sedation
20 interactions related to sedation
zolpidem + melatonin
Combining the Z-drug hypnotic zolpidem with melatonin can produce additive next-day drowsiness, impaired thinking, and reduced motor coordination, with the risk most pronounced in older adults. The interaction is primarily pharmacodynamic.
clonazepam + passionflower
Passionflower contains constituents that bind GABA-A receptors and may enhance the binding activity of benzodiazepines at those receptors. Combined with clonazepam, the effect is additive central nervous system depression and increased sedation.
fluoxetine + kava
Kava carries a documented risk of hepatotoxicity and produces CNS depression, and combining it with fluoxetine raises the risk of additive sedation and liver injury. Kava also inhibits CYP2D6 and CYP3A4, the enzymes that metabolize fluoxetine, which can elevate fluoxetine levels and side effects.
sertraline + kava
Kava (Piper methysticum) has central nervous system depressant effects and a documented risk of hepatotoxicity, and combining it with sertraline raises the risk of additive sedation and liver injury. Sertraline itself is associated with hepatic adverse effects in a small subset of users, and stacking hepatotoxic agents is discouraged.
diazepam + kava
Kava's kavalactones bind GABA-A receptors and produce additive central nervous system depression when combined with diazepam, a long-acting benzodiazepine. Concurrent use is not recommended due to risk of excessive sedation, impaired coordination, and potential additive hepatotoxicity.
alprazolam + melatonin
Melatonin and alprazolam both promote sleep and can produce additive sedation, impaired alertness, and reduced motor coordination when used together. The combination may increase next-day drowsiness and risk during activities like driving.
alprazolam + kava
Kava contains kavalactones that potentiate GABA-A receptor binding, producing additive CNS depression when combined with alprazolam, a benzodiazepine that also enhances GABA-A activity. A published case report describes a 54-year-old man who became semi-comatose after taking alprazolam with kava for three days.
alcohol + kava
Kava and alcohol both depress the central nervous system through GABAergic and other mechanisms, producing additive sedation and motor impairment. More importantly, both substances are hepatotoxic, and concurrent use significantly increases the risk of severe liver injury, including cases of fulminant liver failure requiring transplantation.
diphenhydramine + valerian
Diphenhydramine (a sedating antihistamine) and valerian root both produce CNS depression through GABAergic and histaminergic pathways. Used together, sedation, psychomotor impairment, and respiratory depression risks are additive.
alcohol + amitriptyline
Amitriptyline is a tricyclic antidepressant with strong sedating, anticholinergic, and antihistaminic effects. Combining it with alcohol — also a CNS depressant — produces marked additive sedation, impaired psychomotor performance, and increased risk of falls, accidents, and respiratory depression in overdose.
alcohol + alprazolam
Alcohol and alprazolam (Xanax) both depress the central nervous system through GABA-A receptor potentiation, producing additive sedation, profound respiratory depression, and impaired psychomotor function. The combination significantly increases risk of overdose death, even at moderate doses of each substance.
alcohol + diazepam
Diazepam (Valium) and alcohol are both GABA-A receptor positive allosteric modulators, producing additive and supra-additive CNS depression with profound risk of respiratory depression, coma, and death. Diazepam's long half-life and active metabolites extend the window of dangerous interaction far beyond the dosing interval.
alcohol + zolpidem
Zolpidem (Ambien) and alcohol both potentiate GABA-A receptor activity at the alpha-1 subunit, producing additive sedation, profound impairment of psychomotor performance, and significantly elevated risk of complex sleep behaviors, falls, respiratory depression, and motor vehicle crashes. Alcohol also increases zolpidem absorption and peak concentrations.
alcohol + trazodone
Trazodone and alcohol both depress the central nervous system, producing additive sedation, dizziness, orthostatic hypotension, and impaired psychomotor performance. The combination also increases risk of falls, accidents, and rarely, dangerous arrhythmias related to QT prolongation.
alcohol + mirtazapine
Mirtazapine and alcohol both depress the central nervous system, producing additive sedation, profound drowsiness, impaired psychomotor performance, and increased risk of accidents and falls. Mirtazapine's strong H1-antihistamine activity makes the sedative interaction with alcohol particularly pronounced, especially at lower doses.
valerian tea + benzodiazepines
Valerian (Valeriana officinalis) modulates GABA-A receptors, the same target as benzodiazepines, producing additive central nervous system depression. Co-use can cause excessive sedation, impaired psychomotor performance, and prolonged drowsiness, especially with alcohol or in older adults.
alcohol + valerian
Valerian root acts on GABA-A receptors and may inhibit GABA breakdown, producing sedative effects that are additive with alcohol's CNS depressant effects. The combination produces increased drowsiness, impaired psychomotor performance, and risk of falls, particularly in older adults.
diphenhydramine + melatonin
Both diphenhydramine and melatonin cause sedation through different mechanisms (H1 antagonism and MT1/MT2 agonism). Combined use produces additive CNS depression, next-day drowsiness, impaired cognition, and increased fall risk, especially in older adults.
thc + benzodiazepines
THC and benzodiazepines are both central-nervous-system depressants and produce additive sedation, ataxia, cognitive impairment, and respiratory slowing. THC and CBD components of cannabis also inhibit CYP3A4, which metabolizes alprazolam, midazolam, and triazolam, potentially raising benzodiazepine plasma levels.
cbd + clobazam
CBD strongly inhibits CYP2C19, the enzyme that clears N-desmethylclobazam (the active metabolite of clobazam). Co-administration triples plasma N-desmethylclobazam levels, causing excess sedation, ataxia, and somnolence; this is documented in the FDA-approved Epidiolex prescribing information.