All experiences whether good or ill, in their essence, can be equated to the inter-relations between external stimuli and the internal states of consciousness created by our brains and, in an ultimate sense, by our genes. Most people will concede that no amount of overpowering stimuli, no amount of pretty sunsets, will bring a smile to someone’s face if he is sufficiently depressed – unless one takes the trouble to “hack” his brain directly, such as through opioids or psychedelics. Just as equally, most people (myself included) do not want a world where everyone sits around intracranially self-stimulating, with electrodes, into a state of immitigable bliss and completely unresponsive to the environment. Drugs, or more narrowly, psychotropic drugs, are one way to improve, enhance, or expand the subjective textures of consciousness in some desired direction, for recreation, but on a temporary basis, or to improve cognitive performance in various domains, e.g. some people find that amphetamines allow them to concentrate better on mundane tasks.
All else equal, alcoholism is not adaptive, i.e. unconducive to reproductive success, so agricultural societies that have been exposed to alcohol for many generations have far less alcoholism than hunter-gatherers. The mechanisms that potentiate resistance to it vary. In most populations, it is highly polygenic: the variance in responses to alcohol is distributed across many genetic variants which are all of individually small effect. In East Asia, a lot of it can be traced to a single variant: ALDH2*2, which retards the breaking down of alcohol into acetate (after it has been broken into acetaldehyde), resulting in hayfever-like responses such as rashes and respiratory problems. Alcoholism has a harder time developing when responses to it are so uncomfortable to begin with. It is most common in south-central China and a few regions of Japan. What is interesting to note is that natural selection seems to have responded to different genetic material if, ultimately, to the same ends, which is always to optimise local fitness: the ALDH2*2 variant is not common anywhere outside East Asia. Yet, in Europe for example, different variants have been selected upon. I do not know what their effects are, but I would imagine they are less uncomfortable – the “alcohol flushing” reaction is a characteristically Asian thing.
The potential space of new genetic source code is limited only by human ignorance and the laws of physics, which is why organisms come in such incredible variety. If it is possible for nature to take and run with genetic variants that cause deeply unpleasant reactions to substances, then it is also possible to do the opposite: when all genetic variation in the human species and the rest of animate life is comprehensively mapped and catalogued, one could readily find the genes associated with any kind of psychotropic experience and modulate them to suit one’s purposes: to massively increase tolerance, decrease it, make the most sublime psychedelic experiences sublimer yet, edit out the genetic architecture of “bad trips” and make them more insightful, more expansive, more glorious, make the “withdrawals” smoother and less likely to result in years of rebound anxiety such as often occurs with benzodiazepine withdrawal. Eventually, artificial intelligence will be able to synthesise designer-genes and simulate their downstream consequences for the organism before “applying” them. Piece by piece, the genome will be rewritten to reflect our most cherished values. In some cases, human feedback may be necessary, which will allow the AIs to constantly improve their designs with recursively superior experiences, such as with psychedelics.
Consider that some people are effectively immune to addiction, while others have literally never met a drug that they can control their use of. Consider, also, that there are desert peoples who have evolved to metabolise arsenic at 20 times the “safe” limit, which gives you some idea of what is possible, and the genetic architecture of caffeine experiences, a relatively mundane substance, has already begun to be mapped. Rest assured, if drugs were all legal then similarly dense architectures could be found for the likes of methamphetamine, heroin, psilocybin, and dimethyltryptamine. All of this can be undertaken in conjunction with efforts to make the drugs’ chemical properties intrinsically safer.
With stimulants and opioids the first concern may be safety before getting on to engineering their experiential qualities, whereas with psychedelics, which are already quite safe, we can skip a step and get on to genetically engineering altered states of consciousness that are literally beyond the imagination of current humans or any other species. The most intrepid psychonauts of today have no clue what lies ahead.