LSD is a highly potent hallucinogen which can profoundly alter consciousness. The exact causal mechanism of this drug is unknown, but much information about its effects on the brain has accumulated over the past few decades. Understanding the causal mechanism behind its action may have positive benefit for therapeutic, pharmacological, and scientific applications. The action of LSD in the nervous system can be approached at phenomenological, neurochemical, and neuroanatomical levels. At the neurochemical level, the action of LSD is thought to involve serotonin and dopamine receptors, as well as glutamate and the expression of the genes c-fos and rac. At the neuroanatomical level, LSD action is thought to be focused in the thalamus, raphe nucleus, cortical pyramidal neurons, as well as numerous other locations.
[...] Anden, N.E., Corrodi, H., Fuxe, K., & Hokfelt, T. (1968). Evidence for a central hydroxytryptamine receptor stimulation by lysergic acid diethylamide. British Journal of Pharmacology 1-7. Behrendt, R.P. (2003). Hallucinations: synchronization of thalamocortical oscillations underconstrained by sensory input. Consciousness and Cognition 413-451. Cedarbaum, J.M., & Aghajanian, G.K. (1978). Activation of locus coeruleus neurons by peripheral stimuli: Modification by a collateral inhibitory mechanism. Life Sciences 23. 1383-1392. Crick, F.C., & Koch, C. (2005). What is the function of the claustrum? Philosophical Transactions of the Royal Society 1271-1279. [...]
[...] Observations from LSD research. New York: Viking Press. Grof, S. (1980). LSD Psychotherapy. Pomona, CA: Hunter House. Hoffman, A. (1980). LSD-My Problem Child. New York: Mcgraw Hill. Jaffe, J.H. (1985). Drug addiction and drug abuse. In Gilman, Rall, Rall and Rurad (eds) Goodman and Gilman's the Pharmalogical Basis of Therapeutics. p522-573. New York: McGraw Hill. Kolb, B. & Whishaw, I.Q. (2001). An Introduction to Brain and Behavior. New York: Worth Publishers. Kurland, A. A. (1985). LSD in the supportive care of the terminally ill cancer patient. [...]
[...] In this paper I will review what is known about LSD and how it affects the brain, as well as how these effects may may be linked to the changes in consciousness that LSD brings about. I will begin by arguing for the importance of understanding how LSD works and will briefly review the basic chemical structure. Then, I will discuss the effects of LSD in terms of three explanatory layers: the psychological effects, the neurochemical effects, and the neuroanatomical effects. [...]
[...] For one thing, drawing an experimental causal connection between the subjective effects of LSD and the underlying neurochemistry and/or neuroanatomy, does little to explain how processes at the neural or brain level actually give rise to full-blooded experiences which are had by a real, conscious individuals. But these kinds of problems are, at present, found throughout the neurosciences. Hopefully a more thorough understanding of the mechanisms underlying LSD action will help to overcome these obstacles. Bibliography Aghajanian, G.K. (1980). Mescaline and LSD facilitate the activation of locus coeruleus neurons by peripheral stimuli. [...]
[...] The first problem is that the 5H-T2A hypothesis, which is the view that hallucinogens exert their effects primarily through the 5H-T2A receptor, does not explain the effects of LSD as well as it seems to explain the effects of other hallucinogens. The key problem is that the 5H-T2A hypothesis fails to account for the remarkable potency of LSD. Amphetamine hallucinogens such as DOB and DOI have an affinity for the 5H-T2A receptor which is comparable to that of LSD, yet are 20 to 30 times less potent than LSD either in humans or rats (Nichols 2004)! [...]
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