Coincidentally, the link between mefloquine and madness was the subject of a recent review article in the Journal of the American Academy of Psychiatry and the Law which reads like a cross between an H.P Lovecraft short story and a neuroscience paper.
Case reports suggest that mefloquine intoxication may begin with a variable prodrome which may present with personality change, unease, anxiety, phobias, and a sense of impending doom and restlessness. These prodromal symptoms may progress to outright paranoia, delusions, magical thinking, persecutory mania, restlessness, aggression, and panic attacks…
Mefloquine psychosis frequently includes auditory or true visual hallucinations, frequently involving religious or morbid themes. Auditory hallucinations typically feature voices that may be incoherent or mumbling. Some individuals report a sense of the presence of a nearby nondescript figure. Olfactory hallucinations have also been reported. The often vivid and terrifying nature of the hallucinations produced by mefloquine are illustrated by an early unindexed case report, similar to at least one other published report, describing a man who jumped from his hotel room in the false belief that his room was on fire.
Of note, vivid dreams or horrific, terrifying nightmares, also frequently reported by users of mefloquine, are characterized as having “Technicolor clarity” and being “vividly remembered days later,” suggesting that these may also be prodromal to or inform later symptoms of psychosis.
Disturbance in this region is known to greatly raise the risk of psychosis. For example, people with temporal lobe epilepsy (which some of the limbic system is part of) have a greatly raised risk of psychosis.