Drugs of the future

[Rio Fantastic]

I often find myself wondering about what the recreational drugs of the future will look like.

I've often heard the sentiment that says something along the lines of "We've discovered most of the drugs with recreational value, all that's left to discover are analogues and imitations of substances we've already discovered". I can understand the reasoning, especially when you look at the RC market, but I totally disagree. Before 4-MMC hit the market, it was understood that pure stimulants like cocaine & amphetamine were completely distinct substances to the handful of psychedelic amphetamines like MDMA, MDA etc. Until 4-MMC demonstrated that there were substances that blended these two kinds of highs together and blurred the line between empathogens, stimulants and psychedelic amphetamines, people didn't even realize that it was possible, and had 4-MMC or any of the cathiniones never been synthesized then we still wouldn't know about a whole range of drug experiences that are completely distinct from amphetamine, MDMA and cocaine by mixing elements of the highs of all of them.

I believe that there are probably many, many substances out there that would shake up our categories in the way 4-MMC did. It's unfortunate that the nature of the RC market incentivises analogues and small tweaks of existing molecules rather than actual innovation, but that's an unavoidable consequence of capitalists trying to get a return on their investment in a market where their substance could become illegal at any moment and they have to sell as much as possible as fast as possible. The pharmaceutical industry has the opposite problem with a similar consequence - the length of time & the money required to get a drug to market is such an enormous investment that they too will seek to minimize risk, and the easiest way to do that is by changing a drug with a proven track record in order to re-patent it.

To change either of these markets would require co-ordination and oversight from a governing body that would have to have authority over the industry, as each individual RC chemist or drug company is merely following their obvious incentives and isn't going to break from their own self-interest in order to provide either the pharmaceutical or RC market with the innovation it so desperately needs. I can't help but wonder how many potentially awesome recreational drugs have already been synthesized by pharmaceutical companies and tossed aside when they found that its strongly reinforcing in rats? Or that though their lab monkeys are acting very strangely on the new anxiety medication it appears to cause insomnia? I'd bet that there are many compounds that would have immense recreational value that have been discarded since the pharmaceutical company was obviously not looking for drugs with recreational value.

I think about what one man (a genius, no doubt, but still just one man) accomplished in a lifetime - Shulgin. We owe that one man so, so many substances that just plain wouldn't have existed without him. Can you imagine if there was a coordinated effort between many chemists and the capital/equipment/resources of an actual pharmaceutical company and without legal restrictions? Imagine what they could achieve. Imagine what they could discover. Imagine a team of chemists and some or all of them are as creative, innovative & intelligent as Shulgin. Hell, even one guy like Shulgin doing his work with the backing of a pharmaceutical company rather than from his garage, as he was forced to work for most of his life, could accomplish huge things. If they were legally sanctioned and didn't have to go through the decades of research and billions of dollars required for FDA approval, I'm certain that very quickly we'd have new substances that would be far superior to the endless analogues pumped out by sketchy backdoor Chinese labs.

This isn't all just idle speculation either. There is already ample evidence that there are many substances out there that would have recreational value but because of cost, rarity, difficulty to synthesize or just plain ignorance of their existence they stay unknown. In Russia they use many psychotropic medications that are totally unknown here in the West, including totally novel anti-anxiety drugs and an antidepressant that simultaneously works as a stimulant and an anti-anxiety drug. That right there is another substance that common knowledge would dictate shouldn't exist - a stimulant that actually reduces anxiety! And these aren't some completely unknown drugs that have only been synthesized once and forgotten about - they're used regularly in Russia, but because of the difficulty in patenting them (since their use in Russia means that the FDA doesn't classify them as new compounds) companies have no incentive to pour the enormous sums of money into bringing them to market. In order for these substances to become publicly, legally available, there would have to be some kind-hearted philanthropist CEO of a drug company who's willing to take a loss in order to get a drug out to the public. This is pretty much the exact opposite kind of character that becomes a CEO of a pharmaceutical company, and so whilst Russia enjoys these substances, we are forced to either try and buy them illegally on the internet or just forget about them.

I hope that in the future this stupid situation is remedied. It doesn't have to be like this. It would take a large cultural shift (which is happening slowly - the legalization of weed is paving the way IMO for more acceptance of recreational drug use) and some giant overhauls of the laws and regulations from bodies like the FDA, but it's not impossible. I just hope I'm still alive to see the results when we finally stop fighting the war on drugs and instead beat the drug cartels and organised crime gangs in the only way guaranteed to work - discovering, synthesizing and making available cheaper, healthier and more pleasurable alternatives to the illegal drugs they're peddling and taking the market with the drugs of the future. How long until politicians realize that they're never going to win the War on Drugs?

Didn't mean for the post to be quite this long and I don't know if anyone will read it, but I felt like I needed to rant about it. Even if you don't read my post, I'd love to hear anyone's opinions on the substances of tomorrow - it's a topic that I find myself contemplating a lot!

 

[Rio Fantastic]

Even an authoritarian regime in the Phillipines literally executing drug dealers & users and coming down as hard on them as possible has still not managed to stop the flow of drugs into the country. If hunting users & dealers down in the street and murdering them publicly isn't enough to stop it, then how do our governments expect to ever make any kind of progress? How much longer are we going to burn money arresting, prosecuting and imprisoning drug dealers when the moment they're off the street there will be someone else to take their place? Not a single measure has managed to even make a dent in the number of users or dealers. The rate of substance abuse/misuse can be affected by cultural factors - the infamous Oxycontin to heroin epidemic, for example - and the government is pretty good at encouraging drug use when they neglect vulnerable parts of their population and leave them in ghettos with no opportunities or feasible path out of poverty, but never have they managed to discourage drug use and have any measurable effect on the amount of people selling, buying or using drugs. This enormous, multi-billion dollar industry continually makes vicious, violent organised crime gangs rich, and every time they arrest an El Chapo it just means there's an opportunity for someone else to rise up and take his place. The enormous profits in the drug market ensure that their will always, always be people willing to take the risk, and the buyers are guaranteed because people love to get high. These will always be facts, and until the day when we can start re-designing our the human genome and optimizing our emotions so that we're all naturally feeling great all the time, then the only conceivable way I can see of actually making progress is by legalization and/or finding safer, better alternatives to street drugs.

There are some people who get it! Dr David Nutt, the former drug czar of the UK, is currently developing a version of alcohol called alcosynth, that will provide the pleasurable effects of alcohol without the hangovers & health issues. Nutt figured out that alcohol's action on certain receptors is responsible for the pleasurable effects, whilst the simultaneous action on different receptors is responsible for the side-effects like lack of co-ordination & impaired motor skills, and that the hangover & most of the health issues aren't caused by alcohol at all but by a toxic metabolite of alcohol that is created by the body when breaking alcohol down. With this knowledge it becomes possible to create a molecule that is more selective than alcohol, only targeting the GABA receptors responsible for the pleasurable effects of alcohol that is structurally distinct from alcohol and thus won't be broken down into the toxic metabolite responsible for the health consequences and hangovers. It's far from impossible - it's not an easy task that could be accomplished in a Chinese warehouse, but it's certainly not beyond the capabilities of expert chemists/neuroscientists with labs & money at their disposal (apparently certain alcohol manufacturers first tried to start a smear campaign against David Nutt and his plans, but he claims that he has recently been contacted by them about potentially creating drinks in the future with alcosynth).

Again, just like how one visionary like Shulgin managed to create countless new substances, many of which are used to this day, here we see one guy who thinks outside the box applying himself to an issue and is now on the verge of creating a superior version of alcohol with all the benefits and none of the drawbacks. A similar process could be done for all recreational drugs - experiments could be conducted to try and parse the beneficial, pleasurable effects from the side-effects and drawbacks, and then intelligent drug design could be used to create molecules that maximize the former and minimize the latter. Obviously, it won't always be as clean as what alcosynth aims to do - alcohol is a relatively simple molecule, and I imagine that not all drugs will be so easily & neatly divided into positive receptor action and negative, but I'm sure great strides could be made towards it.

Fortunately, the positive effects of drugs are often separable from the negative. Take MDMA for example. It's neurotoxicity isn't caused just as some unavoidable consequence of that euphoric experience - the neurochemical cascade it causes isn't intrinsically neurotoxic. Though the exact causes of the neurotoxicity are debated, one of the leading theories with the most evidence is that the interactions between MDMA and a metabolite causes dopamine to be transported into serotonin receptors which destroys them. Many other serotonergic drugs do not cause this, so the toxicity isn't inherent to the euphoric experience, and if an intelligently designed substitute can't replicate MDMA's euphoria without the toxicity, then I am certain that if money & research was put into it then another solution, such as co-administration of another substance, would remedy the issue.

Am I a utopian?? Yes. Is this all far off and may not even occur in my lifetime? Sure. Is any of what I'm describing impossible? No, and though progress is slow, and I am encouraged by the direction the culture is moving in.

 

[Xorkoth]

I didn't read it all yet. But to your point at the beginning of the first post, I think it's very likely there are entirely different classes of drugs that nature can show us. For example, certain species of orchids (Dendrophylax lindenii and Dendrobium nobile) are psychoactive, containing examples of a class of drugs that wasn't previously known, and is still not really studied much. I can't find the wiki article that outlines what compounds these are. There are a lot of plants that remain unstudied that are used by indigenous peoples.

Besides that, very recently the phenidines were first synthesized (diphenidine, methoxphenidine and ephedidine), which have an extra phenyl group attached to the phenethylamine skeleton, and are dissociative in nature, but very distinct from the classic acrylhyclohexylamine dissociatives. I see no reason at all to believe we have even come close to discovering all of the potential classes of compounds that are psychoactive.

 

[F.U.B.A.R.]

I remember sometime in the early 80s joking with my friends that "wouldn't it be great if loads of new drugs were invented?". At the time, it seemed like a pipe dream (pun very much intended).

Fast forward to the internet age. New drugs being invented daily and all completely legal. But me too preoccupied with heroin to appreciate them. By the time I woke up, the best had gone.

Story of my fuckin life...

 

[Xorkoth]

There are still some great ones available, but a lot of them have become unicorns and a lot of them are utter shite.

 

[izo]

Besides that, very recently the phenidines were first synthesized (diphenidine, methoxphenidine and ephedidine), which have an extra phenyl group attached to the phenethylamine skeleton, and are dissociative in nature, but very distinct from the classic acrylhyclohexylamine dissociatives.

diphenidine is known since 1924, see the paper From PCP to MXE a comprehensive review of the non-medical use of dissociative drugs.

 

[Xorkoth]

Interesting, I didn't know that, thanks.