Early one night in the fall of 1987, a college freshman ate half of a microdot of lysergic acid diethylamide on his way to a party. He was young, but more than a little familiar with mind-altering chemicals: LSD, mescaline, psilocybin, and other, less common psychedelics. This trip, by comparison, turned out to be only a "mild experience." The tingling euphoria, splendid visuals, and sudden bursts of insight mostly wore off by the time he retired to his dorm. But the following morning, some effects still remained.
"I opened my eyes to see what time it was," he said, on the condition of anonymity. "As I looked away, I immediately realized that the light from the digital clock was streaking." Throughout the day, other signatures of the hallucinogen high struck him. When he shifted his gaze from a page he was reading, a ghostly afterimage of the text materialized in the air, hanging legibly for a few moments. When he turned a page, a long cascading series of replicas trailed behind, like a stroboscopic photograph.
The streaking and trailing and after-imaging persisted for days. He began to panic. "I really lost it," he said. "I was sitting in one of my first college classes and, like, hallucinating." He met with psychologists, who could discern little. He called his parents, who could discern less. He became unhinged, wandering campus in a daze, squinting at the world as if through a kaleidoscope. "I broke down," he said. "I could no longer go to class. I couldn't do anything." He quit school, moved back home, and entered rehab. His search for a diagnosis came up empty: no underlying medical condition, nor had the drug been laced with something sinister. Weeks, months, then years went by. The trip just wouldn't end.
Psychedelic lore is littered with cautionary tales. But it remains to be seen whether reports of hallucinogen persisting perception disorder—quite literally, the persistence of hallucinogen-induced perceptions—should count among them. Hallucinogens are enjoying something of a revival: the drugs are being tried recreationally by nearly one in five American adults(approaching that of the nineteen-sixties), while being tested empirically for their powers to heal alcoholism and other addictions, anxieties from impending death, P.T.S.D., major depression, and even cluster headaches. Reading too much into H.P.P.D., some say, could squelch the renewed intrigue—even though, to some extent, the risk factors, causes, and effective treatments remain a mystery. Others, though, suspect that unraveling this mysterious disorder could reveal clues for the more familiar ones. According to Dr. Henry Abraham, a lecturer in psychiatry at Tufts University School of Medicine who privately sees patients with substance-related disorders, neurophysiological shifts observed in H.P.P.D. patients "may yield useful models for anxiety, depression, psychosis, and even addiction."
A chronic and debilitating condition, H.P.P.D. warps the perceptual faculties: the external senses are marred by a constellation of mostly visual distortions, while the internal ones are paralyzed by a concoction of dissociative symptoms, panic attacks, and depression. The doors of perception are not so much cleansed, as Aldous Huxley famously found after his first experience on mescaline, as they are cracked open and left askew.
H.P.P.D. does not generate hallucinations, technically speaking. Sufferers can appreciate that their perceptual aberrations are unreal—that their surroundings only appear blurred by afterimages (palinopsia) and trails (akinetopsia); shimmered by sparkles and flashed by bright bolts of light; interrupted by transparent blobs of color floating around; electrified by visual snow; magnified or shrunk by "Alice-in-Wonderland" symptoms; adorned by halos around objects, around people's heads. The pseudo-hallucinations are ultimately unconvincing, if deeply unsettling.
Eventually, a sense of permanent unreality casts a pall over the acid-fuelled dreamscape, and sufferers disassociate—from the world, due to derealization, and from themselves, due to depersonalization. At a recent Society of Biological Psychiatry conference, Dr. Abraham presented findings, later published in the S.B.P. 2012 supplement, that suggest up to sixty-five per cent of H.P.P.D patients chronically endure panic attacks, and fifty per cent, major depression. Some patients feel their only relief is suicide.
The cluster of symptoms first appeared in the Diagnostic and Statistical Manual of Mental Disorders in 1986. Ever since, the official diagnosis has been lumped together with "flashbacks." Brief fragments of a trip that occasionally bubble up to one's consciousness, flashbacks may arise from sudden spikes in the cerebral cortex—stirring perceptions, sensations, or emotions mimicking those of the hallucinogen high, in the absence of any chemical. But as the term has been popularized, flashback has been rendered "virtually useless" diagnostically, writes Dr. John Halpern, an assistant professor of psychiatry at Harvard Medical School and lead author of the most recent literature review of H.P.P.D. In the review, published in Drug and Alcohol Dependence, Dr. Halpern reasons that by conflating two distinct diagnoses, a strict definition of H.P.P.D. has remained elusive, leaving its prevalence obscured. Yet, "it seems inescapable," he concludes, based on twenty related studies dating back to 1966, "that at least some individuals who have used LSD, in particular, experience persistent perceptual abnormalities reminiscent of acute intoxication, not better attributable to another medical or psychiatric condition."
Peer-reviewed accounts of drug users whose world had been transfigured permanently can be found as early as 1983, prefiguring the initial D.S.M. entry. In a case-control study of a hundred and twenty-three LSD users, Abraham was among the first to catalogue reports from those who flashed psychedelic and never turned off: a struggling shoe salesman whose dark-brown pairs bled into the navy-blues; a confused student whose text jumbled into "alphabet soup"; a distracted office worker whose flower pot slid back and forth along the windowsill. "This isn't flashbacks," said Abraham. "We have to call it what it is: a persisting perception disorder."
Preliminary estimates of the prevalence of H.P.P.D. dismissed the disorder as an outlier, implicating as few as one in fifty thousand hallucinogen users. The most recent large-scale survey, questioning nearly twenty-five hundred users, found that over one in twenty-five were considering treatment for H.P.P.D.-like symptoms. But because participants, recruited from the popular drug information Web site Erowid, did not represent the average dabbler, and because only a small portion of them had actively sought medical care, the tally remains somewhat inconclusive. "Unfortunately," writes Halpern, assessing the scant literature, "the data do not permit us to estimate, even crudely, the prevalence of 'strict' H.P.P.D."
If "strict" cases of H.P.P.D. turn up only rarely in scientific journals, though, at HPPDonline.com, a Web forum tracking research developments and connecting sufferers, nearly nine thousand monthly visitors give some indication of what lies beyond the academic purview. They report burning and throbbing and numbing and tingling. They claim that surfaces undulate ("breathing walls"), objects vanish ("they mix with the floor"), and beams of light splinter into shards of extended rays ("star-bursting"). They share encounters that seem inexplicable—"fluids flowing down from my left temple," "a chemical aftertaste"—and plead for the group's insight. They raise suspicions: "Every time I walk past a certain type of tree the leaves begin to shake." They despair: "I hear my brain."
And they may be making their symptoms worse. While H.P.P.D. sufferers do misperceive their environment, some researchers suspect that severe anxiety—perhaps an underlying condition—aggravates those misperceptions. As noted by Matthew Baggott, a postdoctoral fellow in psychiatric genetics at University of Chicago, fMRI studies generally show close links between the attention and visual systems.
Such observations have raised doubt over whether hallucinogens are the root cause of the disorder, and even whether H.P.P.D. is a bona-fide diagnosis. "The more you focus on the condition, the more it spirals out of control," said Halpern. "So sufferers must practice letting go, which most Americans tend to struggle with." In one study of five hundred Native American Church members, each of whom had taken peyote hundreds, even thousands of times, no H.P.P.D.-like symptoms were reported. "Our culture is still evolving to deal with what it means to be intoxicated by these substances," Halpern reasons. "H.P.P.D. may be an incomplete description of the syndrome."
But if H.P.P.D. is to some extent self-perpetuated—perhaps by a naïve culture, perhaps by anxiety-prone individuals—it is not self-induced. Running a battery of standard neurological tests on dozens of H.P.P.D. patients throughout the nineteen-eighties and early nineties, Abraham and co-authors Dr. Frank Hopkins Duffy, a neurologist, and Ernst Wolf, a neuroscientist, found evidence suggesting the flow of impulses through the central nervous system has been chronically altered. When a light is flipped on, the brain still registers darkness for a while; when a light flickers, it registers a steady beam; when an array of colors is presented, it confuses those in proximity. Jennifer Groh, a professor of psychology and neuroscience and the director of the Neural Basis of Perception Lab at Duke University, has extensively investigated the visual-processing system. While she has not studied H.P.P.D. specifically, Groh has found that the brain is generally unable to distinguish stimuli according to their source; even a single stimulus, artificially induced over and over, is treated as genuine and novel. The so-called staircase-of-eye-movements effect, Groh reasons, would predict some of the symptoms—at least the trailing, after-imaging, and poor darkness adaptation—observed in H.P.P.D. patients. "Their brain may not recognize the stimuli as simply the same repeated request," she says.
Consistent with Groh's findings, Abraham offers his own account of why H.P.P.D. causes sensory input to linger within neural circuitry, firing even after the stimulus is gone. "What we have proven through psychophysics, electrophysiology, and quantitative analysis," said Abraham, "is that when the brain of an H.P.P.D. person is stimulated by some perceptual force in the environment, mostly visual, the stimulus is disinhibited." Objects of perception, in other words, are not readily disengaged, breaking up an ordinarily seamless flow of conscious experience. If the brain is like a paintbrush, then H.P.P.D. appears to make the bristles sticky, and the old stimuli—colors, shapes, and motions—muddy the new.
Frank Durgin, a professor of psychology and the director of the Perception and Cognition Lab at Swarthmore College, affirmed that Abraham's theory holds promise. "The disinhibition hypothesis is pretty safe as a generic account," said Durgin. "There is a lot of inhibition involved in normal perception. Failure to distinguish and inhibit noise signals is a reasonable first guess about a variety of hallucinogenic effects." The theory seems to be consistent with the current science of perception, according to Irving Biederman, a professor of neuroscience and the director of the Image Understanding Laboratory at the University of Southern California. A healthy brain, Biederman explained, is bathed in inhibitory neurotransmitters—gamma-aminobutyric acid, primarily—in order to mute mild perceptual noise (like visual distortions), and ultimately to safeguard against full-blown cacophony (like seizures). H.P.P.D. patients, he offered, might have "done something structurally to those interneurons, causing perceptual noise to exceed the threshold." (According to some scientists, most psychoactive drugs, including psychiatric medications, can alter the brain's neural structure.) While neither Durgin nor Biederman study such rare perceptual disorders as H.P.P.D., their expertise is illustrative: the symptoms of H.P.P.D. are just the kind of perceptions ordinarily present in the brain, only occluded—or inhibited—from consciousness.
What is least known about H.P.P.D. is treatment. "Unfortunately," Halpern writes, "the literature on this point remains largely anecdotal." Options are limited: palliative care from more drugs (benzodiazepines and anti-epileptics), adjustment through psychotherapy (of the cognitive-behavioral or straight-talking variety), a pair of sunglasses. While the college freshman, now middle-aged, is celebrated by his psychiatrist as "the poster child for healthy adaptation to the disorder," healthy adaptation is no cure.
One day several years ago, he was taking a draw from a cigarette after work when he noticed, for the second time, a sudden shift in his vision. He had finally gotten his life on track—securing a degree, starting a family, building a career—and had managed to bury his past. He occasionally struggled to read fine print, especially late at night, and became disoriented by lane markings, especially on an overcast day. ("And when I smelled pot, I ran for the hills," he said.) But if his inner life was disfigured, few—not even his wife—could tell. Until, he recalls, "something clicked."
What happened next was a blur. "The visuals got ramped up, like somebody raised the volume," he says. "I was sent back immediately into panic mode, going through the emotional roller-coaster ride that I did back in college." Tremors of panic that had been stamped out were swiftly rekindled. "I fell off the grid for a week," he says. He began fearing, perhaps as many others with mental illness do, that the spectre of madness can be raised without warning, that "you may never make it out."
http://www.newyorker.com/online/blogs/elements/2013/05/a-trip-that-lasts-forever.html
