We evaluated CGX-1160 in a Phase Ia clinical trial to determine the safety of escalating doses in patients with central neuropathic pain following spinal cord injury (SCI). Our secondary objective was to detect a trend toward analgesic efficacy. Four subjects received 3 consecutive escalating doses of CGX-1160 starting at 25 μg/h over 6 hours until 2 consecutive subjects experienced any adverse effect; 2 of the 4 subjects received 2 sequences of 3 consecutive dose escalations. Maximum tolerated dose was defined by the development of diarrhea (900 μg/h over 6 hours). Cerebrospinal fluid (CSF) and blood were collected for pharmacokinetic (PK) evaluation. The CSF concentration-versus-time data fit to a biexponential PK model, showing a rapid redistribution phase followed by a significantly slower terminal elimination phase. Incorporating an effect site delay into the model improved the fit to the data (concentration producing 50% of the maximum effect [C50], 58.7 ug/mL at the site of drug effect). Maximal reduction from the baseline pain intensity was 63%. In summary, CGX-1160 was generally well tolerated when administered intrathecally at doses up to 1000 μg/h. Peak analgesic effect occurred after the peak intrathecal concentration, indicating the presence of an effect site compartment to the PK model to represent the concentration and effect profiles for this unique compound.