The Microtubule Cytoskeleton as a Direct On-pathway Target of Psychoactive Compounds  Travis Craddock (Psychology and Neuroscience, Nova Southeastern University, Ft. Lauderdale, FL )   C8

The microtubule cytoskeleton is responsible for maintaining the key structure of the neuron, transporting intracellular materials required for synaptic plasticity, and serves as an ideal substrate for signaling and sub-neural information processing. There are many known drugs which bind to microtubule to prevent their proper function, two of which are colchicine, and the vinca alkaloids. Interestingly, both colchicine, and the vinca alkaloids have been reported to cause hallucinations in some cases [1-3], suggesting that direct modulation of the cytoskeleton may be involved in hallucinogenic experience. Hallucinogens are one of the few known molecular probes of consciousness, the other being anesthetics. It is known that microtubules are direct on-pathway targets of anesthetics [4, 5], and that anesthetics can bind to tubulin [6], and disrupt underlying quantum behavior [7, 8]. Like anesthetics, evidence suggests that classic hallucinogens act via direct modulation of the microtubule cytoskeleton [9]. There appears to be a remarkably consistent structural and functional relationship between the phenylethylamine hallucinogens (mescaline, DOM, etc.) and the microtubule inhibitor colchicine. While, such a consistent relationship is not sustained in simple form through to the indoleamine hallucinogens (LSD, psilocin, DMT etc.) and the indole based vinca alkaloids, this class of potent hallucinogens still retains the full potential to disrupt the structure of the brain's cytoskeleton indirectly via serotonin and the raphe system. Furthermore, very recent evidence shows that tryptophan, an indole based amino acid and the precursor of serotonin, binds directly to tubulin, suggesting that serotonin and indoleamine hallucinogens may exert their influence on the microtubule cytoskeleton by binding to tubulin directly [10]. This is at least supported theoretically in the case of LSD [11]. However, it remains to be determined if such potential interactions could disrupt or modulate quantum effects in microtubules. Here, preliminary work towards this goal will be discussed. References available upon request.