A Review of the Potential Mechanisms of Action of Baclofen in Alcohol Use Disorder

Role of ventral subiculum in context-induced relapse to alcohol seeking after punishment-imposed abstinence. Intra-nucleus accumbens shell injections of R(+)- and S(-)-baclofen bidirectionally alter binge-like ethanol, but not saccharin, intake in C57Bl/6J mice. Site-specific microinjection of baclofen into the anterior ventral tegmental area reduces binge-like ethanol intake in male C57BL/6J mice. Baclofen-induced reduction of alcohol reinforcement in alcohol-preferring rats. Comparison of the effects of allopregnanolone with direct GABAergic agonists on ethanol self-administration with and without concurrently available sucrose. 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.

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Baclofen is being explored as an “opioid replacement” because it has similar pain-relieving qualities to opioids, although it doesn’t interact with the opioid receptors in the brain. If you or someone you know is misusing baclofen, it’s important to understand the side effects, dangers, and treatment options for baclofen use disorder. Pharmacotherapy for anxiety and comorbid alcohol use disorders. Double blind placebo controlled randomized pilot clinical trial of baclofen (Baclosan(R)) for alcohol dependence. A human laboratory pilot study with baclofen in alcoholic individuals. Yamini D, Lee SH, Avanesyan A, Walter M, Runyon B. Utilization of baclofen in maintenance of alcohol abstinence in patients with alcohol dependence and alcoholic hepatitis with or without cirrhosis.

Given that the microinjection of baclofen in the VTA dampens the activity of dopaminergic neurons, it has been hypothesized that baclofen may exert its anti-addictive properties by means of its ability to reduce the activity of dopaminergic neurons (74). That baclofen reduces alcohol consumption in animal models has been further strengthened by the demonstration that R(+)-baclofen, and not S(-)-baclofen selectively reduces self-administration of alcohol in rats (66). These regions are not primarily dopaminergic, but nevertheless receive dopaminergic projections, and, for many of them, they are part of the reward network (38). According to Keegan et al. neuroadaptation mediated by G-proteins correlates with tolerance, while signaling alterations via kinase cascades shows cross-talk between GABA-B receptors and alternative mechanisms that are resistant to desensitization.

Medical uses

Table 3 shows open studies in which baclofen was administered to help AUD patients to achieve abstinence or reduce alcohol consumption see Table 3; (42–47). Three studies found that patients without comorbid mental disorders achieved better results compared to patients with comorbid mental disorders anxiety, depression, and/or borderline personality disorder; 27–29]. The majority of these patients suffered mainly from anxiety and depression (27, 36, 37), whereas two studies were conducted in AUD patients with clinically-significant liver disease (38, 41).

Routes of administration

Agabio R, Leite-Morris K, Addolorato G, Colombo G. Targeting the GABAB receptor for the treatment of alcohol use disorder. The american psychiatric association practice guideline for the pharmacological treatment of patients with alcohol use disorder. A recent meta-analysis also found no difference between baclofen and placebo in reducing both depression and anxiety levels among AUD patients (64). However, in this study, baclofen administration did not significantly reduce anxiety levels. Therefore, these results do not allow us o evaluate whether baclofen efficacy is different in AUD patients with comorbid psychiatric disorders compared to those without. The present narrative mini-review was aimed at investigating the role of psychiatric comorbidity in explaining potential different responses to baclofen treatment among AUD patients.

What may interact with this medication?

Baclofen tablets, USP may also be of some value in patients with spinal cord injuries and other spinal cord diseases. Our Baclofen Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication. During pregnancy, baclofen should be used only when prescribed. Combining baclofen and tricyclic antidepressants may cause muscle weakness. Check with your physician for additional information about side effects.

Withdrawal symptoms are more likely if baclofen is administered intrathecally or for long periods of time (more than a couple of months) and can occur from low or high doses. Baclofen is primarily used for the treatment of spastic movement disorders, especially in instances of spinal cord injury, and multiple sclerosis. Serious side effects, such as seizures and rhabdomyolysis, may occur if use of baclofen is stopped abruptly. Generally speaking, it is very likely that all effective AUD treatments, whether pharmacological, psychological, or using local stimulation, do so by normalizing functional connectivity, possibly leading to a decrease in the strength of appetitive networks and to an increase of that of executive control regions, with a recovery of balanced cross-talk between the different local functions. B, baclofen; Eth, ethanol; VTA-NAc, Ventral Tegmental Area-Nucleus Accumbens; Gaba inhibition, local injection of baclofen+muscimol; TMS, Transcranial Magnetic Stimulation; DBS, Deep Brain Stimulation.

Baclofen may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

This will help them determine if baclofen is right for you. Read and follow the “Instructions for Use” that come with your baclofen. If you take the baclofen oral granules, you can either let them dissolve in your mouth or swallow them. Be sure to check the dosage before you take baclofen liquid. A household spoon is not an accurate measuring device and may cause you to take the wrong dose.

In most cases these cysts disappeared spontaneously while patients continued to receive the drug. Because of the possibility of sedation, patients should be cautioned regarding the operation of automobiles or other dangerous machinery, and activities made hazardous by decreased alertness. Baclofen Tablets, USP 5 mg are available as a White to off white, round flat-faced, beveled edge tablets debossed with “023” on one side and plain on other side, containing 5 mg baclofen USP packaged in bottles of 100 tablets.

• Spatial distribution of GABA(B)R1 receptor mRNA and binding sites in the rat brain.
• Baclofen tablets, USP are not indicated in the treatment of skeletal muscle spasm resulting from rheumatic disorders.
• If it is almost time for your next dose, take only that dose.
• If you take the baclofen oral granules, you can either let them dissolve in your mouth or swallow them.
• For instance, naltrexone and disulfiram are contraindicated amongst patients with clinically-relevant liver diseases; on the other hand, acamprosate is contraindicated in patients with kidney failure.
• On the other hand, inhibition of dopaminergic systems has been consistently related to apathy, anhedonia and depression (78).

Intensive inpatient treatment, also known as “medically managed” treatment, is considered the highest level of care for addiction treatment. Several treatment levels are available, depending on the severity of your addiction. This is why seeking addiction treatment is critical to protecting your well-being and ensuring a safe recovery.

Take the missed dose as soon as you remember it. Your doctor probably will want to decrease your dose gradually. baclofen addiction potential Continue to take baclofen even if you feel well. You may report side effects to FDA at FDA-1088. Call your doctor for medical advice about side effects.

• Do not drive or do other activities that require alertness or coordination until you know how baclofen affects you.
• The interaction may increase the sedative effects of all ingested sedatives and as such is not generally recommended.
• In two studies, participants had high baseline anxiety levels (23, 50), in two other studies high baseline depression levels (52, 58), and in three studies both high baseline anxiety and depression levels (25, 51, 56).

Some side effects can be serious. If you experience either of the following symptoms, call your doctor immediately:

Only a few studies used interviewer-rated scales such as HAM-A (Hamilton Anxiety Rating Scale) for anxiety and HAM-D (Hamilton Depression Rating Scale) or MADRS (Montgomery-Asberg Depression Scale) for depression. Most studies used self-reported rating scales such as STAI (Spielberger State Trait Anxiety Inventory) for anxiety and BDI (Beck’s Depression Inventory) or ZUNG for depression. All the studies, except two (49, 54), reported the mean values of anxiety and/or depression levels. Participants received daily doses of baclofen ranging from 30 to 180 mg for a timeframe ranging from 3 to 26 weeks. The findings of the randomized, double-blind placebo-controlled trials of baclofen in the treatment of AUD are outlined in Table 5 (23–25, 49–59). In the other one, participants had high anxiety levels (see Table 4), but only a few participants had a formal diagnosis, based on DSM-IV, of current anxiety disorders (5 out of 34) or current mood disorder (1 out of 34) (26).

You should not drive until you know how baclofen affects you. Common side effects include dizziness and drowsiness. From 2014 to 2017, baclofen misuse, toxicity and use in suicide attempts among adults in the US increased. At the same time the blood concentration levels are almost undetectable, thus minimizing side effects. 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. Intrathecal baclofen was first introduced in 1984 to treat severe spinal spasticity.

Long-Term Network Alterations

Ameisen O. Are the effects of gamma-hydroxybutyrate (GHB) treatment partly physiological in alcohol dependence? Differential development of tolerance to the functional and behavioral effects of repeated baclofen treatment in rats. Differential effects of chronic amphetamine and baclofen administration on cAMP levels and phosphorylation of CREB in distinct brain regions of wild type and monoamine oxidase B-deficient mice.

Abuse

Swift R. Medications acting on the dopaminergic system in the treatment of alcoholic patients. Baclofen administration for the treatment of affective disorders in alcoholic patients. It is also proposed that this action is made possible by the fact that baclofen and alcohol act on similar brain systems in certain regions of the brain. Besides, it has been shown that stimulation of presynaptic GABA-B receptors decreases the GABAergic effects of alcohol (86), demonstrating that GABA-B activation can moderate the behavioral sensitivity to alcohol.