According to Ayurvedic principles one should avoid combining Ashwagandha with barbituates and other sleep medications/sedatives.
People with very weak metabolism might not get the desired effect of Ashwagandha (or will have to gently stimulate the metabolism first, if appropriate in their particular case).
Also, not really an contra-indication, but something to consider: Ashwagandha has quite powerful purifying qualities, so it's important to make sure that the... ehrm, evacuation of the bowels (I believe that's the medical term?) is working properly while taking Ashwagandha.
I've found the last two to resonate with my own experience (I've never used barbituates or sleep medications, so have no personal experience of that aspect). I haven't used Ashwagandha specifically for methylation purposes, but more for general symptom relief in combination with many other Ayurvedic measures.