NMDA glutamate receptor antagonists like PCP, ketamine, and CGS-19755 cause cognitive and behavioral changes in humans and histopathological and neurochemical changes in rodents. These effects appear to be dose-dependent manifestations of a disinhibition process where NMDA antagonists reduce GABAergic inhibition, leading to excessive release of acetylcholine and glutamate. Low doses can produce memory dysfunction without psychosis, while more severe NMDA receptor hypofunction (NRHypo) can mimic psychotic schizophrenic exacerbation. Sustained severe NRHypo in adult brains is associated with neurotoxicity. This paper reviews these effects, their likely mechanism, and the possible role of NRHypo in idiopathic psychotic disorders.
Consciousness may arise from quantum processes in the brain's microtubules, where quantum superpositions in tubulin proteins self-collapse at a threshold linked to quantum gravity, producing discrete conscious events. This 'orchestrated objective reduction' (Orch OR) model, proposed by Roger Penrose and colleagues, suggests each collapse is a non-computable selection of spacetime geometry, coupling consciousness to fundamental physics. The theory aims to explain enigmatic features of consciousness that conventional neuron-based approaches fail to address, such as qualia. It posits that sequences of these events create a stream of consciousness, with microtubule-associated proteins tuning the quantum oscillations to orchestrate the process.