Microtubules, psychedelics & Orch-OR

Orch-OR (orchestrated objective reduction) is a highly speculative theoretical hypothesis proposing that consciousness would emerge from coherent quantum processes within neuronal microtubules. The plate explores an extension of this idea to psychedelics: these molecules would bind to microtubules and could modulate a possible quantum coherence. The whole is presented as a minority and contested research programme, not as an established fact.

Binding of psychedelics to microtubules

Molecular docking work (Craddock, Tuszynski) suggests that certain psychedelics (N,N-DMT, LSD, psilocybin, 5-MeO-DMT) would bind to hydrophobic pockets of tubulin, distinct from the classical 5-HT2A serotonergic receptors. The affinity would be micromolar (a dissociation constant on the order of 1 to 10 micromolar depending on the molecule), with reversible and non-covalent binding. The hypothetical role put forward is a conformational stabilisation of microtubules, an increase in quantum coherence, and a modulation of intrinsic oscillatory dynamics.

Quantum coherence in microtubules

The plate draws on recent results. Superradiance (Babcock and collaborators, 2024) describes a collective excitonic coherence in tryptophan networks, observed at room temperature (37 degrees), with a duration on the order of 10 to the power minus two to 10 to the power minus six seconds. This is presented as a necessary but not sufficient condition for Orch-OR. Attenuation by anaesthetics (propofol, isoflurane, sevoflurane) would reduce this superradiance and the excitonic coherence, in a manner correlated with loss of consciousness. Stabilisation of microtubules by epothilone B (eNeuro, Khan and collaborators, 2024) would delay loss of consciousness under anaesthesia in rats. The plate stresses the limits: showing coherence does not prove functional quantum computation, decoherence at 37 degrees would be very fast (estimates from Tegmark, 2000, on the order of 10 to the power minus thirteen to 10 to the power minus twenty seconds), and these correlations remain suggestive, not decisive.

Orch-OR theory

According to Hameroff and Penrose, microtubules would orchestrate objective reductions (OR) of quantum states, each reduction corresponding to a conscious moment. Consciousness would emerge from these orchestrated quantum events. The reductions are described as non-computable (irreducible to Turing computation), integrated (unity of experience), instantial (on the order of 10 to the power minus fourteen to 10 to the power minus thirteen seconds) and non-localised (gravitational in nature). Conscious experience would be the union of integrated information (the moment of reduction) and a phenomenal content. Several fundamental unknowns remain: the origin of coherence at 37 degrees in a noisy biological environment, the precise mechanism of the gravitational coupling, and the reason why these processes would give rise to a unified experience.

Central hypothesis and proposed mechanisms

The driving hypothesis is that, if psychedelics increase quantum coherence in microtubules, they could increase the frequency or extent of objective reductions, radically modifying the integration of information and the phenomenal field. This would account for experiences of alternative realities, of self dissolution or of entity encounter. The proposed mechanisms range from binding to allosteric pockets to modulation of microtubule dynamics, including a possible increase in coherence and a facilitation of reduction events.

Epistemic status and debates

The plate is explicit: Orch-OR is very much a minority view in the cognitive neuroscience community. The main criticisms concern decoherence judged too fast (Tegmark, 2000), contested Goedelian arguments (Feferman, McCullough), and the absence of any explanation for the passage from objective reduction to qualia (the hard problem of consciousness). Recent data revive interest without validating the complete theory. Several grey areas remain: the spatio-temporal scale of the reductions, their articulation with classical neuronal activity, the role of associated proteins (MAPs, tau), the origin of qualitatively different effects across molecules, and the ontological nature of encountered entities (generated by the brain or independent realities). The proposed experimental avenues include the direct measurement of coherence in living neurons and the study of the effect of psychedelics on this coherence in vivo. The plate recalls that it has only an informative value and invites the reader to separate what is demonstrated, plausible, speculative or belonging to science fiction.

Sources

• Hameroff and Penrose (2014), the Orch-OR theory of consciousness.
• Penrose, arguments on the non-computability of consciousness (Shadows of the Mind, 1994).
• Craddock and Tuszynski (2012), modelling of molecule binding to tubulin.
• Babcock et al. (2024), UV superradiance in tryptophan networks (microtubules); Kalra et al. (2023), measured excitonic energy migration in microtubules.
• Khan et al. (2024), microtubule stabilisation (epothilone B) and anaesthesia (eNeuro).
• Tegmark (2000), critique of decoherence in the brain.
• Feferman (1995) and McCullough, discussions of the Goedelian arguments.