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Is Modafinil Bad for Your Heart?

Executive Summary

  • Modafinil effects are mediated through multiple pathways and receptors including dopaminergic, noradrenergic, glutamatergic, GABAergic, serotoninergic, orexinergic, and histaminergic interactions.
  • The effects of Modafinil on heart are a major concern for patients. Recent studies have found an association between Modafinil and heart disease, especially increase blood pressure, heart failure, and arrhythmia but the exact pathway or mediators is still unclear.
  • Modafinil affects the heart through a combination of mechanisms including increased cortical serotonin secretion, central dopamine receptor agonist activity, decrease uptake of noradrenaline, and partial alpha-adrenaline agonist activity. Therefore, it is recommended to avoid or limit Modafinil in patients with a history of cardiovascular issues and needs continous monitoring of the patient’s heart for a better outcome.


Modafinil is a brain-stimulating drug, widely used in the treatment of sleep-related disorders (excessive sleepiness disorder) like narcolepsy and obstructive sleep apnea. The chemical structure of the drug is 2-diphenyl-methylsulfonyl-acetamide (C15H15NO2S) and it is categorized as a smart drug because it increases alertness and learning capacity.

The drug got approval in 1998 from the Food and Drug Administration (FDA) for therapeutic use. Analog drugs such as amphetamine, cocaine, and ephedra alkaloids affect the cardiovascular system causing an increased risk of myocardial infarction and extrasystoles.

Considering the rapid adoption of modafinil, it is important to define how the drug modifies autonomic cardiovascular regulation in the human body.

Shift Work Sleep Disorder and Drug Abuse

Modafinil drug abuse is increasing, especially among students as a sleep medicine, to enhance cognitive performance and reduce the need for sleep. A review of the literature highlights that the effect of modafinil regarding cognitive enhancing effects (the increase in alertness) is through the alpha-adrenergic receptor. It also activates orexin neurons, which are related to wakefulness and sleep inhibiting.

According to some studies, modafinil increases the extracellular level of dopamine, providing similar effects as other drugs like amphetamine, cocaine, and ephedra alkaloids. Although many consider it a smart drug, it may have potential risks and can cause addiction due to the increase in dopamine levels.

Modafinil induces CNS stimulant effects by interacting with dopaminergic, noradrenergic, glutamatergic, GABAergic, serotoninergic, orexinergic, and histaminergic receptors.

Why is it important to understand modafinil?

Modafinil is a widely used drug for the treatment of sleep disorders like excessive daytime sleepiness. Is modafinil bad for your heart even if it improves performance and increases alertness, is a question the patient asks the healthcare professional.

Health practitioners generally prescribe the drug at a 100 mg dose once a day and if the patient feels post-noon tiredness, it may be given twice a day. Generally, patients need low doses but some might need high doses due to special conditions. It is also possible that it is safe at low doses but poses a risk to the heart at high doses. Therefore, the physician must have the correct drug information before prescribing it to patients.

Because of its wide use as a therapeutic drug and associated drug abuse, it has become important to understand its side effects to avoid any life-threatening complications.

The effect of modafinil on the heart

Practitioners prescribe modafinil as a common treatment for obstructive sleep apnea. Modafinil is now one of the most common CNS stimulants used to treat excessive sleep disorders.

Due to a lack of understanding regarding its direct path of effect on the heart, it is difficult to conclude the question ‘is modafinil bad for your heart?’ and there is an opposing school of thought regarding the cardiovascular effects of this drug.

According to some case studies and other published literature modafinil alters the cardiovascular system by inducing the secretion of cortical serotonin and activating the adrenergic system.

Case Studies (High Blood Pressure, Heart Failure)

In some studies, a significant drug effect on the heart has been observed. A pharmacovigilance study by the European Medicines Agency (EMA) regarding the side effects of modafinil reported 873 cases of cardiovascular events. Out of these 873 cases, 171 were critical and few of them had a fatal outcome.

In the same report, the incidence of heart failure is also discussed in a significant number of cases. Association of modafinil with cardiomyopathy, mitral valve prolapse, left-ventricular hypertrophy, cardiac arrhythmias, and ischemic heart disease has been reported.1 In younger patients, coronary artery disease (CAD) is usually asymptomatic and the modafinil effects are difficult to assess.

An Inconclusive Mechanism of Action

To date, studies have mainly focused on modafinil’s wake-promoting mechanisms and its CNS receptors, which are yet to be concluded. Multiple neurochemical systems are stimulated by Modafinil, these include Gamma-aminobutyric acid (GABA), glutamate, histamine, serotonin, dopamine, and orexin (also known as hypocretin).

It is observed that modafinil substantially disturbs autonomic cardiovascular regulation by an increase in heart rate along with a significant elevation in diastolic and systolic blood pressure. Autonomic changes of this magnitude encourage caution in the use of modafinil in patients with heart disease. The current research has focused on the possible extracellular activities of modafinil, the intra-cellular effects are yet to be determined.

Clinical pharmacology

Modafinil is insoluble in an aqueous solution and cannot be administered intravenously. However, it is readily absorbed after oral administration. Post 2-4 hours of administration, it achieves peak plasma concentration. Further, the elimination half-life of a single dose is approximately 15 hours in healthy individuals.

The usual dose of modafinil is 200mg once or 100mg twice a day. But it can be adjusted up to 400mg/day depending upon the response and tolerance of the patient. It may be possible the effects reported of modafinil on the heart may appear with higher doses but not at lower doses.

Physiological Reactions Related To Modafinil

The effects of interaction between Modafinil and Serotonin

Modafinil indirectly stimulates the release of cortical serotonin2. Serotonin influences the cardiovascular system, and it induces bradycardia by chemoreflex, which is also associated with hypotension

Serotonin has no significant effect on myocardium activity, but it stimulates the secretion of aldosterone and renin which further increases peripheral resistance. Serotonin affects the heart in a variety of ways, including fibrosis of the cardiac valves, constriction of the coronary blood vessels, arrhythmias, and thrombosis.

It is also associated with hypertension because for the treatment of severe hypertension if serotonin antagonists are given, it helps in reducing the resting systolic and resting diastolic blood pressure.

Adrenomedullary activation using Modafinil

The adrenal medulla is the inner part of an adrenal gland, a small organ on top of each kidney. Modafinil activates the adrenomedullary system3, and it inhibits the reuptake of noradrenalin in the noradrenergic nerve endings. As mentioned in the literature, a major neurohormonal cause of heart failure is the activation of the adrenergic nervous system.

With the indirect effect of modafinil, the chances of heart failure also increase. In a study by the National Institute of Health, modafinil effects on blood pressure and heart rate were observed in several patients, which was linked to the adrenergic activation caused by modafinil. This encourages caution in the use of modafinil in patients with cardiovascular disease or those engaging in strenuous physical activity.


The effect of modafinil on the heart is yet to be concluded however it is recommended to avoid or limit the use of modafinil in patients with a history of high blood pressure, high heart rate, heart attack, and other possible cardiovascular complications. However, it is considered safer than other amphetamine derivatives in terms of cardiovascular side effects.

Nevertheless, the cardiac profile of the patient needs to be continuously monitored for any modafinil-induced arrhythmia. It is still unclear what exactly causes the cardiac arrhythmias linked to modafinil. It is thought that central dopamine receptor stimulation plays a crucial role in the generation of cardiac arrhythmias.


It is generally advised to exercise caution when using CNS stimulants (Central Nervous System), such as modafinil, which are yet to be fully understood by the medical community. This is especially important if the concerned drug has shown deleterious cardiovascular consequences.

Can taking modafinil affect blood pressure, lead to heart attack, irregular heartbeat, or cause chest pain are questions that are still unanswered and are a challenge to the scientific community. It may be possible to create more selective drugs with fewer adverse effects by exploring and understanding the mechanisms of action for these medications.


1.       Canyurt, D., Tanriverdi, L. H., Ozhan, O., Cansel, M., Parlakpinar, H., Vardi, N., Cigremis, Y., Yildiz, A., Karaca, Y., Yasar, S., & Acet, A. (2022). Dose-dependent subacute cardiovascular effects of modafinil in rats. Drug and chemical toxicology, 45(3), 1044–1053.

2.       Kim D. (2012). Practical use and risk of modafinil, a novel waking drug. Environmental health and toxicology, 27, e2012007.

3.       Taneja, I., Diedrich, A., Black, B. K., Byrne, D. W., Paranjape, S. Y., & Robertson, D. (2005). Modafinil elicits sympathomedullary activation. Hypertension, 45(4), 612–618.

4.       Van Puyvelde, M., Van Cutsem, J., Lacroix, E., & Pattyn, N. (2022). A State-of-the-Art Review on the Use of Modafinil as A Performance-enhancing Drug in the Context of Military Operationality. Military medicine187(1-2), 52–64.

5.       Chandra, M., & Chandra, N. (2004, March 20). Serotonergic mechanisms in hypertension. Serotonergic Mechanisms in Hypertension – ScienceDirect;

6.       Lymperopoulos, A., Rengo, G., & Koch, W. J. (2013). The adrenergic nervous system in heart failure: pathophysiology and therapy. Circulation research, 113(6), 739–753.

8.       Kim D. (2012). Practical use and risk of modafinil, a novel waking drug. Environmental health and toxicology, 27, e2012007.

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