I contacted Merial with your question and this is what the response was.
Thank you for your email regarding FRONTLINE© Combo.
In answer to your question, following application as directed, FRONTLINE® Combo rapidly dissolves in the lipid(fat)-rich structures of the skin. It then spreads to all areas of the body surface by diffusion along a concentration gradient, away from the application site, through surface lipid (fat) within 24 hours. This process is aided by the normal body movement of animals.
Fipronil (the active ingredient in FRONTLINE® Combo) concentrates in the sebaceous glands in the skin. The sebaceous glands constantly secrete sebum (the oils found on skin and hair), and with this, Fipronil is secreted to coat the skin and hair. This ongoing secretion following application explains the long term activity against fleas and ticks that FRONTLINE Combo provides.
FRONTLINE® Combo has a non-systemic mode of action, which means that it kills parasites on contact rather than via the pets’ blood, and so they do not need to bite or feed on pets in order to be killed. I’m not sure how this would make your cats behaviour change.
May I suggest you discuss your concerns with your veterinary surgeon who may be able to assist you further.
To put this into layman terms, this medication should not penetrate the blood-brain barrier to cause any personality changes or psychedelic effects as it does not go into the pets blood stream - it stays in the layers of the skin.
This drug is supposed to deter lice and ticks for a month (though my cat still got lice!).
If you have an infestation in your house or high volumes of fleas outside ( I know southern USA has a major problem with fleas) you will still see the occasional one on your pet, the medication will kill it over time.