On psychedelic drugs as medicine.

On psychedelic drugs as medicine.

We are creatures of habit.

learning_to_walk_by_pushing_wheeled_toyLife would be excruciating if we were not.  Can you imagine: consciously remembering to breathe every few seconds?  Concentrating with the intensity of a toddler each time you stand and walk across a room?  Carefully considering the rules of grammar and conjugation when you stop to ask someone for directions?

Our brains zip through so much unconsciously.  Most of us can drift into reverie while driving and still go through all the motions correctly, stopping at red lights, making the appropriate turns, our mind set on autopilot.

We live, and we learn, and our brains constantly change – neurons reach out to form synaptic connections to one another.  Other connections wilt away.  The resultant network determines who we are.  More precisely, the pattern of connections determines which thoughts we are good at having.  Thoughts we’ve thunk before come easily.

But our propensity for habit can hijack our lives.  In David Foster Wallace’s Infinite Jest, viewers of the highly-addictive titular film are unable to think of anything but watching it again.  One taste and you’re hooked!

otto_wegener_vers_1895_2Or, in an example closer to most humans’ experience, Marcel Proust writes of the way our shared experience with a lost love causes the brain to ache each time a similar experience must be forded alone.  Over and over we hurt: going to sleep alongside her was a habit.  Chatting in the evening was a habit.  Walking to the store hand in hand was a habit.  The brain is still wired such that it could effortlessly zip through these tasks, but… she is gone.

In an example that is – unfortunately! – increasingly relevant today, William Burroughs writes that powerful opiates do not hook users right away.  It takes many recurrent episodes to rewire the brain.  In his (overly cavelier) words:

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Painting by Christiaan Tonnis.

The question is frequently asked: Why does a man become a drug addict?

The answer is that he usually does not intend to become an addict.  You don’t wake up one morning and decide to be a drug addict.  It takes at least three months’ shooting twice a day to get any habit at all.  And you don’t really know that junk sickness is until you have had several habits.  It took me almost six months to get my first habit, and then the withdrawal symptoms were mild.  I think it no exaggeration to say it takes about a year and several hundred injections to make an addict.

. . .

You don’t decide to be an addict.  One morning you wake up sick and you’re an addict.

And then, depression.  To perceive the world a shade darker than it ought to be comes easily… to someone who is depressed.  A depressed person’s brain has been rewired through perhaps a lifetime of rumination and pain.  Suicidal ideation gets easier and easier and easier… unless it goes too far, and then it becomes impossible.  Dead matter doesn’t think.

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The Nightmare by John Henry Fuseli.

Cognitive behavioral therapy attempts to use the brain’s own habit-forming capabilities to battle depression.  Because today’s depressed thoughts enable tomorrow’s depression, a conscious effort to find joy and beauty today could ease tomorrow’s struggle.  Phrases like “virtuous cycle” are bandied about.

My wife, each evening, asks me to list four good things that happened during the day; if we forget the ritual through a harried week or two, it’s difficult to start again.  I lay in bed, pondering, “What was good about the day?”  Which should always be easy.  I have two loving children whom I am graced to spend time with.  I am not in jail.  I have a warm, safe place to sleep.  I have enough to eat.  I live near phenomenal libraries.

But the habit of depression digs the mind into a rut.

lsd-clinical-trial-bottleWhich has caused several researchers to wonder, “Would cognitive behavioral therapy work better if a patient could be jolted out of the rut first, then trained in a new virtuous cycle?”  We have access to several potent chemicals that wrest the brain out of its routines.  Psychedelic drugs like lysergic acid diethyl amide, dimethyl tryptamine, and psilocin are powerful beasts.

Which is not to say that, if you’re feeling sad, you should go find that raver dude you know and ask what he’s holding.  For one thing, most psychedelics are illegal in the United States.  This contributes to the dearth of high-quality clinical information about their uses – obtaining permission to run clinical trials with Schedule I compounds is difficult, and drugs can’t be downgraded from Schedule I status without reams of data from clinical trials.  Nonsensical bureaucracy at its best!

Plus, high-quality clinical trials must control for the placebo effect – neither patients nor doctors should know whether an individual is receiving the treatment or a control.  But I’m guessing most recipients recognize the difference between an injection of DMT or saline.  Did your visual field suddenly fragment into geometric patterns?  Did you feel an out-of-body sensation akin to alien abduction?  Did your memories begin to unfold like interlocking matryoshka-doll puzzle boxes?  Those are sensations I rarely experience from salt water.

LauretaAnd the sheer power of psychedelic drugs also makes them dangerous.  Dr. Lauretta Bender, whose least harmful contribution to science was the idea that emotional disturbances could be diagnosed by asking a child to reproduce pictures of geometric shapes, assumed that LSD would cure autism.  If she’d been right, this sort of baseless cognitive leap would’ve been heralded as brilliance.  She injected large doses into the muscles of children as young as five.  Daily.  When that “cure” proved insufficient, she combined it with electroconvulsive therapy: high currents to overwhelm their little brains.

Enforced acid trips in nightmarish environs of total control can ruin lives.

Especially since Dr. Bender was diagnosing autism in routinely-abused orphans based on symptoms like “avoids eye contacts” and “difficulty forming trusting relationships.”

5009548522_6701801dcb_oAcid trips can end lives, too.  At least one involuntary research subject ensnared in the CIA’s efforts to use LSD as mind-control reagent committed suicide.  And there are innumerable horror stories of murders committed by people mired in psychedelic trips.  Then again, most murders are committed by people who haven’t taken psychedelics.  In Ronald Siegel’s Intoxication he writes that:

Many bad trips are a function of personality; not everybody is a good subject for a mind-altering experience.  And even experienced users can have a bad day.  … Harold, a veteran of one thousand LSD trips, wanted to volunteer to be a psychonaut but he had a history of violence, both on and off the drug.  “Ever since I was small,” confessed Harold, “I go ape when I’m bothered.”

.. [a grim description of Harold murdering two hikers outside Santa Barbara in 1984 follows.  Yes, Harold had “drank some beer, smoked a little marijuana, and swallowed a few amphetamine tablets along with a full dose of LSD.”  But he’d also “been bothered by financial problems.  He was passing bad checks and had failed to make child-support payments to his ex-wife.”  So I’m not sure the drugs were at the root of his malaise.]

Cases like Harold’s tend to confuse the issue of intoxication and violence.  Violent people are often intoxicated but the violence is usually rooted in the personality, not the drug.  . . . What seems difficult for us to understand is that despite overt behaviors, the subjective experience can still be fun.  In other words, one’s inner feelings and sensations can be under the influence but such influence may not extend to outside acts in the real world that remain chillingly sober.  This is most difficult to accept if users are obviously intoxicated when they commit criminal acts.  The subjective intoxication can remain an enjoyable experience, despite our desire to blame the fires inside for the destruction outside.

Used incorrectly, psychedelic drugs are awful.  They disrupt habits, seeming to dissolve the mental filters that allow humans to function despite constant bombardment by thoughts and memories and myriad sensations from the world.  This newfound wonderment & reset can help, of course, but for someone in a bad place, it can be horrible.

mdma1Then again, for someone with post-traumatic stress disorder, the world might be horrible already – even if the chance that psychedelics could help were low, they’d be worth investigating.  Thankfully, the FDA finally granted permission for a trial to be run on the use of methylene dioxy methamphetamine (ecstasy – when I was a TA for undergraduate organic chemistry at Stanford, I wrote most of the quizes.  After they learned about acetal protection of ketones, all 200 or so pre-meds wrote out a partial synthesis for MDMA.  The reactants and products were unnamed, so I don’t think the students or the other TAs noticed) to treat PTSD .

In other experiments, LSD and psilocin seem to help terminal cancer patients overcome depression.  Ayahuasca is also being tested as a treatment for depression and those seeking to quit substance abuse (peyote has long been used for the latter), although these studies are far from the FDA clinical ideal.

Many people, as they live, drift into routine and no longer consider the implications of their actions.  I’m well aware that drugs can wreck lives, but sometimes we need a jolt.  I wish people weren’t shunted to jail for drug addiction – and obviously the dudes in there wish they were almost anywhere else – but a surprising number are grateful that something interrupted their habits.  Junkies don’t want to look back on a wasted life, either.

pills-750x400I’m not super keen on the rich & entitled using psychedelics for fun & games, and psychedelics certainly should not be used often.  But these molecules, treated respectfully, can heal damaged lives.

Even in the ostensibly healthy, psychedelics can do good.  Does the way you choose to spend your time benefit the world?

On witchcraft and mass psychogenic illness.

On witchcraft and mass psychogenic illness.

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Because she is N’s best friend’s grandmother, I recently had the pleasure of meeting the researcher who first proposed that the Salem witchcraft trials were inspired by ergot poisoning of rye crops.  And that, of course, is one of the papers I read while researching mass psychogenic illness / conversion disorders / violence against women.

Does it seem controversial to throw that last categorization in there?

Here’s a quick summary: mass psychogenic illness is typically diagnosed when people exhibit strange behavior and those who are making the diagnosis do not know why.  If an episode involves more women than men, that’s considered an indication of mass psychogenic illness — even for contemporary diagnoses, actually, although we now know that women & men metabolize many small molecules differently, which means that equal ingested dosage will often result in higher blood levels for women.

Maybe you read about the recent episode in New York (if not, I’d recommend another lovely article by Susan Dominus, “What Happened to the Girls in Le Roy”).  Teenagers started twitching.  Mostly young women were affected, environmental analysis identified no known toxins, doctors decided it was mass psychogenic illness.

There are non-psychological reasons to believe that certain episodes of strange behavior, tics, convulsions, etc., would affect primarily women, but ever since the diagnosis of “hysteria” was first proposed (in which the womb forgets that it’s supposed to reside near a woman’s belly and begins to wander her body, eventually latching onto the brain and causing her to act strange) the medical community has assumed that most women’s problems are in their heads.

Which isn’t to say that strange behavior like tics, convulsions, etc., cannot have an exclusively neurological cause.  It can.  There are physiological problems that can be caused solely by the brain — usually the initial onset is accompanied by high stress — and, unfortunately, the symptoms also recursively change the brain.  It’s a little bit silly to try to distinguish between psychological and physiological problems, what with the brain also being part of the body, but with conversion disorders an ailment that began as thought will eventually become detectably imprinted in matter.

In case you’re interested, here’s a nice open-source reference by Ali et al. discussing this loop.

Despite my reflexive distaste for most of Malcolm Gladwell’s pithy summaries about how the world works — I’ve read enough social psychology papers to know that the findings are often much weaker than they seem when filtered through popular writing — that lovely phrase “the tipping point” seems very appropriate when thinking about mass psychogenic illness.  There are two stable equilibria that you could roughly designate “acting strange” and “acting normal,” and at some intermediate point they transition sharply from one to the other.

Here, I can draw a graph for you, using tarantism as a model case.  Tarantism, you ask?  People thought that spider bites would be fatal unless those bitten began to dance… so circa the 1380s, every summer there was wild, obscene dancing from Italians trying mightily to stave off death.

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It’s the fact that the amount of dancing in turn contributes to the likelihood of more dancing, that lends the situation a tipping point.  All else being equal, a world in which not many people are dancing will result in little dancing in the future, a world full of revelry will produce more rambunctious behavior.

And there’s a point in the middle, when a small number of people have been affected, that could just as easily swing one way or the other… by next week the “danger” may have passed, or there might be a tremendous outbreak of tarantism.

(Also, my apologies to any math people out there … I realize that this is a nonstandard way to represent an ODE.  I’ve been working on a post about the uncertainty principle and trying to think of ways to use basic math to convey a decent “feel” for complicated equations.  Which is difficult, and is made even more so by the fact that I am so out of practice; since beginning my thesis research project, I’ve never had professional reasons to use anything more complicated than statistics.)

To reach a tipping point, though, there have to be many people experiencing similar levels of stress, along with whatever else might be needed to initiate a conversion disorder.  Which is why I think it’s reasonable to think that outbreaks of mass psychogenic illness are a symptom of pervasive violence against women.  They tend to occur primarily amongst people who have limited opportunities for self-expression: overworked schoolchildren, prisoners, convent residents, and women living in restrictive societies.

Salem_Witch_trial_engravingAnd it is of course possible for other factors to contribute.  That’s the main message I took away from Caporael’s ergotism study — for young women living in puritanical New England, who believed that witchcraft was a very real threat, it wouldn’t take much to push them over the edge.  Exposure to a psychedelic drug could potentially do it.

Which isn’t to say that lysergic acid makes people condemn their compatriots as witches.  Like most drugs, its effects are dictated largely by the mindset of whomever ingests it.  I think this passage from Ronald Siegel’s Intoxication (a somewhat strange book discussing drug use by a variety of animal species) phrases this well:

“Violent people are often intoxicated but the violence is usually rooted in the personality, not the drug.  People may panic under the influence of LSD or any other drug that makes them feel different. . .”

Caporael addressed this in her paper — the idea that neither ergot alone, nor a belief in witchcraft alone, would have resulted in the trials — and suggested that the paucity of similar accusations during that time period lends further credence to the ergotism hypothesis.

“The Puritans’ belief in witchcraft was a totally accepted part of their religious tenets.  The malicious workings of Satan and his cohorts was just as real to the early colonists as their belief in God.  Yet, the low incidence of witchcraft trials in New England prior to 1692 suggests that the Puritans did not always resort to accusations of black magic to deal with irreconcilable differences or inexplicable events.”

Altogether, it’s a nice little paper.  Plus — and this is something I didn’t realize when I first read it — it’s a single-author Science paper written by a twenty-something year-old graduate student based on research she’d done as an undergrad.  The only publication I have from my undergraduate research is an author contribution buried somewhere in the middle of a long list of researchers… for an article that landed in Blood.  Somewhat lower tier than Science.

Ergot growing on rye.

In fact, my only real objection to Caporael’s paper doesn’t address the underlying research.  It’s that I believe the ergotism hypothesis lets the perpetrators of the Salem witchcraft trials off too easily.  Hearing that the accusers might have inadvertently ingested psychedelic drugs (for months!) might make their actions sound less heinous.

And, look, we’ll never know for sure.  Salem’s inhabitants might’ve been under the influence of lysergic acid for that whole time period.

But I think it’s worth pointing out that similar abuses have occurred in the absence of any confounding psychedelics.  Outbreaks of a wide variety of diseases in Europe caused people to blame and murder their jewish neighbors.  Outbreaks of a wide variety of social strife in the United States caused people to blame and murder their black neighbors.  Even the Stanford Prison Experiment documents how easily an imposed worldview can bring forth evil.

If those Stanford students had been indoctrinated from birth to believe in witchcraft and an omnipresent Satan striving to destroy their society, they probably could’ve been convinced to start dunking their classmates in order to identify the witch.

My brother & me. Luckily no one accused us of witchcraft; given our garb, I doubt we coulda beat the rap.
My brother & me. Luckily no one accused us of witchcraft; given our garb, I doubt we coulda beat the rap.