Roger Sullivan: CSU Sacramento, Anthropology, and UC Davis School of Medicine,
Psychiatry and Behavioral Sciences

Neurobiological models of drug abuse propose that drug use is initiated and maintained by
rewarding feedback mechanisms. However, most commonly used drugs are plant neurotoxins
that evolved to punish, not reward, consumption by animal herbivores. Reward models therefore
implicitly assume an evolutionary mismatch between recent drug-profligate environments
and a relatively drug-free past in which a reward center, incidentally vulnerable to neurotoxins,
could evolve. In contrast, emerging insights from plant evolutionary ecology and the genetics
of hepatic enzymes, particularly cytochrome P450, indicate that animal and hominid taxa have
been exposed to plant toxins throughout their evolution. Specifically, evidence of conserved
function, stabilizing selection, and population-specific selection of human cytochrome P450
genes indicate recent evolutionary exposure to plant toxins, including those that affect animal
nervous systems. Thus, the human propensity to seek out and consume plant neurotoxins
is a paradox with far-reaching implications for current drug-reward theory. We sketch some
potential resolutions of the paradox, including the possibility that humans may have evolved
to counter-exploit plant neurotoxins. Resolving the paradox of drug reward will require a
synthesis of ecological and neurobiological perspectives of drug seeking and use.
http://www.bec.ucla.edu/Sullivan.pdf