger then the number of inhibitory signals, the neuron 'activates', which is to say, a chemical-electric signal is generated at the top of the neuron, and makes its way all the way down the axon until it hits the terminal button. The signal at the terminal button is picked up by the dendrites of other neurons, and the process repeats.
The exact nature of how a signal passes from one neuron to another is particularly important. Although neurons do talk to each another through their interconnected axons and dendrites, there is no physical contact between the terminal button of one neuron, and the dendrites of another. Rather, between the axon and the dendrites is a space or gap, which is called the 'synapse'. When the chemical-electric signal of an activated neuron reaches its terminal button, the electrical signal stops, and chemical messengers known as 'neurotransmitters' are introduced into the synapse. These neurotransmitter chemicals float across the synapse and connect in lock-and-key fashion with protein structures known as 'receptors' that are embedded in the walls of the dendrites of the receiving neurons. It is the presence of the neurotransmitter 'keys' opening the receptor 'locks' on the surface of the dendrites of the post-synaptic neurons (and not any electrical signal that jumps the synapse) that excites or inhibits the post-synaptic neurons into activating or not.
After a short while in the synapse, the neurotransmitters that have been released are recalled back into the terminal button in a process called 're-uptake' so that they are available should the neuron need to fire again.
(^) The Neurotransmitters
There are many different chemicals in the brain that function as neurotransmitters, but a small handful do most of the work.
|Neurotransmitter||What it does||What drugs affect it|
|Dopamine||Involved in regulation of movement, reward and punishment, pleasure, energy||Every drug that affects feelings of pleasure, including Cocaine, Amphetamine, opiates, marijuana, heroin and PCP|
|Epinephrine (also called Adrenaline)||Excitatory neurotransmitter involved in arousal and alertness|
|Norepinephrine (also called Noradrenaline)||Involved in arousal and alertness, energy and feelings of pleasure||Stimulants|
|Serotonin||Involved in regulation of mood and impulsivity||Alcohol, Hallucinogens, Stimulants, Anti-depressants|
|Acetylcholine||Inhibitory neurotransmitter involved in movement, memory function, motivation and sleep||PCP and hallucinogens, Marijuana, Stimulants|
|GABA (Gamma Aminobutyric Acid)||Inhibitory neurotransmitter involved in arousal, judgment and impulsiveness||Depressant drugs, Marijuana|
|Endorphins||Substances involved in pain relief and reward/punishment||Opioids, Depressants|
(^) How Drugs Work
Drugs make their effects known by acting to enhance or interfere with the activity of neurotransmitters and receptors within the synapses of the brain. Some neurotransmitters carry inhibitory messages across the synapses, while others carry excitatory messages. Agonistic drugs enhance the message carried by the neurotransmitters; inhibitory neurotransmitters become more inhibitory, and excitatory neurotransmitters become more excitatory. Antagonistic drugs, on the other hand, interfere with the transmission of neurotransmitter messages; the natural action of neurotransmitters is interfered with so that their effects are lessened or eliminated.
There are many ways that a drug can act to enhance (Agonize) a given neurotransmitter:
- An agonistic drug can spur increased production of particular neurotransmitters. When those neurotransmitters are then released into the synapse, they are more numerous than they would normally be, and more of the neurotransmitter substances find their way over to the post-synaptic receptors on the dendrites of the next neuron.
- An agonistic drug can interfere with the re-uptake of neurotransmitter substances which has the effect of forcing them to remain in the synapse and interacting with receptors longer than normal (Cocaine effects the Norepinephrine and Dopamine neurotransmitter systems in just this way).
- An agonistic drug can bypass the neurotransmitter entirely, and simply float out into the synapse and itself bind with and activate the neurotransmitter's receptors.
Similarly, there are many ways that a drug can act to interfere with (Antagonize) a given neurotransmitter:
- An antagonistic drug can interfere with the release of neurotransmitters into the synapse.
- An antagonistic drug can compete with the neurotransmitter for binding to the neurotransmitter's receptor. The antagonistic drug binds to the receptor but does not activate it, thus blocking receptors from being activated by the neurotransmitter.
- An antagonistic drug can causes neurotransmitters to leak out of their containers in the terminal button, into the fluid of the pre-synaptic neuron itself, making the neurotransmitter substance unavailable for release into the synapse. When the neuron is activated, there is less neurotransmitter available to be released into the synapse.
Most of the drugs that get abused are agonists of various neurotransmitters - they work to enhance the natural effect of neurotransmitters.
(^) Mechanisms Of Specific Drug Activity:
Alcohol, Benzodiazepines, Barbiturates and other central nervous system depressant drugs act primarily on a neurotransmitter substance known as GABA (Gamma Aminobutyric Acid). GABA is an inhibitory neurotransmitter that makes other neurons less likely to activate. The depressant drugs are GABA agonists, acting to help GABA reduce neuronal activation more efficiently than it usually would. Alcohol also inhibits (acts as an antagonist against) another excitatory neurotransmitter (Glutamate), making it harder for Glutamate to get the nervous system excited.
Amphetamines have their primary effects on the neurotransmitter Dopamine. Amphetamines both induce the terminal button of Dopamine-producing neurons to let more Dopamine out than normal, and also keep that Dopamine out in the synapse longer than it normally would be allowed to stay. Amphetamine also acts agonistically on receptors for a different neurotransmitter, Norepinephrine, by competing with Norepinephrine for post-synaptic receptors and turning those post-synaptic receptors on.
Cocaine has its major effect by blocking the re-uptake of the neurotransmitters Dopamine and Serotonin.
Opioid drugs bind to special endorphin receptors in the brain (the 'mu', 'kappa', 'sigma' 'delta' and 'gamma' receptors) that have to do with pain. When these receptors are occupied and activated, the perception of pain lessens.
Drug treatments for opioid addictions sometimes include the administration of Naltrexone, which is an opioid antagonist. Naltrexone competes with the opioids for their receptor sites, but is not itself capable of activating those receptor sites. An opioid addict on Naltrexone is thus rendered more or less incapable of getting high from their opioid drug of choice; they may take an opioid, but it will be blocked from the opioid receptors by the Naltrexone, and will not have its effect.
Marijuana has a complex set of effects. It acts on the neurotransmitters Serotonin, Dopamine and Acetylcholine. It also binds to a receptor for a recently discovered neurotransmitter known as Anadamide.
LSD is known to antagonize Serotonin by blocking its release.
Information in this article has been drawn from multiple sources which include:
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