CHAPTER 1
Basic Concepts of Neuroscience and Neuropharmacology
Before addressing issues of psychoactive drugs in general and those with psychedelic properties in particular, it is necessary to be clear about some basic concepts of neuroscience1 that will allow us to understand both drugs’ and specifically psychedelics’ basic mechanisms of action and the elementary terminology necessary to be able to speak about them properly. In addition, you can find some key definitions in the glossary. Let’s start by briefly exploring the terrain.
THE BRAIN AND CENTRAL NERVOUS SYSTEM
In the human body, our thoughts, emotions, and behaviors originate in the most complex and mysterious organ we have: the brain.
This organ is located inside our head and is part of what is known as the nervous system, a system that runs throughout our body and performs numerous functions for our survival, such as regulating and maintaining each vital function, controlling voluntary movements, speech, intelligence, memory, emotions, and processing the information received through the senses. It is the organ where the mind and consciousness of the individual reside.
The brain is the directing part of this complex nerve network that extends throughout the body and allows it to carry out its important functions. Based on these functions and the anatomical structure, human beings divide our nervous system into the central nervous system, or CNS (which includes the brain and spinal cord), and the peripheral nervous system, or PNS (consisting of all the peripheral nerves that are outside the CNS but connect to it).
Both the central nervous system and the peripheral nervous system are made up of many different elements and subunits, but the most famous and important are highly specialized cells known as neurons.
NEURONS, SYNAPSES, NEUROTRANSMITTERS, AND NEURORECEPTORS
The neuron is the specialized cell that makes up the tissue of the nervous system. In the human brain there are around 80,000 million neurons interconnected through a huge tangle of physical "wires" that extend from their bodies and link them together to form a network.
These wires, called axons (which are long and send messages) and dendrites (which are shorter and receive messages), allow communication between the cells through chemical and electrical signals. These electrical impulses that travel through the neuron as if it were a wire are known as action potentials, and they could be compared to telegraph messages using Morse code. They are electrical impulses that can propagate within the neuronal "wiring" of the brain and travel long distances through the nerves of the body at very high speeds.
In any cable network there must be "connectors" that link to each other and to other devices. In the nervous system, the connectors that link the axon of a sending neuron with the dendrites of a receiving neuron are known as synapses, and they are the points where neurons almost touch. But, as they do not really touch each other most of the time, upon reaching these points, the electricity that traveled through the axons (wires) makes some chemical signals "jump" from one neuron’s axon to the next neuron’s dendrite; these chemicals are the neurotransmitters. So, although neurons use electricity to send messages within the different parts of their elongated body, when it comes to passing that message to other neurons, they do so mostly by "splashing" each other with chemicals, called neurotransmitters, which are released when that message in the form of an electrical impulse reaches the end of the axon and must pass on to the next neuron. Although it seems impossible, this process that can seem so complex occurs in intervals of milliseconds, and each neuron can be connected to 10,000 others.
The chemical signals between neurons (neurotransmitters) are quite varied and can send very different messages to the next neuron. We could say that they act as different "keys" that are released by the sending neuron (presynaptic neuron) to the synapse (the "connector") and will only fit in some specific "locks" (called neuronal receptors or neuroreceptors) of the receiving neuron (the postsynaptic neuron). Depending on the type of "doors" the sending neuron wants to open or close in the receiving neuron, the sending neuron will release one type of key or another.
The substances used by the body to send "non-nerve" messages over long distances or throughout the body are known as hormones,2 while neurotransmitters are substances that also send messages but only between neurons and over very short distances in synapses, producing effects that can be immediate, short, and very localized, or propagated throughout the entire neural network. Some hormones that are generally used by the body can also be neurotransmitters, and some neurotransmitters behave like hormones. However, the key is that the electricity we generally associate with neurons and the nervous system in reality only occurs within each neuron; the communication between different neurons is fundamentally chemical and based on neurotransmitters, and they are involved in various processes. For example, some of the most famous neurotransmitters are serotonin, known to many as the "hormone of happiness" (although this is only partially true), or dopamine.
Just as there are multiple neurotransmitters that perform different functions, there are several types of neuroreceptors in the membranes of neurons, which are protein structures that act as locks for these "keys," and that are activated or not depending on the specific neurotransmitter (key) that comes close to them. For the same neurotransmitter there can be several subtypes of neuroreceptor, so it can even be said that some of them are "master keys" insofar as, sometimes, they not only can open a single lock but several of the same type, although they do not always turn equally well in all locks. In neuronal communication, what is ultimately important is not so much the neurotransmitter but what happens at the level of the receptors in the postsynaptic neuron, the locks that are being open, and how they do it.
These neurotransmitters and neuroreceptors can serve many different functions both inside and outside the brain, and, depending on the specific region of the brain or neuronal circuit on which they act, they can even be involved in completely opposite processes; so the generalization that a neurotransmitter only has a specific effect is overly simplistic and not always accurate.
There are many other neurotransmitters and neuroreceptors, as well as other types of molecules that can act as neurotransmitters, although they are not released in the same way, such as oxytocin (related to emotional bonding, childbirth, and breastfeeding) or endorphins (related to analgesia and acting on opioid receptors).
As we can see, all this is not as simple as saying that serotonin is the hormone of happiness, but rather that it acts as a modulator with various functions depending on which of its fourteen different receptors it is activating and in which brain region, or neural network, it is found. Other neurotransmitters with fewer receptors can fulfill functions that are easier to explain, such as glutamate, which activates neurons and increases their electrical excitability, or GABA, which "turns them off " or reduces their electrical excitability. But these effects at the neuronal level do not always translate to the entire brain, and the result also depends on the specific networks that are being activated or deactivated.
Why is it so important to talk about how neurons communicate in this book’s introduction? Because it is this chemical communication between neurons that allows the brain and the other parts of the nervous system to carry out all their functions. Just as it happens inside a computer, the operation of which depends not only on the work of one of its parts but on the interaction (communication) between many of them, a neuron in our brain does not "think"; the neuronal network does. It is at this point that we can start talking about how exogenous molecules,3 like psychoactive substances, influence these processes.
NEUROPHARMACOLOGY
A drug is a molecule that is considered "bioactive" because, due to its structure and chemical configuration, it can interact with protein macromolecules, generally called receptors (locks), located in the membrane, cytoplasm, or nucleus of a cell (such as neurons, for example), giving rise to an action and a noticeable effect. For example, when we take ibuprofen, it reduces pain and inflammation. For this reason, pharmacology is the branch of science that studies how the drug (be it a medicine bought in a pharmacy, a medicinal plant, or a beer served at a bar) interacts with the body—its actions, effects and properties.
Neuropharmacology in particular studies how some drugs act specifically on neurons and the nervous system. Drugs with the ability to interact with our neurons and nervous tissues are called "psychoactive substances" or "psychoactive drugs," and sometimes simply "drugs," and they cover a wide range of molecules such as alcohol, anxiolytics, analgesics, tobacco, cocaine, coffee, LSD, and MDMA.