reefer madness

“Doctor, I’m afraid I might have ruined my brain.” Mr D’s wide brown eyes bore a pleading expression.  He was a young law student with a cherubic dimple set in his left cheek.  He had had no history of psychiatric issues until six months prior to our appointment.  Then, one Saturday evening during his winter recess from school, he’d celebrated the end of the semester with friends by smoking an enormous amount of marijuana and attending a 3-D movie.  

During the movie, he told me, he had a terrifying experience.  “It was as if I’d lost all of my memories.  I knew nothing.  I was nobody.  I was starting over.” During the course of the movie he gradually regained his memories but retained a feeling of foreboding.  Ever since that time he had been having episodes of déjà vu in which otherwise innocuous situations would give him the sense that he was about to be catapulted back into the memoryless state he had experienced in the movie. 

Simple triggers like buying a cup of coffee at his favorite stand would give him a sudden, horrifying feeling that he had been there before, and that he knew what would happen next: He would be thrown back to the place of no memories.  Or, he was having a dream and he would be forced to relive this same sequence in an endless loop, forever.  The feeling would last a few minutes, and then dissipate as surely as it had come. 

He’d been having experiences like this up to thirty times a day, ever since that night at the movies.  They were interfering with his sleep, his work, and his love life. He hadn’t touched marijuana again since that night.  Still, they weren’t going away.  Finally he decided he needed help.  Could I help him?  He spread his hands nervously on his lap. 

Marijuana use has long been associated with increases in psychotic manifestations.   (For many years it was unclear whether marijuana truly tilted the brain towards psychosis, or whether marijuana was simply more appealing to the psychosis-prone brain.  Earlier this year, the results of a decades-long study of marijuana use and psychosis in 3800 individuals were released (McGrath et al).  They confirmed the results of two other large cohort studies that found the longer people had been using marijuana, the more likely they were to report psychotic symptoms.  In addition, this most recent study analyzed sibling pairs and found that the same relationship held true – weakening the argument that some other, unknown genetic or environmental factor might be stacking the deck.) 

However, Mr D.’s symptoms weren’t the classical psychotic signs of hallucinated voices or paranoid delusions.  The déjà vu reminded me more of neurological oddities such as temporal lobe epilepsy than of any psychiatric syndrome.  But this patient had neither a history of epilepsy nor any risk factors for seizure, and the link to marijuana use was too clear to ignore.  I decided to offer Mr D. an antipsychotic – the very sort of drug we give to people who insist that the aliens are after them, or the CIA has bugged their hospital rooms, or they are the Messiah.              

I made the offer tentatively, worried that the very word ‘antipsychotic’ would set alarm bells ringing in Mr D’s formerly entirely sane and rational young head.  I more than halfway expected him to refuse it.  But to my surprise he accepted it eagerly.  “I’ve been living with this for six months,” he explained.  “I just need it to stop.”            

And stop it did.  Two hours after his first dose, Mr D reported to me the next week, he could feel the grip of his illusions relaxing.  Within a few days he went from having thirty episodes per day to having fewer than ten.  After two weeks on the drug he felt he was his old self.  He discontinued the medication without incident.            

There is much we do not know about the neurobiological effects of marijuana.  The psychoactive ingredients, cannabinoids, come in dozens of varieties whose relative proportions vary from plant to plant, presenting a complexity of Gordian proportions to the would-be researcher.   

Our bodies’ cannabinoid receptors (built to respond to our own endogenous cannabinoids but, happily for college students the world over, also responsive to the herbaceous variety) are found generously distributed throughout the brain (Glass et al.), including the frontal cortical areas that are implicated in psychosis.  They seem to act as local modulators, damping the strength of signals coursing through the brain’s circuits – including the frontal dopamine circuits in which hyperactivity seems to underlie psychotic episodes.  Tire out the endocannabinoid ‘braking system’ by flooding it with ganja, and you have an unchecked river of dopamine signaling leading to hallucinations and paranoia (Fernandez-Espejo et al.). 

Why should this cause psychosis long after the marijuana is gone from the system?  I don’t know the answer, but I do know that for Mr D., the way to fix it was to use a dopamine-blocking antipsychotic.  He’s doing well so far, though perhaps a bit wiser and warier. 

family matters

Mrs U first came to my attention some time after the birth of her first child. She was a stately woman, dark and slender, dressed always in brightly colored robes. Her husband brought her to see us because she had stopped speaking. Ever shy, he reported that she'd become gradually more and more taciturn, and at the time of our first meeting she hadn't said a word in several weeks.

At first we were uncertain of the cause. Was she so depressed that she had withdrawn entirely? Did she perhaps have a medical issue, such as insufficient thyroid activity or a vitamin deficiency? Mrs U's thyroid levels, as well as the rest of the blood tests we ran, were entirely normal. We started her on a small amount of an antidepressant, and soon added an antianxiety agent. She started speaking again, though she still had periods of mutism, often when she was stressed or upset.

Around this time, Mrs U and her family took a trip home to Africa, to visit her large and close birth family. They spent several months there. When they returned, Mrs U was a different woman. She smiled pleasantly, laughed at her recollections of her trip, planned eagerly for some classes she intended to take. She remained somewhat shy but the episodes of speechlessness had vanished.
"I could see her getting better by the hour on the plane trip over," Mr U told us. "It was amazing, Doctor. In the airport on this side she seemed anxious, terrified, looking here and there, speaking little. As the hours on the plane passed she began to smile a little. By the time we reached her childhood home she was almost entirely herself again, so that even her own mother could barely notice anything amiss!"

We smiled and nodded, happy to see Mrs U doing so well. She weaned, uneventfully, off her antianxiety medication, though she continued to take the antidepressant. Things remained this way for several months. Then, slowly, she began to deteriorate again.

Her eye contact was the first sign. Though always retiring of manner, when well she met my eyes in conversation, with an occasional frank and open smile. As time passed, though, her eyes began to slide past me even as she answered my questions. They would be fixed on the floor, or out the open window. She maintained our conversation appropriately. Nonetheless she seemed to be elsewhere. I filed that under 'to be kept track of' in my mental cabinet.

Soon after that I began to receive concerned calls from Mrs U's husband. She had begun to say strange things. One day she was convinced that she should leave her husband for a stranger she had seen on the street. Another day she became obsessed with a cartoon she had seen on the television, referring to it over and over. She was unable to keep up with her classes and had to drop them. However, she
always said her mood was fine. She didn't seem anxious or sad in the least, only... strange; and increasingly so. She continued to care for her son ably and with great patience, according to her own word and to her husband's observations. Our original diagnoses of depression and anxiety seemed less and less satisfying.

Ultimately things came to a head when Mrs U began to have frank hallucinations, horrible ones of vermin in her mouth and people under the stairs. That sealed her diagnosis as a psychosis of some form. We started her on an antipsychotic and slowly, things started to improve.

After a couple of weeks of treatment the floodgates opened. Though she'd never before put more than ten words together in my presence, she was fluently talkative. She revealed that she'd been having horrific religiously themed nightmares for a year. Voices of people in her house. A chip implanted in her head. CIA cameras hidden all around her. All very, very classic psychotic symptoms.

I felt silly that I hadn't recognized this before. Mrs A, in her early twenties, was the right age for a first psychotic break. It's very common for schizophrenic patients in the throes of their illness to withdraw completely from the world, unable to give voice to the phantasmagoria in their heads. Easy to recognize after the fact; but since social withdrawal can also reflect depression, anxiety, and other common woes, things are not always clear in the moment.

She did reasonably well on her antipsychotic, though she was still somewhat odd. She would laugh at inappropriate moments and stare vacantly through the window when you talked to her. Her husband was frustrated with our inability to return his wife to her old self. We were frustrated with it as well.

Shortly after starting the antipsychotic, Mrs U took another long trip to her home country. Once again, her symptoms improved. Although she was not able to wean off her medication, she appeared to recover a good deal of her old personality. She was able to interact normally with her family and friends and handled her domestic duties without difficulty. Ultimately her husband decided that his family was best served by staying in their home country. As of this writing Mrs U remains well.

Mental health and mental disease are defined largely by functional capacity. If a person can live, love, and work, we consider him well. But the level of function required for love and work may differ radically from society to society. The 'basic capacities' required to live among secure and supportive extended family, and perhaps do some simple labor under supervision as necessary, are quite different from the 'basic capacities' required to live alone, maintain employment, and manage personal finances complete with lines of credit and other pitfalls.

Schizophrenic patients exist at all levels of functioning, ranging from those who require ongoing institutionalization to extremely high-functioning and high-achieving individuals. The differences among them may be partly due to severity of disease and to innate psychological reserve, but are also strongly dependent on the environment surrounding each.

Over the past six decades, the increasing availability of medication for psychiatric illness, along with factors such as social change and cost concerns, have led to the deinstitutionalization of the mentally ill. In the US, where strong and supportive extended families are not the rule, this has often led to the need for a sort of wraparound care, where a cadre of social workers and psychiatrists helps to guide each patient through the complexities of daily life. In the crudest sense they are functioning as a paid family - much as we in the US have outsourced other former family domains such as child care and elder care. This outsourced domestic work then counts as part of the GDP, and to the economic might of the nation. What isn't clear to me is whether - acknowledging such clear improvements as the reduction in social stigma that attaches to mental illness - such a solution is a gain overall for the mentally ill themselves.

insight into madness

Mr W, a first-break schizophrenic in his twenties, had looked just terrible on initial presentation.  Flat, near-mute, meeting all efforts to initiate discussion with "No comment," or just a hostile wall of blankness.  Gradually the medications began to work their magic and he became more able to relate to others; but he continued to refuse to discuss his symptoms.  He kept it all inside until he'd been on the inpatient unit for over a month.  Then one day, very carefully, judiciously, circumspectly, he allowed: "Well,  I was hearing people talk and relating it all back to me."

The team psychologist ventured softly, Did you ever hear the TV talking to you?

Mr W burst out in surprised laughter, and it all came tumbling out.  He'd kept it to himself for at least a year.  Said it felt like being underwater, where he would be convinced the people on TV were talking about him; then by dint of effort he would pull himself briefly above the waterline - no that's not true that's crazy -  and then be swallowed once again.

He'd gone traveling through Asia for six months, thinking he could leave behind the stress and deconditioning that, he reasoned, must have been the cause of this - this oddness.  But he found that people on the streets, speaking in languages he did not know, were talking about him.  He was utterly certain of this, though he could not understand their speech.  He had several brief relationships with other travelers, women; but they all ended because, well, "Things got weird." 

He recalled talking with the interviewer when he'd first come in, when he would only say "No comment."  He remembered her eyes looked enormous and he was afraid, certain that if he spoke he would come to some vague and terrible harm.

Delusions - fixed false beliefs, characteristic of psychotic states - call up a whole slew of questions related to knowledge.  We know that we know; but how do we know?  (For an interesting discussion of this question, check out Robert Burton's website and his recent book.)

Mr W was madly curious, he wanted to know everything - and what's a neurotransmitter? and are there other ones besides dopamine? and what part of the brain? and how does it all work?  

All good questions, and ones for which the answers are far from clear.  He was fascinated, scared, but also relieved to know this had a name, that others had suffered from it, that he was not alone in this bizarreness.

It is an incredible treat to speak with schizophrenic patients who have such clear insight into their disease.  Many of the patients we see are old and broken from long years in and out of hospitals and many trials of different drugs, both prescribed and recreational.  Even at the best of times, when they are not frankly paranoid or delusional or hallucinating, they typically cannot or will not describe their experience in any kind of meaningful way.   I was fascinated by Mr W, I could have sat and talked with him for hours about his experiences.  I had a similar feeling when I read Elyn Saks' excellent book, The Center Cannot Hold.  It offers a rare and precious chance to hear an eloquent and clear-minded individual recall the alternate reality of psychosis.

it could happen to you

Mr G, a gentleman in his sixties with an engaging manner and a professional degree, had never set foot in a psychiatric unit until today.  Bald and avuncular, with a rich white beard and a mischievous wink, he had a bit of a drinking problem and some deep-buried scars from his time in Vietnam.  But nothing else really, none of the 'meat' of inpatient psychiatry (schizophrenia, schizoaffective, bipolar disorder) that we spend our time handling.

Someone somewhere thought two antidepressants and some Antabuse would be good for him.  In a week or two he had changed his personality entirely, wandered into moving traffic, threatened the police who came to the scene, and attempted to seduce the psychiatry resident who admitted him - nothing anyone who knew him could have believed.  Indeed his family members called daily, frantic for understanding, unable to comprehend how their loved one had been replaced by a stranger.  In short, he had had a manic and psychotic episode.

But what is 'psychotic,' other than a term used loosely by the ignorant to describe the behavior of those who irritate them?  Psychosis is a mental state characterized by the impairment of reality testing.  Any society typically has a consensus about what is 'real' and what isn't.  (Judgements about this may differ between societies, but that's a different treatise.)  People suffering from psychosis have fallen off this bandwagon and have very different ideas about what is 'real' from the man on the street.  But there's a method to the madness: psychosis typically involves several specific, bizarre modes of thought. Auditory hallucinations (usually voices), delusions (fixed false beliefs), and paranoia (the pervasive and unshakable feeling that unknowable dangers lurk) are hallmarks of the syndrome.  Though each patient is unique, themes quickly emerge, and anyone who has spent more than a week or two on an inpatient psychiatric unit will begin to recognize the patterns.

Psychosis, clearly, is not a torture reserved for the unlucky few born to its ravages, like cystic fibrosis or a Thalidomide deformity.  I suspect it may be an alternative mode of function that lies buried in each of us, more deeply for some than for others.  It can be precipitated in otherwise mentally healthy people by pregnancy, medical illness, or - as in Mr G's case - merely the wrong combination of medications.  An unlucky few have the problem of chronic or recurrent psychosis.  This is the disease schizophrenia, a disorder with its peak onset in the normally promising and productive years of early adulthood.

Some are doubtless more susceptible than others; as with every human trait, psychotic tendencies lie along a continuum.  Mr G had always been a bit up-and-down in his moods, and while another person might have been able to tolerate the double-antidepressant regimen, for Mr G it magnified his normal highs and lows into an off-the-charts manic spike that came, as extreme mood disorders sometimes can, with the booster benefit of psychotic symptoms.

But what is this psychosis then, what is it for?  Why does its potential lie buried somewhere in so many of us?  What purpose does it serve?  Some have argued that it is a byproduct of the development of social complexity in the human brain  (see for example, Burns JK).

Unfortunately, this particular argument (and related ones) suffer from a lack of specificity and a paucity of evidence.  They certainly sound reasonable; but the logic boils down to this: Schizophrenia is a complex behavioral disorder - social and creative endeavors require complex processing and behavior - schizophrenics have difficulty with social functioning - ergo, these modules are related.

I don't doubt that schizophrenia (and psychosis more generally) are related to social functioning, given how important social functioning is to humans - almost everything we think or do is related to social functioning, broadly defined.  But that makes the hypothesis that 'schizophrenia is related to social functioning' so broad as to be useless. 

Another line of reasoning jumps off the intriguing finding that artistic inclinations and schizophrenia are often found in the same families (see Horrobin DF), and posits that schizophrenia is merely the other face of the coin of creativity.   This one is slightly more specific (creativity being less of a blanket term than 'social function') and can claim at least some circumstantial evidence to its credit.  

Dr Horrobin also does a nice job of suggesting a biochemical basis, though I am in general skeptical of papers that claim to pinpoint individual biochemical factors or pathways as causative of psychiatric diseases.  Psychiatric illnesses are complex states of the person as a whole, and doubtless they affect and are affected by many, many biochemical pathways (most of which, as we are discovering, interact with each other anyway).  Generally I'd say that trying to pinpoint a single gene, factor, or pathway in the pathogenesis of psychiatric disease is sort of like blaming global warming on a carbon dioxide spike in Juneau in the summer of 1998.  Sure, they're related; but there are a bunch of other factors involved, and who knows which way the causal arrow goes anyway.

In any case, those optimistic scientists who have persisted in trying to pinpoint single specific causes of psychiatric diseases are indeed finding out that the problem is significantly larger than one might have guessed back in the flushed and heady days of the one-disease-one-gene school of thought (Iwamoto and Kato).

I don't doubt that we'll make some interesting progress on this problem once as we develop better tools to manage and investigate complexity in biology.  The ever-growing computational power that's available to us makes it feasible to look at complex interactions in a way that was impossible twenty years ago.  It's going to be an interesting next couple of decades.

truth to power

The unspoken derives its power from its very mystery.  To make explicit is to deprive of power. The psychotic patient knows this, perhaps better than we.  Psychotic patients often seem in touch with a deeper, animal reason.

Mr. B. behaved like nothing so much as a cornered animal in the locked psychiatric unit.  Behind closed doors, he admitted his demons to his worried mother, who relayed them to us; but to the doctors he was close-lipped and angry, hiding with insults his fear at what had happened to him.

His threatening, hostile stare fairly made the air vibrate in the room... yet the moment the attending asked of him, frankly and without guile, "Why are you staring at me?" the spell collapsed, deprived of all its power.

"I'm not staring at you," was his only, weak recourse.

But it was nothing so simple as her bare words that disarmed him.  I pictured the same patient on a gritty street corner, leveling his rapier gaze at a fellow thug.  The same phrase spoken in an equally hostile tone by a burly, puff-jacketed swaggart would have but escalated the situation.  It is the opt-out, the calm inquiry, the untroubled curiosity, that undercuts the threat.

Good therapists wield this tool with skill and precision.  They refuse to play the game, choosing rather to analyze it.  All of us, as humans, have some understanding of this complex social game.  We approach and retreat, feint and parry, dance an endless dance of human relations - all without a word, a world of interactions parallel to but separate from our explicit verbal exchanges.

People who play the game well become leaders, extracting what they wish from others while retaining their loyalty and affection.  People who have a shallow or incomplete understanding of it become recluses, frustrated at every turn by interactions that go awry.

But whether they play it well or poorly, in the normal course of human behavior the game is never made explicit.  To make it explicit is to undermine it entirely.  The therapist does this in a controlled manner, slicing the game out of its skin and dissecting it apart, displaying its innards openly to his patient's wonder and, perhaps, dismay.