Baclofen for Alcoholism and Addiction Treatment
Alcoholism and drug abuse is a major public health problem and affects millions of individuals and their families globally. Various medications have been found to be effective and are recommended as an important treatment option to recover from alcoholism and drug addiction.
Efforts to find treatments for alcohol and drug addiction have led researchers to explore the effects of existing drugs that are used to treat other physical conditions. Baclofen, a medication commonly used to treat back-related conditions, is one of these drugs.
The studies exploring the effectiveness of baclofen have come up with mixed results and it has not yet received approval by the U.S. Food & Drug Administration (FDA) as a safe and effective treatment for alcohol or drug use disorders. The researchers are exploring what factors are predictive of a favorable response to baclofen when used for treatment of alcoholism and drug addiction.
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While commonly used to treat multiple sclerosis and spinal cord injuries, baclofen is still undergoing testing as a treatment for alcoholism.
Baclofen – also known by the brand name Lioresal – received FDA approval in 1977 for its ability to reduce muscle spasms, muscle stiffness and pain associated with back conditions. The effects of balcofen on the reward pathway of the brain have been postulated as possible mechanism of its action. The reward pathway has been identified as an important region in emergence of alcohol and drug dependence.
Baclofen is derived from and shares molecular similarities with the neurotransmitter chemical known as gama-amino butyric acid (GABA). As an inhibitory neurotransmitter, GABA has a calming or “slowing” effect on a person’s mood and overall physical state. Receptors for GABA have been found in the reward centers of the brain and it is likely that any efficacy of baclofen in the treatment alcohol or drug dependency is mediated through these receptors.
Various neurotransmitters have been identified that underlie the pleasurable effects associated with alcohol and drug use. One such neurotransmitter is dopamine. Dopamine is found in neurons (brain cells) throughout the reward pathways of the brain. Many addictive substances, including alcohol, influence the activity levels of dopamine in the brain. In many cases, the feelings of relaxation and happiness associated with the addictive substances in question are linked to the dopaminergic effects.
Dopamine is not thought to function alone as part of the innate reward system. There are also a large number of neurons in the reward pathway that secrete GABA. GABA interacts with specialized proteins known as GABA receptors. GABA receptor activation further impacts the release of dopamine in the reward pathway. Chronic alcohol or other drug use can result in these two neurotransmitter systems, GABA and dopamine, acclimating to the presence of the abused substances. At a certain point, these brain systems can no longer function optimally without the presence of alcohol or a drug. The absence of drugs and/or alcohol in these individuals can disrupt this newly reached state of balance, resulting in a state of dysphoria or uneasiness, which can serve as the basis for cravings for alcohol or a drug.
In theory, since baclofen acts on the GABA receptors, it may help lessen a person’s craving for alcohol and other drugs while simultaneously reducing the withdrawal symptoms that occur when someone stops alcohol or drug use. Since the systems regulating dopamine and GABA are closely intertwined, baclofen may ultimately act by regulating dopamine levels in the brain.
Mood States Affected by Baclofen
Alcohol and other drugs have mood altering properties. Many of those who resort to regular or heavy alcohol or drug use additionally suffer from mental health conditions, including mood disorders. Furthermore, the period of abstinence following regular and heavy use is marred by negative mood states.
In terms of substance abuse recovery, it can be helpful to address this altered mood state following abstinence from alcohol or other drugs. The effects of baclofen on key neurotransmitter systems show promise in its ability to relieve this negative mood state. According to a University of Pennsylvania report, some of the mood states and the neurotransmitter systems involved include:
- Arousal state – Epinephrine and dopamine systems
- Fantasy state – Dopamine, serotonin, and norepinephrine systems
- Satiation state – GABA and endorphin systems
Baclofen acts on the GABA receptors. It also alters the dopamine system and therefore may impact the associated mood states in those with alcohol and other drug use disorders.
The effects of alcohol and drugs on the brain are known to grow increasingly worse with chronic use. The brain’s ability to regulate various chemical processes changes with persistent substance abuse. Because of these time-sensitive alterations in underlying brain chemistry, baclofen’s efficacy in managing substance dependence may be influenced by how long a person has used alcohol or drugs.
Preliminary open-label studies from Italy demonstrated effectiveness of baclofen in reducing alcohol use among the alcoholics. In addition, results from a clinical study conducted by Brown University show alcohol-addicted participants receiving baclofen were able to abstain from drinking for longer periods of time than those who didn’t receive the drug.
A similar clinical study involving participants who drank at moderate levels showed little difference in abstinence rates between those who took baclofen and those who didn’t. These findings indicate more research is needed to better pinpoint baclofen’s effects within the brain at different stages of alcohol and addiction use. Researchers are exploring the possible predictors of response to baclofen when used for treatment of alcohol and drug use disorders.
Baclofen’s Effects on Positive and Negative Reinforcements
Positive and negative reinforcements play key roles in driving a person’s substance addiction. Positive reinforcements have to do with the rewards from using, such as a more relaxed mood or feelings of happiness and euphoria. Negative reinforcements involve the withdrawal effects such as depression, irritability and anxiety, felt when the body craves alcohol or drugs. Baclofen has been postulated to have anti-craving as well as anti-reward effects.
Researchers at the Medical College of Wisconsin observed the effects of baclofen on positive reinforcements by giving the drug to two groups of rats. One group was addicted to heroin while the other group was not. Both groups were allowed to self-administer heroin doses at will, with each dose producing positive physical effects. When given baclofen, both groups of rats showed a decrease in the number of times heroin was self-administered. In effect, the changes in GABA and dopamine levels caused by baclofen reduced the positive reinforcement effects of heroin on brain processes. While these results were seen in animal studies, should a person experience a same phenomenon, it might be easier for him or her to abstain from heroin or at least decrease the amount of heroin ingested per day or per week.
A similar experiment conducted by the University of Adelaide in South Australia and Tehran University of Medical Sciences in Iran examined how baclofen affects the negative effects seen with morphine withdrawal in rats and mice. When given baclofen, both the rats and the mice experienced less intense withdrawal effects when morphine was withheld. Similar effects in a person might help to reduce physical cravings, which also make it easier to abstain from ongoing use.
Craving-suppressant effects of baclofen have been reported by human subjects dependent on alcohol as well in an observational study from France.
Behavior Cues in Drug Testing Trials
Pre-clinical trials used to test the effects of baclofen on different types of drugs reveal promising results when tested with mice. Researchers base these results on behavioral cues that serve as indicators of the craving levels experienced by the test subjects. Behavior cues observed include:
- Cues before and after the mice become addicted to a drug.
- Cues before and after baclofen dosages are given.
- Number of times the mice self-administer a drug, such as heroin or cocaine.
- Behaviors that indicate withdrawal symptoms are present, such as shaking or hiding.
Baclofen use has been associated with certain side effects. When prescribed for alcohol dependence, side effects associated with baclofen included fatigue, sleepiness, insomnia, dizziness, paraesthesia, nausea, vomiting, sensory alterations, sexual changes (decrease or increase of libido), various forms of pain (including headache), bowel disorder (diarrhea or constipation), dysphoria, weight loss or gain, and memory loss, among others side effects. For some people, baclofen may cause more serious side effects, such as seizures and breathing problems.
Baclofen’s effects on the brain’s chemical processes can also offset the effects of any other medications a person is taking. Baclofen can alter the effects of tranquilizers, muscle relaxants, sleep aids and even vitamins depending on a person’s body chemistry. People with certain health conditions such as epilepsy, ulcers, heart-related ailments, or psychological conditions (such as depression and anxiety disorders) may also experience adverse effects when taking baclofen.
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