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by fancy_pantser 3425 days ago
You may be an under-responder. With modafinil there seem to be large populations that are over/under-sensitive.

I bought a box about 4 years ago as well to see if it helped at work. I turned out to be sensitive to it and later investigated studies linking my genotype with sensitivity (specifically a pleiotropic SNP in the COMT gene rs4680/Val158Met). Most sequencing includes this well-studied SNP in the panel if you're curious.

Starting with a "normal" 200mg dose was a disaster. Anxiety, shaking, racing thoughts, nausea, and arrhythmia all struck on the ride to work and lasted 10 hours.

With 50mg taken right after breakfast, I was able to achieve some notable effects and feelings of extra productivity but even a small amount of caffeine or alcohol within 18 hours would make me sick. It proved to not be worthwhile and I quit after a month.

Study on modafinil and Val158Met polymorphism: https://www.ncbi.nlm.nih.gov/pubmed/19037200?dopt=Abstract

More observations on Val158Met expression with links to studies: https://neuroamer.com/2012/06/29/card-sorting-pot-smoking-ha...
1 comments
malandrew 3425 days ago
I have some similar experiences myself. I take modafinil for narcolepsy.

A 200mg dose makes me really sleepy. A 50-100mg dose makes me more alert, especially with a small amount of caffeine. A larger amount of caffeine with 50-100mg makes me sleepy again.

How did you get the sequencing done? I know I've been tested for the gene associated with cataplexy (HLA-DQB1*0602 I think), but not sure about the others you mentioned.

link