UK - Can David Nutt wean us off the demon drink with his alcohol substitute?

[ro4eva]

Sure, Nutt can be fickle, but a liability? A little harsh in my opinion.

Peter Hitchens on the other hand...

 

[CLICKHEREx]

I distinctly remember viewing a British TV doco about this recently, with David Nutt's work being highlighted.

 

[caseface99]

I have a hard time taking any article seriously that involves this Nutt character.

 

[Transform]

I can't believe there's so much dislike for him. He's one of a few people who has been able to bring drugs into the public eye without having any history of drug use, thereby bringing significant legitimacy. On top of that, his academic background gives him well founded authority to speak up.

He may have "extreme" views according to the average daily mail user, but IMHO he is valuable to our cause.

 

[Swarm]

Well said transform, well fucking said!

Being a science guy myelf, I've known about David Nutt since an article I read in new scientist like 8 years ago now while i was looking for phd placements. He's been working on this project for a long time now, he just never drew two much publicity until two separate introductions to the public where made by him back in 2010 was it? Obviously we all know the first example i'm talkin about, when the then Home secretary Alan Johnson forced Professor Nutt to stand down from his chair at the ADMD for material (funded by the fucking govrnement in the first place) that he presented as a visiting lecturer at some uni somewhere.

His other introduction to the public which I referred to actually happened about six months prior to him being sacked and came in the form of a tv documentary on alcohol. In the final third of this hour long programme he let the public in on some of the footage of his long term project to find an alcohol replacement.

I could not have more respect for this guy, he's up there with guy's like Robert Trivers (not that i suppose anyone probably knows who the fuck he is but, it on five seminal papers in socio biology in the early 70's that formed the bulk of what Dawkin's "Selfish Gene" book was essentially about). I've been a fan of every decent news paper article I've read - proper ones he's either the author or is being interviewed. He also wrote a fine "pop science" book recently called "Drugs: without the hot air i believe". As I science guy there wasn't much new to me, but for the audience to which it was written ie. the educated, open minded layman, i have to say that he did an outstanding job.

 

[23536]

I can't believe there's so much dislike for him. He's one of a few people who has been able to bring drugs into the public eye without having any history of drug use, thereby bringing significant legitimacy. On top of that, his academic background gives him well founded authority to speak up.

He may have "extreme" views according to the average daily mail user, but IMHO he is valuable to our cause.

Yeah all the hate seems pretty random.

Imagine if a US drug czar had publicly said that MDMA is not really dangerous in proper doses, and then had been fired for it, and then had gone on to set up a very well publicized research institute for recreational drug use.

Do we consider the directors of MAPS as detrimental clowns? Where is this coming from?

Also, drug trials take many years to complete.

 

[Swarm]

A fun and non-addictive benzo derivative? That'll be the day.

To anyone that know's anything at all about science, the alcohol substitute that nutt is promoting is not a benzo. While ethanol does hit the GABA receptors in the brain, like benzo's, it also hits the NMDA receptros like ketamine at higher doses. It also releases serotonin, noradrenaline (which partly explains why drunk people stay up all night, and maybe why they get aggressive too). At the highest doese it also hits the opiate receptors.

If you're curious as to the reason behind all of this its pure chemistry, and its real easy to explain. Ethanol, ironically, isn't really a drug. I work with it everyday alongside, acetone (nail varnish remover), isopropanol (surgical spirti), and Dichloromethane (paint stripper). In short, its a solvent, and a real simple one at that. The closest thing that it can be related to is proably gbl, however gbl (ghb which is what it converts to in the brain anyway). I kind of view ethanol as the retarded cousin of gbl. Basically, any drug, whether benzo, stimulant, opiate whatever has a complex shape that partly mimics the shape of the bodies internal chemical transmitters. This is the only reason they can work so specifically. They have to appear to the brain to "actually be" the natural chemical. If this wan't the case, then the drug would just float around the bodie, like most hormones are doing all the time anyway, and would eventually be filtered out.

Alcohol by contrast is about as simple a molecule as you can get. This means that it has no binding preferences for anywhere in particular in the brain, it will go anywhere. This is the reason that it has such low potency. If you do the math then a night down the pub where you get through ten pints of stella, you are consuming around a quarter of kilo of ethanol. Thats 250 grams. Imagine taking 250 grams of xanax. Even if we're talking about the big 2mg bars of xanax, you would need to consume 125,000 tabs, yes a quarter of a million in order to injest the same amount of drug by weight alone. When you consiser that the a molecule of xanax weighs six times as much as a molecule of alcohol, you can see that you would be putting 1.5 million times the number of ethanol molecules into your body drinking 10 pints of stella, than you would be consuming 2mg of xanax.

 

[Swarm]

Yeah, this seems kind of maniacal.



Science: now based upon truthiness rather than empirical research.

Nutt made this statement on the back of ten year of research into the drug he is talking about. Sometimes it pays to do a of actual science yourself before expressing an opinion on what science. If you want some hints for where to look at the evidence behind his research try tracing Nutt's work both at Bristol Uni and imperial college london. Don't have to go further back than 10 years for this issue but try and atleast be slightly informed.

 

[Swarm]

And whoever had the brain cells to make the connection between Leary and Nutt - I really can't be bothered to scroll up and down page in order to establish the source of such a retarded statement as that.

Leary was a high profile ivy league prof who publicly took drugs and associated with spirituality guru's like Terrence Mckenna, Alan Ginsberg etc...

Nutt is a high profile scientist who's only drug use he's personally confessesd to, to my knowledge, is the odd glass of wine. More to the point, such is Nutt's respect as an academic and researcher that no less than 7 other high profile members of the ADMD resigned in protest to Nutt's dismissal.

And whoever had the brain cells to make the connection between Leary and Nutt - I really can't be bothered to scroll up and down page in order to establish the source of such a retarded statement as that.

Leary was a high profile ivy league prof who publicly took drugs and associated with spirituality guru's like Terrence Mckenna, Alan Ginsberg etc... and who's only real message I can think of was an empahsis on "setting". Hardly, hard science now is it.

Nutt is a high profile scientist who's only drug use he's personally confessesd to, to my knowledge, is the odd glass of wine. More to the point, such is Nutt's respect as an academic and researcher that no less than 7 other high profile members of the ADMD resigned in protest to Nutt's dismissal.

 

[dopemegently]

One thing I don't get - is this proposed drug to be a drink, or just another pill? Cause I can hardly see people flocking to bars and nightclubs asking for "3 mg of tablet X".

I think there's no chance this proposed drug will ever make it to public sale, but I also respect this David Nutt; alcohol in the UK just causes so much damage through alcoholism, alcohol fueled violence, alcohol poisoning. I've been to hospitals on Saturday nights, and they're packed with casualties directly caused by booze - a legal drug not even considered a drug. The guy kind of reminds me of that Chinese bloke who invented the e-cig; he saw a major problem to society, and used his expertise to create a solution - and it seems to work.

 

[Thorns Have Roses]

Nutt made this statement on the back of ten year of research into the drug he is talking about. Sometimes it pays to do a of actual science yourself before expressing an opinion on what science. If you want some hints for where to look at the evidence behind his research try tracing Nutt's work both at Bristol Uni and imperial college london. Don't have to go further back than 10 years for this issue but try and atleast be slightly informed.

Historically, clinical studies underestimate the abuse/dependence liability of novel GABAergics.

alcohol substitute that nutt is promoting is not a benzo

I didn't say it was, I was just going off the articles statement that "Nutt's alcohol substitute is a benzodiazepine derivative." Anyway, I meant to imply that it acts on the alpha, beta, or gamma subunits of GABA_A, like benzodiazepines and the z-hypnotics.

For commercial reasons, he is not prepared to reveal the drug's identity for the time being.

I might not have dismissed him off hand, if not for this infuriating obscurantism. He's just telling us to believe him because appeal to authority. Posts saying "do the research" in this thread aren't much better. However, I did some looking, so I might share the info.

Pagoclone is a possibility for his mystery drug (Nutt was interested in this one as recently as 2006), a cyclopyrrolone like zoplicone, developed as a potential anti-anxiety medication, Nutt took interest in it. It is rather selective for α2 and α3 (anxiolysis, muscle relaxation, disinhibition), with weaker action at α1 and α5 (sedation, amnesia, psychomotor impairment). Specifically full agonist at α3, and a partial agonist at α1, α2, and α5.¹

On to what this means for Nutt's statements, since we can actually evaluate them now:

It targets the same sites in the brain [as valium], but he believes the drug will not cause the same problems with addiction and withdrawal.

No doubt a deliberate comparison, preliminary evidence suggests pagoclone's abuse potential is on par with that of diazepam.² As a partial agonist, it may indeed prove superior in terms of safety and severity of dependency.

The intoxicating effect of the first three "doses" will be cumulative, he said, but subsequent shots will have no effect

Pagoclone's effects are largely mediated by an active metabolite, 5'-hydroxy pagoclone.¹ So, depending on how it is metabolized, it seems reasonable that it could exhibit a ceiling effect.

Remarkably, he has also created an antidote, or "sober-up pill".

Flumazenil, according to wiki. Hardly remarkable.


Can't say I'm filled with enthusiasm.

 

[Swarm]

The journalis behind the guardian article was either unequipped to deal with the complexity of the science behind nutt's product, or knew that the target audience would be equally ill equiped, therefore a decision was clearly taken to over simplify things, and I'm sure Nutt was willing to oblige in order for the opportunity to covry altest some sort of messsge.

While his new product does act on gaba receptors, it is primarily an nmda antagonist. I've seen footage of a subject administered a prototype of nutt's prospective drink and the results looked very promising. The sobre up pill also worked it's majic.

The ability to create novel state of the art benzo type drugs, that lack nearly all the messiness and abuse potential of those currently out thrre, has been known by top scientists for decades already. The world renowned neuroscientist Joe Ledoux expressed his own disbelief that pharmaceutical companies where not already at his door asking for ways to create safe benzo's. He wrote this ten years ago.

The obvious reason, in my opinion, is that the pharmaceutical companies don't want safer non addictive benzo's, purely for financial reasons. After all, the profits of big pharma are heavily dependent on the dependency of their patients.

In general I find its best to reserve judgement on a complex area of science when your source is the fucking guardian. I got no problem with the paper in general but we're talking about science here, and in this context, a piece in the guardian is no more than the an artical written by hacks, for hacks. There's not a whole lot more to it than that.

 

[23536]

I might not have dismissed him off hand, if not for this infuriating obscurantism. He's just telling us to believe him because appeal to authority. Posts saying "do the research" in this thread aren't much better. However, I did some looking, so I might share the info.

This is pretty standard in the pharmaceutical industry. Usually by the time the trials reach phase III, the identity of the drug has been leaked, but I've often had to sleuth for days in order to find out what a substance in preliminary studies is, and sometines I can't get any further than XZB-9487.

(I make sales pitches to pharmaceutical companies, and knowing the chemical helps me get my foot in the door)

 

[slimvictor]

I was surprised by all the hate for Prof. Nutt.
Personally, I am a fan of his, based on what I have read, though I haven't done any deep research on his life or message...
His academic background as a scientist seems impressive.
But, mostly, anyone who could achieve that position within the government and still tell the truth about drugs is a winner in my book.

 

[Thorns Have Roses]

I find its best to reserve judgement on a complex area of science when your source is the fucking guardian

Touché. Off the top of my head I only remember the daily mail sucks, my exposure to British news-media is primarily from the BBC.

While his new product does act on gaba receptors, it is primarily an nmda antagonist. I've seen footage of a subject administered a prototype of nutt's prospective drink and the results looked very promising.

So my speculative identification completely wrong. I'm pleased to hear that, that drug sounded pretty lame.

Time for more baseless speculating!

I did some more digging, and it seems Nutt was exploring TSPO (peripheral benzodiazapene receptor) agonists in the mid-2000s. They have value as anxiolytics, and are thought to work via increased steroidogenesis (e.g. the GABAergic allopregnenolone). Pregnenolone analogs inhibit NMDAR activity, in addition to retaining the sedative-hypnotic (i.e. GABAergic) effects of the parent compound ². Elevated levels of neuroactive steroids might be partially responsible for ethanol's action.³

Seems like a promising area for a candidate. Or not, I'm unqualified to guess. I'm only doing it for funsies.

I was surprised by all the hate for Prof. Nutt.

He's a bit outré, and he pushes the whole drugs vs ethanol thing way too hard, and/or resorts to it too frequently (I consider it an unproductive avenue for us to go down, if not actively harmful to the cause. Maybe that's because America has a larger, louder group of puritanical tea-totalers.). At this point when his name comes up I just think "Oh, that guy." 8) and I imagine the general populace does the same, he's a side-show amusement the media likes to indulge. I'm not saying that he isn't a real scientist contributing to the body of scientific knowledge.

 

[spacejunk]

I was surprised by all the hate for Prof. Nutt.
Personally, I am a fan of his, based on what I have read, though I haven't done any deep research on his life or message...
His academic background as a scientist seems impressive.
But, mostly, anyone who could achieve that position within the government and still tell the truth about drugs is a winner in my book.

I agree.
He so far has failed to get any entire class of drugs banned (as Leary arguably did with his psychedelic mass media hype), has argued - most rationally in favour of the use of empathogens and similar (as opposed to alcohol) raising the wrath of the UK tabloids and costing him his govt advisory position - and has stood up bravely in favour of sensible drug law reform.
Leary snitched on the Weather Underground that busted him out of prison, scared a whole generation of the establishment of the subversive powers of psychedelic drugs - something we're still trying to recover from.
Sure he didnt single handedly have psilocybin, LSD and mescaline banned - but he certainly helped the thing along. Then later blamed the CIA for his actions.

Professor Nutt is much more balanced, measured and less sensationalist. He's alright with me.
Is it his name that gets people's hackles up??!

 

[Black]

so we're looking at something like a cross between bretazenil and imidazenil here? basically a subtype specific GABA-A partial agonist. could be interesting even when it's probably not going to be as good as ghb (being more pleasant than ethanol is easy) good luck to david nutt, but i don't think it will catch on. people will keep drinking alcohol, because that's what they've always done.

i hope the thing stays legal for long enough so that i can try it someday, but i'd surely prefer a powder or pill instead of a drink.

 

[Swarm]

Interesting thread this turning out to be, too tired to process most of it right now.

Apologies incidently to whoever I called a shit head or whatever I said. the person is clearly intelligent. I think I was in a foul mood anyway and also get wound up whenever Nuyy gets even a hint of crisicism. He's one of my fave people on the planet. plus, my formative years were ruined by alcoholism so I have a special identification for his emphasis on alcohol.