Modafinil and Weight Loss: Unveiling the Truth Behind the Hype

In the ongoing quest for effective weight loss solutions, modafinil, a wakefulness-promoting medication, has garnered attention. This article examines the evidence surrounding modafinil and its potential effects on weight loss, while also addressing its primary uses, side effects, and safety considerations.

What is Modafinil?

Provigil, known generically as modafinil, is a prescription-only, non-amphetamine central nervous system (CNS) stimulant. It is primarily used to promote wakefulness in individuals suffering from excessive daytime sleepiness due to conditions such as:

Narcolepsy: A neurological disorder that causes overwhelming daytime drowsiness and sudden attacks of sleep. Narcolepsy causes a strong urge to sleep during the day and can include symptoms like cataplexy (sudden muscle weakness), sleep paralysis (inability to move or speak while falling asleep or waking up), and hallucinations. Narcolepsy is linked to a lack of the brain chemical hypocretin (orexin), primarily produced in the hypothalamus. Modafinil is not a cure for narcolepsy, but it can help manage the symptoms. While modafinil is primarily used to treat excessive sleepiness, it may also help reduce the frequency and severity of cataplexy attacks in some people. Modafinil is approved for management of narcolepsy with or without cataplexy.
Shift Work Disorder: A condition affecting people who work during normal sleeping hours, leading to insomnia and excessive sleepiness.
Obstructive Sleep Apnea: A sleep disorder characterized by pauses in breathing during sleep, resulting in daytime sleepiness.

Falling asleep during critical tasks may lead to severe injuries and accidents. Provigil (modafinil) is a drug used to treat excessive sleepiness associated with these conditions.

Modafinil's Mechanism of Action

The exact mechanisms of action of modafinil are not fully understood. It is believed that the pharmacological profile of modafinil differs from that of classical stimulants like cocaine or amphetamine. Modafinil binds to both the dopamine and norepinephrine transporter at clinically relevant doses. A large database suggests that the ability of the drug to enhance catecholaminergic activity is crucial to its currently approved therapeutic actions. Modafinil has also been shown to increase serotonin (5-HT) turnover in several brain regions including the frontal cortex, the amygdala, and the dorsal raphe.

Modafinil inhibits dopamine reuptake, increasing its availability in the brain. This action is similar to that of other stimulants, though modafinil is considered to have a lower abuse potential.

Modafinil and Appetite Suppression

Although only a few studies have directly assessed modafinil’s effects on food intake, several have documented decreased appetite as a common side effect. Weight loss wasn’t a reported side effect during 9-12 week clinical studies of Provigil (modafinil) submitted to the FDA for approval. However, nausea, indigestion, and poor appetite are common side effects of Provigil. There is currently not enough research to know the effect Provigil has on weight.

Given the modafinil appetite suppression effect, there is growing interest in exploring modafinil’s potential for treating obesity. A recent area of interest related to therapeutic potentials of modafinil is the treatment of obesity. These neurochemical actions are consistent with effects produced by many medications approved to treat obesity.

Clinical Studies and Findings

In a limited number of studies modafinil has been shown to decrease food intake by laboratory animals and humans. Studies suggest that modafinil may be a promising drug that can reduce both daytime sleepiness and myotonia itself, without significant cardiac conduction effects.

Perez et al. (2008): This study examined the effects of modafinil on food intake in humans living in a residential laboratory during simulated shift work. During this 23-day study, a wide selection of food items and beverages were freely available. Volunteers (N = 11) received oral modafinil dose (0, 200, or 400 mg) one hour after waking for three consecutive days under two shift conditions: day shift and night shift. Shifts alternated three times during the study, and shift conditions were separated by an "off" day. Modafinil (200, 400 mg) dose-dependently decreased total caloric intake by ~18% and ~38%, respectively, regardless of shift condition, without selectively altering the proportion of total calories derived from carbohydrate, fat and protein. Ratings of “Hungry” were also significantly decreased by both active doses, but only immediately before the lunch break period. In addition, tolerance to the anorexic effects of modafinil was not apparent, as these effects remained stable across the three days of modafinil dosing. The present study represents a secondary data analysis, in which the effects of modafinil on several measures of food intake were determined in humans living in a residential laboratory during simulated shift work.
Makris et al. (2004): This research compared the effect of single oral doses of modafinil (1.75, 3.5, 7.0 mg/kg) with oral d-amphetamine (0.035, 0.07, 0.14 mg/kg) during six hour sessions; placebo days were interspersed between active drug days. The researchers reported that modafinil produced food intake reductions comparable to those produced by d-amphetamine. However, modafinil-associated effects were not dose-dependent, as food intake was significantly decreased only by one dose (3.5 mg/kg or ~245 mg).

These studies suggest that modafinil can reduce food intake, possibly due to its effects on appetite regulation.

FDA Reports

As of March 2024, the FDA has received 168 reports of weight loss in patients taking Provigil. However, Provigil is not FDA approved to treat weight loss.

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Common and Serious Side Effects

Understanding and managing these side effects can help you benefit from the medication while minimizing adverse outcomes. Modafinil generally does not cause weight gain. Modafinil is not associated with water retention. Hair loss is not a commonly reported side effect of modafinil.

Common Side Effects

Provigil can cause certain side effects, some of which are more common than others. These side effects may be temporary, lasting a few days to weeks. However, if the side effects last longer than that, bother you, or become severe, be sure to talk with your doctor or pharmacist.

Common side effects of modafinil include:

Headaches: Headaches are one of the most frequently reported side effects of Provigil.
Nausea: Nausea is another of the most frequently reported side effects of Provigil. Patients may experience a queasy or unsettled stomach, which can sometimes be accompanied by vomiting. After starting modafinil treatment, waiting for your body to adapt to the medication is a good tip. Nausea from modafinil typically improves or resolves completely as your body adjusts.
Anxiety
Insomnia
Dizziness
Loss of appetite
Dry mouth

Serious Side Effects

Provigil may cause serious side effects. If you develop serious side effects while taking Provigil, call your doctor right away. If the side effects seem life threatening or you think you’re having a medical emergency, immediately call 911 or your local emergency number. Heart-related side effects may be more likely to happen in people who have a history of heart problems. These side effects can include:

Heart-related issues: Users may experience palpitations, increased heart rate, and high blood pressure. These changes, though typically not severe, require caution, particularly in patients with cardiovascular disease. If you have a preexisting cardiovascular condition, discuss it with your healthcare provider before starting Provigil.
Severe skin reactions: Skin reactions are rare but serious side effects associated with modafinil. Serious rash, including Stevens-Johnson syndrome. Symptoms can include: flu-like symptoms, such as fever or body achespainful, blistering rash.
Mental health disturbances: Modafinil can induce euphoria and mood changes due to its effect on brain chemicals like dopamine, potentially leading to misuse and dependence, especially among those with a past substance use disorder.

Allergic Reactions

As with most drugs, Provigil can cause an allergic reaction in some people. However, this side effect wasn’t reported in clinical trials. Symptoms can be mild or serious and can include:

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Skin rash
Itching
Flushing
Swelling under your skin, typically in your eyelids, lips, hands, or feet
Swelling of your mouth, tongue, or throat, which can make it hard to breathe

For mild symptoms of an allergic reaction, call your doctor right away. They may recommend ways to ease your symptoms and determine whether you should keep taking Provigil. However, if your symptoms are serious and you think you’re having a medical emergency, immediately call 911 or your local emergency number.

Drug Interactions

Opioids: Modafinil may result in a drop in opioid plasma concentrations because of faster clearance of opioids by CYP3A4.
Steroid Hormones: Modafinil may have an adverse effect on hormonal contraceptives (such as birth control pills, patches, etc.) for up to a month after discontinuation.

Precautions and Contraindications

Be sure to talk with your doctor about your health history before you take Provigil. This drug may not be the right treatment option if you have certain medical conditions or other factors affecting your health.

Modafinil is also contraindicated in certain cardiac conditions, including uncontrolled moderate to severe hypertension, arrhythmia, cor pulmonale, and in cases with signs of CNS stimulant-induced mitral valve prolapse or left ventricular hypertrophy.

The package insert in the United States cautions about using modafinil in people with a documented medical history of left ventricular hypertrophy or those diagnosed with mitral valve prolapse who have previously exhibited symptoms associated with the mitral valve prolapse syndrome while undergoing treatment involving central nervous system stimulants.

The reasons why modafinil is contraindicated in certain cardiac conditions are because modafinil affects the autonomic nervous system and, in particular, exerts significant effects on autonomic cardiovascular regulation, leading in some people to notable increases in heart rate and blood pressure. These substantial changes in the autonomic system warrant careful consideration when prescribing modafinil to people with pre-existing cardiovascular conditions.

The increase in heart rate and blood pressure can worsen the symptoms of such pre-existing conditions as hypertension, arrhythmia, and cor pulmonale. These changes in the autonomic system induced by modafinil can increase the risk of heart attack, stroke, and heart failure.

Modafinil can stimulate the release of norepinephrine and epinephrine, hormones that activate the sympathetic nervous system. This can cause vasoconstriction, which is the narrowing of blood vessels, and increase the heart's workload, which is not desired in people with pre-existing heart conditions.

Special Considerations

Mental Health Conditions: If you’ve had depression, psychosis, or mania in the past, Provigil may increase your risk of these conditions. Talk with your doctor if you have a history of mental health conditions. They may monitor you more closely for the development or worsening of mental health conditions. Or they may recommend a treatment other than Provigil for your condition.
Heart-Related Effects: If you have certain heart conditions or high blood pressure, Provigil may make these problems worse. Be sure to tell your doctor if you have any heart-related conditions before starting treatment with Provigil. They will likely recommend more frequent monitoring to assess for heart-related effects. These may include heart rate and blood pressure.
Driving and Operating Machinery: Like other medications, Provigil may affect your judgment, thinking, or motor skills. Your doctor will likely recommend that you avoid driving or operating machinery until you know how Provigil will affect you.
Pregnancy and Breastfeeding: It’s not known whether it’s safe to take Provigil during pregnancy. This is because there haven’t been enough clinical trials with humans to determine what effects the drug might have on pregnancy. It’s not known whether Provigil passes into breast milk or what effects it may have on a child who is breastfed.
Alcohol: You should avoid drinking alcohol while taking Provigil. Consuming alcohol with Provigil can decrease how the drug works, and Provigil is typically prescribed to help you feel less sleepy and tired.

Misuse and Dependence

Provigil may cause changes in your mood, such as feelings of euphoria (intense happiness or excitement). For this reason, some people may misuse Provigil. (Misuse refers to taking a drug in a way other than how a doctor prescribes it.) This may be more likely to happen in people who have a history of drug or alcohol misuse.

Provigil is a controlled substance due to the risk of misuse. Strict rules regulate how doctors and pharmacists prescribe and dispense controlled medications. For more information, talk with your doctor or pharmacist.

You should take only the Provigil dosage that your doctor prescribes for you. If you have a history of drug misuse, talk with your doctor. They will closely monitor you during treatment with Provigil.

Global Regulatory Status

Modafinil's use varies by region.

United States: In the United States, modafinil is classified as a schedule IV controlled substance under US federal law. This means that the drug has a low potential for abuse and dependence compared to other controlled substances.
Australia: In Australia, modafinil is considered to be a Schedule 4 prescription-only medicine.
China: In mainland China, modafinil is strictly controlled like other stimulants such as amphetamines and methylphenidate. It is classified as Class I psychotropic drug. This classification means that modafinil is considered to have a high potential for abuse and dependence, and is therefore subject to strict regulation and control. As a result, modafinil is only available by prescription and cannot be purchased over the counter.
Russia: In Russia, starting from May 18, 2012, modafinil is Schedule II controlled substance. Being classified as a Schedule II controlled substance in Russia means that it is seen as a drug with a high potential for abuse and dependence. This classification imposes strict regulations on the production, distribution, and use of modafinil.

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