Effects of lamotrigine on behavioral and cardiovascular responses to cocaine in human subjects

We evaluated the effects of acute pretreatment with lamotrigine, a putative glutamate release inhibitor, on the physiological and behavioral responses to intranasal cocaine in cocaine-dependent volunteers (N = 8). The study e mployed a double-blind, placebo-controlled, within-subject design. Subjects participated in six experimental sessions. On each study day, placebo, lam otrigine 125 mg, or lamotrigine 250 mg was administered orally in the morni ng, followed 2 hours later by intranasal cocaine 120 mg/70 kg or placebo. M easurements of heart rate and blood pressure were acquired, and subjects re sponded to mood state questionnaires at predetermined time intervals. Cocai ne alone produced increases in heart rate, blood pressure, and several meas ures of pleasurable mood and drug effects. Lamotrigine alone produced a mil d relaxing effect. Lamotrigine pretreatment altered neither the physiologic al responses nor the subjective ratings of cocaine's pleasurable or aversiv e mood effects.