Wrong Track – The Early Hypotheses

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William D.M. Paton is a distinguished British pharmacologist who has expressed great concern over the apparent harmful effects of marijuana on biological cells and systems. Along with Gabriel Nahas, another scientist noted for his concern over marijuana’s effects on the human body, Paton helped to organize international symposiums on marijuana research. These excerpts from Sir Paton’s summaries of these symposia make it clear that speculation about marijuana’s effects on the brain was just that – speculation. At the time of these remarks, and indeed until Herkenham’s breakthrough in 1990, all scientists had were theories about marijuana’s effects on the brain.

“(1975: “[M]any of these studies in cell biology are taking us toward an understanding of possible mechanism of action of THC. Should one think of a cannabinoid receptor? I prefer the idea of hydrophobic spaces in membranes or macromolecules, the average shape and dimensions of which limit their capacity to accept larger lipophilic molecules. Also, some investigators suspect that the characteristics of the site of action for the more toxic effects may differ from that for psychic effects.” W.D.M. Paton (2)

“(1978: “At the neuronal level, the available evidence about THC remains tantalizing. . . [I]t appears reasonable to attribute the central stimulant effects of cannabis to generation of hypersynchronous neural discharge, but how this is brought about is still unsettled. THC depresses rewarding self-stimulation behavior, and tolerance develops to this. But we cannot yet reliably link these results to definite neurological changes. . . we still lack any well-defined type of neurochemical action by THC as a basis for all these effects. Although we must recognize radical differences between THC and general anesthetics, perhaps it is the case that the actions of both of them are to be defined not in terms of specific transmitters, but in terms of some other characteristic of the components of synapses such as size, geometry, or membrane composition.” W.D.M. Paton (3)

“(1984: “Studies on the mechanism of action of delta-[9]-THC have still not resolved the question as to whether the drug acts mainly in a relatively non-specific way in cell membranes, at a receptor, or both. Much evidence is accumulating, however, to suggest that membranes are the preferred site and this is supported by the drug’s effects on a large number of organs and biochemical processes… ” D.J. Harvey & W.D.M. Paton (4)