Naltrexone is a medication prescribed primarily to support individuals managing Alcohol Use Disorder (AUD) and Opioid Use Disorder (OUD). It functions by reducing cravings and blocking the euphoric effects of opioids and alcohol. Many people beginning this treatment report feeling generally “off” or different during the initial adjustment phase. This systemic change, often described as feeling “weird,” is a common experience as the body adapts to the medication’s influence on specific biological systems.
Blocking Opioid Receptors: The Mechanism
Naltrexone is classified as an opioid antagonist, meaning it works by occupying and blocking the body’s opioid receptors. It binds competitively to these sites, preventing both external opioid drugs and the body’s own naturally produced opioids from attaching. This action is the fundamental reason for its therapeutic effect in reducing the likelihood of relapse.
The medication primarily targets the mu-opioid receptor, which mediates pleasure and pain relief, but also affects the kappa and delta receptors. These receptors are widely distributed throughout the body, not just in the brain. Significant populations are located in the central nervous system, including the brain and spinal cord, influencing mood and pain perception.
Opioid receptors are also abundant in the peripheral nervous system, particularly within the gastrointestinal tract. This broader distribution means Naltrexone’s blocking action creates systemic effects that go beyond preventing a euphoric high. The medication interrupts established signaling patterns in multiple body systems simultaneously.
This blockage temporarily disrupts the endogenous opioid system, which relies on natural chemicals like endorphins and enkephalins. Since endorphins regulate mood, stress response, and feelings of well-being, their dampened signaling contributes directly to the feeling of being generally “off” while the body attempts to reach a new internal balance.
Common Physical and Emotional Experiences
One of the most frequently reported physical side effects is gastrointestinal upset, commonly manifesting as nausea or stomach cramping. Because opioid receptors are dense in the gut, their blockage can temporarily disrupt normal digestive motility and sensation. This discomfort is most noticeable when first starting the medication, typically subsiding within the first few weeks of consistent use.
Other common physical sensations include a dull headache, fatigue, and occasional dizziness. Some individuals also report difficulty achieving restful sleep, which may involve trouble falling asleep or maintaining sleep. These effects are often transient, reflecting the body’s initial physiological resistance to the altered signaling pathways.
The medication’s primary action in the brain can result in significant changes in mood and emotional experience. Many users describe emotional blunting or flatness, where the normal peaks and valleys of daily feelings are muted. This feeling is known as dysphoria, a state of unease or generalized dissatisfaction.
This emotional shift is closely tied to the disruption of the brain’s reward circuitry, which relies on opioid signaling for processing pleasure and motivation. By blocking these receptors, Naltrexone interferes with the mechanism that reinforces positive experiences. The temporary reduction in reward response can leave individuals feeling anxious, irritable, or lacking their usual sense of drive.
A general feeling of malaise, a vague sense of discomfort, illness, or uneasiness, is common during this adjustment phase. This feeling combines the mild physical symptoms with the emotional shifts, contributing significantly to the overall sensation of “weirdness.”
Strategies for Minimizing Discomfort
Simple adjustments to the dosing routine can alleviate the common discomforts associated with starting Naltrexone. Taking the oral tablet with a meal or a small snack is recommended, as this reduces the likelihood and severity of nausea and other gastrointestinal side effects.
For individuals experiencing fatigue or dizziness during the day, adjusting the timing of the dose can be helpful. Taking the medication in the evening, shortly before bedtime, may allow the most intense initial side effects to occur while the person is asleep. If insomnia is an issue, however, a morning dose may be more appropriate to prevent nighttime wakefulness.
Maintaining consistent hydration is an effective strategy for managing malaise and headaches. For some patients, physicians may initiate treatment using a lower starting dose, often referred to as titration, gradually increasing it to the full prescribed amount. Any change in standard OUD or AUD dosing should only be implemented after consulting with the prescribing physician.
Recognizing Serious Side Effects
While most side effects are mild and temporary, it is important to recognize signs of a severe adverse reaction requiring immediate medical attention. Naltrexone carries a potential, though rare, risk of liver damage (hepatotoxicity). Warning signs include persistent, severe abdominal pain, dark urine, or jaundice (yellowing of the skin or eyes).
Signs of a serious allergic reaction, such as hives, severe swelling of the face, tongue, or throat, or difficulty breathing, warrant emergency care. Any severe or sudden changes in mood, including the onset of deep depression or suicidal ideation, must be reported to a healthcare provider without delay.
A significant safety concern is the attempt to overcome the medication’s blocking effect by using a very large dose of opioids. This practice is extremely dangerous because the blockade is temporary and can be bypassed with massive amounts of opioids. When the Naltrexone wears off, the high concentration of opioids can lead to immediate, fatal respiratory depression and overdose.