Chapter 5: Psychopharmacology

5.5: How Drugs Affect Neurotransmitters

The chapter concludes with some examples and animations of how drugs like alcohol, caffeine, cannabis, and opiates work at the level of neurotransmitters and synapses (The Brain from Top to Bottom, n.d.). These examples are adapted from the website The Brain from Top to Bottom. ( Animations and descriptions of other drugs, including nicotine, amphetamines, ecstasy, and benzodiazepine, can be found there.


Alcohol passes directly from the digestive tract into the blood vessels. In minutes, the blood transports the alcohol to all parts of the body, including the brain.

Alcohol affects the brain’s neurons in several ways. It alters their membranes as well as their ion channels, enzymes, and receptors. Alcohol also binds directly to the receptors for acetylcholine, serotonin, GABA, and the NMDA receptors for glutamate.

Watch the animation to learn about how a GABA synapse functions without alcohol and with alcohol. GABA’s effect is to reduce neural activity by allowing chloride ions to enter the post-synaptic neuron. These ions have a negative electrical charge, which helps to make the neuron less excitable. This physiological effect is amplified when alcohol binds to the GABA receptor, probably because it enables the ion channel to stay open longer and thus let more Cl- ions into the cell.

The neuron’s activity would thus be further diminished, thus explaining the sedative effect of alcohol. This effect is accentuated because alcohol also reduces glutamate’s excitatory effect on NMDA receptors.

However, chronic consumption of alcohol gradually makes the NMDA receptors hypersensitive to glutamate while desensitizing the GABAergic receptors. It is this sort of adaptation that would cause the state of excitation characteristic of alcohol withdrawal.

Alcohol also helps to increase the release of dopamine by a process that is still poorly understood but that appears to involve curtailing the activity of the enzyme that breaks down dopamine.



The stimulant effect of coffee comes largely from the way it acts on the adenosine receptors in the neural membrane. Adenosine is a neuromodulator that has specific receptors. When adenosine binds to its receptors, neural activity slows down, and you feel sleepy. Adenosine thus facilitates sleep and dilates the blood vessels, probably to ensure good oxygenation during sleep.

Caffeine acts as an adenosine-receptor antagonist. This means that it binds to these same receptors but without reducing neural activity. Fewer receptors are thus available to the natural “braking” action of adenosine, and neural activity therefore speeds up (see animation).

The activation of numerous neural circuits by caffeine also causes the pituitary gland to secrete hormones that cause the adrenal glands to produce more adrenaline. Adrenalin is the “fight or flight” hormone, so it increases your attention level and gives your entire system an extra burst of energy. This is exactly the effect that many coffee drinkers are looking for.

In general, you get some stimulating effect from every cup of coffee you drink, and any tolerance you build up is minimal. On the other hand, caffeine can create a physical dependency. The symptoms of withdrawal from caffeine begin within one or two days after you stop consuming it. They consist mainly of headaches, nausea, and sleepiness and affect about one out of every two individuals.

Lastly, like most drugs, caffeine increases the production of dopamine in the brain’s pleasure circuits, thus helping to maintain the dependency on this drug, which is consumed daily by 90% of all adults in the U.S.




The sensations of slight euphoria, relaxation, and amplified auditory and visual perceptions produced by marijuana are due almost entirely to its effect on the cannabinoid receptors in the brain. These receptors are present almost everywhere in the brain, and an endogenous molecule that binds to them naturally has been identified: anandamide (Devane et al., 1992). We are thus dealing with the same kind of mechanism as in the case of opiates that bind directly to the receptors for endorphins, the body’s natural morphines.

Anandamide is involved in regulating mood, memory, appetite, pain, cognition, and emotions. When cannabis is introduced into the body, its active ingredient, Delta-9-tetrahydrocannabinol (THC), can therefore interfere with all of these functions.

THC begins this process by binding to the CB1 receptors for anandamide. These receptors then modify the activity of several intracellular enzymes, including cAMP, whose activity they reduce. Less cAMP means less protein kinase A. The reduced activity of this enzyme affects the potassium and calcium channels so as to reduce the amount of neurotransmitters released. The general excitability of the brain’s neural networks is thus reduced as well.

However, in the reward circuit, just as in the case of other drugs, more dopamine is released. As with opiates, this paradoxical increase is explained by the fact that the dopaminergic neurons in this circuit do not have CB1 receptors but are normally inhibited by GABAergic neurons that do have them. The cannabis removes this inhibition by the GABA neurons and hence activates the dopamine neurons.

In chronic consumers of cannabis, the loss of CB1 receptors in the brain’s arteries reduces the flow of blood, and hence of glucose and oxygen, to the brain. The main results are attention deficits, memory loss, and impaired learning ability.


Opiates (heroin, morphine, etc.)

The human body naturally produces its own opiate-like substances and uses them as neurotransmitters. These substances include endorphins, enkephalins, and dynorphins, often collectively known as endogenous opioids. Endogenous opioids are produced within the body and modulate our reactions to painful stimuli. They also regulate vital functions such as hunger and thirst and are involved in mood control, immune response, and other processes.

The reason that opiates such as heroin and morphine affect us so powerfully is that these exogenous substances (originating from outside the body) bind to the same receptors as our endogenous opioids. There are three kinds of receptors widely distributed throughout the brain: mu, delta, and kappa receptors.

These receptors, through second messengers, influence the likelihood that ion channels will open, which in certain cases reduces the excitability of neurons. This reduced excitability is the likely source of the euphoric effect of opiates and appears to be mediated by the mu and delta receptors.

This euphoric effect also appears to involve another mechanism in which the GABA-inhibitory interneurons of the ventral tegmental area come into play. By attaching to their mu receptors, exogenous opioids reduce the amount of GABA released (see animation). Normally, GABA reduces the amount of dopamine released in the nucleus accumbens. By inhibiting this inhibitor, the opiates ultimately increase the amount of dopamine produced and the amount of pleasure felt.

Chronic consumption of opiates inhibits the production of cAMP, but this inhibition is offset in the long run by other cAMP production mechanisms. When no opiates are available, this increased cAMP production capacity comes to the fore and results in neural hyperactivity and the sensation of craving the drug.


Text Attributions

This section contains material adapted from:

The Brain from Top to Bottom website

Content of the site The Brain from Top to Bottom is under copyleft.


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Biological Psychology Copyright © 2024 by Michael J. Hove and Steven A. Martinez is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License, except where otherwise noted.

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