sedation
20 interactions related to sedation
diazepam + kava
Kava's kavalactones act on the GABA-A receptor, the same system diazepam enhances, so combining them produces additive central nervous system depression and excessive sedation. A published case report describes a man who became semicomatose within days of adding kava to a benzodiazepine. Kava also carries a separate, documented liver-safety signal.
zolpidem + melatonin
Zolpidem and melatonin are both used to help with sleep, so people sometimes take them together. On paper their sedative effects could add up, but the only controlled study to test the combination directly found that adding melatonin did not measurably worsen next-morning alertness, coordination, or driving compared with zolpidem alone. The realistic concern is mild additive grogginess in sensitive people, especially older adults.
clonazepam + passionflower
Clonazepam is a benzodiazepine that calms the brain by enhancing GABA, its main inhibitory neurotransmitter. Passionflower appears to act on the same GABA system and may increase the sedative effect of benzodiazepines. Taken together, the most likely result is additive drowsiness. The human evidence is limited and mostly suggestive, so this is best treated as a caution rather than a proven hazard.
fluoxetine + kava
Kava carries a well-documented risk of serious, unpredictable liver injury and acts as a central nervous system depressant, so combining it with fluoxetine raises concern about additive sedation and liver harm. Kava also inhibits the liver enzymes that clear fluoxetine, though this has only been shown in laboratory studies and any rise in fluoxetine levels in people remains theoretical.
sertraline + kava
Kava (Piper methysticum) is a central nervous system depressant with a documented risk of serious liver injury, and combining it with sertraline raises the chance of additive sedation and additive liver stress. Kava also inhibits drug-metabolizing enzymes, and a case report describes prolonged serotonin syndrome in a patient taking kava alongside a serotonergic antidepressant.
alprazolam + melatonin
Alprazolam and melatonin both promote sleep and can produce additive sedation, so taking them together may increase drowsiness, slow reaction time, and carry over into next-day grogginess. The combination is generally manageable but warrants your prescriber's awareness, especially for older adults and anyone who drives in the morning.
alprazolam + kava
Kava's active compounds (kavalactones) act on the brain's GABA-A receptor, the same inhibitory system that alprazolam, a benzodiazepine, enhances. Taken together they cause additive central nervous system depression. A published case report describes a previously healthy 54-year-old man who became semi-comatose after three days of combining kava with his prescribed alprazolam, recovering once the kava was stopped. Kava also carries an independently documented risk of liver injury.
alcohol + kava
Kava and alcohol both depress the central nervous system, producing additive sedation and impaired coordination. More importantly, both are hepatotoxic: kava is a well-documented cause of severe and occasionally fatal liver injury, and alcohol adds a second liver stressor.
diphenhydramine + valerian
Diphenhydramine (a sedating antihistamine) and valerian root both depress the central nervous system, through histaminergic and GABAergic pathways respectively. Taken together their sedative effects add up, increasing drowsiness, next-day impairment, and fall risk.
alcohol + zolpidem
Zolpidem (Ambien) and alcohol both increase activity at the GABA-A receptor, producing additive sedation, impaired psychomotor performance, and an elevated risk of complex sleep behaviors, falls, and — at higher levels of intoxication — respiratory depression. The combination is an additive pharmacodynamic effect; the FDA interaction study found no change in zolpidem blood levels from alcohol.
alcohol + amitriptyline
Amitriptyline is a sedating tricyclic antidepressant with strong antihistaminic and anticholinergic effects. Combining it with alcohol — also a central nervous system depressant — produces additive drowsiness, impaired coordination and reaction time, and a greater risk of falls and accidents. The FDA label warns explicitly that amitriptyline may enhance the response to alcohol.
alcohol + alprazolam
Alcohol and alprazolam (Xanax) both depress the central nervous system by enhancing GABA-A receptor activity. Taken together they produce additive — and sometimes synergistic — sedation, slowed breathing, and impaired coordination, which substantially raises the risk of overdose and death even when neither is taken in a large amount.
alcohol + diazepam
Diazepam (Valium) and alcohol are both central nervous system depressants that act on the GABA-A receptor, producing additive and sometimes greater-than-additive sedation with a real risk of dangerously slowed breathing, loss of consciousness, and death. Diazepam and its active breakdown products linger in the body for days, so the dangerous window extends well beyond a single dose.
alcohol + trazodone
Trazodone and alcohol both depress the central nervous system, producing additive sedation, dizziness, orthostatic hypotension, and impaired coordination. The FDA label states trazodone may enhance the response to alcohol, and combining the two raises the risk of falls and accidents. Rarely, trazodone is associated with QT prolongation, orthostatic syncope, and priapism.
alcohol + mirtazapine
Mirtazapine and alcohol both depress the central nervous system, producing additive sedation, drowsiness, and impaired coordination and judgment. Mirtazapine's strong H1-antihistamine activity makes the sedative interaction with alcohol particularly pronounced, and the FDA label specifically advises avoiding alcohol during treatment.
valerian tea + benzodiazepines
Valerian (Valeriana officinalis) appears to act on the same GABA-A receptor system as benzodiazepines, so taking the two together may add to the sedative effect. The human evidence is largely theoretical and case-level, but the plausible result is extra drowsiness, slower reaction time, and more next-day grogginess.
alcohol + valerian
Valerian and alcohol both act on the GABA-A receptor system and are central nervous system depressants. Combining them carries a recognized possibility of additive sedation — more drowsiness, slower reactions, and impaired coordination than either alone. Most of this rests on shared mechanism and expert caution rather than large human outcome trials, but the practical concern is real: impaired driving and falls, particularly in older adults.
diphenhydramine + melatonin
Diphenhydramine and melatonin both promote sleepiness through different mechanisms (H1 antihistamine blockade and MT1/MT2 receptor activation). Used together they have an additive sedating effect, which can mean heavier-than-expected drowsiness, lingering next-day grogginess, slower reaction time, and a higher fall risk, especially in older adults.
thc + benzodiazepines
THC (the main psychoactive compound in cannabis) and benzodiazepines both depress the central nervous system, so combining them adds up to stronger sedation, impaired coordination, memory problems, and slowed breathing. Cannabinoids, especially CBD, can also inhibit the liver enzyme CYP3A4 that clears several benzodiazepines, raising and prolonging their levels.
cbd + clobazam
CBD inhibits CYP2C19, the enzyme that clears N-desmethylclobazam, the active metabolite of clobazam. Taking the two together raises N-desmethylclobazam levels substantially, increasing sedation, drowsiness, drooling, and unsteadiness. This interaction is documented in the FDA-approved Epidiolex prescribing information and in clinical studies in children with epilepsy.