Modafinil, sold in the US as Provigil, has become one of the hottest keywords in nootropics because of its clear benefits for wakefulness and low potential for addiction. However, as with most off-label usages – especially amongst the biohacking community – the side effects are often overlooked in exchange for performance. This might be a fair trade for the entrepreneur working a week of 18 hour days to finish a project, but what about the rest of us that want to increase our focus daily while still feeling normal and avoiding side effects? Tranquility Labs has you covered, of course, but first let’s shed some light on what modafinil is and what the side-effects are.
Modafinil was originally created by French neurophysiologists in the late 1970s. There, it became an experimental treatment for narcolepsy in 1986 and received US approval for the same in 1998. In 2003, it was also approved for shift work sleep disorder and lethargy due to obstructive sleep apnea. In addition to these approved treatments, modafinil has also been used in attempts to treat a variety of other issues such as weight loss, bipolar depression, opiate and cocaine dependence, Parkinson’s disease, schizophrenia, ADHD, and SAD (just to name a few) – having varying degrees of effectiveness. Many of these additional treatments have not been tested thoroughly (trials or pilot studies), some show contradictory results (Modafinil’s parent company filed a patent to use it as an appetite stimulant, not a weight loss agent), and some show no significant improvement over traditional treatments (no proven benefit for cocaine dependence). What we do know for certain is that modafinil can keep you awake when you should be tired but still allow you to sleep when desired.
What is actually happening in the brain that has folks attempting to use modafinil for everything from premature ejaculation to a doping agent in sports? A common misunderstanding is that modafinil is just a super-enhanced caffeine substitute, but it’s more complicated than that. In fact, science still does not know exactly how modafinil works, or what the long-term effects are! That certainly doesn’t sound like something you’d want to take daily without a strong medical reason. In fact, Provigil is classified similarly to Xanax and Ambien as a Schedule IV controlled substance. The National Institute on Drug Abuse (NIDA) has stated that healthy individuals should not take Provigil and the manufacturer agrees with this stance.
Modafinil’s Impact on Neurotransmitters
One of the more apparent ways that modafinil affects the brain is by blocking the re-uptake of dopamine. Dopamine is part of the “reward system” in the brain and is released when we perform actions we think of as “good.” It helps us tie positive associations with accomplishing tasks or positive behaviors. Dopamine also supports communication between neurons. When re-uptake is blocked, dopamine accumulates in the space between neurons and can be reused more readily – which causes physical stimulation and motivating effects. This might be how modafinil works, but its direct influence on dopamine transporters was only recently revealed.
As we know here at Tranquility Labs, dopamine is one of the most important neurotransmitters in the brain. In addition to motivation it regulates cognition, learning, and alertness, as a well as other neurotransmitters like norepinephrine – which is associated with concentration. Clearly dopamine is a huge part of nootropic, or “smart drug” performance.
Unfortunately, this mechanism of action – directly blocking the dopamine transporters in the brain – is the same method used by addictive drugs like methamphetamines, though to a much lesser degree. One study showed that the dopamine changes in the brain on modafinil were similar to those caused by Ritalin. Very few cases of modafinil dependence have been reported, but they do exist and the potential for abuse and habit forming behavior are there. 
This is not the case through the mechanism of action used by our natural nootropic Focusene – which is to support the production of dopamine naturally through its precursor phenylalanine; an amino acid found in nuts and legumes.
Another method of action for modafinil is to reduce the amount of GABA in the brain. GABA is known to promote relaxation and reduce anxiety. That’s why we support its production in both Tranquilene and Focusene. However, GABA can promote sleepiness and modafinil’s primary purpose is wakefulness, so it reduces GABA in favor of glutamate – which is a neurotransmitter involved in learning. Anxiety is a potential side effect of modafinil use and this could be one mechanism by which that effect is produced. At Tranquility Labs we feel that balanced GABA production, and the feeling of well-being associated with it, is more beneficial to focus and learning than risking the distractions of an anxious mind.
The neurotransmitter serotonin – supported naturally here – is also increased indirectly by modafinil. Serotonin has been associated with memory as well as stimulating the creation of new neurons (neurogenesis). Some people have reported improved mood on modafinil, while others say they become withdrawn, less emotional, or even “snappy” with people when their focus is broken.
Other Modafinil Side Effects and Considerations
Modafinil affects the brain in more ways than we have time to talk about here, so the last major effect we’ll cover is the increase of histamines in the hypothalamus. The hypothalamus controls important things like body temperature, hunger, thirst, fatigue, and sleep. Histamine has been linked to sleep because histamine appears to promote wakefulness. It’s found in the highest concentration when we are awake, and animal studies have demonstrated the ability to produce insomnia by increasing histamine and hypersomnia by blocking it. This is of major benefit for folks using modafinil as a narcolepsy medication.
Common side effects of modafinil (from the Provigil website) include headache, back pain, nausea, nervousness, stuffy nose, diarrhea, anxiety, trouble sleeping, dizziness, and upset stomach. It also increases resting heart rate and blood pressure. Anecdotal reports also include frequent urination with an unpleasant odor. This frequent urination combined with the tendency to focus for long uninterrupted periods could be responsible for the headache and dehydration reported above.
As infamous biohacker and author Tim Ferriss likes to say, there’s no biological “free lunch.” Pharmaceutical drugs have significant effects, but also come with a price beyond the copay. Modafinil is clearly of vital importance to those with medical diagnoses whose benefits outweigh the risks. The same may not apply to healthy individuals looking for a little brain boost. Yes modafinil has been shown to improve some types of cognition and learning, but not all (it has been shown to decrease creativity), and not always by a large margin. A June 2015 study concluded that “modafinil does not enhance the global cognitive performance of healthy non-sleep deprived students.” A review published in November 2015 analyzed 24 placebo-controlled studies on the cognitive effects of modafinil on healthy, non-sleep-deprived humans. They found a lot of mixed results. In short, modafinil definitely enhances executive function (planning, prioritizing, organization, etc.) but has less reliable effects on attention, learning, and memory in simple tests. In more complicated tests, attention, learning, and memory appear positively affected; but that could be primarily due to the heightening of executive function providing “top-down” benefits.
Modafinil vs. Natural Nootropics
Fortunately, a study has been done attempting to compare modafinil to two common naturally occurring nutraceuticals: ginseng and bacopa (both found in Focusene). It found that ginseng and bacopa produced effects that were comparable to modafinil – but in different cognitive domains. Modafinil scored highest in visuospatial memory (remembering shapes in relation to one another), ginseng in simple reaction time, and bacopa in delayed word recall. The importance is that all natural nootropics were able to produce the same magnitude of cognition enhancing effects as their pharmaceutical cousin, and without the same potential for side effects. Bacopa comes with the caveat of needing to be taken regularly to see its effects, which is one reason we recommend taking Focusene daily. Bacopa enhances learning and memory, while ginseng improves long term memory and working memory tasks. Unlike modafinil, natural nootropics come with long histories of use, few side effects, no risk of dependence, and are intended for daily use with the goal of not only improved cognitive function, but also a healthy and balanced brain.
