Homo medicus: The transition to meat eating increased pathogen pressure and the use of pharmacological plants in Homo.

The human lineage transitioned to a more carnivorous niche 2.6 mya and evolved a large body size and slower life history, which likely increased zoonotic pathogen pressure. Evidence for this increase includes increased zoonotic infections in modern hunter-gatherers and bushmeat hunters, exceptionally low stomach pH compared to other primates, and divergence in immune-related genes. These all point to change, and probably intensification, in the infectious disease environment of Homo compared to earlier hominins and other apes. At the same time, the brain, an organ in which immune responses are constrained, began to triple in size. We propose that the combination of increased zoonotic pathogen pressure and the challenges of defending a large brain and body from pathogens in a long-lived mammal, selected for intensification of the plant-based self-medication strategies already in place in apes and other primates. In support, there is evidence of medicinal plant use by hominins in the middle Paleolithic, and all cultures today have sophisticated, plant-based medical systems, add spices to food, and regularly consume psychoactive plant substances that are harmful to helminths and other pathogens. We propose that the computational challenges of discovering effective plant-based treatments, the consequent ability to consume more energy-rich animal foods, and the reduced reliance on energetically-costly immune responses helped select for increased cognitive abilities and unique exchange relationships in Homo. In the story of human evolution, which has long emphasized hunting skills, medical skills had an equal role to play.

The low prevalence of female smoking in the developing world: gender inequality or maternal adaptations for fetal protection?

BACKGROUND: Female smoking prevalence is dramatically lower in developing countries (3.1%) than developed countries (17.2%), whereas male smoking is similar (32% vs 30.1%). Low female smoking has been linked to high gender inequality. Alternatively, to protect their offspring from teratogenic substances, pregnant and lactating women appear to have evolved aversions to toxic plant substances like nicotine, which are reinforced by cultural proscriptions. Higher total fertility rates (TFRs) in developing countries could therefore explain their lower prevalence of female smoking. OBJECTIVE: To compare the associations of TFR and gender inequality with national prevalence rates of female and male smoking. METHODS: Data from a previous study of smoking prevalence vs gender inequality in 74 countries were reanalysed with a regression model that also included TFR. We replicated this analysis with three additional measures of gender equality and 2012 smoking data from 173 countries. RESULTS: A 1 SD increase in TFR predicted a decrease in female smoking prevalence by factors of 0.58-0.77, adjusting for covariates. TFR had a smaller and unexpected negative association with male smoking prevalence. Increased gender equality was associated with increased female smoking prevalence, and, unexpectedly, with decreased male smoking prevalence. TFR was also associated with an increase in smoking prevalence among postmenopausal women. CONCLUSIONS: High TFR and gender inequality both predict reduced prevalence of female smoking across nations. In countries with high TFR, adaptations and cultural norms that protect fetuses from plant toxins might suppress smoking among frequently pregnant and lactating women.

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.

Most globally popular drugs are plant neurotoxins or their close chemical analogs. These compounds evolved to deter, not reward or reinforce, consumption. Moreover, they reliably activate virtually all toxin defense mechanisms, and are thus correctly identified by human neurophysiology as toxins. Acute drug toxicity must therefore play a more central role in drug use theory. We accordingly challenge the popular idea that the rewarding and reinforcing properties of drugs "hijack" the brain, and propose instead that the brain evolved to carefully regulate neurotoxin consumption to minimize fitness costs and maximize fitness benefits. This perspective provides a compelling explanation for the dramatic changes in substance use that occur during the transition from childhood to adulthood, and for pervasive sex differences in substance use: because nicotine and many other plant neurotoxins are teratogenic, children, and to a lesser extent women of childbearing age, evolved to avoid ingesting them. However, during the course of human evolution many adolescents and adults reaped net benefits from regulated intake of plant neurotoxins.

But is it evolution ?

We applaud Müller & Schumann (M&S) for bringing needed attention to the problem of motivation for common non-addictive drug use, as opposed to the usual focus on exotic drugs and addiction. Unfortunately, their target article has many underdeveloped and sometimes contradictory ideas. Here, we will focus on three key issues.

Revealing the paradox of drug reward in human evolution.

Neurobiological models of drug abuse propose that drug use is initiated and maintained by rewarding feedback mechanisms. However, the 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 centre, incidentally vulnerable to neurotoxins, could evolve. By 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.

The effects of an indigenous muscarinic drug, Betel nut (Areca catechu), on the symptoms of schizophrenia: a longitudinal study in Palau, Micronesia.

OBJECTIVE: This study tested the findings of a prior study indicating a therapeutic relationship between consumption of betel nut and symptoms of schizophrenia. METHOD: The subjects were 65 outpatients with diagnoses of schizophrenia or schizoaffective disorder. Symptoms rated with the Positive and Negative Syndrome Scale were compared between high- and low-consumption betel chewers in a repeated-measures design. Movement disorders were assessed with the Abnormal Involuntary Movement Scale and Simpson-Angus Rating Scale. Global health and social functioning were assessed with the Medical Outcomes Study 12-item and 36-item Short-Form Health Surveys, respectively. RESULTS: Male high-consumption betel chewers had significantly milder positive symptoms than low-consumption chewers over 1 year. Betel chewing was not associated with global health, social functioning, or movement disorders. Betel chewing was associated with tobacco use but not with cannabis or alcohol. CONCLUSIONS: These findings have clinical significance in betel-chewing regions and broader implications for theory of muscarinic neurophysiology in schizophrenia.