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Biology 202
2004 First Web Paper
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LSD- Origins and Neurobiological Implications

Michael Fichman

D-Lysergic acid diethylamide, commonly known as the drug LSD was discovered serendipitously in 1938 by Dr. Albert Hofmann during an attempt to synthesize coramine, a circulatory and breathing stimulant. (1) The compound was considered chemically uninteresting and was ignored until 1943 when Hofmann, while reopening his research of lysergic compounds accidentally ingested some of the compound and he "suddenly became strangely inebriated. The external world became changed as in a dream. Objects appeared to gain inrelief; they assumed unusual dimensions; and colors became more glowing. Even self-perception and the sense of time were changed." (2) How was it that Hofmann, who subsequently became the father of psychopharmacology, hallucinated after ingesting d-lysergic acid diethylamide? How was his perception of reality changed? Most importantly, how did LSD affect his Central Nervous System, physically and otherwise, in order to bring about these effects, and what do these effects imply about the Central Nervous System and the neurobiology of behavior as they relate to an alteration or a divergence of consciousness?
Physical Response
LSD is a structure comprised of four cyclic structures and three notable functional groups- two ethyl groups and a methyl group. The structure of LSD bears a striking similarity to that of serotonin, which is the molecule principally responsible for determination of mood. (3) A useful explanation for the brain's receptivity to LSD is its structural similarity to serotonin. A C14 marking of ingested LSD shows that about 10% of LSD molecules ingested by a subject pass through the blood brain barrier and bind to serotonin receptors in the hypothalamus. (4) The hypothalamus is part of the limbic system, which has a diverse array of functions associated with homeostasis, movement and more importantly emotion and organization of responses. (5) Once the LSD molecule binds to the serotonin site, it alters the responsiveness of the subject's neurotransmitters. A hallucinogen produces the sensory distortion known as hallucination by lowering the threshold at which nerves produce a response signal. This means that neurons which normally require a large chemical stimulus to produce a signal which is then sent to the brain produce signals at the slightest chemical prompting. (6) This increased volume of neuron activity and signaling means more sensory information is being sent to the brain than it can handle.
The consequence of this mechanism is that LSD molecules, when introduced into the system can become an inhibitor of serotonin. This may cause depression depending on other factors. However, non-hallucinogenic LSD derivatives such as 2-brominated-LSD can be used as serotonin inhibitors to control chemically-based psychological disorders. (7)
Consciousness and Mind Expansion
If the hypothalamus, a center of organizational control and emotion is adversely affected by the binding of LSD to its serotonin receptor sites and functioning irregularly, the outward effects of LSD seem sensible. However, this explanation of neurochemical phenomena barely begins to address the idea of altered and different forms of consciousness. Once one becomes able to see sounds and hear smells, and experience a trip outside of his normal neurological configuration, one could truly say he has experienced a different form of consciousness. (8) Could thoughts generated during an acid trip have been generated under "normal" conditions? If consciousness is merely a function of the pattern or manner of impulse generation and reception, can consciousness be electrically manipulated?
The most profound manifestation of this difference in consciousness is the flashback. In a flashback, an individual returns unexpectedly to the mental state of an acid trip. Whether there are residual LSD molecules involved in a flashback, it is unclear, but a flashback, with its deviation from an individual's perceived reality, provides an excellent juxtaposition between the individual's normative consciousness and the consciousness generated by LSD. The flashback concept also introduces the idea of an LSD placebo of sorts. A brain can generate an LSD-like consciousness state without the aid of the drug itself, showing an ability to redirect the processing of neuron impulses in ways usually thought to be automated.
Ultimately the barrier to LSD research is the inherently philosophical nature of the drug itself (not to mention its illegality). The realms of consciousness reserved for psychology are yet to be blended with the realms of neurophysiology and biochemistry. LSD is peculiar amongst drugs in that it produces emotions and sensations which bend the realm of ordinary human conceptions of consciousness and defy chemical and scientific description at our current level of scientific advancement.


1) "Stanislav Grof interviews Dr. Albert Hofmann, Esalen Institute, Big Sur, California, 1984," MAPS, Volume XI, Number 2, Fall 2001.

2)Hofmann, Albert. LSD- My Problem Child. McGraw Hill: New York, 1980.

3)C. D. Nichols, J. Ronesi, W. Pratt and E. Sanders-Bush, "Hallucinogens and Drosophila: Linking Serotonin Receptor Activation to Behavior," Neuroscience, Volume 115, Issue 3, 9 December 2002, Pages 979-984

4) "Stanislav Grof interviews Dr. Albert Hofmann."

5) David B. Givens, "The Hypothalamus, "Center for Nonverbal Studies, 2001.

6) Anna Bacon, Heather Cagle, Paul Mikowski, Michael Rosol, "The Effect of LSD on the Human Brain," Michigan State University, 1996.

7)See "Stanislav Grof interviews Dr. Albert Hofmann" as well as the journal article by Watts, Val J.; Lawler, Cindy P.; Fox, David D.; Neve, Kim A.; Nichols, David E.; Mailman, Richard B. "LSD and structural analogs: pharmacological evaluation at D1 dopamine receptors." Psychopharmacology (Berlin) 
(1995),  118(4),  401-9.  CODEN: PSCHDL  ISSN: 0033-3158.  Journal  written in English.    CAN 123:74809    AN 1995:603436    CAPLUS.

8) National Institutes of Health, "NIDA factsheet," 2003.

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