Many drugs affect GABA levels in the brain, such as alcohol, benzodiazepines, barbiturates, z-drugs, and gabapentin.
How Does GABA Work in the Brain?
Gamma-aminobutyric acid, or GABA, is the main inhibitory neurotransmitter in the human brain. GABA receptors are some of the most common neurons in the mammalian nervous system, including the human central nervous system (CNS). It is estimated that about 40 percent of the synapses in the brain uses GABA, so they have GABA receptors.
As an inhibitory neurotransmitter, GABA slows down reactions or communication between neurons. This is in contrast to excitatory neurotransmitters like glutamate, which augment the nerve impulses in the neuron, leading to faster communication.
This neurotransmitter has important effects on the brain’s regular functioning. Too much GABA, and you will be physically slower, lower energy, relaxed, or sleepy. Too little GABA, and you will struggle with anxiety, panic attacks, or even seizures.
Substances and GABA Levels
Many mental health conditions need a balance of GABA for you to feel normal, so there are several medications that adjust GABA levels in different ways. There are also some recreational drugs that can cause surges of GABA, which in turn cause a release of mood-changing neurotransmitters like dopamine and serotonin. This can lead to compulsive behaviors, repeated substance abuse, and eventual addiction.
When GABA is boosted in the brain, neurons fire less often, and there is a release of dopamine into the nucleus accumbens, the reward center in the brain. This dopamine surge makes you feel happy and euphoric. When this mood-elevating neurotransmitter triggers the reward center, you will associate good outcomes with the substance that triggered it. In the case of intoxicating drugs, either prescription or non-medical, this surge can lead to compulsive behaviors to trigger more dopamine surges.
With so many substances affecting GABA, it is important to understand how prescription use, recreational misuse, or abuse of these drugs can change brain chemistry and require different approaches to treatment. GABA(A) receptor drugs are the most common, while there are a few GABA(B) receptor drugs. Intoxicating substances like alcohol tend to have a broad effect on GABA receptors, while newer prescription drugs often have a targeted approach to reduce the risk of addiction.
Which Substances Bind to GABA Receptors On Neurons?
There are several drugs that impact GABA levels in the brain, and many of these are prescription medications that treat anxiety disorders, panic attacks, phobias, seizure disorders like epilepsy, and withdrawal symptoms from other substances, like alcohol.
The most widely used substances that impact how the brain manages the GABA neurotransmitter include:
Alcohol
While this recreational intoxicant is legal for adults in the United States who are 21 and older, it is also one of the most widely abused recreational drugs in the country. Different types of alcohol have been part of human civilization for thousands of years, although the most common forms used today are:
- Beer, which is 4 to 6 percent alcohol by volume (ABV) per 12-ounce serving.
- Wine, which is between 7 and 15 percent ABV per 5-ounce serving.
- Hard liquor, which is around 40 to 95 percent ABV per 1.5-ounce serving.
The average, healthy adult metabolizes one serving of alcohol in about one hour. Drinking more than this means the liver does not process alcohol very quickly, and it remains in the blood for longer, so you will feel drunk.
People who drink alcohol, even casually and safely, want the relaxing effects of the substance, which can lead to slowed reaction times and reflexes, slowed heart rate, sleepiness, and lowered inhibitions. These effects are caused by metabolites from alcohol binding to receptors in the brain and allowing more GABA to be available to slow down firing between neurons.
In large amounts, alcohol can lead to memory problems, liver damage, and poisoning. Drinking a lot of alcohol over a long time can cause damage to the body and brain. This intoxicant is very toxic to several major organ systems.
If you become dependent on it, some of the withdrawal symptoms can be deadly. One such withdrawal condition is delirium tremens, which involves the following symptoms:
- Body tremors
- Delirium
- Intense confusion
- Hallucinations
- Extreme sleepiness
- Fever
- Seizures
Because alcohol abuse and dependence can have such a strong impact on GABA in the brain, detox must be carefully managed by medical professionals. It may involve small, supervised doses of other sedatives that manage GABA, like benzodiazepines. However, some of these drugs are addictive, so they must be managed carefully.
Benzodiazepines
This is a class of sedative drugs designed to treat anxiety, insomnia, panic attacks, and some types of seizure disorders. There are three basic types of benzodiazepines:
- Short-acting
- Intermediate
- Long-acting
Depending on how the medication is prescribed, the drug may be taken as needed to manage a panic attack, help the person go to sleep one night, or manage a seizure disorder.
With few exceptions, people who receive prescriptions for benzodiazepines should not take them for more than a few weeks, and they should only take them as prescribed by their supervising physician because they can quickly lead to physical dependence and tolerance. This is associated with their effect on GABA in the brain.
People who struggle with general anxiety, anxiety associated with depression, or insomnia may have high levels of stress because their brains naturally produce less GABA. When a drug adds more GABA, the feeling of relaxation, happiness, and relief can lead to compulsive behaviors or emotional dependence on the drug. Then, the brain becomes used to the drug’s presence, and it comes to rely on it to manage any GABA in the brain. Eventually, a larger dose is needed to release an amount of GABA that will allow the person to feel calm or “normal.”
Benzodiazepines target GABA(A) receptors more specifically than earlier forms of sedatives, like barbiturates. Many people abuse benzodiazepines, especially alongside other addictions like opioids or alcohol. These people need medically supervised detox and rehabilitation.
Barbiturates
These medications were once prescribed for anxiety, panic, insomnia, epilepsy, to relax muscles, and as part of anesthesia. While they are still sometimes used for seizures, muscle relaxing, and anesthesia, they are much rarer now due to their high rates of addiction, abuse, and overdose.
Barbiturates were some of the first sedative medications that targeted the GABA receptors, acting primarily on the GABA(A) receptors, which are also involved in the brain’s reward system.
Barbiturate abuse has declined since the 1970s, and they are rarely found on the black market or as prescription drugs. Other sedatives are much more available, and newer versions of sedative drugs are easier to manufacture in clandestine laboratories. Drugs like benzodiazepines or sedative-hypnotics are more available through diversion or illegal manufacture, so barbiturates are less desired.
Gabapentin
This medication was approved by the U.S. Food and Drug Administration (FDA) in 1993, and at the time, it was considered a “miracle drug” in the treatment of epilepsy and nerve pain from shingles. It is most famously sold under the brand name Neurontin, but generic gabapentin has been available since 2004.
It is still one of the most popular prescription medications in the U.S., used in the treatment of several nerve-related conditions. Because of its availability, it is also widely abused by those who receive it as a prescription, people who steal it from friends or family, or those who get it on the black market.
Since gabapentin works on the GABA receptors to manage neuron transmissions, it is also abused alongside other drugs, often to enhance the effects of the main substance of abuse. Gabapentin has been associated with opioid abuse in several fatal overdoses, where the drug may have been abused to make the opioid high more intense.
Z-Drugs
Medications in this group include Ambien and Lunesta — prescription drugs that are used to manage insomnia. Like benzodiazepines, z-drugs were designed for short-term treatment — a week or two at most of regular use, as chronic insomnia is treated more effectively with behavioral counseling.
While there are fewer reports of addiction to z-drugs, there are serious side effects from taking these substances, including driving while drowsy or drugged and experiencing parasomnias like walking, eating, or driving while asleep.
Treatment for Substance Abuse with GABA-Affecting Drugs
While some newer versions of GABA-managing drugs, like z-drugs or gabapentin, may or may not be addictive, these substances still lead to physical dependence, even when taken as prescribed. This means that your doctor will need to oversee the process of withdrawing from these prescriptions, which should involve tapering slowly until your body no longer needs them.
If you take any prescription drugs outside of how your doctor prescribes it — in larger doses, more often, or more regularly — this is a form of misuse, and that puts you at physical risk of dependence. Other drugs, like barbiturates, benzodiazepines, and alcohol, have long histories of addiction. If you find you cannot control your actions around these substances, get help from addiction specialists to safely detox and find recovery.
