Except the case of toad toxins (which, anyway, are used as drugs by very few people), all addictive foods and drugs, from chocolate and caffeine to nicotine, heroin and cocaine, represent plant poisons. Plants normally synthesize toxins for impeding their consumption by herbivores, and this is the paradox: instead of this, humans and other mammals are not only not affected by these chemicals, but even become addicted to them. A new meta-analysis published in "Proceedings of the Royal Society B" analyzes both aspects: the plants should never have synthesized toxins that reward animals when consumed and humans should never have gotten addictions for toxic plants. The origins of drug addiction are significantly more complex than previously believed.

"The paradox has deep implications for current drug reward theory because it implicitly suggests that many of the key assumptions in current drug reward theory are flawed," co-author Roger Sullivan from California State University told PhysOrg.com.

Plant toxins usually imitate their own enzymes controlling metabolism, growth and reproduction. In animals, they affect their neural signaling process.

Currently, it is believed that the plant toxins cause rewiring in the brain's reward center and circuits, falsely mimicking a positive fact or blocking painful sensations. But the new study shows this theory assumes that humans evolved in environments devoid of toxins, and that the brain never developed protective mechanisms against these drugs.

But several studies point that the animals' detoxification enzymes, developed by bacteria about 3.5 billion years ago, were present in animals at least 400 million years ago, when plants started developing their toxins. Thus, animals and plants rather coevolved genes reacting to the response of each other.
Other researchers point that humans inherited the detox genes from mammalian ancestors. Even if many mammal species can tolerate plant toxins, the resistance varies among species (correlated with different detox function levels). One example is the high tolerance of humans to chocolate, and the sensitivity of the dogs and cats to it.

This resistance varies even among different human populations. In many cases, human populations have more toxin-metabolizing genes in the origin area of an addictive plant species. One example is made by the human populations in and near Turkey, which have a very high number of enzymes metabolize opiates, and the opiate poppy (from which heroin is extracted) originated in Turkey. The paradox is even greater, as the brain, in the case of this coevolution, shouldn't be fooled by the drugs.

The research found contradictory evidence for whether drugs have turned more or less potent as they've been domesticated. Another hampering in investigating addiction to plant toxins is that, currently, most explanations for drug reward mechanisms don't make the difference between various drugs, and opiates (heroin and cocaine) and cannabis, for example, are extremely different.

Some studies point that there may be a trade-off and the plant toxins may actually also benefit the animals. As their toxicity varies among species, the more resistant species could in fact consume toxin amounts that are tolerable to themselves but extremely harmful for the predators, parasites or pathogens consuming them. The situation is common amongst insects and amongst caterpillars and butterflies developing from them: the monarch butterfly is toxic for birds because of the toxins accumulated by the caterpillar from the spurges it consumes.
Our ancestors consumed nicotine in small doses and could have experienced less parasitic infections.

"We are planning field studies looking for relationships between human drug use and protection from helminth (worm) parasites," said Sullivan.