Overweening Generalist

Friday, April 15, 2016

The Drug Report: Life Extension, LSD, Oddities, Sundries

I didn't do a drug report last month, so you might say I've been "clean" for at least a month. Add to that: I haven't smoked any pot for at least 20 minutes, as of this writing. Sooo: two and a half cheers for moi?

On with it...

Possible Life Extension Drug: Metformin
If you're the sorta dreamer I am, you long for the day when you swallow one or what the hell: a handful of pills and they:

  1. Stop your telomeres from fraying while continuing to do what they did when you were 15
  2. Wipe out any and all cancers forming while not throwing your hardy-yet-delicate immunological systems out of orbit
  3. Erase all plaques that gum up your aorta and arteries and that crap that leads to Alzheimer's
  4. Level the playing fields of life by making you really pretty and attractive to possible sex partners
  5. Laughs: life will be full of 'em with this/these new drugs
Those of you trained in cryptanalysis and steganography might notice the first letters of my five here spell out SWELL. Yea, it would be real swell if we had drugs that did this stuff, but no matter how optimistic/hedonistic/giddy or just plain stoned we are, let's get real.

As I handicap a bevy of life extension drugs over the past three years, a diabetes drug called Metformin looks fairly promising. And I confess the older I get and the more I accumulate readings of articles about the Possible Miracle Drug For Everything, the less sanguine I've become. But Metformin has about 60 years of safety. For Type 2 diabetics it suppresses the liver's glucose production and increases sensitivity to insulin. It's increased the lifespan in worms and mice. Researchers think there's a physiological basis in this diabetes drug that delays the aging that gives rise to diseases. Ones even worse than diabetes, like dementia, cancer and heart disease.

Here's the crux: doctors and researchers need to convince regulators and research funding agencies to give 'em the money to test this. What are they gonna test? How long will it take? Will I be dead by the time it hits the market? Probably not: under the TAME (Targeting Aging With Metformin) clinical trial they'll take over 3000 70-80 year old folks who have one or two of these lovely maladies: cancer, heart disease, or cognitive impairment, give them Metformin, then see if it forestalls these septuagenarians and octogenarians from getting those other brutal disease they don't already have.

It'll take five to seven years and cost $50 million.

I know, I know: this is not what you wanted to read about. But you tell me what's out there that's more robust and promises more in the way of longevity.

The horrible truth is, if you have dementia but don't already have cancer or heart disease, you're gonna get one or both of those others before you kick off for the Big Dirt Nap. Talk about a reality sandwich!

Researchers caution: this is not an "immortality" drug! (As if they needed to tell us, after what you've just read.) The big deal here seems to be: Metformin is a well-accepted drug for Type 2 diabetes. But: the TAME study, if it pans out, will establish Metformin as a drug that delays aging. And aging is statistically linked with nasty-ass degenerative diseases, which have already been named in this article, no need to give them more press here. The Unistat FDA says they are open to the study. Researchers want merely to "extend a person's healthy years by slowing down processes that underlie common diseases of aging."

So, in closing I must confess what I know about myself. I read this stuff and one part of my brain - the part that I associate with non-magical thinking and statistics, knowledge of inherent human biases, and appreciation of ever-changing information about the complexity of systems - this part thinks "this seems pretty realistic and at least it's something." But I also know I will wake up tomorrow, and sometime after lunch, catch myself dreaming of the True Wonder Pills, the ones that will do the SWELL stuff. Am I the only one?

Instead of Exercise, Take a Pill? (Just: Not Yet)
I confess I love exercise, sweating, stretching, getting all breathless, even if it has nothing to do with sex. I do yoga and cycle, love hiking, but Cross-Fit seems vaguely fascistic to me, but I digress...

So, a welter of exercise physiologists have determined that, when we're exercising - not doggin' it, but really working up a sweat and approaching oxygen debt - we experience over 1000 molecular changes in our skeletal muscles. And who knew? What's going on at that level rarely crosses my mind as I approach a 1500 foot uphill climb on my bike. My thinking's more along the lines of, "If my heart explodes and they find me dead and my bike in the middle of the road here, after a cement truck and school bus run my body over, it's good I brought my ID with me so they can notify next-of-kin, but at least I can say I wore a helmet if I wasn't already dead" or "this ascent looks like a mutha; just think of the endorphin buzz I'll cop about 40 minutes after I summit." Stuff like that.

But: if we know the 1000 molecular changes that happen, maybe we can just mimic those in a pill! It's all just biochemistry, isn't it? Hey yea: they're working on it. For reals! (Or they're fucking with science writers and the public, hoping for more funding to do far less romantic research, but I don't want to be a bummer, especially after that take on Metformin.)

There are a lot of people who can't exercise, so this would really help them. It would be a godsend for the obese, for people with diabetes, heart disease, etc. One article I read on this research said it would be really great for people who already exercise. That sounded gluttonous to me.

The sobering news here: it's gonna be at least ten years, as one researcher said, "before a pill could conceivably be available." Let's hope the Metformin we'll be able to take will get us there at a young enough state that...oh hell: I need a drink.

Maurice Mikkers: Microscopy and Drugs = Art
If you have the time, check out the gorgeous colors and lines in drugs. This link begins with what Mikkers calls "party drugs" but I really only think of GHB and MDMA/Ecstasy and maybe amphetamine as drugs to "party" with. DMT, 2C-B, and LSD should be used in the proper set and setting, which often is NOT a "party" in the sense most of us think of parties. But aside from that, who knew these drugs were so beautiful, under the microscope, enlarged 40x-400x?

The MDMA/Ecstasy was breathtaking to me. Of course Ecstasy would do that.

Check out Mikkers's website for tonnes of astonishing photography, especially if you need a contact high.

Also, nota bene: it's officially been declared, by the International Moral Credit League ("Oh yea, the IMCL? Great buncha people...") that if you just "take a languid gander" at an "exhibit" - that's the way I see how Mikkers has laid out his wares online here - then you get "credit" for not going to the actual brick and marble Museum this month. I mean, what it'll cost you here? 12 minutes? Think about it. This offer only good through April of 2016; after that you must feel vaguely guilty again on May 1st until you go to the museum or talk or poetry reading. Just floatin' that out there. Hey, facts are facts.

                                            Robin Cahart-Harris, PhD

Recent LSD Research
Just in time for April 19th/AKA "Bicycle Day" and I'm no doubt writing yet another Epistle to the Converts, but what the hell, I just have to mention it. The Beckley Institute crowd-funded a study on LSD and got some stellar drug researchers from Imperial College in London to conduct it. The eminent Dr. David Nutt was the study's lead author, and Robin Cahart-Harris led the study. These are not lightweights. What did they find?

After giving 20 healthy volunteers injections of 75 micrograms of LSD (and others got a lousy placebo, but it was FOR SCIENCE!), the trippers had their brains imaged three ways: with fMRI, something called "arterial spin labelling" (don't ask), and magnetoencephalography. The study said the LSD users tripped for "six hours."

Aside: every LSD trip I've done was at minimum 200 mikes, but always on blotter. And it always lasted at least 10 hours. This Imperial College London stuff Nutt got must have been really righteous! Moving on...

So: there are numerous reports on this study, but the finding that most intrigued me: neural networks in the adult brain normally "talk" to closely-connected networks nearby. It's about specialized function. To rehash basic developmental neuroscience, we have way more neurons as babies, but they get pruned away with experience in the world, which we can call "learning." The stuff that's not pruned gets reinforced and the connections get stronger. We develop neural pathways that "know" how to do millions of things. Neurons are use-it or lose it: what's not recruited in learning/experience in the world gets flushed, literally. Eventually, we develop a sense of our "self" and some sort of "ego," hopefully a relatively healthy one.

What this study did was show how LSD gets the brain to "talk" and connect to other areas it usually doesn't, and therefore it was likened to a return to a "childhood" sense of wonder and imagination. It also reduced the "normal" connectivity we usually experience. What it taketh away it more than giveth backeth in spadeths.

In the past 30 years, neuroscience has continually found more fascinating aspects of how "plastic" the brain can be, even in adults, in the right circumstances. This is termed "neuroplasticity" and is the main reason why even stodgy old farts can still learn a thing or two.

As I read the articles about this study, certain lines jumped out. LSD and presumably other psychedelics "might help some users return to a childlike sense of wonder and imagination." (Most of these quotes are from Cahart-Harris or David Nutt.) When I read this, I think my first reaction was, "I wonder how many church-goers privately think, "This ain't working for me, but it's what's expected...I need to show up at least..." Well, what you REALLY want is a return to a childlike sense of awe and wonder, where parts of your brain get to know other parts for the first time, then you'll know what true religion is. But here of course I'm biased.

In a repetition of research with psilocybin over the past five years (or more), it was observed that the users experienced "improvements in well-being" after the effects of the drug wore off. Psilocybin research showed that one trip significantly changed people towards more openness for the rest of their lives. I know it's an olde riff, but if we could only get this stuff in the punchbowl at the Republican National Convention, amirite?

Cahart-Harris: "This experience is sometimes framed in a religious or spiritual way, and seems to be associated with improvements in well-being after the drug's effects have subsided." Yes, and it's once again suggested by people with actual PhDs from high-ranking universities - actual scientists, not assholes like Ted Cruz or some raging right wing pastor who thinks Jesus needs more nuclear missiles so we get to live out the book Revelation.

But Cahart-Harris also addresses a point I blogged on a few weeks ago: why must psychedelic experience use religious language? I recently read Dennis McKenna's book Brotherhood of the Screaming Abyss and here's a PhD psychonaut of impeccable credentials who has managed to develop a vocabulary to talk about psychedelic experience that's drawn from cosmology, phenomenological philosophy, science fiction, and the arcana of alchemy.

We have our work cut out for us, friends.

Once again, hard-core researchers are suggesting these drugs might or can or should be used for depression, addiction and - presumably if Metformin and the exercise pill never get here in time - for end-of-life anxiety.

I will close with a quote from the estimable British drug researcher, Dave Nutt, talking about this latest LSD research:

This is to neuroscience what the Higgs boson was to particle physics.

And with that, I bid you all a fondue.


Eric Wagner said...

Great article. I wonder what research will emerge in the next few years.

michael said...
This comment has been removed by the author.
michael said...


As far as emerging research in longevity drugs, the smart bet is on a non-drug technology called CRISPR, which allows us to edit the genomes of plants, animals and humans in the same way you edit a piece of writing you're doing on a digital gizmo, like the one you're reading from now.

I've been studying CRISPR for 4 months or so and there's so many wild tributaries I go down one, am blown away, then double back to the mouth of CRISPR. The learning curve for me seems quite steep, however: anything but boring. It seems to me (and almost all of the scientists I read on this) that the potential for human good is positively utopian; the downsides look like the worst bio-disaster horror flick.

If you crash on CRISPR for two weeks, I'm pretty sure you'll find it difficult to NOT want to buttonhole all your friends are start telling them about it.

Right now, at my current level of ignorance, I don't see how this won't be massive game-changer for the human race. I know that sounds hyperbolic, but in case you haven't checked it out...Maybe start by Googling "Jennifer Doudna."

Eric Wagner said...

Thanks for your responses. I wonder what sort of tetrad McLuhan would make out of life extension?

Enhances: Education, fiscal responsibility
Makes obsolete: The idea of life as brutish, nasty, and short (although it may remain that way for the poor in many countries and for non-human animals)
Retrieves: Multi-generational family relationships
Flips into: Science fiction

Speaking of McLuhan, I just watched a show about the history of American Idol on my DVR. It mentioned Ryan Seacrest teaching the audience how to text in 2003. The season six winner said her mother learned how to text so as to vote on American Idol. Also, one producer commented that AI's audience did not sit passively watching but rather sat of the edge of their seats, actively engaged in the process.

michael said...

Nice work with the Tetrad vis a vis medium: life extension!

Rushkoff has been using the Tetrad recently in talks about his new book _Throwing Rocks At The Google Bus_, esp in discussing what a Peer-To-Peer Economy would look like.

I tried to watch American Idol once, but couldn't take Simon Cowell playing sadist to the hapless not-so-talented (masochistic?) folks they threw out there into his lion's den.