One pathway important to understanding the effects of drugs on the brain is called the reward pathway. The reward pathway involves several parts of the brain: the ventral tegmental area (VTA), the nucleus accumbens, and the prefrontal cortex.
The central job of the reward pathway is to make us feel good when we engage in behaviors that are necessary for our survival. These beneficial behaviors include eating, drinking and sex. As a person introduces illicit substances into their body, unfortunately, this pathway is also triggered from substance use.
As a person continues to use drugs, the brain adjusts to the excess dopamine by making less of it and/or reducing the ability of cells in the reward circuit to respond to it. This reduces the high that the person feels compared to the high they felt when first taking the drug—an effect known as tolerance. They might take more of the drug, trying to achieve the same dopamine high. It can also cause them to get less pleasure from other things they once enjoyed, like food or social activities.
Long-term use also causes changes in other brain chemical systems and circuits as well, affecting functions that include:
What Is Neurotransmission?
A person reads. The words on the page enter the brain through the eyes and are converted into information that is relayed, from one neuron to the next, to regions that process visual input and attach meaning and memory. When inside neurons, the information takes the form of an electrical signal. To cross the tiny gap, or synapse, that separates one neuron from the next, the information takes the form of a chemical signal. The specialized molecules that carry the signals across the synapses are called neurotransmitters.
The ebb and flow of neurotransmitters—neurotransmission—is thus an essential feature of the brain’s response to experience and the environment. To grasp the basic idea of neurotransmission, think of a computer. A computer consists of basic units, semiconductors, which are organized into circuits; it processes information by relaying an electric current from unit to unit; the amount of current and its route through the circuitry determine the final output. The brain’s corresponding basic units are the neurons—86 billion of them. The brain relays information from neuron to neuron using electricity and neurotransmitters; the volume of these signals and their routes through the organ determine what we perceive, think, feel, and do.
Of course, the brain, a living organ, is much more complex and capable than any machine. Neurons respond with greater versatility to more types of input than any semiconductor; they also can change, grow, and reconfigure their own circuits.
What Changes Occur With Chronic Drug Use?
During the early phase of an individual’s drug experimentation, neurotransmission normalizes as intoxication wears off and the substance leaves the brain. Eventually, however, repeated drug use leads to changes in neuronal structure and function that cause long-lasting or permanent neurotransmission abnormalities. These alterations underlie drug tolerance (where higher doses of the drug are needed to produce the same effect), withdrawal, addiction, and other persistent consequences.
Some longer-term changes begin as adjustments to compensate for drug-induced increases in neurotransmitter signaling intensity. For example, the brain responds to repeated drug-induced massive dopamine surges in part by reducing its complement of dopamine receptors. This alleviates the drugs’ overstimulation of the dopamine system, but also contributes to features of drug dependence (e.g., susceptibility to drug withdrawal) and of addiction (e.g., compromised ability to respond to normal dopamine fluctuations produced by natural rewards). Similarly, methadone and some other opioids induce neurons to retract a portion of their mu opioid receptors, making them unavailable for further stimulation. The retraction is short-lived, after which the receptors return to the neuron surface, restoring normal responsiveness to subsequent stimulation. This dynamic of reducing and then restoring receptor availability may thwart the development of tolerance to these drugs. (Morphine, in contrast, does not cause receptors to retract, and the resulting opioid overstimulation triggers intracellular adjustments that appear to promote opioid tolerance.)
The drug-related mechanisms producing cumulative changes in neurotransmission sometimes are epigenetic in nature. While a drug cannot change a person’s genes, drugs can prod some genes to increase or decrease their production of proteins, leading to changes in neuron function or even actual reshaping of the physical structure of neurons. For example, in mice, cocaine alters important genetic transcription factors and the expression of hundreds of genes. Some of the resulting changes in the brain’s complement of proteins have been associated with increased drug-seeking and addiction-like behaviors in animals. Other changes, such as proliferation of new dendrites (branchlike structures on neurons that feature neurotransmitter receptors on their surface) may be compensatory. Some epigenetic changes can be passed down to the next generation, and one study found that the offspring of rats exposed to THC—the main psychotropic component of marijuana—have alterations in glutamate and cannabinoid receptor formation that affects their responses to heroin.
Some drugs are toxic to neurons, and the effect accumulates with repeated exposures. For example, the club drug methylenedioxymethamphetamine (MDMA [Ecstasy/Molly]) damages axons (the branch of a neuron that releases its neurotransmitter into the synapse) that release serotonin; the result is disruption of serotonin neurotransmission that may underlie the memory problems that are sometimes experienced by heavy users. Similarly, methamphetamine damage to dopamine-releasing neurons can cause significant defects in thinking and motor skills; with abstinence, dopamine function can partially recover, but the extent to which cognitive and motor capabilities can recover remains unclear. Source
This graph above depicts a Google trend of drug use by country. The United States is the leading country in drug use.