Eating healthy foods (fruits, vegetables, royal jelly?) should exercise Constitution, and eating unhealthy foods (candy bar, cream pie, etc) should abuse it.

An unaligned artifact amulet versus poison which also confers sickness resistance, half physical damage, and raises Constitution to 25 when worn. Tentatively named “The Eye of [something]”.

Mummies have a constitution-draining touch attack, which possibly also inflicts a ‘withering’ intrinsic that deals damage over time and abuses Constitution every turn.

Mummies could also “cast” a curse on you, not to curse your items, but to make you sink through the floor, sending you down 1-3 levels.

Make it so that dying in a polyform carries a severe, possibly permanent penalty, such as losing some Constitution, maximum HP, or forcing you to a low percentage of current HP regardless of what you had when you first polymorphed.

Healers start with a very high Constitution score.

A race whose gimmick is to continually lose Constitution points every couple hundred turns; going below 1 (or 3?) results in death.

Being strangled for more than a couple turns starts to reduce your Constitution (or maxHP).

All the various fruits and vegetables have slightly different (and generally good) non-nutritional effects, like with carrots and blindness. Ideas:

• Apples exercise Consitution (and make nurses flee?).
• Pears heal d3 hit points.
• Oranges restore one lost ability point.
• Bananas cure stunning.

Lemons, a comestible that deals 1 point of damage when eaten unless acid resistant and exercises Constitution. If you are killed by eating a lemon, the death reason is “killed by citric acid”.

Condensing all of NetHack’s poison mechanics into one unified mechanic:

• Dexterity and Constitution poisons are removed. Quasits (the only AD_DRDX attack) might still directly harm Dex, but it’s no longer flavored as poison. Rabid rats (the only AD_DRCO attack) don’t cause poison, they cause disease, which hits Constitution. Poison will now only affect Strength.
• Poison is now implemented as a timing-out trinsic. The amount of Str loss is a direct function of how much timeout is left, so Str will gradually recover as the poison goes away.
• Passing Con saving throws could give small bonuses to decreasing the timeout faster than normal.
• While poisoned, HP regeneration is either impeded or stopped entirely, or else the player’s HP is damaged every turn, or every several turns.
• It could also heavily abuse Str while it lasted instead of being directly tied to Str.