On drugs and drug laws.

On drugs and drug laws.

Humans have been ingesting dimethyltryptamine, a potent psychedelic, for over a thousand years.  We’ve been using cocaine even longer.  Marijuana was used medicinally in China thousands of years ago; soon after, celebrants in India began to ingest it as a psychedelic to potentiate religious experience.  Mind-altering experiences were so prized in ancient Greece that prophets huffed narcotic vapors.

The Oracle of Delphi.

Our ancestors began intentionally brewing alcohol nearly 10,000 years ago.  We’ve been using opium as a sacrament – not just a painkiller – for perhaps 3,000 years.

Drugs are very important to our species. 

Not all drug use is good, obviously.  Narcotics like opium, heroin, oxycontin, et al., can latch onto a person’s mind and compel continued use at any cost.  Somebody told me recently, “I knew I was gonna get caught.  I’m on probation, they drug test me all the time.  I mean, I was thinking about it while I was cutting it up: if I do this, they’re gonna catch me.  I was thinking about it while I was loading the syringe: if I do this, they’re gonna catch me. I thought I’d only have to do a week, though, and that seemed okay. Which is insane! I know it’s insane, but that’s what I was thinking.  I guess I was wrong. I’ve been here three weeks and I still haven’t had my court date.”

Even fish, if they get hooked, will risk their lives for another dose.  When human parents are snared by addiction, they endanger their children. The man whom I quoted above? He’d managed to stay sober for almost seven months, but relapsed the night of his son’s second birthday. His wife had to break down the bathroom door. After the ER, they brought him straight to jail.

In class together, we read Josh Rathkamp’s “Single Father,” in which the narrator fears that his diabetes will cause him to fall out and be unable to help his daughter.  Several parents recognized their own dread. Then we read “Daddy Wake Up” by local poet Travis Combs. Combs loves his son, but, like a diabetic, a person suffering from opiate addiction might find himself paralyzed, “a mass of mess.”

DADDY WAKE UP

Travis Combs

I hear the sound of his little feet running

down the hall, I look to make sure the door

is locked, I pull the plunger back, I hear

his joy as he yells, I’m superman.

       I do the shot

                      thinking What if?

       What if I fall out, what if he finds

me here, what if his little fingers have to

press 911, something we all teach them to do.

The fear in his voice when he says Daddy

won’t get up.  The pain in his heart when

he shakes me, yelling daddy wake up, daddy

wake up.

              Then I do wake, the needle

still in my arm, I feel his tears on my chest

as he lays there hugging me, crying, daddy

wake up.

Psychedelic drugs are safer.  They tend to be non-addictive. Most are relatively non-toxic. And a single dose can initiate self-discovery that buoys a person’s spirits for six months or more.

But psychedelic drugs are tightly controlled.  Despite thousands of research findings to the contrary, they’re classified by the U.S. government as having no accepted medical treatment use.  Possession is a felony.

Perhaps this shouldn’t seem surprising.  Spiritual drug use has been prized by our ancestors for thousands of years, but most cultures closely regulated which people would be privileged with access to those sacraments.  Depending on the time and place, only wealthy people would be allowed to use drugs, or only people born to a certain caste, or only men.

In the United States, cocaine was rightfully recognized as a wonder drug for decades, but then a cadre of white supremacist politicians claimed that cocaine would turn black men into monsters.  Prohibition was mediated through racism.

It’s true that cocaine is dangerous – both psychologically and physiologically – if you’re ingesting the purified compound.  But coca tea is no more dangerous than earl grey.  Indeed, if you decided to purify caffeine from tea leaves and snort it, you might die.

Marijuana was also legal in the United States until the racist propaganda machine started spinning stories about what would happen when people from Mexico smoked it.

And even now, wealthy people throughout the Bay Area blithely use psychedelic drugs.  Authors like Ayelet Waldman and Michael Pollan openly publicize their experiences flaunting the law.

Yet when people in Denver supported a ballot initiative that reduces the legal risk of possessing psilocybin-containing mushrooms, Pollan wrote an editorial denouncing the initiative.  Yes, there is some nuance; Pollan states that

No one should ever be arrested or go to jail for the possession or cultivation of any kind of mushroom – it would be disingenuous for me to say otherwise, since I have possessed, used and grown psilocybin myself.

And he claims, oddly, that the ballot initiative would be merely symbolic, citing as evidence the fact that only 11 psilocybin cases have been prosecuted in the last three years, out of approximately 150 arrests.  I personally have never been prosecuted for a crime, nor even arrested, but I’ve been told that it’s a very traumatic experience.  I’ve heard this from very reliable sources, men who have been through all sorts of horrific trauma in addition to their arrests. 

For all the people subject to this trauma – not to mention everyone more deterred than Pollan himself by the current legal status of this medicine – the initiative would have very meaningful consequences.

Michael Pollan. Photograph by Sage Ross on Wikipedia.

Instead, Pollan centers his cautionary argument on the idea that psilocybin “is not for everyone.

That idea is true enough, as far as things go.  Some people probably shouldn’t use psilocybin.  Some people feel traumatized by the bad experiences they go through while under its influence.  But I would argue that arrest is more traumatizing, and that the very illegality of the substance increases the likelihood that someone will go through a bad trip.

And the regulations seem absurd compared to how we treat other drugs.  For instance, someone with a predisposition to develop schizophrenia could be pushed closer to this condition by ingesting psilocybin.  The drug can hurt someone who uses it.  But alcohol, which is totally legal for most U.S. citizens over 21 years of age to purchase and consume, causes a huge amount of harm even to people who abstain.  Alcohol is the psychoactive drug that causes the most harm to others. 

Graph made by Tesseract2 on Wikimedia.

It’s unlikely that our sitting Supreme Court justices would have sexually assaulted anyone while using psilocybin for a meditative journey of self-discovery.  Indeed, that sort of experience might have led someone to develop much more empathetic political views. 

Because alcohol consumption is so likely to lead to poor decision-making and violence, it’s illegal for people on probation to drink.  Many have to check in at “blow & go” breathalyzer stations once or twice a day, which is really tough for people whose drivers’ licenses are suspended.  But, still, we passed this law to keep other people safe.

Or consider antibiotics.  Every time you use antibiotics, you make the world a little worse.  With every dose, there’s a risk that the bacteria you’re hoping to kill off will instead evolve to resist them.

And yet, even though using antibiotics hurts everybody else, they’re regulated much less than other drugs.  If you take psilocybin, it’s not going to hurt me at all.  But if you take an antibiotic – or, worse, if you decide to manufacture huge quantities of antibiotics and them inject 80% of them into cows, pigs, and chickens, all of whom are being raised in fetid conditions – you’re making it much more likely that I will die.

In the past, somebody might get scratched by a cat … and die.  Any infection could turn septic and kill you.

In the future, a currently-treatable infection might kill me.  Or kill my children.

Because we’ve allowed people to be so cavalier with antibiotics, medical professionals expect that within a generation, more people will die from bacterial infections than from cancer.

Obviously, this terrifies me.

But we’re not stopping the meat industry from using them.  We’re not using our legal system to protect all of humanity from their misuse.  Instead we’ve outlawed psilocybin, a compound that could usher you through a spiritual experience that helps you become a kinder, happier person.

Is that reasonable?

On memory (part three): getting rid of memories.

Exposed brain and magpie.  By Curious Expeditions on Flickr.
Exposed brain and magpie. By Curious Expeditions on Flickr.

This is third in a series.  See parts one and two.

Not all memories are good, obviously.  I’ve done plenty of stupid things, blurted out plenty of awkward remarks in conversations, that I’d prefer to forget.  And those are harmless.  They might make me flush and feel retroactively embarrassed if I think of them at night, but, big deal.

Other people have seen far worse things than me.  Their memories, instead of minor self-consciousness, lead to post-traumatic stress disorder (PTSD): sleeplessness, headaches, stress biomarkers suggestive of shortened lifespan, proclivity toward substance abuse, etc.

PTSD is bad news.  Very bad news.  There’s no data yet on what causes it — why does one person subject to a horrible event pull through fine, but another contracts the nightmares?  There’s simply too much we don’t understand about the brain.

Mostly this essay is going to be about memory erasure — if we could consistently & specifically delete memories, that’d go a long way toward curing PTSD.  And I have a minor ulterior motive for slapping up a few scientific references for memory erasure: because misplaced memories are essential for the plot of The Ramayana, I tucked the concept into my book.  When I first wrote those passages, they were moderately speculative, but in the intervening years our scientific understanding has actually caught up appreciably.

MV5BMTM3OTA2MjcwMl5BMl5BanBnXkFtZTcwNjU2ODYyMQ@@._V1__SX1156_SY499_But first I wanted to give a small shout-out for the film Renegade.  Despite being a terrible cowboy film, Renegade is also the best depiction I’ve seen of using psychedelics to treat PTSD.  Which maybe sounds a little odd, but there are reasons to expect why it might work (as opposed to, say, attempting to use psychedelics to cure autism, which is every bit as ill-reasoned and abusive as it sounds).

Cognitive behavioral therapy (CBT) seems to be the leading non-pharmaceutical strategy to treat depression, sleep disorders, and other crummy brain states including PTSD.  The basic idea is that thoughts are reinforcing.  Thoughts you’ve had once are easier to have again, which is why studying works, why practice makes perfect.  But people can get stuck in ruts, looping through the same negative thoughts over and over.  CBT aims to replace those ruts with new virtuous cycles of helpful thoughts.

And that’s why psychedelics might make CBT more effective: the therapy will reinforce itself once it gets going, but actually jolting someone out of their initial rut seems difficult.  Mind-altering substances might provide a window of time during which a new cycle of thoughts can be more readily inoculated into someone’s brain.

This is speculative, of course.  FDA restrictions have made it difficult to conduct research using psychedelics.  Not many studies have been done so far, and a lot of our nation’s more illustrious research groups haven’t been involved; if your research is already going well, investigating psychedelics probably seems like a lot of hassle for little payoff.

BLUEBERRY
Still from Renegade.

But, let’s say you were a film director who’d been given a reasonably high budget to create an adaptation of a French comic book but instead used much of that money to take ayuhuasca hundreds of times in Peru … would you care that the ideas are speculative?  I think not.  Jan Kounen, who directed Renegade, certainly didn’t.  The scaffolding film is a cheesy western, but the central premise deals with overcoming the curse of a traumatic memory.  And, sure, the trippy CGI fractal swirls are often vaguely reminiscent of screensavers, but I appreciate the director’s ambitious attempt to depict visually what was happening in his protagonist’s mind as he reconciled himself with his past.  I think Renegade does a better job of depicting these unarticulated inner states than, say, Eternal Sunshine of the Spotless Mind, Inception, or Dark City.

Even if psychedelics could help people with PTSD, though, it seems inconceivable that the drugs alone would be effective — the only reasonable mechanism I can come up with is that the drugs might make someone more receptive to CBT.  And the therapy takes time, takes a lot of concentrated effort from both patient and therapist, and probably seems like it’s not accomplishing anything for most of the initial sessions.  About a third of people with PTSD who have participated in CBT research studies drop out of treatment, and in general practice this number might be even higher.

It’d be nice if we could address the underlying traumatic memories directly.  Delete them specifically from someone’s brain.

And we can’t, obviously.  As per my previous post in this series, we can’t identify memories based on brain structure alone.  That rules out opening up someone’s head and attempting to physically ablate the offending thoughts… although it’s quite clear that physical disruption could remove memories.  Here’s the first paragraph of Henry Marsh’s Do No Harm:

418tSpTGIdL._SY344_BO1,204,203,200_I often have to cut into the brain and it is something that I hate doing.  With a pair of diathermy forceps I coagulate the beautiful and intricate red blood vessels that lie on the brain’s shining surface.  I cut into it with a small scalpel and make a hole through which I push with a fine sucker — as the brain has the consistency of jelly a sucker is the brain surgeon’s principal tool.  I look down my operating microscope, feeling my way downwards through the soft white substance of the brain, searching for the tumour.  The idea that my sucker is moving through thought itself, through emotion and reason, that memories, dreams and reflections should consist of jelly, is simply too strange to understand.  All I can see in front of me is matter.  Yet I know that if I stray into the wrong area, into what neurosurgeons call eloquent brain, I will be faced by a damaged and disabled patient when I go round to the Recovery Ward after the operation to see what I have achieved.

We could delete memories, but given our current understanding of the brain we would be wrecking them at random.

What else do we know about erasing memories?

My favorite model is that memories, when used, seem to be replaced — details that weren’t included in an initial act of remembrance are often lost forever, which could indicate that a new memory of that remembrance does something like overwriting it.  And this would explain why our most vivid recollections are of things we seldom think about — as in Proust, a rare smell or sound or physical sensation can spur our sharpest memories.

Conversely, repeated remembrance seems able to dim a memory.  But there’s a trick — that whole problem with mental ruts.  Typically remembrance dims the initial memory, but encodes new information.  Whatever we think about while remembering becomes the memory (in part this seems to be why eyewitness testimony is so often wrong — poor police practice can easily allow a new, wrong memory to be encoded and reinforced before a trial).

To erase a memory, it would have to be recalled but not replaced.

One method for this is termed “thought substitution” — actively trying to make your mnemonic records incorrect.  If you try your darnedest to think about something else while remembering a traumatic event, you might be able to replace the traumatic memory with an innocuous thought.

…although (and this isn’t addressed in the paper I cited above), it seems possible that you would instead link horrible emotions to the previously innocuous replacement thought you tried to overwrite your trauma with.  I’m not sure whether there’s any reason to expect the transfer to be unidirectional.

Ravivarmapress_Rama_familyAnd, right, I first began researching memory because it is integral to the Ramayana.  There’s an incident of brutal sexual violence (perpetrated by the heroes!!), which, right, often results in PTSD.  And there are less horrific instances of memory loss throughout the myth — the central protagonist has to forget his divine origin in order to be sufficiently human (i.e., weak) to slay the erudite vegetarian ruler of Lanka, and the heroic monkey has to forget his powers so that he doesn’t destroy sacred temples in his exuberant rampages.

So I had to put memory erasure into my book, despite this being beyond the ken of contemporary science.  My assumption was, if memories are accessed at a time when there is pharmaceutical destabilization of firing synapses or even just inhibition of synaptic connection reinforcement, those memories might well be diminished.  The biggest problem, from a pharmaceutical perspective, is one of targeting: epigenetic phosphorylation seems to be essential to maintain long-term memories, and inhibition of the phosphorylase that maintains them (PKMζ) seems to erase memories, but we can’t deliver an inhibitor specifically to potentiated synapses.  Memory erasure is still science fiction — but doesn’t seem to be unreachably far away.