What organ does diazepam affect? Understanding its impact beyond the brain

October 15, 2025 •

4 min read

According to a 2025 study, diazepam exposure was associated with an increased risk of acute kidney injury in children, though this is not its primary function. When considering what organ does diazepam affect most significantly, the answer is the central nervous system (CNS), which includes the brain and spinal cord.

Quick Summary

Diazepam primarily impacts the central nervous system by enhancing the neurotransmitter GABA. The liver is vital for its metabolism, and the kidneys for elimination.

Key Points

Central Nervous System: Diazepam's primary effects are on the brain and spinal cord, where it enhances the calming neurotransmitter GABA to produce anxiolytic, sedative, muscle relaxant, and anticonvulsant effects.
The Liver's Role: The liver is responsible for metabolizing diazepam into active, long-lasting metabolites. This process is impaired in individuals with liver disease, leading to increased drug accumulation and adverse effects.
The Kidneys and Elimination: The kidneys are vital for the excretion of diazepam's metabolites. Renal impairment can slow this process, increasing the risk of toxicity, and recent research points to a potential link with acute kidney injury.
Respiratory Depression Risk: As a CNS depressant, diazepam can slow breathing, a significant risk particularly at high doses or when combined with other depressants like alcohol or opioids.
Systemic Side Effects: The multi-organ involvement of diazepam can lead to systemic side effects, including cognitive issues like amnesia, and potential cardiovascular effects, particularly in overdose situations.

The Central Nervous System: Diazepam's Primary Target

The central nervous system (CNS), encompassing the brain and spinal cord, is the primary target organ for diazepam's therapeutic effects. Diazepam, a benzodiazepine, achieves its calming and sedative effects by enhancing the activity of gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the CNS. It does this by binding to specific benzodiazepine sites on the GABA-A receptor, altering its shape and making it more receptive to GABA. This mechanism leads to several key effects:

Anxiolytic effects: By slowing down nerve signals, diazepam reduces the overactive brain signals associated with anxiety. This can lead to a reduction in both the mental and physical symptoms of anxiety, such as restlessness and sleep disturbances.
Sedative and hypnotic effects: The enhancement of GABA's inhibitory action produces a sedative effect, causing drowsiness and promoting sleep. For this reason, diazepam is used for insomnia and as a pre-medication before surgery.
Anticonvulsant effects: By blocking abnormal electrical signals in the brain, diazepam can effectively stop seizures. This is why it is used for status epilepticus, a severe type of seizure.
Muscle relaxant effects: The drug acts on GABA receptors in the spinal cord, blocking nerve signals that cause unnecessary muscle contraction. This helps relieve muscle spasms.
Anterograde amnesia: A significant side effect of diazepam is anterograde amnesia, an impaired ability to form new memories after the drug is administered. This is believed to result from increased inhibition in the hippocampus, a brain region critical for memory consolidation.

Potential CNS Side Effects

While diazepam's effects on the CNS provide therapeutic benefits, they can also lead to side effects such as drowsiness, dizziness, confusion, and impaired coordination. These effects are more pronounced with higher doses and long-term use. Chronic use can lead to dependency and tolerance, requiring higher doses for the same effect. Abrupt discontinuation after prolonged use can trigger severe withdrawal symptoms, including seizures and hallucinations.

The Liver: Metabolism and Potential for Injury

After administration, diazepam is absorbed and transported to the liver, the primary organ responsible for its metabolism. The liver uses enzymes, primarily CYP2C19 and CYP3A4, to break down diazepam into several active metabolites, including nordazepam and temazepam. These metabolites also have sedative and anxiolytic effects, but they have a longer half-life, meaning they remain in the body for an extended period.

For most healthy individuals, diazepam use does not cause liver damage. However, for people with pre-existing liver disease, the body's ability to metabolize the drug is impaired. This can lead to an accumulation of diazepam and its metabolites in the body, increasing the risk of adverse effects. In extremely rare cases, clinically apparent liver injury has been reported, with the pattern typically being cholestatic or mixed.

The Kidneys: Elimination of Metabolites

Once diazepam is metabolized by the liver, its inactive products are eliminated from the body primarily through the kidneys via urine. The kidneys are therefore crucial for clearing the drug and its byproducts from the system. As with liver issues, individuals with renal impairment must be monitored carefully, as reduced kidney function can lead to an accumulation of diazepam's metabolites.

Recent research has brought new attention to the drug's impact on kidneys. A 2025 study found that diazepam exposure was associated with an increased risk of acute kidney injury (AKI) in children. While the exact mechanism is still being investigated, this highlights the importance of careful dosing and monitoring in all patients, especially those with pre-existing kidney issues or who are taking other potentially nephrotoxic drugs. A case report from 1985 also suggested a link between diazepam and allergic interstitial nephritis, which reversed upon discontinuation of the drug.

The Respiratory System: Risk of Depression

While diazepam's primary effects are on the CNS, its influence can extend to the respiratory system. As a central nervous system depressant, diazepam can slow down breathing, especially at high doses or when combined with other substances that depress the CNS, such as alcohol or opioids. This respiratory depression can be severe and even fatal in cases of overdose. In patients with pre-existing lung conditions, such as chronic obstructive pulmonary disease (COPD), the risk of respiratory depression is heightened.

Comparison of Diazepam's Effects on Key Organ Systems


Organ System	Primary Effect	Mechanism	Risks/Side Effects
Central Nervous System	Calming, sedative, muscle relaxation, anticonvulsant	Enhances GABA-A receptor activity, increasing inhibitory signals.	Drowsiness, dizziness, cognitive impairment, anterograde amnesia, dependence, withdrawal.
Liver	Metabolism of diazepam and its active metabolites	Cytochrome P450 enzymes (CYP2C19, CYP3A4) break down the drug.	Impaired metabolism with pre-existing liver disease; rare but possible drug-induced liver injury.
Kidneys	Elimination of metabolites	Filtration of inactive metabolites from the blood for excretion in urine.	Accumulation of metabolites with renal impairment; increased risk of acute kidney injury (especially in children).
Respiratory System	Depression of respiratory drive	General CNS depressant effect, slowing down breathing rate.	Respiratory depression, especially in high doses or with co-ingestion of other depressants.

Conclusion: A Multi-Organ Impact Requires Care

While the CNS is the main site of action for diazepam, its journey through the body involves and affects several other vital organs. The liver metabolizes the drug, and the kidneys are responsible for clearing it from the system. As such, any pre-existing conditions involving these organs must be carefully considered by a healthcare professional before and during treatment. The potential for respiratory depression also highlights the need for careful use, particularly avoiding combination with other CNS depressants. Understanding the full multi-organ impact of diazepam is crucial for both managing its therapeutic benefits and mitigating its potential risks, a process best managed under professional medical supervision, as detailed in the NCBI Bookshelf entry on the drug.

Frequently Asked Questions

When you take diazepam, it binds to special sites on GABA-A receptors in the brain. This enhances the effect of GABA, an inhibitory neurotransmitter, which slows down nerve signals. This produces a calming effect that can reduce anxiety, relax muscles, and prevent seizures.

Long-term, heavy use of diazepam can have powerful and potentially permanent effects on the brain, including cognitive issues like memory loss. Chronic use can also lead to dependence and withdrawal symptoms, which can be severe.

Clinically apparent liver injury from diazepam is exceedingly rare. However, as the liver metabolizes the drug, individuals with pre-existing liver disease have an increased risk of complications due to the drug and its metabolites accumulating in the body.

The kidneys are responsible for eliminating the metabolites of diazepam from the body. Individuals with renal impairment need to use the drug with caution, as it can accumulate. Some studies also suggest a link to acute kidney injury, particularly in children.

Respiratory depression is the slowing down of breathing. It is a serious risk with diazepam, especially at high doses or when combined with other CNS depressants like alcohol or opioids. In overdose cases, it can be fatal.

Yes, diazepam has well-documented amnestic properties, particularly causing anterograde amnesia, which is the inability to form new memories after the drug is administered. Long-term use can also contribute to memory loss.

Patients with chronic lung disease or other breathing problems should use diazepam with caution, as it can cause respiratory depression. Dosage and patient condition must be carefully monitored by a healthcare provider.