Drugs That Affect the Brain and Its Chemicals
The trend in addiction research and treatment has been to view addiction as a biological phenomenon (a brain disease) that results in an individual being unable to resist urges to use their drug of choice. While there is some validity to this viewpoint, it is not entirely valid. Many researchers now refer to the addicted brain and concentrate on biological processes as opposed to concentrating on the actual person. It is important to understand that people develop addictions (substance use disorders) and that brains actually do not become addicted, but people become addicted.
The development of a substance use disorder is a complex phenomenon that includes biological influences, personal choice, social influences, and past experience. No person is born with a substance use disorder; this even includes infants who are born to mothers who are addicts and have physical dependence on drugs or alcohol because physical dependence alone is not sufficient for a diagnosis of a substance use disorder. These disorders develop in a person as a result various combinations of these factors.
Neuroplasticity and Addictive BehaviorThe term neuroplasticity has become popular with the lay media. This concept has been around for quite a long time and simply refers to how the brain changes as a result of experience. Individuals reading this article are experiencing minor brain changes as they read. The brain adapts to environmental experience in order to make it more efficient at performing tasks that are repeated, to maintain balance within the system, and to learn to correct mistakes.
The brain changes as a result of nearly any environmental experience, and experiences that are repeated over and over result in more lasting changes, even if these experiences are detrimental. The relative level of change that occurs in the brain depends on how often the experience has occurred and for how long a time the individual has had repeated experiences.
Many of the changes that occur in the brain may not fully resolve. For instance, one of the best examples of this comes from the early work of the memory researcher Hermann Ebbinghaus. Ebbinghaus memorized long lists of nonsense words (two consonants and a vowel) and then did not practice them for years. Years later, he found that was able to learn words that had been memorized previously far more easily than new words, thus inferring that the brain changes that occurred as a result of attempting to memorize these old nonsense words were still intact. The use of drugs and for alcohol also results in changes in an individual’s brain.
Use of Drugs and Their Effects on the Reward System of the Brain
One of the earliest studies that helped to delineate the neurobiology of addictive behaviors occurred in the 1950s when researchers planted electrodes in the brains of rodents and stimulated them with an electrical current. Researchers James Olds and Peter Milner found that when the area of the brain known as the septal area was stimulated after rodents pressed a lever, the rodents would continue to press the lever in an attempt to receive further stimulation to this area of the brain. Stimulating other areas of the brain after the lever was pressed did not achieve this result.
The septal area of the brain became widely referred to as the “pleasure center of the brain,” although this is a bit of a misnomer. Subsequent research found that the reward centers of the brain (the area of the brain that is activated when an individual is reinforced for performing behaviors) primarily involves the use of the neurotransmitter dopamine.
Two specific brain pathways that were important in addictive behaviors were identified, although numerous areas of the brain have been studied regarding their contribution to the development of addictive behaviors: the mesocortical brain pathway and the mesolimbic brain pathway. Both of these areas of the brain are connected to various other areas of the brain, and they are involved with aspects of directing attention, cognition, emotion, and motivation, and repeating reinforcing behaviors. These brain pathways are also involved in complex thinking abilities, impulse control, and judgment.Most drugs of abuse activate these brain pathways and activate dopamine indirectly as a result of being reinforced for using drugs or alcohol. When these pathways are repeatedly activated because individuals want to receive the feelings of euphoria associated with drug use, their structure is also altered. When a specific brain pathway is repeatedly activated and the neurotransmitter is released in large quantities in the brain, the system attempts to reduce the number of neuron receptors for this neurotransmitter in order to maintain balance (a process known as downregulation). Stimulant drugs like methamphetamine and cocaine activate dopaminergic pathways directly by increasing the amount of dopamine in the system and indirectly as a result of reinforcement. These drugs often result in significant down regulation of dopamine neurons when they are abused. Other neurotransmitters that may be inhibited as a result of the release of dopamine may experience an upregulation (more receptor sites) to maintain overall balance.
Eventually, these changes can lead to severe issues with judgment, problems with impulse control, and a loss of actual pleasure when an individual uses the drug but an increased desire to get the drug. This sounds a bit complex and it is, but most individuals who have used drugs or alcohol can relate to the old notion that “the first high is the best,” which reflects this process.
Because dopamine is a neurotransmitter that is activated whenever an individual is reinforced for repeating a behavior, the repeated use of drugs or alcohol involves activating areas of the brain that rely on dopamine. As mentioned above, the actions of some drugs also directly affect the levels of dopamine in the system, and this results in even greater activation of the neurotransmitter. Over time, structural changes may occur in the neurons that use dopamine that can lead to significant cognitive issues, such as difficulty experiencing pleasure (as a result of the down regulation of dopamine neurons), issues with self-control, and other detrimental effects.
Other Neurotransmitters That Are Activated by Drug Use
While dopamine is involved in nearly all instances of drug abuse, it is not the major neurotransmitter activated by many drugs. The same principles of upregulation and downregulation of receptor sites apply with these other drugs of abuse that may have actions on different neurotransmitter systems. The research regarding how drugs affect specific neurotransmitters is still in its infancy, but there are some general principles that can be mentioned.
Narcotic or opiate drugs like heroin, Vicodin (acetaminophen and hydrocodone), OxyContin (oxycodone), codeine, etc., have direct effects on endorphins and enkephalins. These neurotransmitters are associated with naturally controlling levels of pain and stress.
Tobacco products activate the nicotinic cholinergic receptors in the brain; your brain has readymade neurons that are specialized for nicotine.
Alcohol is believed to play a major portion in activating the inhibitory neurotransmitter GABA (gamma-aminobutyric acid) as well as blocking the mechanism of the excitatory neurotransmitter NMDA (N-methyl-D-asparate, a subtype of glutamate) as well as affecting levels of serotonin.
Methamphetamine (crystal meth) and cocaine use is known to increase the actions of excitatory neurotransmitters, such as norepinephrine and NMDA, and boost dopamine levels.
Benzodiazepines, such as Valium (diazepam) and numerous others, are also central nervous system depressants that primarily work on the inhibitory neurotransmitter GABA.
Phencyclidine (PCP) is believed to affect numerous neurotransmitters, including norepinephrine, serotonin, NMDA, and dopamine.
In addition to affecting dopamine, the use of cannabis products results in the activation of numerous neurotransmitters, particularly transmitters known as cannabinoids receptors located in the cerebral cortex, the limbic system (primarily concerned with the experience of emotion and with memory), and the cerebellum (a complex structure at the back of the brain that is involved in various areas of cognition and movement).
Ecstasy (MDMA) results in a massive release of the neurotransmitters serotonin and norepinephrine as well as a release of dopamine. The release of serotonin is believed to account for the mood-enhancing effects of ecstasy.
Habitually using drugs in combination can result in differential effects on the neurotransmitter systems in the brain and lead to significant structural changes.
Individuals who repeatedly use these drugs of abuse will experience structural changes in their brain over time. Drugs like ecstasy, cocaine, and methamphetamine often result in massive releases of neurotransmitters like serotonin and dopamine when abused, and once an individual has stopped using the drug, the levels of these neurotransmitters are depleted. This results in the potential for significant damage to an individual’s brain and the experience of an emotional letdown (e.g., apathy, severe depression, etc.) after the individual has stopped using the drug.
Over time, these alterations of neurotransmitters in the brain as a result of drug use (significant increases of neurotransmitters due to the mechanism of the drug followed by massive depletions of neurotransmitters after the person stops using the drug for a while) can result in abundant structural changes in the brain that can have detrimental effects on the individual’s cognition and mood. It is not unusual for individuals to experience depression, anxiety, problems with attention, trouble forming new memories, and longer-term problems as a result of massive structural damage that the use of drugs and/or alcohol produce over time. Many drugs of abuse are associated with development of severe chronic conditions, such as dementia, ataxia (problems with movement), seizure disorders, etc., even after the person has discontinued them.
Just Try and Stop
One of the features of chronic drug abuse that has contributed to the notion that addiction is a brain disease is the observation that once an individual has developed a moderate to severe substance use disorder, it is extremely hard for them to stop using their drug of choice. Because relapse is so common, many researchers have concluded that the structural changes that occur in the brain as a result of chronic drug abuse lead to this extreme difficulty in recovery. There are numerous theories as to why this may happen.Positive incentive theory is relatively straightforward. This theory posits that individuals experience the overwhelming anticipation of pleasure that giving in to their drug cravings will induce. This is based on biological factors, such as an increase in neurotransmitter availability when the drug taken (increase in pleasure), and an increase in cravings when the drug is not being used (decrease in anticipated pleasure). The incentive sensitization model posits that as an individual develops tolerance to their drug of choice, they experience a decline in the actual level of pleasure they get when they use the drug. Individuals begin to crave using the drug as a response to the anticipated pleasure they believe they will get from use of the drug. These sensations are based on structural changes in the brain and result in the idea that it is not the actual euphoria one receives from using their substance of choice that drives their continued use (because this declines over time and with repeated usage), but the anticipated pleasure they think they will get that continues to drive their drug use. Priming is a behavioral theory that explains how an individual’s brain can become sensitized and activated by cues or “triggers.” Triggers or cues are environmental reminders that an individual has associated with their experience of using a drug or drinking alcohol. When an individual is exposed to one of these situations, their brain becomes activated similarly to the way that it would be activated if they actually used the drug, and the individual begins to crave the drug. As anyone in recovery knows, triggers are very hard to avoid, and individuals must develop a plan to deal with them.
Even the development of physical dependence (developing both tolerance and withdrawal syndromes to specific drugs) represents structural changes that occur with repeated use of the drug. Tolerance to a drug occurs as the individual system begins to adjust to continually receiving the drug, and the person finds they need more of the drug over time to achieve effects that were achieved at lower doses, most likely due to down-regulation of receptor cites.
Withdrawal symptoms occur as a result of an individual central nervous system attempting to maintain balance despite chronic drug abuse. The neurotransmitters that are directly activated by use of the drug, such as dopamine, are down regulated, whereas other structural areas that engage in functions that produce the opposite effect of the drug (e.g., anxiety, depression, etc.) may be up regulated. When an individual stops using the drug, their system is thrown out of balance, and these opposing processes become dominant, resulting in withdrawal. Individuals undergoing withdrawal symptoms are motivated to continue using their drug of choice to relieve these unpleasant symptoms.
How Recovery Changes the Brain
When an individual is able to stop using their drug of choice, different structural changes begin to occur. People learn to deal with stress on a positive basis, cope with cravings, and are able to negotiate the withdrawal syndrome with the assistance of a medical detox program. All of these activities, including medically assisted treatments, participating in therapy and social support groups, etc., result in changes in an individual’s neuroanatomy that help them to stop using drugs or alcohol.
However, recall the case of Hermann Ebbinghaus. Even some time after not practicing his nonsense words, he found he was able to learn words that he had previously memorized far more quickly than the new words he was not exposed to previously. Likewise, many individuals who relapse find that they very quickly return to their old ways, and they often report that their addictive behaviors are even worse during relapse than they were initially. This makes an important case for abstinence from drugs and alcohol as opposed to attempting a program of controlled or moderate use for individuals who have had moderate to severe substance use disorders.
Individuals in recovery need to continue to participate in treatment-related activities that help them to remain abstinent for years following initially stopping use of drugs or alcohol. Many individuals remain involved in recovery-related activities, such as social support group participation, for decades or even for life. This continued exposure results in significant structural changes in the brain that can help to counteract the changes incurred during active addiction. Many individuals remain at an increased risk to return to old behaviors if they begin using drugs or alcohol even after years of abstinence.
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