Because of the drugs very long half-life, the Centers for Disease Control originally recommended a mefloquine dosage of 250 mg every two weeks; however, this caused an unacceptably high malaria rate in the Peace Corps volunteers who participated in the approval study, so the drug regimen was switched to once a week.By 1991, Hoffman was marketing the drug on a worldwide basis.By the 1992 UNITAF, Canadian soldiers were being prescribed the drug en masse.By 1994, medical professionals were noting "severe psychiatric side effects observed during prophylaxis and treatment with mefloquine", and recommending that "the absence of contraindications and minor side effects during an initial course of mefloquine should be confirmed before another course is prescribed." Other doctors at the University Hospital of Zurich noted in a case of "a 47-year-old, previously healthy Japanese tourist" who had severe neuropsychiatric side-effects from the drug that
The neuropsychiatric side effects of the antimalarial drug mefloquine are well documented. They include anxiety, depression, hallucinations, acute psychosis, and seizures. The incidence of these side effects is 1 in 13,000 with prophylactic use and 1 in 250 with therapeutic use. The first randomized, controlled trial on a mixed population was performed in 2001. Prophylaxis with mefloquine was compared to prophylaxis with atovaquone-proguanil. Roughly 67% of participants in the mefloquine arm reported greater than or equal to one adverse event, vs 71% in the atovaquone-proguanil arm.
Canadian soldiers who took mefloquine when deployed overseas have claimed they have been left with ongoing mental health problems. Research
In June 2010, the first case report appeared of a progressive multifocal leukoencephalopathy being successfully treated with mefloquine. Mefloquine can also act against the JC virus. Administration of mefloquine seemed to eliminate the virus from the patients body and prevented further neurological deterioration.Mefloquine alters cholinergic synaptic transmission through both postsynaptic  and presynaptic actions. The postsynaptic action to inhibit acetylcholinesterase changes transmission across synapses in the brain. References
Further reading
Chen LH, Wilson ME, Schlagenhauf P (May 2007). "Controversies and misconceptions in malaria chemoprophylaxis for travelers". JAMA. 297 (20): 2251–63. doi:10.1001/jama.297.20.2251. PMID 17519415. Schlagenhauf P, Adamcova M, Regep L, Schaerer MT, Rhein HG (December 2010). "The position of mefloquine as a 21st century malaria chemoprophylaxis". Malar. J. 9: 357. doi:10.1186/1475-2875-9-357. PMC 3224336. PMID 21143906. External links

"Mefloquine". Drug Information Portal. U.S. National Library of Medicine.