Baclofen should be avoided in the setting ofchronic kidney disease andend stage renal disease as even small doses can cause excessive toxicity.[13] Common side effects include sleepiness, weakness, and dizziness.[7] Serious side effects, such asseizures andrhabdomyolysis, may occur if use of baclofen is stopped abruptly.[7] Use duringpregnancy is of unclear safety, whilst use duringbreastfeeding is likely safe, and even more so if oral administration is avoided.[14]
The adverse effects and safety profile associated with baclofen when it is combined withsedative drugs (for examplealcohol orbenzodiazepines) range depending on the dose and the individual. The interaction may increase the sedative effects of all ingested sedatives and as such is not generally recommended.[15] In high doses the interaction can causede novo seizures.[16]
Baclofen is primarily used for the treatment ofspastic movement disorders, especially in instances of spinal cord injury, andmultiple sclerosis.[21] Use in people withstroke,cerebral palsy, orParkinson's disease is not recommended.[21] Intrathecal baclofen is used for severe spasticity of spinal cord origin, that is refractive to maximum doses of oral antispasmodic agents, or who experience intolerable side effects.[22][23]
Baclofen may be used off-label as a treatment foralcohol use disorder to reduce the risk ofrelapse, and to increase the number of days that a person can go without drinkingalcohol (abstinence days).[9]
It is sometimes used for the treatment ofopioid withdrawal symptoms, and may be superior for this purpose to the more-commonly usedclonidine.[10][11]
Baclofen is also used in the treatment of sleep-related painful erections.[24]
Discontinuation of baclofen can be associated with a withdrawal syndrome which resemblesbenzodiazepine withdrawal andalcohol withdrawal.Withdrawal symptoms are more likely if baclofen is administeredintrathecally or for long periods of time (more than a couple of months) and can occur from low or high doses.[25] The severity of baclofen withdrawal depends on the rate at which it is discontinued. Thus to minimise withdrawal symptoms, the dose should be tapered down slowly when discontinuing baclofen therapy. Abrupt withdrawal is more likely to result in severe withdrawal symptoms. Acute withdrawal symptoms can be eased or completely reversed by re-initiating therapy with baclofen.[26]
Russian baclofen (trade name "Baclosan") 25 mg tablets with a warning: "Caution: the drug maysuppress psychomotor reactions"
Baclofen, at standard dosing, does not appear to possessaddictive properties, and has not been associated with any degree ofdrug craving.[27][28] Euphoria is however listed as a common to very common side-effect of baclofen in theBNF 75.[29] There are very few cases ofabuse of baclofen for reasons other thanattempted suicide.[27] In contrast to baclofen, another GABAB receptor agonist,γ-hydroxybutyric acid (GHB), has been associated with euphoria, abuse, and addiction.[30] These effects are likely mediated not by activation of the GABAB receptor, but rather by activation of theGHB receptor.[30] Baclofen possesses bothsedative andanxiolytic properties.[28]
Baclofen produces its effects by selectively activating theGABAB receptor. Baclofen is postulated to block mono-and-polysynaptic reflexes by acting as an inhibitory ligand, inhibiting the release of excitatory neurotransmitters. Baclofen does not have significant affinity for theGHB receptor, and has no known abuse potential.[34] Agonism of GABAB receptors is thought to be responsible for baclofen's range of therapeutic properties, asGABAB knockout mice are unresponsive to the neurobiological effects of baclofen.[35]
Similarly tophenibut (β-phenyl-GABA), as well aspregabalin (β-isobutyl-GABA), which are close analogues of baclofen, baclofen (β-(4-chlorophenyl)-GABA) has been found to blockα2δ subunit-containingvoltage-gated calcium channels (VGCCs).[36] However, it is weaker relative to phenibut in this action (Ki = 23 and 39 μM forR- andS-phenibut and 156 μM for baclofen).[36] Moreover, baclofen is in the range of 100-fold more potent by weight as an agonist of the GABAB receptor in comparison to phenibut, and in accordance, is used at far lower relative dosages. As such, the actions of baclofen on α2δ subunit-containing VGCCs are likely not clinically relevant.[36]
For drug-reward and addiction, baclofen's mechanism of action is thought to be through its effect on the mesolimbic dopamine pathway, specifically leading to a decrease in dopamine release associated with alcohol.[9] GABAB receptor activation (GABAB receptor agonist activity) may decrease or inhibit alcohol's ability to activate or fire dopaminergic neurons following exposure to alcohol. Baclofen's mechanism of action when used to treat alcohol use disorder is not thought to be mediated through its muscle-relaxing or sedative properties, however there is evidence to suggest that the GABAB receptor-activation in the limbus may also reduce feelings of anxiety in people with alcohol use disorder.[9]
The drug is rapidly absorbed after oral administration and is widely distributed throughout the body. Biotransformation is low: the drug is predominantly excreted unchanged by the kidneys. The serumhalf-life of baclofen is roughly 2–4 hours;[7] however, one source gives a half-life of 6.8 hr, using a more complex calculation combining urinary and serum data.[37] It therefore needs to be administered frequently throughout the day to control spasticity appropriately.
Historically, baclofen was designed as a drug for treating epilepsy. It was first synthesized atCiba-Geigy by the Swiss chemist Heinrich Keberle in 1962.[38][39] Its effect on epilepsy was ineffective, but it was found that in certain people, spasticity decreased. In 1971, it was introduced as a treatment for certain form of spasticity. It was approved by theUS Food and Drug Administration (FDA) in 1977.[40]
Intrathecal baclofen was first introduced in 1984 to treat severe spinal spasticity. This administration route aimed to avoid supraspinal side effects.[41][42]
Baclofen can be administered, orally, intrathecally (directly into the cerebral spinal fluid) using a pump implanted under the skin, or transdermally as part of a pain-relieving and muscle-relaxing topical cream mix (also containing gabapentin and clonidine) prepared at a compounding pharmacy.[12][43]
Intrathecal pumps offer much lower doses of baclofen because they are designed to deliver the medication directly to the spinal fluid rather than going through the digestive and blood system first. A drug concentration in the cerebrospinal fluid more than 10 times greater than when given orally is achieved with this route. At the same time the blood concentration levels are almost undetectable, thus minimizing side effects.[43]
Besides those with spasticity, intrathecal administration is also used in patients withcerebral palsy[43] ormultiple sclerosis who have severe painful spasms which are not controllable by oral baclofen.[citation needed] With pump administration, a test dose is first injected into the spinal fluid to assess the effect, and if successful in relieving spasticity, a chronic intrathecal catheter is inserted from the spine through the abdomen and attached to the pump which is implanted under the abdomen's skin, usually by the ribcage.[citation needed] The pump is computer-controlled for automatic dosage and its reservoir can be replenished bypercutaneous injection.[citation needed] The pump also has to be replaced every five to seven years or so.[44]
Baclofen is being studied for the treatment of alcoholism.[27] Evidence as of 2019 is not conclusive enough to recommend its use for this purpose.[27][46] In 2014, the French drug agencyANSM issued a three-year temporary recommendation allowing the use of baclofen in alcoholism.[47] In 2018, baclofen received a Marketing Authorization for use in alcoholism treatment from the agency if all other treatments are not effective.[48]
From 2014 to 2017, baclofen misuse, toxicity and use in suicide attempts among adults in the US increased.[53]
In his 2008 book,Le Dernier Verre (translated literally asThe Last Glass orThe End of My Addiction), French-American cardiologistOlivier Ameisen described how he treated his alcoholism with baclofen. Inspired by this book, an anonymous donor gave $750,000 to theUniversity of Amsterdam in the Netherlands to initiate a clinical trial of high-dose baclofen, which Ameisen had called for since 2004.[54] The researchers concluded, "In summary, the current study did not find evidence of a positive effect of either low or high doses of baclofen in AD patients. However, we cannot exclude the possibility that baclofen is an effective medication for the treatment of severe, heavy drinking AD patients not responding to or not accepting routine psychosocial interventions."[55]
^abAhmadi-Abhari SA, Akhondzadeh S, Assadi SM, Shabestari OL, Farzanehgan ZM, Kamlipour A (February 2001). "Baclofen versus clonidine in the treatment of opiates withdrawal, side-effects aspect: a double-blind randomized controlled trial".Journal of Clinical Pharmacy and Therapeutics.26 (1):67–71.doi:10.1111/j.1365-2710.2001.00325.x.PMID11286609.S2CID28295723.
^El-Husseini A, Sabucedo A, Lamarche J, Courville C, Peguero A (26 October 2011). "Baclofen toxicity in patients with advanced nephropathy: proposal for new labeling".American Journal of Nephrology.34 (6):491–495.doi:10.1159/000333247.PMID22041434.
^World Health Organization (2025).The selection and use of essential medicines, 2025: WHO Model List of Essential Medicines, 24th list. Geneva: World Health Organization.hdl:10665/382243.
^abGrenier B, Mesli A, Cales J, Castel JP, Maurette P (1996). "[Severe hyperthermia caused by sudden withdrawal of continuous intrathecal administration of baclofen]".Annales Françaises d'Anesthésie et de Réanimation.15 (5):659–662.doi:10.1016/0750-7658(96)82130-7.PMID9033759.
^abcdLeggio L, Garbutt JC, Addolorato G (March 2010). "Effectiveness and safety of baclofen in the treatment of alcohol dependent patients".CNS & Neurological Disorders Drug Targets.9 (1):33–44.doi:10.2174/187152710790966614.PMID20201813.
^abvan Nieuwenhuijzen PS, McGregor IS, Hunt GE (January 2009). "The distribution of gamma-hydroxybutyrate-induced Fos expression in rat brain: comparison with baclofen".Neuroscience.158 (2):441–455.doi:10.1016/j.neuroscience.2008.10.011.PMID18996447.S2CID22701676.
^Perry HE, Wright RO, Shannon MW, Woolf AD (June 1998). "Baclofen overdose: drug experimentation in a group of adolescents".Pediatrics.101 (6):1045–1048.doi:10.1542/peds.101.6.1045.PMID9606233.
^"Product Information Clofen".TGA eBusiness Services. Millers Point, Australia: Alphapharm Pty Limited. 7 June 2017.Archived from the original on 15 August 2017. Retrieved15 August 2017.
^abcZvejniece L, Vavers E, Svalbe B, Veinberg G, Rizhanova K, Liepins V, et al. (October 2015). "R-phenibut binds to the α2-δ subunit of voltage-dependent calcium channels and exerts gabapentin-like anti-nociceptive effects".Pharmacology, Biochemistry, and Behavior.137:23–29.doi:10.1016/j.pbb.2015.07.014.PMID26234470.S2CID42606053.
^Wuis EW, Dirks MJ, Termond EF, Vree TB, Van der Kleijn E (1989). "Plasma and urinary excretion kinetics of oral baclofen in healthy subjects".European Journal of Clinical Pharmacology.37 (2):181–184.doi:10.1007/BF00558228.PMID2792173.S2CID23828250.
