Evaluating the Neurophysiologic and Clinical Effects of Single Dose Drug Challenge

Inclusion Criteria: * Subjects ages 18-45, with FXS who completed the study entitled "Mechanisms and brain circuits underlying fragile X syndrome" (IRB # 2015-8425) or appropriate baseline measures through Biorepository (2013-7327). * FXS is defined as full FMR1 mutations (\>200 CGG repeats) confirmed by genetic testing. * General good health as determined by physical exam, medical history and laboratory work up. * Stanford Binet IQ \<85 * Stable dosing of psychotropic drugs for at least 4 weeks. Exclusion Criteria: * Subjects with a history of intolerance to baclofen, roflumilast, or memantine will be excluded. * Subjects will also be excluded if they have taken any investigational drug within 3 months, have a history of substance abuse or dependence within 6 months, or significant psychiatric or CNS neurological disease unrelated to FXS. * Uncontrolled seizures or history of epilepsy with a seizure in the past 6 months * Auditory or visual impairments that cannot be corrected based on visual and auditory screener benchmarks. * Moderate to severe renal or hepatic impairment and determined by a study physician incorporating data from exam, medical history and laboratory value evaluation among other data points. * Use of barbiturates, benzodiazepines, antiepileptics, or other GABAergic or glutamatergic modulators * Current use of: Amifampridine, Butalbital, Codeine, Doxylamine, Ethanol, Hydrocodone, Isocarboxazid, Kava, Metoclopramide, Midazolam, Oxybate, Phenelzine, Promethazine, Thalidomide, Tranylcypromine, Trimethobenzamide, Erythromycin, Ketoconazole, Fluvoxamine, Enoxacin, and Cimetidine. * Those taking other psychiatric medications must be on stable doses for 4 weeks before the baseline visit. * Pregnancy or breast-feeding. For female subjects of child bearing potential, a urine pregnancy test will be performed. * Potential subjects with a creatinine clearance \< 50 mL/min will be excluded. * Identified medical issues, inability to tolerate study procedures or study drug per the discretion of the Principal Investigator.