Psychopharmacology (2008) 199:77–88 Table 2 Peak amplitudes (μV) and latencies (ms) of N1 83 SD 0.23 17.13 Amplitude (μV) Latency (ms) Baseline Mean −0.67 119.44 SD 0.40 30.08 Low DMT Mean −0.34 112.44 SD 0.34 19.18 High DMT Mean −0.58 109.33 SD 0.63 27.99 Low S-ketamine High S-ketamine Mean −0.86 119.78 SD 0.48 25.73 Mean −0.57 111.67 factors drug (F[1, 8]=6.94, p=0.034) and ISI (F[1, 8]= 12.74, p=0.009). Hence, the “BX” error rate was higher under the DMT conditions compared to S-ketamine. N1 peak amplitude and latency Mean peak amplitudes and latencies of N1 are displayed in Table 2. The separate ANOVAs for the two drugs with the factor condition (baseline, low dose, high dose) revealed a significantly diminished amplitude of N1 only after DMT intake compared to baseline (F= 6.20, df= 2.7, p= 0.028). The post-hoc tests revealed a lower peak amplitude of the low DMT dose compared to baseline (p = 0.008). The second ANOVA with the factors drug and dosage revealed a significant main effect of drug indicating a lower amplitude of N1 under the DMT condition compared to S-ketamine (F= 5.62, df= 1.8, p =0.045). There where no significant changes in N1 latencies between the different conditions in all performed ANOVAs. MMN surface waveforms The grand average MMN surface waveforms of the electrodes F3, Fz, and F4 are presented in Fig. 4. For the duration-deviant-induced MMN, we found a significant effect of the factor condition over all three waveforms only for S-ketamine (F[2, 7] =4.97, p =0.045) but not for DMT. For the frequency-deviant-induced MMN, the factor condi- tion showed only a trend for S-ketamine (F[2, 7] =3.70, p= 0.08). In the second ANOVA with the factors drug and dosage, there was a significant effect of the factor drug (F [1, 8]= 9.01, p =0.017), indicating a lower MMN peak amplitude under the S-ketamine condition compared to DMT. MMN source activity The time course of duration-deviant-induced MMN activity at the four sources is presented in Fig. 5. In the separate ANOVAs for each drug, we found a significant main effect for S-ketamine at all four sources, S1 (F[2, 7] = 6.31, p= 0.027), S2 (F[2, 7] = 9.48, p= 0.01), S3 (F[2, 7] =6.46, p= 0.026), and S4 (F[2, 7] = 5.09, p = 0.043), and for DMT only at S1 (F[2, 7]= 5.04, p= 0.044). These results indicate a diminished MMN activity in the drug conditions compared to baseline. The significant results of the post-hoc LSD tests are presented in Fig. 5. In the second ANOVA with the factors drug and dosage, we found only a significant effect of the factor drug at S4 (F[1, 8]=5.62, p=0.045) and a significant interaction of drug and dosage at S3 (F[1, 8]= 11.81, p=0.009). These results indicate that only S-ketamine affects the frontal generator. The frequency-deviant-induced MMN at the four sources is presented in Fig. 6. In the separate ANOVA for S- ketamine, we found a marginal effect of condition at S3 (F[2, 7]=4.17, p=0.064) and S4 (F[2, 7]=4.19, p=0.064). The separate ANOVA for DMT revealed a significant effect of condition at S1 (F[2, 7]=5.22, p=0.041) and S3 (F[2, 7]= 4.86, p=0.048).The significant results of the post-hoc LSD tests are presented in Fig. 6. The second ANOVA with the factors drug and dosage revealed no significant effects. Discussion The present investigation studied the influence of the two hallucinogens N,N-DMT and S-ketamine on the generation of MMN and performance in an AX-CPT. Overall, the intensity of the hallucinogenic effects of both drugs was similar; however, phenomena that resemble positive symp- toms of schizophrenia were more pronounced after DMT intake, and phenomena that resemble negative and catatonic symptoms of schizophrenia were clearly more pronounced after S-ketamine intake (Gouzoulis-Mayfrank et al. 2005). Taken together, these results are in line with the assumption that the two classes of drugs tend to model different aspects of psychoses. The NMDA antagonist state (S-ketamine) may be an appropriate model for psychoses with prominent negative and possibly also catatonic features, while the 5- HT2A agonist state (DMT) may be a better model for psychoses with prominent positive symptoms (Abi-Saab et al. 1998; Gouzoulis-Mayfrank et al. 2005). Inspection of the descriptive data suggests a decrease in the generation of MMN under both substances. However, this effect was more pronounced after S-ketamine. The analyses of the grand average data showed that the MMN to the duration deviant was significantly reduced by S- ketamine. Moreover, there was a trend reduction for the frequency-deviant-induced MMN. According to the source analyses, S-ketamine reduced the duration-deviant MMN