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. 

designer brains for all!

So let me say up front that this is a Rant, one inspired by the fifth young go-getter this week to walk across my threshold demanding I diagnose him with AD(H)D and prescribe him Adderall to get him through his dissertation/term paper/research proposal/whatever.

In my (not so) humble opinion, AD(H)D is not so much a disease (in the sense of a physiologic malfunction) as an unfortunate interaction of personality x environment. Certain personality types just don’t do well with being required to sit in a chair for 8 hours a day. A lot of those same people would probably do phenomenally well at running around outside spearing buffalo, (see Kuo and Taylor), but sadly for them, that’s not the environment in which they find themselves.

So, we have medication that can alter these people’s brains so they conform more acceptably to the society where they do find themselves. We could have another very long and involved discussion about whether that’s a good choice or not but my feeling is, if a pill is the difference between good function and borderline or poor function, then please, weigh the pros and cons and make your own decision. It’s your brain. Not my business to dictate whether you ‘need’ it or not.

What I really don’t like is the cultural apparatus that is telling us the suboptimally attentive have a Disease, because the only legitimate reason to take a drug is if you have a Disease, and therefore that these people who take stimulants so they can function more effectively at work or school must have a Disease, because that is the only socially acceptable way that they can take their medication.

And what I really, really don’t like is that as a physician I am being put in the middle of this. I am being told that the only way these people can have their medication is if I diagnose them with a Disease and prescribe them the medication to Treat it. There’s no box to check that says “This could help you do better than you are doing now, and I don’t mind if you take it, so long as you understand the risks and benefits.” There’s only the Disease box and the No-Disease box. And I can’t give out the drug unless I check the right box.

The thing about treating this Disease with stimulants is that, in the right dosage and formulation, they are going to be performance enhancers for *most people.* How many thousands of students and professional writers have used a jot of speed to get them through that important deadline? I’m currently working in our university’s student health center, where I see a lot of people who are coming to me for stimulants so they can make their already excellent function even better. I honestly do not mind if people want to take brain-altering chemicals to help them write their papers – I’m swigging a bolt of caffeine as I write this post – but I do get a squicky feeling when I’m asked to write a doctor’s note about their ‘disease’ and a prescription so that they can ‘treat’ it.

So in my perfect world there would be public recognition of the wide latitude of uses for psychotropic medications, the terribly broad and nonspecific symptom clusters that constitute what we refer to as psychiatric disease , and the many reasons why people might want to take a drug that improves their ability to get their work done (see interesting perspectives on this from Nature and the Guardian) - even if their current abilities are well within the broad range of normal. Will the public accept the availability of a smorgasbord of designer psychotropics for your business and recreational neuroenhancement needs? Maybe, maybe not. But please, let’s stop putting doctors in the middle by maintaining the fiction of a ‘disease’ for which stimulants are the ‘cure.’

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.

Prozac for the unhappy marriage?

(The characters sketched in this piece are composites of several individuals I’ve encountered in my training and my life. They contain elements of real patients and acquaintances but do not represent strictly true accounts of specific people.)

The couple who walked into my office for a consultation the other week seemed, at first, similar to many of the South Asian immigrants I've met. He, confidently dressed in Western clothing, entered and spoke first. She, slim and even-featured in a brightly colored sari, had a diffident smile and walked a step or two behind her husband.

They'd come, he (and she) said, because she was depressed. She seemed sad, a bit withdrawn, wasn't sleeping well. Could I help?

The husband graciously offered to leave the room so I could talk privately with the patient. She remained vague about her concerns. She reiterated that she felt a bit down, but then said that really she was feeling all right. She admitted to waking frequently at night but then said really she felt well rested enough. She agreed she'd lost some weight, but then volunteered that she'd been about this weight before the birth of her first child so that seemed all right to her. And her marriage? Well, yes, perhaps there were some problems in her marriage. What problems? Oh, nothing. Well, maybe something. Maybe nothing important.

I probed gently, cautiously. The marriage was an arranged one. I nodded, unsurprised. At twenty years of age, this woman had married a man she'd known only a couple of weeks and then followed him to the farthest corner on the globe from her family and his. Since then they'd had two children together, and made a place and a life for themselves in a local community of similar immigrants. On the surface, things were fine.

And beneath that? Well, perhaps their sex life wasn't... what she would wish. She was resolutely vague on this matter, absolutely unwilling to offer up any detail or clarification.

We made no headway until the patient's husband returned and revealed the room's elephant: He was gay. He had had several homosexual encounters with men over the course of the marriage. He understood this was contributing to his wife's pain. He wondered whether I would be willing to help her out. With an antidepressant.

In truth, I was stunned. Evidently the man did not see his homosexuality as any significant barrier to maintaining his marriage. I glanced at the woman. She had turned her face entirely away from both of us and was staring resolutely at the door. Every tendon in her taut pose said I want out of here.

Open homosexuality in India is, frequently, tantamount to social suicide. The term 'gay' is used as an insult, indicating unmanliness or cowardice. Avowed homosexuals are often treated as outcasts from mainstream society. Nonetheless, since the decriminalization there of homosexual intercourse in 2009, gay social scenes have blossomed cautiously in the larger cities. Yet in a nation in which three-quarters of the population lives in rural areas, this is still a drop in the bucket. Indian society is structured around the extended family unit. A single person past the age of marriage generally loses social status and suffers gossip and stigma. Marry one must then, and present one's parents with healthy and studious heirs.

Any wonder, then, that many of India's gay population simply bow to the cultural expectation of marriage? No need to suffer the singles scene; marriage to someone suitable can be arranged swiftly enough to avoid tripping the gaydar of the lucky bride (or groom). If s(he) has any. One can easily be married in India far younger than the age when many gay Westerners discover their own true sexual orientations.

And then what?

Escape to the West offers some slippage of the knot. Far from the watchful eyes of family and neighbors, hairline cracks in the marriage eggshell are not so visible. If one spends a lot of time with male friends, if one's wife seems saddened and distracted, who is to notice really? And if one can grit one's teeth and think of England enough times to produce a male heir, then none will be the wiser.

But with freedom comes peril. Divorce is not so taboo here. In India, a divorcee can expect social opprobrium and little chance of remarriage. The cost associated with leaving an unsuitable husband may thus be far greater than the benefit. (Divorced men have more hope of a second chance.) But in the West, that calculus can be reversed.

What to do with the couple before me? An antidepressant seemed unlikely to improve the situation. The wife had no past history of any mood disorder, and antidepressants don't fix trying life circumstances. Counseling seemed in order, but I wasn't culturally equipped to provide it. What would be the goal? To maintain the marriage? To dissolve it? The husband's wishes seemed clear but I wasn't sure the wife would ever say enough to me for us figure out what it was she wanted.

Ultimately I told them I'd ask my colleagues to see if I could find them a referral to a South Asian psychiatrist who, I felt, might have a better chance of helping them. Neither of them seemed particularly happy with that - after all, there is also a stigma against mental illness among Indians that presents a strong barrier to either consulting a psychiatrist or becoming one. It had probably taken a good deal of courage and need for them to come to me in the first place, and here I was passing the buck to somebody else. I felt sorry for these two people, yoked sadly in an arrangement that fulfilled neither. But the pills and workbooks in my arsenal were not designed for such a situation. What they seemed to need, I thought, was the answer to Reinhold Niebuhr's Serenity Prayer: serenity to accept the things one cannot change, courage to change the things one can, and the wisdom always to know the difference.

(A little note about my extended absence: After a promising start, I let this blog go by the wayside just about a year ago, shortly before I had my first baby. I find being a parent is absolutely fantastic and also supremely absorbing and time-intensive. My daughter is now ten months old and I'm just starting to recover my interest in the world around me. It seems like a good time to revive the blog.)

Now that I spend three days a week at home with my daughter, I'm listening to a lot of talk radio to get my grownup time.

Yesterday morning while supervising the gleeful mashing of banana into hair, I heard a fascinating NPR interview with Barbara Strauch.


She's the science editor for the New York Times who recently wrote a book called "The Secret Life Of The Grownup Brain."

I've yet to read it (though it's now on my list!), but based on the interview Ms Strauch's book is an exploration, not of the decline and fall of the aging brain, but the changes - some for ill but some for good - that come to cognition with middle age. The young brain may be better at rapid calculation and short-term memory, but the aging one seems to be better at recognizing where information fits into existing patterns.

"We are better at getting the gist of arguments," she says. "We are better at recognizing categories. And we're much better at sizing up situations. We're better at things like making financial decisions, which reaches a peak in our 60s. Social expertise -- in other words, judging whether someone's a crook or not a crook, improves and peaks in middle age."

Now this doesn't quite fit with the common perception that the brain just gets mushier and mushier with age. Interviewer Terry Gross was posing questions from the point of view that the brain goes into a smartness free-fall after somewhere around age 25. As evidence, she pointed out that synapses - the electrical connections between nerve cells - decrease in number over time. She assumed this meant a parallel decline in cognitive capacity, as if synapse number were equivalent to 'smartness dose.' More connections mean more braininess, right?

Well, it may be a little more complicated than this.

One might think that you'd gain synapses as you learn things; but actually, the brain has the most synapses at a time when it knows the least. Synapses are overproduced in childhood and then reduced as the brain matures. As you grow and learn, some existing connections are strengthened and new synapses are formed - but more are weakened and pruned away.

J Comp Neurol. 1997 Oct 20;387(2):167-78.
Regional differences in synaptogenesis in human cerebral cortex.
Huttenlocher PR, Dabholkar AS.


This pruning isn't simply the death of brain tissue and reduction in cognitive capacities. It is more like specialization: as a sculptor carves away excess marble to reveal his intended form, so the brain prunes away excess connections to reveal a latticework of meaning. We are still pretty far from understanding exactly how this works, but here is a really nice paper from a few years ago that proposes a model of how changes in the strengths of nerve cell connections might underlie learning:

Fusi, S., Drew, P. and Abbott, L.F. (2005) Cascade Models of Synaptically Stored Memories. Neuron 45:599-611.


So Strauch's thesis, that the middle-aged brain is better at putting things into context, parallels the common understanding that as we gain life experience, we are more able to assimilate new information in terms of the many things we already know. It's called wisdom, and older people in traditional cultures around the world are revered for it. Funny that we should require all the power of modern neuroscience to remind us of this!