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

Antimicrobial Use and Veterinary Care among Agro-Pastoralists in Northern Tanzania

Frequent and unregulated use of antimicrobials (AM) in livestock requires public health attention as a likely selection pressure for resistant bacteria. Studies among small-holders, who own a large percentage of the world's livestock, are vital for understanding how practices involving AM use might influence resistance. We present a cultural-ecological mixed-methods analysis to explore sectors of veterinary care, loosely regulated AM use, and human exposure to AMs through meat and milk consumption across three rural to peri-urban Tanzanian ethnic groups (N = 415 households). Reported use of self-administered AMs varied by ethnic group (Maasai: 74%, Arusha: 21%, Chagga: 1%) as did consultation with professional veterinarians (Maasai: 36%, Arusha: 45%, Chagga: 96%) and observation of withdrawal of meat and milk from consumption during and following AM treatment (Maasai: 7%, Arusha: 72%, Chagga: 96%). The antibiotic oxytetracycline was by far the most common AM in this sample. Within ethnic groups, herd composition differences, particularly size of small-stock and cattle herds, were most strongly associated with differences in lay AM use. Among the Arusha, proxies for urbanization, including owning transportation and reliance on "zero-grazing" herds had the strongest positive associations with veterinarian consultation, while distance to urban centers was negatively associated. For Maasai, consultation was negatively associated with use of traditional healers or veterinary drug-shops. Observation of withdrawal was most strongly associated with owning technology among Maasai while Arusha observance displayed seasonal differences. This "One-Health" analysis suggests that livelihood and cultural niche factors, through their association with practices in smallholder populations, provide insight into the selection pressures that may contribute to the evolution and dissemination of antimicrobial resistance

Tobacco use vs. helminths in Congo basin hunter-gatherers: self-medication in humans?

We tested a novel hypothesis that recreational use of neurotoxic plants helps defend against parasites. Spec ifically, we investigated the relationship between smoking and helminthiasis among the Aka, a remote population of Central African foragers who are avid tobacco smokers, suffer high rates of helminthiasis, and have little-to-no access to commercial anthelmintics. Two hundred and six healthy Aka men provided saliva and stool samples. Saliva samples were assayed for cotinine, a nicotine metabolite; a subsample was genotyped for the CYP2A6 enzyme, which metabolizes nicotine. Stool samples were assayed for intestinal helminth eggs as an index of worm burden. After 1 year, a subsample of participants was located and provided additional saliva and stool samples. We found (1) an exceptionally high prevalence of tobacco use, (2) a significant negative correlation between cotinine (a nicotine metabolite) and worm burden, (3) that treating helminths with albendazole, a commercial anthelmintic, reduced cotinine concentration two weeks later, compared to placebo controls, (4) among treated participants, higher cotinine concentrations in year 1 predicted less reinfection by year 2, and (5) younger and older participants with slow nicotine-metabolizing CYP2A6 alleles had lower worm burdens compared to those with extensive metabolizing alleles. These results provide the first evidence of a link between helminthiasis and smoking. They also suggest that, in populations where intestinal helminths are endemic, tobacco use might protect against helminth infection and reduce worm burden among infected individuals, and that individuals modulate nicotine exposure in response to infection. The results thus support the hypothesis that substance use helps defend against parasites

Reduced models for multiple regression showing significant culture-specific effects on AM use, vet consultation (VC), and observance of withdrawal (OW) by Maasai (bold) and <i>Arusha (italic)</i>.

<p>VC and OW coefficients are presented as logits with positive values indicating log-odd increases in reporting of a behavior and negative indicating a decrease in log-odds.</p

Items included in PCA analysis.

<p>Items included in PCA analysis.</p

Proportion antibiotic use and sectors of care among livestock owners^*.

<p>Proportion antibiotic use and sectors of care among livestock owners^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0170328#t003fn001" target="_blank">*</a>}.</p

Common livestock illnesses and frequency of antibiotic use for these presumptive diseases in Maasai households.

<p>Common livestock illnesses and frequency of antibiotic use for these presumptive diseases in Maasai households.</p

Most recent reported human treatments by household^*.

<p>Most recent reported human treatments by household^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0170328#t006fn001" target="_blank">*</a>}.</p

A two-month follow-up evaluation testing interventions to limit the emergence and spread of antimicrobial resistant bacteria among Maasai of northern Tanzania

Background: In sub-Saharan Africa, efforts to control antimicrobial resistance (AMR) are aggravated by unregulated drug sales and use, and high connectivity between human, livestock, and wildlife populations. Our previous research indicates that Maasai agropastoralists—who have high exposure to livestock and livestock products and self-administer veterinary antibiotics—harbor antibiotic resistant Escherichia coli (E. coli). Here, we report the results of a public health intervention project among Maasai aimed at reducing selection and transmission of E. coli bacteria