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Provigil Addiction

This entry was posted in Addiction on by .
Medically Reviewed Fact Checked

Last Updated on April 3, 2023 by Diane Ridaeus

Alternative to Meds Editorial Team
Medically Reviewed by Dr Samuel Lee MD

Provigil addiction may be more problematic, and more prevalent than was previously thought, according to medical researchers in JAMA published findings.1

Insights on Provigil Addiction

provigil dopamine fluctuationsHow serious is the risk of Provigil addiction? The exact mechanisms of action of Provigil are still unknown. According to the National Institute on Drug Abuse, Dr. Nora Volkow, Dr. Joanna Fowler, and their team of researchers have shown that Provigil may possibly act on dopamine receptors in ways that are similar to, but less aggressive than other stimulant drugs like cocaine and amphetamines.1,2

The degree to which Provigil is dopaminergic is unknown. It has been established, however, that any potential dopaminergic action of Provigil appears to be less instantaneous and less intense than cocaine or meth. Considerable debate continues on whether Provigil may or may not affect serotonin, GABA, norepinephrine, and other neurotransmitters. This lack of definitive understanding of how the drug works may be something of a wake-up call in itself, for physicians as well as consumers who might casually opt to take it off-label for “cognitive enhancement” or for its “wake-up” and euphoric effects. The NIDA study showed that due to lacking more complete information, doctors have largely overlooked the risk potential for addiction and other adverse reactions. Though rarely reported, Provigil does present a very real risk of addiction, dependence, or abuse for some. Promoters of this “wake-up” drug have somewhat blindly focused on its non-addictive characteristics. And in so doing, may have influenced physicians and others to start on a path that may have inadvertently ended up in unintentional drug dependence. 3-6,15

Signs of Provigil addiction may include:
  • Needing to increase the frequency or dosage to get the same effects
  • Worsened lethargy, increased periods of drowsiness during the day
  • If a dose is missed, headache, nausea, anxiety, nervousness, or abnormal vision
  • Hand tremors if a dose is skipped
  • A sense of well-being or euphoria is only achieved when taking the drug

Provigil Use on Job and School-related Issues

provigil wakefulness effectsProvigil and its generic versions have been studied for decades since their release. Provigil is FDA-approved for treating narcolepsy, shift-work sleep disorder, and obstructive sleep apnea that continues despite the use of a CPAP device.13

It is still not completely understood how the drug creates the wakefulness effects. The research of Greenblatt and Adams suggests a weak inhibitory effect on dopamine reuptake. While in vivo tests showed no affinity for serotonin or norepinephrine transporters, elevated levels of these neurochemicals were found concentrated in the prefrontal cortex after taking modafinil. It is not understood why these secondary effects occur, and research is ongoing on how Provigil may or may not affect dopamine, serotonin, GABA, norepinephrine, glutamate, histamine, and other natural neurochemicals.3,15,16

A person needing to stay awake on the job or stay up all night cramming for a test may feel a benefit from the occasional use of a stimulant such as Provigil, though it is FDA-approved only for chronic fatigue, narcolepsy, and ongoing sleep troubles. Where possible, the best approach would be to find out what is causing the tiredness, whether it is occasional or chronic, and fix that. Alternative (drug-free) wakefulness solutions and treatments may be of great help without the Provigil addiction or dependency risks. For people with a history of addiction, the abuse potential of Provigil or other chemical stimulants can present a compounded health risk.4 Alternative treatments provide a safer treatment option.

Off-Label Uses of Provigil

Provigil is not approved for children under the age of 18, mainly due to the dermatologically toxic reactions in clinical trials — yet it is prescribed off-label for ADHD in both children and adults. Other off-label uses have arisen such as cocaine addiction treatment, recovery after surgical anesthesia, and treating depressive episodes in bipolar disorders. Off-label prescriptions are largely experimental to see if “this” or “that” will work. Some would say this is lazy doctoring, as no attempts are usually made to investigate the why behind the lack of energy. Perhaps in desperation, some physicians prescribe Provigil as an add-on medication to make SSRIs more “effective” when the antidepressants alone are not producing the desired result.13

Provigil Adverse Effects to Be Aware of

Provigil can cause mild to severe adverse reactions. Some, though rare, can be life-threatening. The FDA has reported on numerous adverse effects that emerged during clinical trials.14 These are summarized and briefly defined in the list below.

Provigil Adverse Effects

  • provigil side effectsSJS 8 Stevens-Johnson Syndrome — sheetlike loss of skin and mucous tissues, life-threatening.
  • Toxic epidermal necrolysis or TEN — the erosion of skin and mucous membranes, life-threatening.
  • DRESS 7 (drug reaction with eosinophilia and systemic symptoms) — symptoms include fever, rash, liver impairment, painful skin eruptions, blood disorders, and potentially fatal drug reaction)
  • Suicidal ideation
  • Mania
  • Psychosis, hallucinations, paranoid delusions
  • Angioedema 9 — swelling of face, eyes, tongue, lips, larynx, potentially fatal drug reaction.
  • Anaphylactoid reactions 10
  • Pruritis 11 — severe chronic itching
  • Asthenia — weakness, tiredness, chronic fatigue
  • Myocarditis (inflammation of the heart muscle)
  • Leukopenia (low white blood cell count)
  • Thrombocytopenia (deficiency of platelets leading to bruising, bleeding, clotting)
  • Hypertension (high blood pressure)
  • Anxiety, nervousness
  • Depression
  • Alterations of mood, perception, thinking, and feelings, similar to other CNS stimulants
  • Confusion
  • Agitation
  • Headache
  • Nausea
  • Loss of appetite
  • Insomnia
  • Rhinitis (inflammation of the nasal tissue, runny nose, sneezing, stuffiness)
  • Dizziness
  • Diarrhea
  • Euphoric effects
  • Hoarseness, difficulty breathing or swallowing

Drug Interactions With Provigil (modafinil)

Doctors recommend not taking Provigil concurrently with certain other drugs due to interactions that may negatively impact health. For example, diazepam and triazolam are metabolized by CYP enzymes which could warrant an adjustment in dosage due to the combined effects of these drugs and Provigil. Always consult your prescriber before combining drugs.1,2,14

Addiction Treatment Help for Provigil Dependence

Alternative to Meds Center has provided help for Provigil addiction treatment for many years. Programs are individually designed to not only gradually eliminate medications safely but to discover the underlying causes for symptoms that led to drug dependence, overuse, and addiction. Addressing the root cause of unwanted symptoms such as narcolepsy, chronic fatigue, etc., is what leads to freedom and Provigil addiction or dependence recovery.

Want More Information?

We are ready to help you or your loved one.

Holistic treatment is waiting for you or your loved one, within a world-class facility, founded on scientific principles and evidence for a full recovery. Alternative to Meds Center’s focus is on finding and treating the root causes for daytime sleepiness or other troubling symptoms. You or your loved one can discover new drug-free ways to promote energy, well-being, and optimal natural mental health. Please see the services available when a person enrolls in treatment at Alternative to Meds Center.

Contact us at Alternative to Meds Center to find out more about our Provigil addiction treatment and Provigil tapering programs.


1. Volkow, N. D., Fowler, J. S., Logan, J., Alexoff, D., Zhu, W., Telang, F., Wang, G. J., Jayne, M., Hooker, J. M., Wong, C., Hubbard, B., Carter, P., Warner, D., King, P., Shea, C., Xu, Y., Muench, L., & Apelskog-Torres, K. (2009). Effects of modafinil on dopamine and dopamine transporters in the male human brain: clinical implicationsJAMA301(11), 1148–1154. https://doi.org/10.1001/jama.2009.351 [cited 2023 April 3]

2. Darwish M, Kirby M, Robertson P Jr, Hellriegel ET. Interaction profile of armodafinil with medications metabolized by cytochrome P450 enzymes 1A2, 3A4 and 2C19 in healthy subjects. Clin Pharmacokinet. 2008;47(1):61-74. doi: 10.2165/00003088-200847010-00006. PMID: 18076219.  [cited 2023 April 3]

3. Greenblatt K, Adams N. Modafinil. [Updated 2020 Sep 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK531476/ [2021 Aug 10] [cited 2023 April 3]

4. Lazenka MF, Negus SS. Oral modafinil facilitates intracranial self-stimulation in rats: comparison with methylphenidate. Behav Pharmacol. 2017 Jun;28(4):318-322. doi: 10.1097/FBP.0000000000000288. PMID: 28125506; PMCID: PMC5422118.  [cited 2023 April 3]

5. Lin JS, Hou Y, Jouvet M. Potential brain neuronal targets for amphetamine-, methylphenidate-, and modafinil-induced wakefulness, evidenced by c-fos immunocytochemistry in the cat. Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14128-33. doi: 10.1073/pnas.93.24.14128. PMID: 8943072; PMCID: PMC19505. [cited 2023 April 3]

6. Wisor JP, Nishino S, Sora I, Uhl GH, Mignot E, Edgar DM. Dopaminergic role in stimulant-induced wakefulness. J Neurosci. 2001 Mar 1;21(5):1787-94. doi: 10.1523/JNEUROSCI.21-05-01787.2001. PMID: 11222668; PMCID: PMC6762940.[cited 2023 April 3]

7. Choudhary S, McLeod M, Torchia D, Romanelli P. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome. J Clin Aesthet Dermatol. 2013;6(6):31-37. [cited 2023 April 3]

8. Oakley AM, Krishnamurthy K. Stevens Johnson Syndrome. [Updated 2021 Apr 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459323/ [cited 2023 April 3]

9. Memon RJ, Tiwari V. Angioedema. [Updated 2021 Mar 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538489/ [cited 2023 April 3]

10. Reber LL, Hernandez JD, Galli SJ. The pathophysiology of anaphylaxis. J Allergy Clin Immunol. 2017;140(2):335-348. doi:10.1016/j.jaci.2017.06.003 [cited 2023 April 3]

11. Song J, Xian D, Yang L, Xiong X, Lai R, Zhong J. Pruritus: Progress toward Pathogenesis and Treatment. Biomed Res Int. 2018;2018:9625936. Published 2018 Apr 11. doi:10.1155/2018/9625936 [cited 2023 April 3]

12. Ballon JS, Feifel D. A systematic review of modafinil: Potential clinical uses and mechanisms of action. J Clin Psychiatry. 2006 Apr;67(4):554-66. doi: 10.4088/jcp.v67n0406. PMID: 16669720. [cited 2023 April 3]

13. Kumar R. Approved and investigational uses of modafinil : an evidence-based review. Drugs. 2008;68(13):1803-39. doi: 10.2165/00003495-200868130-00003. PMID: 18729534. [cited 2023 April 3]

14. FDA label PROVIGIL (modafinil) tablets [published 2007 Aug 17]  [cited 2023 April 3]

15. Krishnan, R., & Chary, K. V. (2015). A rare case modafinil dependenceJournal of pharmacology & pharmacotherapeutics6(1), 49–50. https://doi.org/10.4103/0976-500X.149149  [cited 2023 April 3]

16. Qu WM, Huang ZL, Xu XH, Matsumoto N, Urade Y. Dopaminergic D1 and D2 receptors are essential for the arousal effect of modafinil. J Neurosci. 2008 Aug 20;28(34):8462-9. doi: 10.1523/JNEUROSCI.1819-08.2008. PMID: 18716204; PMCID: PMC6671058. [cited 2023 April 3]


Originally Published by Diane Ridaeus Published May 11, 2020


This content has been reviewed and approved by a licensed physician.

Dr. Samuel Lee

Dr. Samuel Lee is a board-certified psychiatrist, specializing in a spiritually-based mental health discipline and integrative approaches. He graduated with an MD at Loma Linda University School of Medicine and did a residency in psychiatry at Cedars-Sinai Medical Center and University of Washington School of Medicine in Seattle. He has also been an inpatient adult psychiatrist at Kaweah Delta Mental Health Hospital and the primary attending geriatric psychiatrist at the Auerbach Inpatient Psychiatric Jewish Home Hospital. In addition, he served as the general adult outpatient psychiatrist at Kaiser Permanente.  He is board-certified in psychiatry and neurology and has a B.A. Magna Cum Laude in Religion from Pacific Union College. His specialty is in natural healing techniques that promote the body’s innate ability to heal itself.

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