Baclofen

4-amino-3-(4-chlorophenyl)butanoic acid

Overview

Baclofen belongs to Depressants.

Key safety note: Common effects are dose-related CNS depression: drowsiness, dizziness, weakness/hypotonia, fatigue and nausea.[4][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.
  • At therapeutic doses the wanted effect is muscle relaxation and relief of painful spasms and spasticity, usually with some drowsiness and a sense of heaviness or fatigue.
  • At higher doses baclofen produces sedation, mild euphoria or a relaxed, anxiolytic feeling and reduced alcohol craving, the basis of its off-label use in alcohol use disorder, but also dizziness, muscle weakness, confusion and clumsiness.
  • It is not strongly reinforcing and rarely causes drug craving at normal doses, but tolerance and a dangerous physical dependence/withdrawal develop with regular use.
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, Intrathecal (implanted pump). Baclofen is a prescription medicine that must be titrated up slowly and tapered down slowly, never stopped abruptly. High-dose regimens used off-label for alcohol dependence are controversial and add sedation/overdose risk. These are medical reference ranges, not recreational guidance.

Dose ranges

Oral (spasticity, adult)

Start 5 mg 3×/day, titrate up, usual 40–80 mg/day (≈80 mg/day max)

Alcohol use disorder (off-label)

Higher, individualised supervised doses, regimens vary widely

Intrathecal

micrograms/day via pump, individualised after a test dose

Duration

onset

≈1 h oral (peak ~2–3 h)

total

Dosed ~3×/day (t½ ~3–4 h)

Chemical & Physical Properties
FormulaC10H12ClNO2
Molar mass213.66 g/mol
StateSolid
Melting point206–208 °C
Boiling pointNot reported
DensityNot reported
Vapor pressureNot reported
pKa≈9.5 (amine) and ≈3.9 (carboxyl): zwitterionic
LogP-1 (predicted, XLogP3)
SolubilitySlightly soluble in water (~4 mg/mL)
Refractive indexNot reported
Identifiers & Synonyms
CAS1134-47-0
CAS (enantiomer)
PubChem CID2284
InChIKeyKPYSYYIEGFHWSV-UHFFFAOYSA-N
InChIInChI=1S/C10H12ClNO2/c11-9-3-1-7(2-4-9)8(6-12)5-10(13)14/h1-4,8H,5-6,12H2,(H,13,14)
SMILESC1=CC(=CC=C1C(CC(=O)O)CN)Cl

Synonyms

    Pharmacodynamics & Biochemistry

    Baclofen is a selective agonist at the metabotropic GABA-B receptor: a lipophilic analogue of the inhibitory neurotransmitter GABA (β-(4-chlorophenyl)-GABA) built to cross the blood–brain barrier, which GABA itself cannot. Activating these Gi/o-coupled receptors reduces presynaptic Ca²⁺ influx (cutting excitatory neurotransmitter release) and opens postsynaptic K⁺ channels (hyperpolarising neurons). Together this damps mono- and polysynaptic spinal reflexes and relaxes skeletal muscle. Baclofen is marketed as the racemate, but essentially all the GABA-B activity resides in the (R)-enantiomer, arbaclofen: the (S)-form is largely inactive, so half of a racemic dose is pharmacologically inert. It is a low-potency agonist (GABA-B Kᵢ in the low-micromolar range, see the binding table), which is why clinical doses are comparatively large. Because oral baclofen penetrates the CNS poorly, severe spasticity is often treated by delivering it straight into the cerebrospinal fluid through an implanted intrathecal pump, reaching CSF concentrations more than ten times higher than oral dosing at a fraction of the systemic exposure.

    Biological targets

    • GABA-B

    Binding & functional measurements

    TargetMeasurementSpecies
    GABAB receptorpKi 5.25Human
    Pharmacokinetics
    Bioavailability≈70–85% oral, with dose-dependent (saturable) absorption
    Tmax≈2–3 h
    Half-life≈2.5–7 h (commonly ≈3–4 h)
    VdNot reported
    Protein binding≈30%
    MetabolismMinimal: ~15% hepatic deamination. The drug is largely not metabolised
    ExcretionRenal: ~70–85% excreted unchanged. Reduce dose in renal impairment
    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

    Common effects are dose-related CNS depression: drowsiness, dizziness, weakness/hypotonia, fatigue and nausea. Overdose causes marked CNS and respiratory depression, coma, bradycardia, hypotension, hypothermia and paradoxical seizures, can mimic brain death, and may outlast measurable drug levels. Self-poisoning with baclofen has risen. The most dangerous feature is WITHDRAWAL: abruptly stopping baclofen, above all an intrathecal-pump failure, triggers a rapidly escalating, potentially fatal syndrome of rebound spasticity, high fever, rigidity, rhabdomyolysis, autonomic instability, hallucinations/delirium, seizures and multi-organ failure, resembling severe sedative/alcohol withdrawal. Baclofen must always be tapered, never stopped suddenly.[4][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.
    Interactions & Contraindications

    Drug interactions

    Alcohol, Benzodiazepines, Opioids Additive sedation and respiratory depression, including with sedating antihistamines.[3]
    Tricyclic antidepressants May potentiate baclofen's effect (pronounced muscle hypotonia has been reported).[3]
    Antihypertensive drugs Additive hypotension. Drugs that impair renal function can also raise baclofen levels, as it is renally cleared.[4]

    Contraindications

    Known hypersensitivity to the drug hypersensitivity to baclofen.[3]
    Kidney or liver impairment renal impairment, so dose-reduce (the main route of elimination).[3]
    Current or prior seizure disorder baclofen can lower the seizure threshold, and withdrawal provokes seizures.[4]
    Abrupt discontinuation after regular use (withdrawal and seizure risk) taper to avoid a life-threatening withdrawal syndrome.[4]
    Respiratory disease or sleep apnoea and caution in the elderly and in significant psychiatric disease.[3]
    Usage & Context
    • A first-line oral and intrathecal antispastic for spasticity of multiple sclerosis, spinal-cord injury and cerebral palsy.
    • Used off-label for alcohol use disorder to reduce craving (notably in France, which gave it specific regulatory support), a Cochrane review finds limited, uncertain benefit, and tried for hiccups, GERD and opioid withdrawal.
    • Occasionally misused for its sedative/euphoric effects. More commonly a cause of accidental or intentional overdose.
    Sources & Evidence

    Further Information