Plant neurotoxins and the paradox of drug reward

Tobacco is the number one risk factor for disease burden in developed countries, and of all substance use categories carries the highest mortality risk, accounting for an estimated 12% of global morality. Worryingly, its use is rapidly increasing in the developing world. Current neurobiological theory of drug use is based on the observation that all addictive drugs induce changes in activity of dopaminergic circuitry, interfering with reward processing, and thus enhancing drug seeking and consumption behaviors. Current theory of drug origins, in contrast, views almost all major drugs of abuse, including nicotine, cocaine and opiates, as potent plant neurotoxins that evolved to punish and deter herbivores. According to this latter view, plants should not have evolved compounds that reward or reinforce plant consumption. Mammals, in turn, should not have evolved reinforcement mechanisms easily triggered by toxic substances. Situated in an ecological context, therefore, drug reward is a paradox. We are investigating several potential resolutions of this paradox. For example, humans, like other animals, might have evolved to co-opt plant neurotoxins. Specifically, a propensity to seek out and consume toxic plants might have evolved as a means to fight pathogens.

Associated personnel

Related publications

PDF Hagen EH and Blackwell A and Lightner A and Sullivan RJ 2023. Homo medicus: The transition to meat eating, increased pathogen pressure, and the constitutive and inducible use of pharmacological plants in Homo. American Journal of Biological Anthropology.
PDF Hagen EH 2022. The hungry, striving, sociable, parasitized, and slightly buzzed monkey. American Journal of Biological Anthropology.
PDF Placek CD, Magnan RE, Srinivas V, Jaykrishna P, Ravi K, Khan A, Madhivanan P and Hagen EH 2020. The impact of information about tobacco-related reproductive vs. general health risks on South Indian women's tobacco use decisions. Evolutionary Human Sciences, e4.
PDF Hagen EH and Tushingham S 2019. The prehistory of psychoactive drug use. Cognitive Archaeology: Psychology in Prehistory. Tracy B. Henley, Matthew Rossano and Edward Kardas, Eds. Routledge.
PDF Hagen EH and Sullivan RJ 2018. The evolutionary significance of drug toxicity over reward. Routledge Handbook of Philosophy and Science of Addiction, S. Ahmed and H. Pickard, eds.
PDF Placek CD, Madhivanan P, and Hagen EH 2017. Innate food aversions and culturally transmitted food taboos in pregnant women in rural southwest India: Separate systems to protect the fetus?
PDF Hagen EH, Garfield M, Sullivan RJ 2016. The low prevalence of female smoking in the developing world: gender inequality or fetal protection? Evolution, Medicine, and Public Health.
PDF Roulette CJ, Hagen EH and Hewlett BS 2016. A biocultural investigation of gender differences in tobacco use in an egalitarian hunter-gatherer population. Human Nature.
PDF Placek CD and Hagen EH 2015. Fetal protection: The Roles of Social Learning and Innate Food Aversions in South India. Human Nature.
PDF Roulette CJ, Kazanji M, Breurec S, and Hagen EH 2015. High Prevalence of Cannabis Use Among Aka Foragers of the Congo Basin and Its Possible Relationship to Helminthiasis. American Journal of Human Biology.
PDF Roulette CJ, Mann H, Kemp BM, Remiker M, Roulette JW, Hewlett BS, Kazanji M, Breurec S, Monchy D, Sullivan RJ, and Hagen EH 2014. Tobacco use vs. helminths in Congo basin hunter-gatherers: Self-medication in humans? Evolution and Human Behavior, 35, 397–407.
PDF Hagen EH, Roulette CJ and Sullivan RJ 2013. Explaining human recreational use of 'pesticides': The neurotoxin regulation model of substance use vs. the hijack model and implications for age and sex differences in drug consumption. Frontiers in Psychiatry, 4.
PDF Sullivan RJ and Hagen EH 2011. But is it evolution...? Behavioral and Brain Sciences, 34, 322-323.
PDF Hagen EH, Sullivan RJ, Schmidt R, Morris G, Kempter R and Hammerstein P 2009. Ecology and neurobiology of toxin avoidance and the paradox of drug reward. Neuroscience, 160, 69-84.
PDF Schmidt R, Morris G, Hagen EH, Sullivan RJ, Hammerstein P, and Kempter R 2009. The dopamine puzzle. Proceedings of the National Academy of Sciences.
PDF Sullivan RJ, Hagen EH and Hammerstein P 2008. Revealing the paradox of drug reward in human evolution. Proceedings of the Royal Society of London, B, 275, 1231-1241.
PDF Hagen EH and Sullivan RJ 2007. Plant neurotoxins and brain development: Implications for encephalization in Homo. Human Biology Association Annual Meeting, Philadelphia.
PDF Sullivan RJ and Hagen EH 2002. Psychotropic substance-seeking: evolutionary pathology or adaptation? Addiction, 97, 389-400.