Is Modafinil a Stimulant?

Written on February 14, 2022 by | Reviewed by William Gallagher, MNeuroSci

Lately, a number of online discussions have questioned the classification of modafinil as a stimulant and whether it is an effective treatment for fatigue and mental illness.

Modafinil is classified as a Schedule 4 substance in the U.S., meaning it has an accepted medical use with severe restrictions on distribution.

It's considered to be a schedule IV controlled substance under US law, though no addiction potential has been identified.

Some users will take modafinil daily to increase their alertness, focus and energy. In fact, there are many everyday users who purchase their monthly supply online without needing a prescription.

So let's address the first question: Is Modafinil really a stimulant?

The short answer: yes. The long answer is: Yes, but it's a bit more complicated than it sounds.

Modafinil's Stimulatory Effects

The most important distinction to make between Modafinil and other stimulants is its mechanism of action.

Most stimulants (like amphetamine, methylphenidate, cocaine, etc.) act upon the central nervous system by binding to specific proteins and altering neurotransmission.

This is what causes the euphoria associated with them because dopamine levels spike.

That being said, Modafinil is more complicated than that.

Its mechanism of action in the brain isn't focused on changing dopamine or norepinephrine levels; it affects the arousal centers of the brain indirectly through GABA receptors.

Modafinil doesn't inhibit GABA directly, but it does influence how other chemicals in your body interact with these receptors.

It also influences glutamate levels by increasing dopamine activity through D1 receptors on neurons.

This unusual mechanism of action allows modafinil to be unique in psychiatric treatment. The drug does not cause any serious sedation or drowsiness; instead, it improves wakefulness in people who have sleep disorders like narcolepsy or obstructive sleeping apnea.

How Modafinil Stimulates The Brain

The general public's impression of Modafinil is that it is a "smart drug".

That is because Modafinil, while acting on similar brain systems to Ritalin and Adderall, also has some very non-stimulant effects.

First, we need to know how the brain systems work for normal wakefulness and alertness.

In a simplified sense: The hypothalamus produces histamine which makes you wake up (it's the same molecule that makes you itch).

The cortex needs dopamine for focused attention on tasks at hand (dopamine release generates the pleasure sensation of eating sugary food such as chocolate).

Modafinil is a stimulant in the sense that it activates the histamine system, and blocks the reuptake of dopamine, serotonin, and norepinephrine.

It does not actually increase the concentration of any of these transmitters.

The user feels awake and attentive because histamine is being produced, and dopamine is being prevented from being sequestered by normal mechanisms (reuptake) which would normally clear neurotransmitters out of the synapse.

Non-stimulant Actions

However, Modafinil also has important non-stimulant actions.

For example: It upregulates GABA transporters: increasing GABA uptake into neurons so that GABA acts longer on its receptors.

It also promotes glutamate activity in some brain areas. One could say that Modafinil controls neuronal excitability at transmitter sites for most major brain signaling molecules:

  • Dopamine
  • Norepinephrine
  • Serotonin/Melatonin
  • GABA/Glutamate.

It takes about 16-20 hours for the drug to leave the body, so it is a very long-lasting molecule.

So yes, Modafinil is a stimulant.

Even though it feels like a stimulant, to most users, Modafinil does not feel like amphetamine or meth so it is unlikely that the user will overuse Modafinil.

Modafinil seems to act in the same way on a given brain area as amphetamine does (e.g., promoting histamine production; blocking the reuptake of dopamine).

But there are other effects that are much different from amphetamine (e.g., upregulating GABA transporters; also has many effects on glutamate activity).

What Modafinil does in your brain will vary somewhat depending on which of these effects predominate in each person, and how they interact with all of your genes and with everything else that happens to you during your day.

References:

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604337/ (The Unique Psychostimulant Profile of (±)-Modafinil: Investigation of Behavioral and Neurochemical Effects in Mice)
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472902/ (Modafinil improves attentional performance in healthy, non-sleep deprived humans)
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813072/ (Direct comparison of the acute subjective, emotional, autonomic, and endocrine effects of MDMA, methylphenidate, and modafinil in healthy subjects)
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983674/ (Repeated methamphetamine and modafinil induce differential cognitive effects)
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880463/ (Psychostimulants and Cognition: A Continuum of Behavioral and Cognitive Activation)
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4946060/ (Dopamine Transporter Correlates and Occupancy by Modafinil in Cocaine-Dependent Patients: A Controlled Study With High-Resolution PET and [11C]-PE2I)