Table I. Comparison of effects of psilocybin (0.2-0.24 mg/kg PO), S-ketamine (0.01-0.02 mg/kg/min), and 3,4-methylenedioxymethamphetamine (MDMA) (1.5-1.7 mg/kg PO), and symptoms in schizophrenias (summarized from references 10-12, 28-31, and 33-41). 5-HT, 5 hydroxytryptamine; GABA, γ-aminobutyric acid; NMDA, N-methy!-D-aspartate; mGluR, metabotropic glutamate receptor; D1, D2, dopamine receptors; H1, histamine receptor; α2, α2 adrenergic receptor. * MDMA has highest affinity for the 5-HT transporter (Ki= 0.61 µM)and lesser for α2 (Ki=3.6 µM) and 5-HT2 receptors (Ki5.1µM) in rat brain. * * Chronic administration of NMDA antagonists in rats decreases frontal cortical activity.
| Psilocybin | Ketamine | MDMA | Schizophrenias | |
| Receptor level | ||||
| Primary locus of action | 5-HT2A, 5-HT1A | NMDA | 5-HT transporter,* | Unknown |
| 5-HT2A, 5-HT1A | ||||
| α2, H1 | ||||
| Downstream effects on | GABA, D1 | 5-HT2A | D1, D2 | |
| D2, mGluR | GABA, D1, D2 | |||
| mGluR | ||||
| Psychopathology | ||||
| Positive symptoms | ||||
| • Hallucination/illusions | ++ | + | - | ++ |
| • Delusions | + | + | - | ++ |
| • Thought disorder | + | ++ | + | ++ |
| Negative symptoms | ||||
| • Blunted affect | 0- + | + - ++ | - | ++ |
| • Withdrawal | + | + - ++ | - | ++ |
| Depersonalization | + - ++ | ++ | + | ++ |
| Derealization | + | ++ | + | ++ |
| Neuropsychology | ||||
| • Attention disturbance | + - ++ | + | + | ++ |
| • Distractibility | + | ++ | - | ++ |
| • Working memory | + | ++ | ? | ++ |
| • Associative deficits | + | + - ++ | ? | ++ |
| • Planning/mental flexibility | ++ | ? | ? | ++ |
| Cortical activity | ||||
| • Frontal (PET) | ++ (acute) | ++ (acute) | (+) | ++ (acute) |
| - - (chronic)** | - - (chronic) |