Triazolam

8-chloro-6-(2-chlorophenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine

Overview

Triazolam belongs to Depressants / Benzodiazepines.

Key safety note: Triazolam carries the benzodiazepine class risks, amplified by its high potency and ultra-short action.^[2]

Effects

Subjective effects vary. What a substance feels like depends on dose, individual physiology, mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or desirable outcomes.

Rapid drowsiness and sleep onset within about 15–30 minutes.
Pronounced anterograde amnesia (little memory of the period after taking it), with impaired coordination and, sometimes, next-morning grogginess.
On waking or stopping: rebound insomnia and daytime anxiety, with regular use, tolerance and dependence. Occasionally paradoxical agitation.

Dosing & duration

Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a “safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start low, go slow, wait for full effects before redosing, and never assume an unknown product matches these figures. Missing data is not evidence of safety.

Oral (tablets), prescribed and dose-adjusted by a clinician. Figures are therapeutic (prescribing) context, not a recreational guide.. Triazolam is a prescription hypnotic taken immediately before bed for a short course. The lowest effective dose is used, with the dose halved in the elderly and debilitated. It should not be combined with alcohol, opioids or other sedatives, or with strong CYP3A4 inhibitors, and the user should allow a full night's sleep because of its amnestic effect.

Dose ranges

Insomnia (adult)

0.125–0.25 mg at bedtime (max 0.5 mg)

Elderly / debilitated

0.125 mg at bedtime

Duration

onset

≈15–30 min

total

Short (t½ ≈1.5–5.5 h)

after effects

Rebound insomnia/anxiety. Possible amnesia for the night

Chemical & Physical Properties

Formula	C17H12Cl2N4
Molar mass	343.2 g/mol
State	Solid
Melting point	233–235 °C
Boiling point	Not reported
Density	Not reported
Vapor pressure	4.5×10⁻⁹ mmHg at 25 °C (estimated)
pKa	Not reported
LogP	2.42
Solubility	Poorly soluble in water (≈4.53 mg/L at 25 °C, estimated). Soluble in alcohol
Refractive index	Not reported

Identifiers & Synonyms

CAS	28911-01-5
CAS (enantiomer)
PubChem CID	5556
InChIKey	JOFWLTCLBGQGBO-UHFFFAOYSA-N
InChI	InChI=1S/C17H12Cl2N4/c1-10-21-22-16-9-20-17(12-4-2-3-5-14(12)19)13-8-11(18)6-7-15(13)23(10)16/h2-8H,9H2,1H3
SMILES	CC1=NN=C2N1C3=C(C=C(C=C3)Cl)C(=NC2)C4=CC=CC=C4Cl

Synonyms

Halcion

Pharmacodynamics & Biochemistry

Triazolam (Halcion) is a triazolobenzodiazepine, a benzodiazepine bearing a fused triazole ring, used as an ultra-short-acting hypnotic. Like the rest of the class it is a positive allosteric modulator at the benzodiazepine site of the GABA-A receptor (the α/γ2 subunit interface): in the presence of GABA it increases the frequency of chloride-channel opening, enhancing inhibitory neurotransmission to produce sedation, hypnosis, anxiolysis, muscle relaxation and anticonvulsant effects. It binds the benzodiazepine-sensitive α1/α2/α3/α5 subunit-containing receptors with sub-nanomolar affinity (see binding data). Its defining pharmacokinetic feature is speed: rapid absorption gives an onset of about 15–30 minutes, and a very short elimination half-life of roughly 1.5–5.5 hours means it is largely gone by morning: the basis for its use in sleep-onset insomnia and jet lag, and for its comparatively low next-day accumulation. It is metabolised almost entirely by hepatic CYP3A4 to α-hydroxytriazolam (a short-acting metabolite of minor clinical importance), so it forms no long-lived active metabolites, but this also makes it highly sensitive to CYP3A4 inhibitors (see interactions). Triazolam is achiral (it has no stereocentre). The combination of high potency, rapid onset and ultra-short duration makes it prone to pronounced anterograde amnesia and rebound insomnia, and it was at the centre of the early-1990s 'Halcion' safety controversy that led several countries to restrict or withdraw it.

Biological targets

GABA-A

Binding & functional measurements

Target	Measurement	Species
GABAA receptor α2 subunit	pKi 9.2	Human
GABAA receptor α1 subunit	pKi 9.1	Human
GABAA receptor α1 subunit	pKd 9	Human
GABAA receptor α3 subunit	pKi 8.8	Human
GABAA receptor α5 subunit	pKi 8.8	Human
GABAA receptor α5 subunit	pKd 8.4	Human
GABA-A benzodiazepine site	EC50 83 nM Emax 257%	Rat
GABA-A α1β2γ2 receptor	EC50 52 ± 8.0 nM Emax 132 ± 6%	Human
GABA-A α2β2γ2 receptor	EC50 44 ± 5.0 nM Emax 255 ± 11%	Human
GABA-A α2β2γ3 receptor	EC50 168 ± 14 nM Emax 61 ± 3%	Human
GABA-A α3β2γ2 receptor	EC50 63 ± 7.0 nM Emax 270 ± 13%	Human
GABA-A α5β2γ2 receptor	EC50 52 ± 5.0 nM Emax 165 ± 8%	Human

Pharmacokinetics

Bioavailability	Oral ~44% (sublingual ~53%)
T_max	≈1.5–2 h (peak effect)
Half-life	≈1.5–5.5 h (ultra-short)
V_d	Not reported
Protein binding	Not reported
Metabolism	Hepatic CYP3A4 oxidation to α-hydroxytriazolam (short-acting, minor). No long-lived active metabolites
Excretion	Renal (as metabolites)

Toxicology & Safety

Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual health factors. Missing harms should never be interpreted as evidence of safety.

Not reported

Triazolam carries the benzodiazepine class risks, amplified by its high potency and ultra-short action. It causes marked, dose-dependent anterograde amnesia (impaired memory for events after dosing), sedation, impaired coordination and next-morning 'hangover' effects, and, because it clears so quickly, pronounced rebound insomnia and daytime anxiety, which can appear even after a single dose. Paradoxical reactions (agitation, disinhibition, hallucinations, and rarely aggression or depression) were reported often enough that triazolam became the subject of a major safety controversy in the early 1990s: after 161 psychiatric adverse-reaction reports among 390 total, the UK's Committee on Safety of Medicines suspended its licence in October 1991 (revoked 1993) and the US FDA lowered the recommended dose. Like all benzodiazepines it produces tolerance, physical dependence and a withdrawal syndrome (rebound insomnia and anxiety, tremor and, after high-dose or abrupt cessation, seizures). Its short half-life tends to make dependence and inter-dose/withdrawal symptoms come on quickly. It causes respiratory depression that is dangerous with opioids, alcohol or other CNS depressants: the usual mechanism of benzodiazepine-related death. Because it depends on CYP3A4, strong inhibitors (azole antifungals, some protease inhibitors, nefazodone, grapefruit juice) can raise its levels dramatically and are contraindicated. Use is short-term and at the lowest effective dose, with reduced doses in the elderly.^[2]

Legal Status

Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status, prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.

US: Schedule IV. UK: Class C (Schedule 4). DE: BtMG Anlage III

Interactions & Contraindications

Drug interactions

CYP3A4 inhibitors (ritonavir, azole antifungals, macrolides, grapefruit) Azole antifungals (ketoconazole, itraconazole), ritonavir, nefazodone and grapefruit juice greatly increase triazolam levels and effects, and are contraindicated.^[2]

Opioids Additive respiratory depression and sedation: a leading cause of benzodiazepine-related death (regulatory boxed warnings).^[2]

Alcohol, Benzodiazepines, Gabapentinoids (gabapentin, pregabalin) Additive sedation and respiratory depression, including with barbiturates and sedating antihistamines.^[2]

CYP3A4 inducers (rifampicin, carbamazepine) Rifampicin, carbamazepine or St John's wort can reduce its effect.^[2]

Contraindications

Concurrent strong CYP3A4 inhibitor (ketoconazole, itraconazole, ritonavir) concurrent strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, nefazodone).^[2]

Pregnancy or breastfeeding US Pregnancy Category X, and breastfeeding.^[2]

Respiratory disease or sleep apnoea sleep apnoea syndrome or severe respiratory insufficiency.^[2]

Combining with alcohol or other CNS depressants acute alcohol or other CNS-depressant intoxication.^[2]

Myasthenia gravis^[2]

Kidney or liver impairment severe hepatic impairment, with caution in the elderly.^[2]

Usage & Context

A prescription hypnotic for the short-term treatment of acute insomnia, especially difficulty falling asleep, and for circadian disruptions such as jet lag, taken immediately before bed.
Its very short duration is the selling point (little next-day carry-over), but the same profile drives strong rebound insomnia and amnesia, so courses are kept brief.
Withdrawn or restricted in several countries after the Halcion controversy (UK 1991, and others), while remaining available, at low doses, in the US and elsewhere.

Sources & Evidence

Further Information

More in this subclass