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Comment · Thu, October 31, 2013

How and why I take modafinil. A neuroscience grad and trainee doctor's guide.

Original post in this thread

[deleted] · 10 points

The average human sleeps 8 hours a night and lives to around 70 years old – that is 203,840 hours spent asleep! Obviously sleep has many benefits to the self-optimiser such as memory consolidation and learning… But just imagine what you could achieve with just 1-2 hours less a night from your normal routine?

Background:
Modafinil is often described in the literature as a ‘wakefulness-promoting agent’,not as a stimulant (e.g caffeine, amphetamines and Ritalin), this means it shouldn’t produce a high or a buzz like stimulants do. The key difference here is that stimulants typically increase various excitatory neurotransmitters in the brain, such as dopamine, serotonin and glutamate to create the feeling of being wide awake and full of energy. Modafinil on the other hand, although undoubtedly affecting these systems in some way, is more related to turning down the inhibitory pathways, such as GABA transmission. A simple way to think of this is that stimulants are like putting your foot down on the accelerator on a car, whereas modafinil is more like taking the hand-break off that you had forgotten about! It’s for this reason that Mod is prescribed for ‘disorders of consciousness’ su…

What they were answering

Direct reply to the original post — see the thread post above.

u/MisterYouAreSoDumb

Modafinil increases extracellular dopamine by blocking the DAT.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696807/

Your equivocation for modafinil and a car is simply incorrect. It's not just letting off the brakes, or decreasing GABA as you explained. It is doing exactly what cocaine does. Albeit with a less affinity. Modafinil even decreased cocaine's binding potential. So we know the mechanisms are very similar.

Yes, modafinil has been shown to increase GABA efflux from the cerebral cortex. However, it does this indirectly via modulating the 5-HT2 receptors. It also decreases GABA release in the medial preoptic area and the posterior hypothalamus. Again, it is postulated that this is due to modulation of the 5-HT receptors. In this case, the 5-HT3 receptors.

http://www.ncbi.nlm.nih.gov/pubmed/1620245

http://www.ncbi.nlm.nih.gov/pubmed/8977135

So it's not a stimulant in the sense of sympathomimetics. However, it does act centrally like many other stimulants. It just lacks the peripheral stimulation of a traditional sympathomimetic.

I also don't think you should be recommending 3 hours of sleep, or taking modafinil before bed. That's just improper use of the drug, and is going to have lasting adverse effects if you keep it up for too long.

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