Sahakian & Morein-Zamir [9] suggested that in the near future there might be a drug with increased beneficial effects and reduced side effects and that there might be less objection to take those kinds of drugs. When comparing the side effects of atypical and traditional antipsychotic medication or selective serotonin uptake inhibitors to previous antidepressant drugs, the side effects are clearly less severe in the newer drugs. It is thus likely that advances in science would lead to a drug with reduced side effects, but this should however not lead to the assumption that further research would be able to create a drug that has no or negligible side effects. In his chapter on moral enhancement, Douglas [10] creates a fictional scenario. Part of this scenario is the assumption that: “The only effects of Smith’s intervention will be (a) to alter Smith’s psychology in those (and only those) ways necessary to bring about the expectably better post-motives ….” (p.473.). This argument is based on the assumption that a drug can be developed that has no side effects. Additionally there are a number of other papers where the authors make the assumption that there soon will be a drug with no or negligible side effects (e.g., Berghmans et al. [8]; Dees [7]). For example, in their article Berghmans et al. [8] suggested that so called neuroceuticals for therapy and enhancement will become possible: “Unlike today’s pharmaceuticals, neuroceuticals will be efficient neuromodulators with negligible side effects. By being able to target multiple receptors in specific neural circlets, neuroceuticals will create the possibility for dynamic intracellular regulation of an individual’s neurochemistry.” (pp. 128). However when discussing safety issues associated with enhancing drugs, Dees [7] acknowledged that concerns about side effects might prevent the use of enhancing drugs “right now”.

There is No Drug with No Side Effects

To date no psychotropic drug has been identified that has no or negligible side effects. For example prominent side effects of SSRIs include: headache, nervousness, insomnia, sweating, dizziness, sexual dysfunction, and tremor. There is also some inconsistent evidence that SSRI might elicit the sudden emergence of intense suicidal preoccupations [11]. Indeed, Sahakian & Morein-Zamir [9] stated that currently a main concern of using psychotropic medication for treatment as well as for enhancing purposes are the side effects, which thus have to be weighed against the benefits for every case individually. The authors also stated that the exact mechanisms and long term side effects are not yet fully understood.

There Never Will Be a Drug with No Side Effects

Since the 19th century we have understood that the brain works in complex networks. Thus the brain works locally and globally, as well as dynamically. Phase locked high- frequency electromagnetic oscillations can make up a functional network, forming the basis of information processing [12]. In their review Bullmore and Sporns [12] address the use of graph theory (a new mathematical tool to analyse complex networks, such as the brain) to gain insight into the anatomical and functional complexity of brain networks. The authors found that, from a network perspective, the function of an individual node is partly determined by its interconnecting notes, such that the functional properties are the result of the action of an entire network. One example of this is intelligence. For example, da Rocha et al. [13] demonstrated, using EEG, that a distributed network, rather than a localised region, is likely to be the neural basis of intelligence. Thus, it is likely to be a structural entailment of neuroanatomy that impacting any system in the brain must impact on others.

For demonstration purpose, we decided to examine a theoretical case of enhancing a seemingly strongly localised brain function. One might agree, that enhancement of complex functions such as empathy, intelligence, or morality might be controlled by numerous brain regions and neurotransmitters, but we want to demonstrate that even in the case of enhancing a “pure” and simple function, large neuronal networks are involved. Thus, we decided to describe the scenario of enhancement of visual edge detection to the right corner in stereoscopic vision in monkeys. Using single cell recordings, Von der Heydt et al. [14] found that cells in V2 of the visual cortex selectively respond to the direction of edges during the coding of stereoscopic figures. Research in molecular biology has shown, that in V2 62 % of cells possessed the acetylcholine receptor subtype M1 AChR-ir and 43 % of acetylcholine receptor subtype M2 AChR-ir [15]. Importantly, this however is not specific to this region; research conducted for example by Spencer et al. [16] revealed that the receptor density for muscarinic acetylcholine receptors was also high in numerous other brain regions. For the M1 AChR-ir subtype high density was also found in the dentate gyrus, the medial amygdala, the caudate nucleus, and the putamen. In addition to V2, the M2 AChR-ir subtype high density was found in the putamen, thalamic areas, and brainstem. Additionally, we do not even considered the effect that modulating the effects of one neurotransmitter could have on numerous other neurotransmitters. It thus becomes clear that even if a drug was developed that specifically targeted the M1 AChR-ir receptor that would enhance edge detection in the visual system of monkeys, due to the distribution of these receptors throughout the brain in various other regions there would most likely be numerous side effects. Thus any attempt to pharmacological modify such higher order brain functions as “....memory, self- discipline, patients, empathy, a sense of humour, optimism, and just having a sunny temper” ([6], p.11) would be even more likely to be associated with significant side effects.

Additionally, a further example of a biological intervention that affects more than one target is an experiment on genetically modified mice Tang et al. [17].The authors found that genetically modified mice showed improved capacities for learning and memory. The smart mice had increased performance compared to controls on a variety of standard learning tests, such as novelty object recognition, but also extinction of fear. These mice contained a transgene encoding the NR2B subunit of the NMDR receptor. Compared to NR2A subunits NR2B contribute to more persistent excitatory post-synaptic potentials, and thus enhance long term potentiating. However, since the specific subunit of the NMDA receptor is also involved in numerous different processes in addition to memory for example pain processing; “smart mice” were also hypersensitive to pain. Cooke and Bliss [18] speculate that enhanced cognitive performance, such as 100 % memory function, might not have evolved – even though it would have evolutionary benefit – because it would be necessarily coupled with disadvantageous effects. In conclusion, due to the molecular and anatomical arrangements of brain structures, it is likely to be physically impossible to pharmacologically target only one specific function, and thus to ever have a drug with no or negligible side effects.

Decisions about enhancement could thus be understood as a pragmatic choice between the benefits of possibly minor effects (e.g., as described in the meta-analysis of antidepressant use for enhancing purposes; Repantis et al. [4]) and adverse side effects (such as nausea, and anxiety]. Additionally, the risk of drug addiction should be taken into account. Since the desired effect and the severity of any side effects will be dependent on individual variation it would be difficult to determine a general rule as to when the desired effect of a particular drug would outweigh consequences of any side effects. Therefore pragmatic decisions would have to be made on an individual basis.