Yes, benzodiazepines reduce cortisol levels. They suppress both baseline cortisol and the cortisol spikes triggered by stress, though the effect is most pronounced in the short term. With long-term use, the suppression becomes much less significant, and stopping benzodiazepines can cause a rebound surge in cortisol that may partly explain withdrawal symptoms.
How Benzodiazepines Lower Cortisol
Your body produces cortisol through a chain reaction that starts in the brain. A region called the hypothalamus releases a signaling hormone, which tells the pituitary gland to release another signal, which finally tells the adrenal glands (sitting on top of your kidneys) to pump out cortisol. This entire chain is called the HPA axis, and it ramps up whenever you’re stressed, anxious, or in pain.
Benzodiazepines work by enhancing the activity of GABA, the brain’s primary calming neurotransmitter. GABA acts as a brake on neural activity, and when benzodiazepines boost its signal, that brake gets applied to the very first step of the cortisol chain. The hypothalamus releases less of its initial signaling hormone, and the whole cascade slows down. The result is lower cortisol output from the adrenal glands.
What Happens With a Single Dose
A single dose of a benzodiazepine can measurably suppress cortisol within hours. In studies comparing different benzodiazepines in healthy volunteers, peak cortisol suppression typically occurs about three hours after taking the drug, though the exact timing varies by compound. Nitrazepam, a longer-acting benzodiazepine, reaches maximum cortisol suppression around three hours, roughly one hour after its blood levels peak. Oxazepam follows a similar timeline but shows a temporary return to baseline cortisol levels before suppression resumes, suggesting the relationship between drug concentration in the blood and cortisol suppression isn’t straightforward.
This cortisol-lowering effect is one reason benzodiazepines are sometimes given before surgery. In studies of pre-operative patients, diazepam and bromazepam both blunted the cortisol spike that normally accompanies the stress of anesthesia and surgery. Patients who received these medications before their procedure showed a smaller rise in cortisol compared to those who received no sedative.
Short-Term vs. Long-Term Use
The cortisol-suppressing effect of benzodiazepines is well established for short-term use, but the picture changes considerably over months and years. A large study from the Netherlands Study of Depression and Anxiety tracked salivary cortisol in people who had been using benzodiazepines daily for a median of about 26 months at a median dose equivalent to 6 mg of diazepam per day.
Daily users did have slightly lower evening cortisol levels compared to non-users, but the difference was small (a statistical effect size of 0.24, which is considered modest). Infrequent users showed an even smaller reduction. More importantly, the study found no significant differences in the cortisol awakening response (the natural surge that happens when you wake up), the overall daily cortisol pattern, or the results of a standard test used to assess HPA axis function. The researchers concluded that long-term benzodiazepine use is not convincingly associated with meaningful changes to the stress hormone system. In other words, the body appears to partially adapt.
Cortisol Rebound During Withdrawal
If benzodiazepines suppress cortisol by putting a GABA-driven brake on the stress system, withdrawal essentially releases that brake all at once. Discontinuing benzodiazepines leads to a rebound activation of the HPA axis, causing cortisol levels to spike.
This rebound isn’t just a lab curiosity. Research on patients with depression who were tapering off benzodiazepines found that those who experienced the most severe withdrawal symptoms also showed significantly higher cortisol and ACTH (the pituitary’s stress signal) responses on testing done before the taper even began. This suggests that people whose stress systems are already more reactive may be especially vulnerable to difficult withdrawals. The anxiety, agitation, and insomnia that characterize benzodiazepine withdrawal may be partly driven by this surge in stress hormones flooding a system that had grown accustomed to being chemically suppressed.
Effects on Cortisol’s Daily Rhythm
Cortisol follows a predictable 24-hour cycle. It’s lowest in the late evening, stays quiet for about four to five hours during the early part of sleep, then begins rising in the early morning hours and peaks shortly after waking. This pattern is one of the most reliable circadian rhythms in the human body.
Benzodiazepines can shift the timing of this cycle. In a study using the short-acting benzodiazepine triazolam to help subjects adapt to an eight-hour time shift (simulating jet lag), the drug delayed the onset of nighttime cortisol secretion by about an hour and a half on the first night compared to placebo. By the third day, the delay had grown to nearly two hours. Triazolam also increased the relative amplitude of the 24-hour cortisol cycle, meaning the difference between peak and trough levels became more pronounced. These shifts suggest benzodiazepines don’t just lower cortisol overall; they influence when and how strongly the body releases it.
What This Means in Practice
For people taking a benzodiazepine occasionally or for a short course, the cortisol-lowering effect is real and may contribute to the sense of calm the drug provides. Anxiety and cortisol fuel each other in a feedback loop: stress raises cortisol, and elevated cortisol amplifies the brain’s threat signals, which generates more anxiety. By dampening both the subjective feeling of anxiety and the hormonal response driving it, benzodiazepines interrupt this cycle from two directions simultaneously.
For long-term users, the cortisol effect largely fades. The slight reduction in evening cortisol that persists is unlikely to cause clinical problems like adrenal insufficiency, which is a concern with other cortisol-suppressing drugs like corticosteroids. The more relevant concern for long-term users is what happens when they stop: the rebound in stress hormones can make withdrawal genuinely difficult and may require a slow, gradual taper rather than abrupt discontinuation.
One study on panic disorder patients found reduced urinary cortisol during benzodiazepine treatment, hinting that the drugs may help normalize an overactive stress system in people with anxiety disorders specifically. However, clinical reviews of benzodiazepines for panic disorder focus on symptom improvement rather than hormone levels, so cortisol normalization isn’t currently used as a treatment target or measure of success.