As with any other type of drug abuse, too much baclofen can also lead to sudden death. Taking more than 200 mg of baclofen can worsen the chance of life-threatening outcomes. People in the withdrawal process and relapse are at a higher risk of overdose. In the case of baclofen, kidney damage, liver disease, and memory impairment are just some outcomes that could permanently impact your quality of life with baclofen misuse.
It’s available in both a tablet and liquid form taken orally or an injectable form, which has the strongest effects. Those without a prescription for baclofen may obtain it and take it because it relieves pain and baclofen addiction potential relaxes the body, which can lead to feelings of elatedness in large quantities. It’s typically given to patients experiencing muscle stiffness and tightness due to conditions such as spinal cord injuries and diseases.
- Lu et al. reported strong expression of GABBR1 in the medial habenula, hippocampus, hypothalamus (supraoptic and suprachiasmatic nuclei), and cerebellum; intermediate expression in thalamus and brainstem nuclei containing monoaminergic neurons; and low expression in globus pallidus, ventral pallidum, and substantia nigra pars reticulata (23).
- The main difference between alcohol and baclofen is that alcohol progressively produces a state of dependence, while this is not the case with baclofen (although a few cases have been reported 133—likely because these are exceptional).
- Patients should also be cautioned that the central nervous system effects of baclofen may be additive to those of alcohol and other CNS depressants.
- Effect of brain structure, brain function, and brain connectivity on relapse in alcohol-dependent patients.
The Road to Misuse and Abuse
Baclofen is a gamma-aminobutyric acid (GABA) analog that activates the GABA-B receptor subtype, and is used worldwide in neurology for the treatment of spasticity due to its myorelaxant properties (1). However, none of these biological effects fully explain the mechanism of action of baclofen in AUD. In studies with animals baclofen has been shown to have general CNS depressant properties as indicated by the production of sedation with tolerance, somnolence, ataxia, and respiratory and cardiovascular depression.
- Clinical studies have shown that baclofen has anxiolytic effects in patients with AUD (31) and it has been hypothesized that the anticraving effects of baclofen could be related to an anxiolytic effect (5, 6, 32).
- Patients indifferent to alcohol are no longer interested in alcohol, but they experience normal enjoyment for the other aspects of their life.
- The most common side effects of baclofen are listed below.
- Lyon J. More treatments on deck for alcohol use disorder.
- Adverse effects generally occur before anticraving effects during baclofen treatment of AUD, especially when baclofen is used in order to make patients reach a state of complete indifference, for which high or very high doses are most often necessary.
What should I tell my healthcare provider before using baclofen?
The Keegan et al. study shows that chronic baclofen treatment also produces a sustained increase in kinase cascades activity in other regions, namely the cortex, thalamus, and hippocampus for FAK; the cortex, thalamus and septum for GSK3ß; and the cortex, thalamus, hippocampus and amygdala for DARPP-32. However, adverse and anxiolytic effects generally occur during the first days or weeks of treatment, while a state of complete indifference most often occurs much later, after one or several months of treatment (depending on the dose needed and the protocol of dose increase). Hyperactivity of serotonin raphe neurons or hyperactivity of the amygdala are mechanisms known to produce anxiety; baclofen acutely inhibits serotonin neurons and serotonin release (27, 28) while short-term baclofen treatment inhibits amygdala reactivity to incentive cues (29). Theses symptoms may be explained by an action of baclofen on GABA-B receptors in the brainstem and hypothalamus, which are among the structures most strongly activated by baclofen, and which control basic states of vigilance (in particular through the suprachiasmatic nucleus). Conversely, a study using immunohistochemistry and focusing selectively on midbrain monoaminergic nuclei showed that GABA-B receptors are present in neurons of the VTA and raphe nuclei (no comparison in terms of density of receptors was made with other parts of the brain) (25). The variable densities of GABA-B receptors may have important implications regarding the use of baclofen in the treatment of AUD, given that, when a patient takes baclofen activation of regions with high densities should have clearer and more immediate physiological and behavioral consequences than the activation of regions with low densities.
The gamma-aminobutyric acid b receptor in depression and reward. Lyon J. More treatments on deck for alcohol use disorder. WFSBP task force on treatment guidelines for substance use disorders. The GABAB receptor represents a promising pharmacological target, a concept that has been supported by a plethora of animal studies.
Human Laboratory Studies
Clinical studies have shown that baclofen has anxiolytic effects in patients with AUD (31) and it has been hypothesized that the anticraving effects of baclofen could be related to an anxiolytic effect (5, 6, 32). It is tempting to hypothesize that these approaches are complementary, and that they could be synthesized in the proposition that baclofen may suppress the Pavlovian association between cues and rewards through an action in a critical part of the dopaminergic network (the amygdala), thereby normalizing the functional connectivity in the reward network. More importantly, the clinical experience shows that the states of sedation, apathy, disinhibition, or hypomania have no relation to the therapeutic effect of baclofen; they occur independently of an anti-craving effect, and these symptoms are commonly considered as side-effects of baclofen. Indeed, acute administration of baclofen may produce sedation, and sedation could be related to an inhibition of dopaminergic systems, but baclofen often produces a behavioral disinhibition, and quite frequently an evident hypomania (approximately 15% of patients). These effects have been shown not only for alcohol consumption, but also for the consumption of cocaine (67), amphetamine (68), and even of non-drug reinforcers such as sucrose, saccharin, or regular food pellets, suggesting that baclofen produces a generalized suppression of reward-motivated behaviors (2). It may be hypothesized that structures showing desensitization could be involved in the adverse effects of baclofen, which all tend to vanish over time, while structures showing no desensitization are involved in the therapeutic effect on baclofen in AUD—these last structures being possibly involved in the indifference toward alcohol.
What Are Side Effects of Baclofen
This includes increased awareness, careful prescription practices, and providing support and treatment for those struggling with dependency. It can cause mood swings, depression, and anxiety, significantly impacting a person’s quality of life and mental health. However, its sedative effects can lead to an escalation in dosage without medical guidance, tipping the balance from therapeutic use to dependency and abuse. It functions by inhibiting nerve signals in the brain and spinal cord, leading to muscle relaxation. Comorbidity between substance use disorders and psychiatric conditions. Alcohol addiction–the safety of available approved treatment options.
Seeking Treatment for Baclofen Abuse
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. Despite being one of the leading causes of morbidity and mortality worldwide (2, 3), only a limited number of medications are available to help AUD patients achieve abstinence or reduce their alcohol consumption (4, 5). Activation of GABA(B) receptors inhibits protein kinase B/glycogen synthase kinase 3 signaling. Ghosh S, Bhuyan D. Baclofen abuse due to Its hypomanic effect in patients with alcohol dependence and comorbid major depressive disorder. Correlates of baclofen effectiveness in alcohol dependence. Yamada J, Saitow F, Satake S, Kiyohara T, Konishi S. GABA(B) receptor-mediated presynaptic inhibition of glutamatergic and GABAergic transmission in the basolateral amygdala.
In 1971, it was introduced as a treatment for certain form of spasticity. The serum half-life of baclofen is roughly 2–4 hours; however, one source gives a half-life of 6.8 hr, using a more complex calculation combining urinary and serum data. Baclofen does not have significant affinity for the GHB receptor, and has no known abuse potential. Chemically, baclofen is a derivative of the neurotransmitter γ-Aminobutyric acid (GABA). Symptoms may persist even after the point at which serum baclofen levels are undetectable.
Levels of Care
The analysis of the mechanisms potentially involved in the dose-dependent, and often abrupt, passage from a state of extreme vulnerability to compulsive drinking to a state of complete indifference is critical in addressing the question of the mechanism of action of baclofen in the treatment of AUD. Besides, acute treatment with baclofen in rats produces an activation of a number of brain nuclei, mostly in the hypothalamus, the amygdala, and the brainstem, and has no detectable effect in reward-relevant regions such as the nucleus accumbens, striatum, or ventral tegmental area (26). The Chu et al. binding study (using baclofen) showed highest densities of GABA-B receptors in the medial habenula, thalamus, cerebellum, cortex and colliculus; while ventral tegmental area and mesolimbic dopaminergic projections were among the structures with the lowest binding (19). The effects of baclofen in the treatment of alcohol dependence have been thoroughly described by a physician suffering from AUD, Olivier Ameisen, who reported the cure of his alcohol dependence with a high dose of baclofen, first in an article published in 2005, then later in a book published in 2008 (3, 14).
RxList does not provide medical advice, diagnosis or treatment. You are encouraged to report negative side effects of prescription drugs to the FDA. Absorption may be dose-dependent, being reduced with increasing doses. The precise mechanism of action of baclofen is not fully known. Safety and effectiveness in pediatric patients below the age of 12 years have not been established.
However, this relationship was not observed in other studies. Baclofen administration induced contrasting results regarding alcohol consumption. Human laboratory studies. Observational and retrospective studies. Recently, several factors have been considered and analyzed to shed light on the potential reasons and mechanisms underlying the inconsistent treatment results obtained until now.
Baclofen-induced suppression of alcohol deprivation effect in Sardinian alcohol-preferring (sP) rats exposed to different alcohol concentrations. GABA(B) receptor-mediated modulation of the firing pattern of ventral tegmental area dopamine neurons in vivo. Effects of baclofen on dopamine-dependent behaviors in mice. The action of baclofen on neurons of the substantia nigra and of the ventral tegmental area.
The two substances share many similar effects, but the substitution substance is less prone than the substance of abuse to induce dependence, or not prone at all to do so. Patients taking baclofen often spontaneously notice these similarities. Both can also reduce anxiety (89, 90). Both can produce unsteady gait, dizziness, feelings of drunkenness, mood alterations, sensory alterations, confusion, impairment in attention and memory, and sleep disorders, among others (16, 88). It is proposed that this delay is necessary to completely suppress the Pavlovian association between the cue and the reward. It reduces the strength of excitatory (glutamate) and inhibitory (GABA) transmission in the amygdala by a presynaptic mechanism (131).
Baclofen (Lioresal, Fleqsuvy, and others) – Uses, Side Effects, and More
Your healthcare provider can tell you how to stop baclofen to reduce the risk of withdrawal reactions. Do not stop using baclofen without talking with your healthcare provider. If you stop using baclofen suddenly, it can lead to withdrawal symptoms, which may be life-threatening. Do not drive or do other activities that require alertness or coordination until you know how baclofen affects you.
Keegan et al. have shown that rats treated chronically with baclofen have significant decreases in G-protein-dependent signal transduction (measured by GTP-gamma-S binding) in the frontal cortex, septum, amygdala, and parabrachial nucleus (37). Baclofen could possibly improve anxiety through a rapid normalizing effect on amygdala GABA tone. Baclofen can also frequently promote anxiolysis; this could possibly be explained by an early occurring effect of baclofen on serotonin neurons and on the amygdala. For example, the most common and early occurring baclofen adverse effects include fatigue, diurnal somnolence and nocturnal insomnia. Binding and expression of GABA-B receptors have been studied in rodents. GABA-B receptors are coupled via G-proteins to potassium and calcium channels, and to adenylate-cyclase (18).