A very similar organisational closure is seen in the biochemical system. When Pert first discovered the opiate receptor in 1972 this was a landmark in the understanding of human function. Just as the nerves do not transport any quality, the cell does not receive any qualitative signal. The receptor is the quality. Every physiological process everywhere in the body is mediated by such receptors and the condition and reaction of a cell is determined by the equipment and the function of its receptors.

Receptors are not stable. Their function is nonlinear and history dependent (Pert 1999). They are non-trivial machines (chap. 4.5). Even the manipulation of a single receptor might lead to a divergent behaviour of the whole organism (Daniels et al 2005). The consequence is that the linear models are not able to provide enough information to understand the actual effect of a therapy. This shall be demonstrated with a dark chapter from the history of medicine.

Benzodiazepine was once widely used, as it provided many beneficial effects in the reductionist research. Its story reads like this (Shooter 2003):

What has gone wrong in this or in many similar cases? Was it only the financial interest of companies and the carelessness of the physicians and politicians? No. There is something more essential in it.

Benzodiazepines do not treat certain more or less ambiguous diseases or conditions according to signalling pathways found in reductionist research. They perturb the inner structure of the autopoietic unit human on different levels using the receptors of the cells.

The so-called ‘valium receptor’ was not made by nature for valium to work (Pert 2001). Or more generally spoken: when a drug works, there has to be a receptor for it and this receptor has a meaning in the inner organisation.

An analysis of the effect of psychoactive drugs provides a better understanding of this essential process. All kind of psychoactive substances work only, because the organism itself produces similar compounds. Cannabis-like substances (endocannabinoids) seem to limit psychotic experience and depression (Nowak 2004), play a role in stress-related situations (Di et al 2005), in immune response (Karasek et al 2007) and have a lot of other hormone like functions (Pagotto et al 2006). Harmine-like compounds are ubiquitous in our body resembling dimethyltryptamine (DMT), a psychoactive drug producing schizophrenia like states. The drug has also an antidepressive effect (Melton 2004).

As a matter of fact, psychoactive drugs resemble spontaneous inner conditions and are able to create pictures like schizophrenia or bipolar disease (Podvoll 1990, Heimann 1990). “The key difference between morphine, heroine, and your own internal drugs is that it’s real hard to get rid of morphine or heroine once you have a shot of it. The only way it gets broken down is in your liver, and that takes hours and hours. In contrast, what the endorphins and all of these different peptides do is: they flicker” (Pert 2001). That is, schizophrenia, bipolar diseases and altered states as in cannabis or LSD consumption are normal physiological states. Their only problem is their duration. They should last only for a very short time.

The repeated use of drugs might lead to an adaptation. Adaptation in this case means the reaction of the organism when forced to remain in this state for longer than intended by the inner regulation. It might have different forms:

• The drug consumption creates a habituation with no altered mental state anymore.
  
• The altered state is (more quickly) terminated when the substance is broken down.
  
• The consumption of drugs facilitates the ‘spontaneous’ outbreak of pathological states. For example, the use of cannabis is linked in a dose dependent fashion to schizophrenia and other psychoses (Zammit et al. 2002) increasing the risk to a factor 6 (Arseneault et al 2002).
  
• The normal function does not resume, although the bioactive substance has been metabolised. In such cases of an ‘eternal trip’ madness becomes an eigen-value (chap. 4.2).
  

Many cellular mechanisms contribute to the adaptation of the organism. The density of the receptors of a cell might decrease. Then a higher dose is necessary to induce the same effect. The organism might metabolise the drug more quickly and/or antagonistic mechanisms might become more prominent leading to a shorter duration of the drug effect. All mechanisms have something in common. They tend to reduce the reagibility of the organism to the administered substance. It is a typical teleological strategy (chap. 4.7) which aims to stick to a certain set-pint (chap. 4.4). That is, the organism learns to live with the administration of the drug, and this learning ‘spreads’ slowly through the whole organism leading to a different homeostasis (chap. 6.7).

When a different homeostasis is attained, it is not easy anymore to discontinue the drug. The organism has become dependent on its supply from outside. This is called addiction. It happened with diazepam. It happens with many substances, as this tendency to create a dependent state is inherent in the current therapeutic paradigm (chap. 4.6.b).

In such a case of discontinuation the cell often multiplies its receptors (Pert 1999). As a result, a smaller doses and/or the internally produced compounds have more effect. Moreover, a later dose of the psychoactive drug will provoke a stronger reaction than the same dose weeks or months before.

These are strategies of the organism to adhere to a certain state (chap. 4.11). But this is not the only possible reaction. What is called phase transition in physics (chap. 4.11) can be seen in medicine, as well. A phase transition occurs when the further administration of a certain energy leads to a total new behaviour of the system. This is seen in the spontaneous outbreak of a psychiatric diseases as through cannabis or an eternal trip as through LSD. Logically, similar events have to be expected in every therapy using the receptors of a cell. The adverse reactions type B belong into this category (chap. 4.1).

In this autopoietic view diseases like psychosis or schizophrenia are not a definite entity. They are more a repository for different conditions of the function and the metabolism of the brain (Helmuth 2003), on the basis of the inner structure and organisation of the human, maintained out of certain inherent reasons. This has not only fundamental consequences for the diagnoses, but also for the therapeutic strategies.

Important questions in such a view would be:

• What kind of organisation facilitates such an outbreak?
  
• What maintains the stability of a situation?
  
• What factors might induce an 'unlearning', a change of the set-point?
  

Less important questions would be:

What provoked the outbreak? - It might have been a minor event.


What is the exact signalling pathway? - Due to equifinal processes different pathways might lead to the same outcome. The equifinal situation is stressed by the fact that many psychoactive drugs do not only stimulate similar receptors, but they also use the same pathways. This is seen in dopaminergic agonists (such as D-amphetamine), serotonerigc agonists (such as LSD), and glutamatergic antagonists (such as PCP). Although the pathways are similar they lead to different states of consciousness (Svenningsson et al. 2003). In contrast, different pathways might lead to the same result (chap. 2.4.d).


What genes are associated with this state? - The relation between a certain trait and a gene is often as low as 8 % for most of today’s ‘genetically caused diseases’ (chap. 3.5).

Although this is already complicated enough, it does not end here. The neuronal and chemical pathways are interwoven such that the distinction between a neural and a humoural system, or between the brain and the body does not make too much sense. It is as justified to speak of a chemical brain as of a nervous brain. Stress is as neural as it is humoural. Even the insulin response in diabetes is altered by ‘mental factors’ (Gelling et al 2006).

That is, to assess the reaction of the organism to a perturbation (a drug therapy, for example), the whole organisation of the autopoietic unit has to be taken into account. All the nontrivial reactions seen during a specific or an unspecific therapy cannot be attributed to the neural or of the biochemical system alone. Such nontrivial reactions are mostly not investigated, except in hormesis research (chap. 4.11; 6.10). Some of these typical nontrivial courses of events are:

• the same individual reacts differently to the same perturbation at different times. Sacks describes in his Awakenings that one patient (Martha N) took L-DOPA six times, and she reacted differently each time (Sacks, 1990),
  
• doubling the dose does not double the effect,
  
• small doses produce a different pattern than higher doses,
  
• a substance that might provoke a state it is able to alter it (Bastide 1998).