Background: It has been reported that baclofen, a drug used in the treatment of spasticity, reduces the severity of withdrawal symptoms and substance use disorders (SUDs) for some psychoactive drugs. Aims and Methods: To evaluate the effectiveness and safety of baclofen in the treatment of withdrawal syndrome and/or SUDs, providing (1) an outline of its pharmacological features; (2) a summary of studies that have suggested its possible effectiveness in the treatment of SUDs, and (3) a review of randomized, controlled trials (RCTs) on baclofen and SUDs. Results: Baclofen tolerability is generally considered to be good. Eleven RCTs investigated its effectiveness in the treatment of SUDs. Of these, 5 RCTs found that baclofen is effective, 5 RCTs found that it is ineffective and the results of 1 RCT were not appreciable because it did not achieve the preplanned level of participation. Conclusions: The number of RCTs on baclofen and SUDs is still low, and their results are divergent. Further RCTs should be undertaken, particularly with higher doses of baclofen. Its administration may be suggested in patients who fail to respond to other approved drugs or who are affected by liver disease that prevents their administration, or in patients affected by SUDs for which no approved drugs are available. Treatment should be conducted under strict medical supervision.

1.
Mark TL, Kassed CA, Vandivort-Warren R, Levit KR, Kranzler HR: Alcohol and opioid dependence medications: prescription trends, overall and by physician specialty. Drug Alcohol Depend 2009;99:345-349.
2.
Grant BF: Barriers to alcoholism treatment: reasons for not seeking treatment in a general population sample. J Stud Alcohol 1997;58:365-371.
3.
Schomerus G, Lucht M, Holzinger A, Matschinger H, Carta MG, Angermeyer MC: The stigma of alcohol dependence compared with other mental disorders: a review of population studies. Alcohol Alcohol 2011;46:105-112.
4.
Miller NS, Sheppard LM, Colenda CC, Magen J: Why physicians are unprepared to treat patients who have alcohol- and drug-related disorders. Acad Med 2001;76:410-418.
5.
Jupp B, Lawrence AJ: New horizons for therapeutics in drug and alcohol abuse. Pharmacol Ther 2010;125:138-168.
6.
Tyacke RJ, Lingford-Hughes A, Reed LJ, Nutt DJ: GABAB receptors in addiction and its treatment. Adv Pharmacol 2010;58:373-396.
7.
Bowery NG: GABAB receptor: a site of therapeutic benefit. Curr Opin Pharmacol 2006;6:37-43.
8.
Dario A, Tomei G: A benefit-risk assessment of baclofen in severe spinal spasticity. Drug Saf 2004;27:799-818.
9.
Abbruzzese G: The medical management of spasticity. Eur J Neurol 2002;9:30-34.
10.
Cryan JF, Kaupmann K: Don't worry ‘B' happy!: a role for GABA(B) receptors in anxiety and depression. Trends Pharmacol Sci 2005;26:36-43.
11.
Breslow MF, Fankhauser MP, Potter RL, Meredith KE, Misiaszek J, Hope DG Jr: Role of gamma-aminobutyric acid in antipanic drug efficacy. Am J Psychiatry 1989;146:353-356.
12.
Drake RG, Davis LL, Cates ME, Jewell ME, Ambrose SM, Lowe JS: Baclofen treatment for chronic posttraumatic stress disorder. Ann Pharmacother 2003;37:1177-1181.
13.
Krupitsky EM, Burakov AM, Ivanov VB, Krandashova GF, Lapin IP, Grinenko AJ, Borodkin YS: Baclofen administration for the treatment of affective disorders in alcoholic patients. Drug Alcohol Depend 1993;33:157-163.
14.
Broft AI, Spanos A, Corwin RL, Mayer L, Steinglass J, Devlin MJ, Attia E, Walsh BT: Baclofen for binge eating: an open-label trial. Int J Eat Disord 2007;40:687-691.
15.
Bigelow LB, Nasrallah H, Carman J, Gillin JC, Wyatt RJ: Baclofen treatment in chronic schizophrenia: a clinical trial. Am J Psychiatry 1977;134:318-320.
16.
Gulmann NC, Bahr B, Andersen B, Eliassen HM: A double-blind trial of baclofen against placebo in the treatment of schizophrenia. Acta Psychiatr Scand 1976;54:287-293.
17.
Hering-Hanit R, Gadoth N: The use of baclofen in cluster headache. Curr Pain Headache Rep 2001;5:79-82.
18.
Cossentino MJ, Mann K, Armbruster SP, Lake JM, Maydonovitch C, Wong RK: Randomised clinical trial: the effect of baclofen in patients with gastro-oesophageal reflux - a randomised prospective study. Aliment Pharmacol Ther 2012, E-pub ahead of print.
19.
Orr WC, Goodrich S, Wright S, Shepherd K, Mellow M: The effect of baclofen on nocturnal gastroesophageal reflux and measures of sleep quality: a randomized, cross-over trial. Neurogastroenterol Motil 2012;24:553-e253.
20.
Burke AM, White AB, Brill N: Baclofen for intractable hiccups. N Engl J Med 1988;319:1354.
21.
Froestl W: Chemistry and pharmacology of GABAB receptor ligands. Adv Pharmacol 2010;58:19-62.
22.
Emson PC: GABAB receptors: structure and function; in Tepper JM, Abercrombie ED, Bolam JP (eds): Progress in Brain Research. Amsterdam, Elsevier, 2007, pp 43-57.
23.
Lal R, Sukbuntherng J, Tai EH, Upadhyay S, Yao F, Warren MS, Luo W, Bu L, Nguyen S, Zamora J, Peng G, Dias T, Bao Y, Ludwikow M, Phan T, Scheuerman RA, Yan H, Gao M, Wu QQ, Annamalai T, Raillard SP, Koller K, Gallop MA, Cundy KC: Arbaclofen placarbil, a novel R-baclofen prodrug: improved absorption, distribution, metabolism, and elimination properties compared with R-baclofen. J Pharmacol Exp Ther 2009;330:911-921.
24.
Urwyler S, Mosbacher J, Lingenhoehl K, Heid J, Hofstetter K, Froestl W, Bettler B, Kaupmann K: Positive allosteric modulation of native and recombinant gamma-aminobutyric acid(B) receptors by 2,6-Di-tert-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) and its aldehyde analog CGP13501. Mol Pharmacol 2001;60:963-971.
25.
Urwyler S, Pozza MF, Lingenhoehl K, Mosbacher J, Lampert C, Froestl W, Koller M, Kaupmann K: N,N'-Dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine (GS39783) and structurally related compounds: novel allosteric enhancers of gamma-aminobutyric acidB receptor function. J Pharmacol Exp Ther 2003;307:322-330.
26.
Urwyler S: Allosteric modulation of family C G-protein-coupled receptors: from molecular insights to therapeutic perspectives. Pharmacol Rev 2011;63:59-126.
27.
Koob GF, Volkow ND: Neurocircuitry of addiction. Neuropsychopharmacology 2010;35:217-238.
28.
Chen G, Cuzon Carlson VC, Wang J, Beck A, Heinz A, Ron D, Lovinger DM, Buck KJ: Striatal involvement in human alcoholism and alcohol consumption, and withdrawal in animal models. Alcohol Clin Exp Res 2011;35:1739-1748.
29.
Colombo G, Agabio R, Carai MAM, Lobina C, Pani M, Reali R, Addolorato G, Gessa GL: Ability of baclofen in reducing alcohol intake and withdrawal severity. I. Preclinical evidence. Alcohol Clin Exp Res 2000;24:58-66.
30.
Gerkin R, Curry SC, Vance MV, Sankowski PW, Meinhart RD: First-order elimination kinetics following baclofen overdose. Ann Emerg Med 1986;15:843-846.
31.
Wuis EW, Dirks MJ, Termond EF, Vree TB, Van der Kleijn E: Plasma and urinary excretion kinetics of oral baclofen in healthy subjects. Eur J Clin Pharmacol 1989;37:181-184.
32.
Smith CR, LaRocca NG, Giesser BS, Scheinberg LC: High-dose oral baclofen: experience in patients with multiple sclerosis. Neurology 1991;41:1829-1831.
33.
Chen KS, Bullard MJ, Chien YY, Lee SY: Baclofen toxicity in patients with severely impaired renal function. Ann Pharmacother 1997;31:1315-1320.
34.
El-Husseini A, Sabucedo A, Lamarche J, Courville C, Peguero A: Baclofen toxicity in patients with advanced nephropathy: proposal for new labeling. Am J Nephrol 2011;34:491-495.
35.
Ghose K, Holmes KM, Matthewson K: Complications of baclofen overdosage. Postgrad Med J 1980;56:865-867.
36.
Ochs G, Struppler A, Meyerson BA, Linderoth B, Gybels J, Gardner BP, Teddy P, Jamous A, Weinmann P: Intrathecal baclofen for long-term treatment of spasticity: a multi-centre study. J Neurol Neurosurg Psychiatry 1989;52:933-939.
37.
Awaad Y, Rizk T, Siddiqui I, Roosen N, McIntosh K, Waines GM: Complications of intrathecal baclofen pump: prevention and cure. ISRN Neurol 2012;2012:575168.
38.
Nasti JJ, Brakoulias V: Chronic baclofen abuse and withdrawal delirium. Aust NZ J Psychiatry 2011;45:86-87.
39.
Perry HE, Wright RO, Shannon MW, Woolf AD: Baclofen overdose: drug experimentation in a group of adolescents. Pediatrics 1998;101:1045-1048.
40.
Weißhaar GF, Hoemberg M, Bender K, Bangen U, Herkenrath P, Eifinger F, Rothschild M, Roth B, Oberthuer A: Baclofen intoxication: a ‘fun drug' causing deep coma and nonconvulsive status epilepticus - a case report and review of the literature. Eur J Pediatr 2012;171:1541-1547.
41.
Lee TH, Chen SS, Su SL, Yang SS: Baclofen intoxication: report of four cases and review of the literature. Clin Neuropharmacol 1992;15:56-62.
42.
Berger B, Vienenkoetter B, Korporal M, Rocco A, Meinck HM, Steiner T: Accidental intoxication with 60 mg intrathecal baclofen: survived. Neurocrit Care 2012;16:428-432.
43.
Ferner RE: Atropine treatment for baclofen overdose. Postgrad Med J 1981;57:580-581.
44.
Hsieh MJ, Chen SC, Weng TI, Fang CC, Tsai TJ: Treating baclofen overdose by hemodialysis. Am J Emerg Med 2012;30:1654.e5-1654.e7.
45.
Lipscomb DJ, Meredith TJ: Baclofen overdose. Postgrad Med J 1980;56:108-109.
46.
Romijn JA, van Lieshout JJ, Velis DN: Reversible coma due to intrathecal baclofen. Lancet 1986;ii:696.
47.
Saltuari L, Baumgartner H, Kofler M, Schmutzhard E, Russegger L, Aichner F, Gerstenbrand F: Failure of physostigmine in treatment of acute severe intrathecal baclofen intoxication. N Engl J Med 1990;322:1533-1534.
48.
Sauneuf B, Totouom HK, Savary B, Varin L, Dupeyrat J, Ramakers S, Hanouz JL: Clinical and EEG features of acute intrathecal baclofen overdose. Clin Neurol Neurosurg 2012;114:84-86.
49.
Sullivan R, Hodgman MJ, Kao L, Tormoehlen LM: Baclofen overdose mimicking brain death. Clin Toxicol (Phila) 2012;50:141-144.
50.
Wall GC, Wasiak A, Hicklin GA: An initially unsuspected case of baclofen overdose. Am J Crit Care 2006;15:611-613.
51.
Chong CF, Wang TL: An unusual presentation of baclofen overdose. Emerg Med J 2005;22:673-674.
52.
Saissy JM, Vitris M, Demazière J, Seck M, Marcoux L, Gaye M: Flumazenil counteracts intrathecal baclofen-induced central nervous system depression in tetanus. Anesthesiology 1992;76:1051-1053.
53.
Dias LS, Vivek G, Manthappa M, Acharya RV: Role of hemodialysis in baclofen overdose with normal renal function. Indian J Pharmacol 2011;43:722-723.
54.
Wu VC, Lin SL, Lin SM, Fang CC: Treatment of baclofen overdose by haemodialysis: a pharmacokinetic study. Nephrol Dial Transplant 2005;20:441-443.
55.
Leo RJ, Baer D: Delirium associated with baclofen withdrawal: a review of common presentations and management strategies. Psychosomatics 2005;46:503-507.
56.
Barker I, Grant IS: Convulsions after abrupt withdrawal of baclofen. Lancet 1982;ii:556-557.
57.
Greenberg MI, Hendrickson RG: Baclofen withdrawal following removal of an intrathecal baclofen pump despite oral baclofen replacement. J Toxicol Clin Toxicol 2003;41:83-85.
58.
Karol DE, Muzyk AJ, Preud'homme XA: A case of delirium, motor disturbances, and autonomic dysfunction due to baclofen and tizanidine withdrawal: a review of the literature. Gen Hosp Psychiatry 2011;33:84.e1-84.e2.
59.
Malhotra T, Rosenzweig I: Baclofen withdrawal causes psychosis in otherwise unclouded consciousness. J Neuropsychiatry Clin Neurosci 2009;21:476.
60.
Ratnayaka BD, Dhaliwal H, Watkin S: Drug points: neonatal convulsions after withdrawal of baclofen. BMJ 2001;323:85.
61.
Ross JC, Cook AM, Stewart GL, Fahy BG: Acute intrathecal baclofen withdrawal: a brief review of treatment options. Neurocrit Care 2011;14:103-108.
62.
Specchio N, Carotenuto A, Trivisano M, Cappelletti S, Vigevano F, Fusco L: Prolonged episode of dystonia and dyskinesia resembling status epilepticus following acute intrathecal baclofen withdrawal. Epilepsy Behav 2011;21:321-323.
63.
Terrence CF, Fromm GH: Complications of baclofen withdrawal. Arch Neurol 1981;38:588-589.
64.
Green LB, Nelson VS: Death after acute withdrawal of intrathecal baclofen: case report and literature review. Arch Phys Med Rehabil 1999;80:1600-1604.
65.
Meinck HM, Tronnier V, Rieke K, Wirtz CR, Flügel D, Schwab S: Intrathecal baclofen treatment for stiff-man syndrome: pump failure may be fatal. Neurology 1994;44:2209-2210.
66.
Kleber HD, Weiss RD, Anton RF Jr, George TP, Greenfield SF, Kosten TR, O'Brien CP, Rounsaville BJ, Strain EC, Ziedonis DM, Hennessy G, Connery HS, McIntyre JS, Charles SC, Anzia DJ, Cook IA, Finnerty MT, Johnson BR, Nininger JE, Summergrad P, Woods SM, Yager J, Pyles R, Cross CD, Peele R, Shemo JP, Lurie L, Walker RD, Barnovitz MA, Gray SH, Saxena S, Tonnu T, Kunkle R, Albert AB, Fochtmann LJ, Hart C, Regier D; Work Group on Substance Use Disorders; American Psychiatric Association; Steering Committee on Practice Guidelines: Treatment of patients with substance use disorders, second edition. American Psychiatric Association. Am J Psychiatry 2007;164(4 suppl):5-123.
67.
Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA; Cochrane Bias Methods Group; Cochrane Statistical Methods Group: The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928.
68.
Higgins JP, Thompson SG, Deeks JJ, Altman DG: Measuring inconsistency in meta-analyses. BMJ 2003;327:557-560.
69.
Egger M, Davey Smith G, Schneider M, Minder C: Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629-634.
70.
Duval S, Tweedie R: A nonparametric ‘trim and fill' method of accounting for publication bias in meta-analysis. J Am Stat Assoc 2000;95:89-98.
71.
DerSimonian R, Laird N: Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-188.
72.
Rosenthal R: The ‘file drawer problem' and tolerance for null results. Psychol Bull 1979;86:638-641.
73.
Addolorato G, Caputo F, Capristo E, Domenicali M, Bernardi M, Janiri L, Agabio R, Colombo G, Gessa GL, Gasbarrini G: Baclofen efficacy in reducing alcohol craving and intake: a preliminary double-blind randomized controlled study. Alcohol Alcohol 2002;37:504-508.
74.
Addolorato G, Leggio L, Ferrulli A, Cardone S, Vonghia L, Mirijello A, Abenavoli L, D'Angelo C, Caputo F, Zambon A, Haber PS, Gasbarrini G: Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomised, double-blind controlled study. Lancet 2007;370:1915-1922.
75.
Addolorato G, Leggio L, Ferrulli A, Cardone S, Bedogni G, Caputo F, Gasbarrini G, Landolfi R: Dose-response effect of baclofen in reducing daily alcohol intake in alcohol dependence: secondary analysis of a randomized, double-blind, placebo-controlled trial. Alcohol Alcohol 2011;46:312-317.
76.
Ahmadi-Abhari SA, Akhondzadeh S, Assadi SM, Shabestari OL, Farzanehgan ZM, Kamlipour A: Baclofen versus clonidine in the treatment of opiates withdrawal, side-effects aspect: a double-blind randomized controlled trial. J Clin Pharm Ther 2001;26:67-71.
77.
Akhondzadeh S, Ahmadi-Abhari SA, Assadi SM, Shabestari OL, Kashani AR, Farzanehgan ZM: Double-blind randomized controlled trial of baclofen vs. clonidine in the treatment of opiates withdrawal. J Clin Pharm Ther 2000;25:347-353.
78.
Assadi SM, Radgoodarzi R, Ahmadi-Abhari SA: Baclofen for maintenance treatment of opioid dependence: a randomized double-blind placebo-controlled clinical trial [ISRCTN32121581]. BMC Psychiatry 2003;3:16.
79.
Franklin TR, Harper D, Kampman K, Kildea-McCrea S, Jens W, Lynch KG, O'Brien CP, Childress AR: The GABA B agonist baclofen reduces cigarette consumption in a preliminary double-blind placebo-controlled smoking reduction study. Drug Alcohol Depend 2009;103:30-36.
80.
Garbutt JC, Kampov-Polevoy AB, Gallop R, Kalka-Juhl L, Flannery BA: Efficacy and safety of baclofen for alcohol dependence: a randomized, double-blind, placebo-controlled trial. Alcohol Clin Exp Res 2010;34:1849-1857.
81.
Heinzerling KG, Shoptaw S, Peck JA, Yang X, Liu J, Roll J, Ling W: Randomized, placebo-controlled trial of baclofen and gabapentin for the treatment of methamphetamine dependence. Drug Alcohol Depend 2006;85:177-184.
82.
Kahn R, Biswas K, Childress AR, Shoptaw S, Fudala PJ, Gorgon L, Montoya I, Collins J, McSherry F, Li SH, Chiang N, Alathari H, Watson D, Liberto J, Beresford T, Stock C, Wallace C, Gruber V, Elkashef A: Multi-center trial of baclofen for abstinence initiation in severe cocaine-dependent individuals. Drug Alcohol Depend 2009;103:59-64.
83.
Lyon JE, Khan RA, Gessert CE, Larson PM, Renier CM: Treating alcohol withdrawal with oral baclofen: a randomized, double-blind, placebo-controlled trial. J Hosp Med 2011;6:474-479.
84.
Shoptaw S, Yang X, Rotheram-Fuller EJ, Hsieh YC, Kintaudi PC, Charuvastra VC, Ling W: Randomized placebo-controlled trial of baclofen for cocaine dependence: preliminary effects for individuals with chronic patterns of cocaine use. J Clin Psychiatry 2003;64:1440-1448.
85.
Daoust M, Saligaut C, Lhuintre JP, Moore N, Flipo JL, Boismare F: GABA transmission, but not benzodiazepine receptor stimulation, modulates ethanol intake by rats. Alcohol 1987;4:469-472.
86.
Quintanilla ME, Perez E, Tampier L: Baclofen reduces ethanol intake in high-alcohol-drinking University of Chile bibulous rats. Addict Biol 2008;13:326-336.
87.
Smith BR, Boyle AEL, Amit Z: The effects of GABAB agonist baclofen on the temporal and structural characteristics of ethanol intake. Alcohol 1999;17:231-240.
88.
Stromberg MF: The effect of baclofen alone and in combination with naltrexone on ethanol consumption in the rat. Pharmacol Biochem Behav 2004;78:743-750.
89.
Colombo G, Serra S, Brunetti G, Vacca G, Carai MAM, Gessa GL: Suppression by baclofen of alcohol deprivation effect in Sardinian alcohol-preferring (sP) rats. Drug Alcohol Depend 2003;70:105-108.
90.
Colombo G, Serra S, Vacca G, Carai MAM, Gessa GL: Baclofen-induced suppression of alcohol deprivation effect in Sardinian alcohol-preferring (sP) rats exposed to different alcohol concentrations. Eur J Pharmacol 2006;550:123-126.
91.
Anstrom KK, Cromwell HC, Markowski T, Woodward DJ: Effect of baclofen on alcohol and sucrose self-administration in rats. Alcohol Clin Exp Res 2003;27:900-908.
92.
Besheer J, Lepoutre V, Hodge CW: GABAB receptor agonists reduce operant ethanol self-administration and enhance ethanol sedation in C57BL/6J mice. Psychopharmacology (Berl) 2004;174:358-366.
93.
Duke AN, Kaminski BJ, Weerts EM: Baclofen effects on alcohol seeking, self-administration and extinction of seeking responses in a within-session design in baboons. Addict Biol 2012, E-pub ahead of print.
94.
Janak PH, Gill TM: Comparison of the effects of allopregnanolone with direct GABAergic agonists on ethanol self-administration with and without concurrently available sucrose. Alcohol 2003;30:1-7.
95.
Liang JH, Chen F, Krstew E, Cowen MS, Carroll FY, Crawford D, Beart PM, Lawrence AJ: The GABAB receptor allosteric modulator CGP7930, like baclofen, reduces operant self-administration of ethanol in alcohol-preferring rats. Neuropharmacology 2006;50:632-639.
96.
Maccioni P, Serra S, Vacca G, Orrù A, Pes D, Agabio R, Addolorato G, Carai MA, Gessa GL, Colombo G: Baclofen-induced reduction of alcohol reinforcement in alcohol-preferring rats. Alcohol 2005;36:161-168.
97.
Maccioni P, Colombo G: Role of the GABA(B) receptor in alcohol seeking and drinking behavior. Alcohol 2009;43:555-558.
98.
Maccioni P, Zaru A, Loi B, Lobina C, Carai MAM, Gessa GL, Capra A, Mugnaini C, Pasquini S, Corelli F, Hyytiä P, Lumeng L, Colombo G: Comparison of the effect of the GABAB receptor agonist, baclofen, and the positive allosteric modulator of the GABAB receptor, GS39783, on alcohol self-administration in three different lines of alcohol-preferring rats. Alcohol Clin Exp Res 2012;36:1748-1766.
99.
Walker BM, Koob GF: The γ-aminobutyric acid-B receptor agonist baclofen attenuates responding for ethanol in ethanol-dependent rats. Alcohol Clin Exp Res 2007;31:11-18.
100.
Maccioni P, Bienkowski P, Carai MA, Gessa GL, Colombo G: Baclofen attenuates cue-induced reinstatement of alcohol-seeking behavior in Sardinian alcohol-preferring (sP) rats. Drug Alcohol Depend 2008;95:284-287.
101.
Bechtholt AJ, Cunningham CL: Ethanol-induced conditioned place preference is expressed through a ventral tegmental area dependent mechanism. Behav Neurosci 2005;119:213-223.
102.
Arias C, Mlewski EC, Molina JC, Spear NE: Naloxone and baclofen attenuate ethanol's locomotor-activating effects in preweanling Sprague-Dawley rats. Behav Neurosci 2009;123:172-180.
103.
Boehm SL 2nd, Piercy MM, Bergstrom HC, Phillips TJ: Ventral tegmental area region governs GABAB receptor modulation of ethanol-stimulated activity in mice. Neuroscience 2002;115:185-200.
104.
Chester JA, Cunningham CL: Baclofen alters ethanol-stimulated activity but not conditioned place preference or taste aversion in mice. Pharmacol Biochem Behav 1999;63:325-331.
105.
Holstein SE, Dobbs L, Phillips TJ: Attenuation of the stimulant response to ethanol is associated with enhanced ataxia for a GABAA, but not a GABAB, receptor agonist. Alcohol Clin Exp Res 2009;33:108-120.
106.
Petry NM: Benzodiazepine-GABA modulation of concurrent ethanol and sucrose reinforcement in the rat. Exp Clin Psychopharmacol 1997;5:183-194.
107.
Czachowski CL, Legg BH, Stansfield KH: Ethanol and sucrose seeking and consumption following repeated administration of the GABA(B) agonist baclofen in rats. Alcohol Clin Exp Res 2006;30:812-818.
108.
Ameisen O: Complete and prolonged suppression of symptoms and consequences of alcohol-dependence using high-dose baclofen: a self-case report of a physician. Alcohol Alcohol 2005;40:147-150.
109.
Bucknam W: Suppression of symptoms of alcohol dependence and craving using high-dose baclofen. Alcohol Alcohol 2007;42:158-160.
110.
Pastor A, Jones DM, Currie J: High-dose baclofen for treatment-resistant alcohol dependence. J Clin Psychopharmacol 2012;32:266-268.
111.
Agabio R, Marras P, Addolorato G, Carpiniello B, Gessa GL: Baclofen suppresses alcohol intake and craving for alcohol in a schizophrenic alcohol-dependent patient: a case report. J Clin Psychopharmacol 2007;27:319-320.
112.
Dore GM, Lo K, Juckes L, Bezyan S, Latt N: Clinical experience with baclofen in the management of alcohol-dependent patients with psychiatric comorbidity: a selected case series. Alcohol Alcohol 2011;46:714-720.
113.
Addolorato G, Caputo F, Capristo E, Colombo G, Gessa GL, Gasbarrini G: Ability of baclofen in reducing alcohol craving and intake. II. Preliminary clinical evidence. Alcohol Clin Exp Res 2000;24:67-71.
114.
Flannery BA, Garbutt JC, Cody MW, Renn W, Grace K, Osborne M, Crosby K, Morreale M, Trivette A: Baclofen for alcohol dependence: a preliminary open-label study. Alcohol Clin Exp Res 2004;28:1517-1523.
115.
Rigal L, Alexandre-Dubroeucq C, de Beaurepaire R, Le Jeunne C, Jaury P: Abstinence and ‘low-risk' consumption 1 year after the initiation of high-dose baclofen: a retrospective study among ‘high-risk' drinkers. Alcohol Alcohol 2012;47:439-442.
116.
de Beaurepaire R: Suppression of alcohol dependence using baclofen: a 2-year observational study of 100 patients. Front Psychiatry 2012;3:103.
117.
Evans SM, Bisaga A: Acute interaction of baclofen in combination with alcohol in heavy social drinkers. Alcohol Clin Exp Res 2009;33:19-30.
118.
Leggio L, Zywiak WH, McGeary JE, Edwards S, Fricchione SR, Shoaff JR, Addolorato G, Swift RM, Kenna GA: A human laboratory pilot study with baclofen in alcoholic individuals. Pharmacol Biochem Behav 2013;103:784-791.
119.
Leggio L, Garbutt JC, Addolorato G: Effectiveness and safety of baclofen in the treatment of alcohol dependent patients. CNS Neurol Disord Drug Targets 2010;9:33-44.
120.
File SE, Zharkovsky A, Gulati K: Effects of baclofen and nitrendipine on ethanol withdrawal responses in the rat. Neuropharmacology 1991;30:183-190.
121.
Knapp DJ, Overstreet DH, Breese GR: Baclofen blocks expression and sensitization of anxiety-like behavior in an animal model of repeated stress and ethanol withdrawal. Alcohol Clin Exp Res 2007;31:582-595.
122.
Humeniuk RE, White JM, Ong J: The effects of GABAB ligands on alcohol withdrawal in mice. Pharmacol Biochem Behav 1994;49:561-566.
123.
Addolorato G, Caputo F, Capristo E, Janiri L, Bernardi M, Agabio R, Colombo G, Gessa GL, Gasbarrini G: Rapid suppression of alcohol withdrawal syndrome by baclofen. Am J Med 2002;112:226-229.
124.
Addolorato G, Leggio L, Abenavoli L, DeLorenzi G, Parente A, Caputo F, Janiri L, Capristo E, Rapaccini GL, Gasbarrini G: Suppression of alcohol delirium tremens by baclofen administration: a case report. Clin Neuropharmacol 2003;26:258-262.
125.
Stallings W, Schrader S: Baclofen as prophylaxis and treatment for alcohol withdrawal: a retrospective chart review. J Okla State Med Assoc 2007;100:354-360.
126.
Addolorato G, Leggio L, Abenavoli L, Agabio R, Caputo F, Capristo E, Colombo G, Gessa GL, Gasbarrini G: Baclofen in the treatment of alcohol withdrawal syndrome: a comparative study vs. diazepam. Am J Med 2006;119:276.e13-276.e18.
127.
Liu J, Wang L: Baclofen for alcohol withdrawal. Cochrane Database Syst Rev 2011;19:CD008502.
128.
Brebner K, Phelan R, Roberts DC: Effect of baclofen on cocaine self-administration in rats reinforced under fixed-ratio 1 and progressive-ratio schedules. Psychopharmacology (Berl) 2000;148:314-321.
129.
Campbell UC, Lac ST, Carroll ME: Effects of baclofen on maintenance and reinstatement of intravenous cocaine self-administration in rats. Psychopharmacology (Berl) 1999;143:209-214.
130.
Roberts DCS, Andrews MM, Vickers GJ: Baclofen attenuates the reinforcing effects of cocaine in rats. Neuropsychopharmacology 1996;15:417-423.
131.
Roberts DCS, Andrews MM: Baclofen suppression of cocaine self-administration: demonstration using a discrete trials procedure. Psychopharmacology (Berl) 1997;131:271-277.
132.
Shoaib M, Swanner LS, Beyer CE, Goldberg SR, Schindler CW: The GABAB agonist baclofen modifies cocaine self-administration in rats. Behav Pharmacol 1998;9:195-206.
133.
Munzar P, Kutkat SW, Miller CR, Goldberg SR: Failure of baclofen to modulate discriminative-stimulus effects of cocaine or methamphetamine in rats. Eur J Pharmacol 2000;408:169-174.
134.
Brebner K, Childress AR, Roberts DC: A potential role for GABA(B) agonists in the treatment of psychostimulant addiction. Alcohol Alcohol 2002;37:478-484.
135.
Kaplan GB, McRoberts RL 3rd, Smokler HJ: Baclofen as adjunctive treatment for a patient with cocaine dependence and schizoaffective disorder. J Clin Psychopharmacol 2004;24:574-575.
136.
Ling W, Shoptaw S, Majewska D: Baclofen as a cocaine anti-craving medication: a preliminary clinical study. Neuropsychopharmacology 1998;18:403-404.
137.
Rotheram-Fuller E, De La Garza R 2nd, Mahoney JJ 3rd, Shoptaw S, Newton TF: Subjective and cardiovascular effects of cocaine during treatment with amantadine and baclofen in combination. Psychiatry Res 2007;152:205-210.
138.
Lile JA, Stoops WW, Allen TS, Glaser PE, Hays LR, Rush CR: Baclofen does not alter the reinforcing, subject-rated or cardiovascular effects of intranasal cocaine in humans. Psychopharmacology (Berl) 2004;171:441-449.
139.
Haney M, Hart CL, Foltin RW: Effects of baclofen on cocaine self-administration: opioid- and nonopioid-dependent volunteers. Neuropsychopharmacology 2006;31:1814-1821.
140.
Bartoletti M, Colantoni A, De Luca V, Gaiardi M: Single and repeated baclofen treatment attenuates the discriminative stimulus effects of morphine in rats. Pharmacol Biochem Behav 2010;97:279-283.
141.
Xi ZX, Stein EA: Baclofen inhibits heroin self-administration behavior and mesolimbic dopamine release. J Pharmacol Exp Ther 1999;290:1369-1374.
142.
Bexis S, Ong J, White J: Attenuation of morphine withdrawal signs by the GABA(B) receptor agonist baclofen. Life Sci 2001;70:395-401.
143.
Diaz SL, Kemmling AK, Rubio MC, Balerio GN: Lack of sex-related differences in the prevention by baclofen of the morphine withdrawal syndrome in mice. Behav Pharmacol 2001;12:75-79.
144.
Kemmling AK, Rubio MC, Balerio GN: Baclofen prevents morphine withdrawal irrespective of seasonal variation. Behav Pharmacol 2002;13:87-92.
145.
Zarrindast MR, Mousa-Ahmadi E: Effects of GABAergic system on naloxone-induced jumping in morphine-dependent mice. Eur J Pharmacol 1999;381:129-133.
146.
Krystal JH, McDougle CJ, Kosten TR, Price LH, Aghajanian GK, Charney DS: Baclofen-assisted detoxification from opiates. A pilot study. J Subst Abuse Treat 1992;9:139-142.
147.
Corrigall WA, Coen KM, Adamson KL, Chow BL, Zhang J: Response of nicotine self-administration in the rat to manipulations of mu-opioid and gamma-aminobutyric acid receptors in the ventral tegmental area. Psychopharmacology (Berl) 2000;149:107-114.
148.
Fattore L, Cossu G, Martellotta MC, Fratta W: Baclofen antagonizes intravenous self-administration of nicotine in mice and rats. Alcohol Alcohol 2002;37:495-498.
149.
Paterson NE, Froestl W, Markou A: The GABAB receptor agonists baclofen and CGP44532 decreased nicotine self-administration in the rat. Psychopharmacology (Berl) 2004;172:179-186.
150.
Le Foll B, Wertheim CE, Goldberg SR: Effects of baclofen on conditioned rewarding and discriminative stimulus effects of nicotine in rats. Neurosci Lett 2008;443:236-240.
151.
Fattore L, Spano MS, Cossu G, Scherma M, Fratta W, Fadda P: Baclofen prevents drug-induced reinstatement of extinguished nicotine-seeking behaviour and nicotine place preference in rodents. Eur Neuropsychopharmacol 2009;19:487-498.
152.
Fadda P, Scherma M, Fresu A, Collu M, Fratta W: Baclofen antagonizes nicotine-, cocaine-, and morphine-induced dopamine release in the nucleus accumbens of rat. Synapse 2003;50:1-6.
153.
Varani AP, Moutinho LM, Calvo M, Balerio GN: Ability of baclofen to prevent somatic manifestations and neurochemical changes during nicotine withdrawal. Drug Alcohol Depend 2011;119:e5-e12.
154.
Cousins MS, Stamat HM, de Wit H: Effects of a single dose of baclofen on self-reported subjective effects and tobacco smoking. Nicotine Tob Res 2001;3:123-129.
155.
Nanjayya SB, Shivappa M, Chand PK, Murthy P, Benegal V: Baclofen in cannabis dependence syndrome. Biol Psychiatry 2010;68:e9-e10.
156.
Haney M, Hart CL, Vosburg SK, Comer SD, Reed SC, Cooper ZD, Foltin RW: Effects of baclofen and mirtazapine on a laboratory model of marijuana withdrawal and relapse. Psychopharmacology (Berl) 2010;211:233-244.
157.
Brebner K, Ahn S, Phillips AG: Attenuation of d-amphetamine self-administration by baclofen in the rat: behavioral and neurochemical correlates. Psychopharmacology (Berl) 2005;177:409-417.
158.
Li SM, Yin LL, Ren YH, Pan LS, Zheng JW: GABA(B) receptor agonist baclofen attenuates the development and expression of d-methamphetamine-induced place preference in rats. Life Sci 2001;70:349-356.
159.
Ranaldi R, Poeggel K: Baclofen decreases methamphetamine self-administration in rats. Neuroreport 2002;13:1107-1110.
160.
Muralidharan K, Rajkumar RP, Mulla U, Nayak RB, Benegal V: Baclofen in the management of inhalant withdrawal: a case series. Prim Care Companion J Clin Psychiatry 2008;10:48-51.
161.
Vlachou S, Markou A: GABAB receptors in reward processes. Adv Pharmacol 2010;58:315-371.
162.
Colombo G, Addolorato G, Agabio R, Carai MA, Pibiri F, Serra S, Vacca G, Gessa GL: Role of GABA(B) receptor in alcohol dependence: reducing effect of baclofen on alcohol intake and alcohol motivational properties in rats and amelioration of alcohol withdrawal syndrome and alcohol craving in human alcoholics. Neurotox Res 2004;6:403-414.
163.
Mordenti J: Man versus beast: pharmacokinetic scaling in mammals. J Pharm Sci 1986;75:1028-1040.
164.
Morris TH: Antibiotic therapeutics in laboratory animals. Lab Anim 1995;29:16-36.
165.
Johnson BA: Medication treatment of different types of alcoholism. Am J Psychiatry 2010;167:630-639.
166.
Sturgess JE, George TP, Kennedy JL, Heinz A, Müller DJ: Pharmacogenetics of alcohol, nicotine and drug addiction treatments. Addict Biol 2011;16:357-376.
167.
Heydtmann M: Baclofen effect related to liver damage. Alcohol Clin Exp Res 2011;35:848.
168.
Cartlidge NE, Hudgson P, Weightman D: A comparison of baclofen and diazepam in the treatment of spasticity. J Neurol Sci 1974;23:17-24.
169.
Roussan M, Terrence C, Fromm G: Baclofen versus diazepam for the treatment of spasticity and long-term follow-up of baclofen therapy. Pharmatherapeutica 1985;4:278-284.
170.
Leggio L, Kenna GA, Swift RM: New developments for the pharmacological treatment of alcohol withdrawal syndrome. A focus on non-benzodiazepine GABAergic medications. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:1106-1117.
171.
Macaigne G, Champagnon N, Harnois F, Cheiab S, Chayette C: Baclofen-induced acute hepatitis in alcohol-dependent patient. Clin Res Hepatol Gastroenterol 2011;35:420-421.
172.
Bombardier CH, Blake KD, Ehde DM, Gibbons LE, Moore D, Kraft GH: Alcohol and drug abuse among persons with multiple sclerosis. Mult Scler 2004;10:35-40.
173.
Turner AP, Hawkins EJ, Haselkorn JK, Kivlahan DR: Alcohol misuse and multiple sclerosis. Arch Phys Med Rehabil 2009;90:842-848.
174.
Saddichha S, Jayaram N, Manjunatha N, Benegal V: Baclofen-induced morbiliform rashes: a case series. J Clin Pharmacol 2011;51:1733-1734.
175.
Rolland B, Bordet R, Cottencin O: Alcohol-dependence: the current French craze for baclofen. Addiction 2012;107:848-849.
176.
Gorsane MA, Kebir O, Hache G, Blecha L, Aubin HJ, Reynaud M, Benyamina A: Is baclofen a revolutionary medication in alcohol addiction management? Review and recent updates. Subst Abus 2012;33:336-349.
177.
Enserink M: Addiction research. Anonymous alcoholic bankrolls trial of controversial therapy. Science 2011;332:653.
178.
Filip M, Frankowska M, Przegaliński E: Effects of GABAB receptor antagonist, agonists and allosteric positive modulator on the cocaine-induced self-administration and drug discrimination. Eur J Pharmacol 2007;574:148-157.
179.
Lhuillier L, Mombereau C, Cryan JF, Kaupmann K: GABAB receptor-positive modulation decreases selective, molecular and behavioral effects of cocaine. Neuropsychopharmacology 2007;32:388-398.
180.
Paterson NE, Vlachou S, Guery S, Kaupmann K, Froestl W, Markou A: Positive modulation of GABAB receptors decreased nicotine self-administration and counteracted nicotine-induced enhancement of brain reward function in rats. J Pharmacol Exp Ther 2008;326:306-314.
181.
Slattery DA, Markou A, Froestl W, Cryan JF: The GABAB receptor-positive modulator GS39783 and the GABAB receptor agonist baclofen attenuate the reward-facilitating effects of cocaine: intracranial self-stimulation studies in the rat. Neuropsychopharmacology 2005;30:2065-2072.
182.
Smith MA, Yancey DL, Morgan D, Liu Y, Froestl W, Roberts DC: Effects of positive allosteric modulators of the GABAB receptor on cocaine self-administration in rats. Psychopharmacology (Berl) 2004;173:105-111.
183.
Adams CL, Lawrence AJ: CGP7930: a positive allosteric modulator of the GABAB receptor. CNS Drug Rev 2007;13:308-316.
184.
Agabio R, Maccioni P, Carai MAM, Gessa GL, Froestl W, Colombo G: The development of medication for alcohol-use disorders targeting the GABAB receptor system. Recent Pat CNS Drug Discov 2012;7:113-128.
185.
Muzyk AJ, Rivelli SK, Gagliardi JP: Defining the role of baclofen for the treatment of alcohol dependence: a systematic review of the evidence. CNS Drugs 2012;26:69-78.
186.
Mark TL, Kranzler HR, Song X, Bransberger P, Poole VH, Crosse S: Physicians' opinions about medications to treat alcoholism. Addiction 2003;98:617-626.
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