1. Searching for evolutionary explanations for mental disorders and addictions?
Dr. Paul St John-Smith M.A. B.M. B.Ch.
F.R.C.Psych.
Feb 17thth 2013

2. "Nothing in biology makes sense except in the light of evolution".
Why do people take unpleasant , harmful and addictive drugs?
ALSO......Why do plants produce toxic chemicals so active in humans, other animals and insects?

3. Why, what and how questions in medicine
The questions as to what things are for & how they got there has been neglected in medicine. 
Evolution is not about an individual!
There is no evolutionary explanation for why one individual gets a disease and another does not.
Evolutionary explanations are inherently about traits in populations.

4. Nothing in biology makes sense except in the light of evolution
Scientists often have a naive faith that if only they could discover enough facts about a problem, these facts would somehow arrange themselves in a compelling and true solution”
Theodosius Dobzhansky 1973

5. What has Evolution got to do with it?
Evolution proceeds by the natural selection of those traits that promote reproductive fitness
Humans, like all other organisms, are highly evolved for their own survival and propagation.
Evolution has shaped our brains to optimise reproductive fitness.
An EVOLUTIONARY perspective sheds light on a wide range of biological, psychological, social facts and mechanisms in substance misuse
(Dobzhansky, 1973).

6. When does Evolution occur?
Evolution occurs when heritable differences become more common or rare in a population due to increases or decreases in reproductive fitness in a given environment associated with those differences.
For a given trait to evolve in a population, three conditions should be present: a genetic component, variation in the trait, and effects of the trait on reproductive fitness.
(Nesse and Dawkins, 2010).

7. Evolutionary or Darwinian medicine?
It is a central tenet that a trait cannot evolve if it reduces the overall reproductive success of its carrier.
So, from an evolutionary perspective, how does drug use, a seemingly maladaptive trait persist in the general population?
There must be a ‘trade off’, e.g. some other selective advantages/benefits outweighing risk, leading to enhanced reproductive success even at the expense of long term better health
(Smith, 1999).

8. Causation and Tinbergen’s 4 questions
Tinbergen pointed out that a complete biological explanation of a behaviour or response required four components:
(1) mechanism,
(2) personal development,
(3) function, and
(4) phylogeny.
3&4 are about Evolution!

9. Darwinian Fitness and Emotions
Emotions have common substrates in men and animals.
They have a genetics basis.
From an evolutionary perspective, then, it makes sense that neural circuitry has undergone strong selective pressure and extensive modification towards behaviours that promote survival and reproduction, including acquiring and defending resources, sexual success and protection of progeny (attachment)
(Panksepp et al., 2002; Lende, 2007; Nesse and Ellsworth, 2009). (Darwin, 1890; Panksepp, 1998)

10. Valence of emotions
Positive emotions motivate the organism to take advantage of environmental opportunities and to recognize when it has succeeded in doing so.
Negative emotions motivate the organism to avoid misfortune by escaping, attacking, or preventing harm or by repairing damage when it has already occurred.
The different emotional reactions correspond to differences in appraisal that result from individual differences in personal values, experiences, and goals.

11. Darwinian Fitness Primary emotional systems have evolved to produce :-
1) pleasurable affects in response to propitious circumstances or stimuli indicating adaptive success, and
2) aversive affects, in response to environmental or other threats, indicating reduced adaptive success.
These primary emotional systems often have specific neurotransmitter signatures
(Di Chiara et al., 1999) (Panksepp, 1998).

12. Darwinian Fitness
Drugs (of abuse) may be utilised to diminish aversive or unpleasant, though usually protective, affects (e.g. opiates), or to increase positive affect (e.g. stimulant drugs which increase dopamine transmission).
These drugs override the adaptive functions of the primary emotional systems.
Whilst using the drug the individual experiences the increase in positive affect, or decrease in negative affect, independently of any change in environmental success or threat.

13. Darwinian Fitness
Thus, through the use of psychoactive substances emotional systems become decoupled from environmental success or threat.
Individuals may then continue to consume the drug despite mounting harm.
In other words, these drugs bypass the evolved protective mechanisms, used to signal real success or danger
(Nesse, 1994).

14. Darwinian Fitness
It is expected that people who experience high levels of negative affect, or low levels of positive affect in response to insurmountable adverse circumstances, will use pharmacological means to overcome this.
Evolution has endowed organisms with the capacity to learn from the environment.
(Wang et al., 2010; Becker, 2005) (Becker, 2005).

15. Darwinian Fitness
Those who have experienced abusive and unpredictable care in childhood, view the world as perilous and unpredictable.
Under these conditions a strategy of immediate gratification appears adaptive, leading these children to greater risk-taking, reward dependence, and opportunistic behaviour
This is in contrast to stable families where better developmental outcomes may be reliably obtained in the long term

16. This reports on drug use among vulnerable young people aged 10 to 24.
The Home Office report Drug use among vulnerable groups of young people
This reports on drug use among vulnerable young people aged 10 to 24.
It identifies vulnerable groups as those who have ever been in care, those who have ever been :-
homeless
truants
those excluded from school
and serious or frequent offenders.
In 2003, while those in vulnerable groups represented 28% of the young people sampled, they accounted for 50% of any drug and 61% of Class A drug users in the year prior to interview.
Statistics on Drug Misuse: England, 2011findings from the 2003 Crime and Justice Survey

17. More about Evolution and emotion
Emotions are useful if they are expressed in the situation they evolved for, otherwise they are considered to be abnormal.
People with excessive emotions, or whose emotions are expressed in the wrong situation, do not do well.
Panic is life-saving when being chased by a lion but, in a romantic situation, panic can severely decrease reproductive success!
Humans, comprising the genus Homo, appeared between 1.5 and 2.5 million years ago, a time that roughly coincides with the start of the Pleistocene 1.8 million years ago. Because the Pleistocene ended a mere 12,000 years ago, most human adaptations either newly evolved during the Pleistocene, or were maintained by stabilizing selection during the Pleistocene. Evolutionary psychology therefore proposes that the majority of human psychological mechanisms are adapted to reproductive problems frequently encountered in Pleistocene environments.

18. Smoke detector theory
The costs of not expressing a defense when it is needed are so huge relative to the costs of false positive alarms that the optimal threshold allows for many false alarms.
This smoke detector principle explains why blocking a defense is often safe:.
We judge if the response is necessary or whether it can safely be turned off with medication.
Defenses have been shaped by natural selection/ evolution to be expressed when they were needed on the average, in the long run (trade-off).

19. Part 2 Palaeo-anthropology of drug abuse Reproduction, fitness, survival and long life
Humans with a propensity (Genetic) to be able to use certain beneficial chemicals or plants and/or who genetically could tolerate some of their non-therapeutic side effects
and/or those who were intelligent enough to see and exploit the therapeutic effects might have survived better to reproduce before the long term harmful effects of the substances became evident.

20. Timelines- 3000K and 10K

21. Palaeolithic evolutionary problems
In broad terms, these Palaeolithic evolutionary problems include those of survival, growth, development, differentiation, feeding, maintenance, mating, parenting, and social relationships.

23. Possible driver mechanisms for co-evolution of plants and animals
Natural selection and survival of the fittest
Animals “exploiting” plants
Plants defending themselves against the animals
Plants “exploiting” animals
Chance/random processes e.g. mutations
Evolution may be expressed as the-
“Non-random selection of random mutation- variation”
Are these observed in practice?

24. Plant chemical punishment of herbivores
The other side of survival !
The relationship between living plants and the animals that feed on them is antagonistic, forged by an intense and ongoing evolutionary arms race.

25. Evolution of human emotion was driven by environmental pressure
Evolutionary psychology proposes that the majority of genetically inherited human psychological mechanisms are adapted to reproductive problems frequently encountered in Pleistocene environments.

26. The value of stimulants?

27. The co evolution of plants containing drugs and animals
Opiates (morphine, and synthetic analogues) are related chemically to endorphins, a group of polypeptides (short proteins) that serve as neurotransmitters in reward centres of the brain stem.
Normally, the centres are activated only when a human or animal has done something right e.g. it is physically active, having sex or caring for young.

28. But how did plant poisons such as opiates, evolve to mimic some of the endogenous opiates and their functions?
Poppy plants cannot escape or hide to defend themselves. Those that initially survived better in the wild, often had mutations that had evolved biochemical time bombs, full of toxins to deter their predators.

29. Plant Survival
For the poppy, the chance solution to survival was a mutation – a narcotic opiate that induced sleepiness in small doses, and death in large ones, for the animals that tried to feed on the plant.
Drugged animals, in turn, are eaten by their predators, rescuing the poppy.
Relatively small amounts of morphine are enough to defend the wild poppy—it does not have to manufacture large quantities of the drug.

30. Neolithic and modern Changes
During the Neolithic period farming etc. would transform the small, mobile and fairly egalitarian groups of hunter-gatherers that had hitherto dominated human history, into sedentary societies based in built-up villages and towns.
This radically modified their physical and emotional environment and RISKs
Specialized cultivation and storage allowed extensive surplus production.

31. EEA becomes the ”Neolithic Revolution” 10-12K ya
EEA becomes the ”Neolithic Revolution” K ya. Less than 1% of Human History
The Neolithic Revolution was the first agricultural revolution or transition from hunter gatherer communities and bands, to farming and settlements

32. Neolithic Revolution
Changes in the way we live have caused new problems including:-
Stresses on our relationships and consequently brain pharmacology .
Our cultural evolution may be accelerating faster than a level with which our genes or brains can cope.

33. Dietary surplus issues and mismatch
Bible reference:  Genesis 9
Incident shown:  Noah has fallen drunkenly to the floor. 

34. Adverse Consequences
Surpluses lead to dietary and medical problems e.g. drunkenness ,obesity, diabetes and some addictions.
The rapid cultural changes led to psychosocial problems e.g. war and environmental catastrophes.

35. Mismatch Theory of substance abuse (Post Neolithic cultivation etc)
Pure and large amounts of psychoactive drugs and direct routes of administration are new!
Drugs of abuse happen to be inherently pathogenic because they bypass adaptive information processing systems and act directly on ancient brain mechanisms that control emotion and behaviour.

36. Resume:-What are reward systems for?
The major addictive drugs in effect hijack ancient biological systems, bypassing them.
Furthermore, the reward, being concentrated in chemical form far beyond what nature can provide endogenously, can be overwhelming in its intensity.

37. The self-perceived survival ability and reproductive fitness (SPFit) theory of substance use disorders.
Drugs that induce positive emotions give a false signal of a fitness benefit.
This signal hijacks incentive mechanisms of "liking" and "wanting," and can result in continued use of drugs that no longer bring pleasure.
Natural transmitter production may be shut off causing withdrawal symptoms and dependence.

38. Do plants genes manipulate humans
Do plants genes manipulate humans? Or are plant products exploited by humans?
This suggests the co evolution of plants that modify our behaviour for their own reproductive fitness
Evolutionary rationales that can accommodate current drug-reward models might include that the most commonly used plant drugs cultivated today (selected by humans) exploited human needs or pleasurable ‘tastes’ and encouraged domestication, much in the way that sweet tasting fruits and nectar promote seed and pollen dispersal by animals.
(Nesse 2002).

39. But what about Poisonous Plants?
Intellectually aware humans evolved to counter-exploit plant neurotoxins.
As a key facet of their chemical defense, many plants have coevolved compounds that are either identical to or closely mimic these signaling molecules; thus enabling them to subject herbivores to disrupting chemical attacks.

40. ‘Pharmacophagy’
A number of plant alkaloids consumed by humans, including caffeine, nicotine and arecoline/betel nut, demonstrate anti-helminthic activities (see table below).
In the parasite rich environment where our shorter-lived ancestors evolved, the toxic effects of these alkaloids may have been outweighed by the anti-parasitic benefits.
Consequently, the consumption of plant alkaloids may have contributed to reproductive fitness and a taste for these substances would have been selected for.
This pharmacological exploitation of plants is referred to as ‘pharmacophagy’
(Seibt et al., 2000; Sullivan et al., 2008).

41. Selective toxicity
Note that some recreational drugs attack human pathogens.
For example, of the world's three most popular alkaloid drugs—caffeine (coffee), nicotine (tobacco) and arecoline (betel nut)—two, in the form of nicotine sulphate and arecoline hydrobromide, are potent commercial anthelmintics used in animals
(Eckert et al. 1981; Hammond et al. 1997).

42. Relationships between CNS receptors and plant neurotoxins commonly used as drugs.
Toxin (typical source) Receptor Effect
Nicotine (tobacco) Nicotinic acetylcholine endurance, antihelminthic
Arecoline (betel nut) Muscarinic acetylcholine endurance, antihelminthic
Cocaine (coca) Adrenergic, Dopaminergic endurance, appetite regulation
Ephedrine (khat) Adrenergic, Dopaminergic endurance, antihelminthic
Caffeine (coffee) Adenosine endurance, antihelminthic
Theophylline (tea) Adenosine antibacterial
Theobromine (chocolate) Adenosine endurance, antihelminthic
Morphine (opium poppy) Opioid pain relief
D9-THC (cannabis) Cannabinoid pain relief, appetite regulation

43. Humans discovering the pain-deadening effects of ingesting a poppy extract, began using it for pain relief.
Neolithic and modern cultivation then increased access!

44. The fitness-enhancing aspects of the use of psychotropic substances in our evolutionary past.
The reduction of stress, improvement in performance, increased sociability, or the simple reinforcing properties faltering psychic state, the use of psychotropic substances could have directly affected fitness.
Use of psychotropic substances could have been favoured by those who were particularly sensitive to the reward and other effects, and in responding they might accrue slight fitness advantages over those less susceptible
This tendency could have been held in check during the course of the evolution of modern humans by the lack of large quantities of highly potent psychoactive drugs.

45. Useful effects of plant toxins
Toxins in fava beans and cassava might be effective against Plasmodium falciparum infections in humans
Spices are an adaptation to exploit plant alkaloids to combat bacterial infections of food
(Jackson 1990, 1996), (Billing & Sherman 1998),

46. Hornworm larvae that consumed food containing nicotine were themselves protected from parasitism by the wasp Cotesia congregata.

47. Human pharmacophagy
There is evidence that primates and other animals use the toxic properties of plants to self-medicate, especially against gastrointestinal parasites, may provide an evolutionary basis for human medicinal behaviour
(Johns 1990, 1999; Huffman 1997).

48. Trade-offs
However any potential benefits from the antihelmenthic properties of nicotine are nowadays outweighed by the considerable health costs of tobacco consumption in long- lived, resource-rich Western populations with low parasite loads.
In the shorter-lived, nutritionally stressed populations with higher parasite loads, such as those in which our ancestors evolved, the antihelmenthic properties of cholinergic plant toxins may have constituted a significant adaptive opportunity.

49. Dried tobacco leaves, stalks and the whole herb are still employed by farmers in parts of the developing world to treat helminth infections in livestock, and it has been shown that an aqueous extract of nicotine from tobacco leaves is quite effective against helminth infections in cattle and sheep
Like nicotine, modern anthelmintics such as levamisole and tetrahydropyrimidines target nicotinic acetylcholine receptors on somatic muscle cells, inducing spastic paralysis and parasite expulsion
Nicotinic receptors are also targeted by recently developed ‘neo-nicotinoid’ agents effective against fleas, ticks and other arthropod
(Msolla et al. 1987; Iqbal et al. 2006). (Kohler 2001).
parasites (Tomizawa & Casida 2005).

50. Were some “addictions” useful in some situations; maybe historically?
If humans are partly dependant on reward biochemistry, why do some people have different genes more likely to facilitate addiction?
The questions then become not only why do some people become addicted to plant toxins ,
Why don’t most people become addicted?—
As we all share the same neurotransmitter biochemistry- What other processes are going on?

51. ‘Human Pharmacophagy’ Other reasons for natural selection of people that were attracted to use alcohol. Alcohol recognition and desire may be adaptive in selecting ripe fruits Secondarily , Beer drinkers in urban cultures may have suffered less waterborne diseases. Alcohol metabolism and desire to drink it was a chance adaptation and the drinkers were then more genetically successful?

52. Shorter lifespan but initially healthier and reproductively more successful
In the shorter-lived, nutritionally stressed populations with higher parasite loads, such as those in which our ancestors evolved, the antihelmenthic properties of cholinergic plant toxins may have constituted a significant adaptive opportunity.

53. Why aren’t we all pain-killer or stimulant addicts?
Most people, though, see the overwhelming feelings of drug-induced excitement or well-being or euphoria as false pleasures, forced from the outside and eventually leading only to despair.
Long-term planning (having something to loose or aspire to) in the human brain makes it possible for most of us to resist the short-term temptations of addictive drugs.

54. Conclusions
This presentation has sought to illuminate some of the multiple relationships between evolutionary biology and the neurobiology's reward model.
The evolved function of plant drugs and the probable co evolution of plant defensive compounds and herbivore nervous systems is complex and sometimes apparently paradoxical.
Drugs are probably an evolutionary novelty; humans (and mammals) are inherently vulnerable; and hedonic reward often best characterizes the psychological and physiological responses to drug exposure.

55. Common evolutionary hypotheses involve the Neolithic agricultural revolution and cultivation of crops exposing people to high toxic levels from one or only a few crops.
Also the consequent food production excesses can lead to preservation techniques such as fermentation with resultant exposure to alcohol in unfamiliar quantities (Mismatch).

56. An initial hypothesis is also presented that some human substance seeking may have evolved to exploit the anti-parasitic properties of commonly used plant toxins, despite them being unpleasant but there are, of course, other possibilities.
Lastly pleasurable or medically useful crops may have “trained” humans to cultivate them resulting in their increased prevalence and potency.

57. Conclusions
The concept that both drug addiction and social processes may enlist common emotional brain systems raises many questions about how personality development and social dynamics might play an important role in both predisposing to as well as discouraging drug addiction.

58. Appendix1
Environmental mismatch theories explain how benefits in one environment may be outweighed by harms in another.
Pharmacological manipulation of the brain’s emotional systems may create false emotional indicators of increased Darwinian fitness, including feelings of positive emotions e.g. attachment, security or achievement or alternatively a reduction of protective negative emotions such as pain, loneliness, fear and anxiety
These emotional effects may be the initial reason for these substances being used
Thereafter, classical conditioning, receptor density changes, and epigenetic modifications may lead to cycles of increasing drug use
(Di Chiara et al., 1999). (Wang et al., 2010).

59. Appendix 2 (Goldilocks’ value)
An Evolutionary fitness advantage exists in deploying genetically derived mechanisms selectively only when their potential benefits outweigh such costs. (Goldilocks’ value)
Their deployment is controlled at several levels, including through higher neural “top down” processes in certain cerebral cortical areas.
Neural control provides advantages in that deployment can be based on tradeoffs that take into account relevant health circumstances.