Monday, August 9, 2010

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.