Friday, April 16, 2010

DMT is in your head, but it may be too weird for the psychedelic renaissance

By John Horgan

You know that psychedelics are making a comeback when the New York Times says so on page 1. In “Hallucinogens Have Doctors Tuning In,” John Tierney reports on how doctors at schools like Harvard, Johns Hopkins, UCLA and NYU are testing the potential of psilocybin and other hallucinogens for treating depression, obsessive-compulsive disorder, post-traumatic stress disorder, alcoholism—and for inducing spiritual experiences.

Tierney’s brisk overview neglects to mention the most mind-bending of all psychedelics: dimethyltryptamine, or DMT. It was first synthesized by a British chemist in the 1930s, and its psychotropic properties were discovered some 20 years later by the Hungarian-born chemist Stephen Szara, who later became a researcher for the National Institute on Drug Abuse.

Why is DMT so fascinating? For starters, DMT is the only psychedelic known to occur naturally in the human body. In 1972, the Nobel laureate Julius Axelrod of the National Institutes of Health discovered DMT in human brain tissue, leading to speculation that the compound plays a role in psychosis. Research into that possibility—and into psychedelics in general--was abandoned because of the growing backlash against these compounds.

In 1990, however, Rick Strassman, a psychiatrist at the University of New Mexico, obtained permission from federal authorities to inject DMT into human volunteers. Strassman, a Buddhist, suspected that endogenous DMT might contribute to mystical experiences. From 1990 to 1995, he supervised more than 400 DMT sessions involving 60 subjects at the University of New Mexico. Many subjects reported that they dissolved blissfully into a radiant light or sensed the presence of a powerful, god-like being.

On the other hand, 25 subjects underwent what Strassman called “adverse effects,” including terrifying hallucinations of “aliens” that took the shape of robots, insects, or reptiles. Some subjects remained convinced that these aliens were real in spite of Strassman’s efforts to convince them otherwise. In part out of concern about these adverse effects, Strassman discontinued his research, which he describes in his 2000 book DMT: The Spirit Molecule.

DMT is also the primary active ingredient of ayahuasca, a tea that Amazonian tribes brew from two plants and drink as a sacred medicine. After hearing about ayahuasca from the legendary Harvard botanist Richard Shultes, the beat writer William Burroughs traveled to South America and swilled the stuff in 1953. In a letter to the poet Allen Ginsberg, Burroughs said that during his first ayahuasca trip he thought he had been poisoned, and he felt himself turning into half-man-half-woman. Burroughs nonetheless drank the tea again and praised its ability to facilitate “space time travel.”

By the mid-20th century ayahuasca had also been adopted as a sacrament by several urban sects in Brazil. The largest of these is the Uniao Do Vegetal, which combines elements of Christianity with indigenous Indian beliefs. Researchers led by the UCLA psychiatrist Charles Grob (who is mentioned in Tierney’s story) have reported that Brazilian UDV members are on average healthier physiologically and psychologically than a control group. UDV members also claimed that ayahuasca had helped them overcome alcoholism, drug addiction and other self-destructive behaviors. A decade ago, a branch of the UDV based in New Mexico sued for the right to consume ayahuasca legally in the U.S. In 2006 the U.S. Supreme Court ruled in favor of the group.

In Antipodes of the Mind, the Israeli psychologist Benny Shanon, who has consumed ayahuasca more than 100 times, provides a gripping account of his own and others’ visions. Shanon says the tea transformed him from a “devout atheist” into a spiritual believer awestruck by the mysteries of nature and the human mind. Yet Shanon, like Strassman, acknowledges that these hallucinogenic experiences pose risks. Quoting one ayahuasca shaman, Shanon warns that ayahuasca can also be “the worst of liars,” leaving some users gripped by delusions.

I drank ayahuasca a decade ago while researching my book Rational Mysticism . It tastes like stale beer dregs flavored with cigarette butts. After I threw up, I had a cosmic panic attack, in which I was menaced by malevolent, dayglo-hued polyhedra. I have no desire to repeat this experience.

I applaud the psychedelic renaissance, with this caveat: Spiritual texts often emphasize the dangers of mystical experiences, whether generated by drugs, fasting, meditation or other means. That is the theme of an old Talmudic tale in which four rabbis are brought into the presence of God. One becomes a heretic, one goes crazy, one drops dead and one returns home with his faith affirmed.

Thursday, April 1, 2010

Communication Breakdown in Brain Caused by a Gene Defect May Contribute to Schizophrenia

15 years after a gene defect was found to increase the risk of schizophrenia 30-fold, scientists have figured out how it might cause the brain disorder's debilitating symptoms

By Katie Moisse

More than 15 years after a genetic variant was shown to predispose its carriers to schizophrenia, scientists have finally uncovered how the chromosomal abnormality might cause symptoms of the brain disorder. By studying mice with a similar gene defect, the research team from Columbia University Medical Center linked abnormalities in behavior to a faulty connection between the hippocampus and the prefrontal cortex—two brain areas important for learning and memory.

"We know that this genetic deficit predisposes us to schizophrenia, and now we have identified a clear pathophysiological mechanism of how [it] confers this risk…," Maria Karayiorgou, co-author on the study published April 1 in Nature and lead author on the 1994 publication identifying the genetic variant in Brain Research, said in a prepared statement. (Scientific American is part of Nature Publishing Group.)

Thirty percent of people carrying the variant—a small deletion of genetic material on chromosome 22—will go on to develop the schizophrenia, making it "one of largest genetic risk factors" for the disease, according to senior author Joshua Gordon. The odds of someone in the general U.S. population developing the disorder are one in 100, but those odds jump to one in 10 for people with an affected first-degree relative, and one in three for people with a schizophrenic identical twin, highlighting the role of genes in the development of the disease.

People with schizophrenia suffer from a loss of contact with reality, confused thinking, delusions and hallucinations—usually hearing internal voices. Scientists think that no single gene defect causes the disease. Rather, they theorize that several genetic variations passed on haphazardly from one generation to the next are to blame, along with certain environmental factors—making it harder to understand how various neurological processes might be going wrong. But by spotting interrelated behavioral and physiological differences in their mouse model, the Columbia team has implicated communication between brain areas as one such process.

The researchers measured the neural activity between the hippocampus and the prefrontal cortex while normal mice and those with the genetic deletion performed a task—learning and remembering the whereabouts of a food reward on a T-shaped maze. "We found that successful completion of the task in our healthy mice required the two regions of the brain—the hippocampus and the prefrontal cortex—to work together," Gordon said in a prepared statement. "And in our mouse model, the information transfer was less efficient or was unable to take place at all." The experiment even revealed a dose effect—the mice who had the least communication between the hippocampus and the prefrontal cortex turned in the worst performances negotiating the maze.

The researchers are excited to have discovered a possible mechanism linking the genetic variant to the behavioral deficits in schizophrenia. "We now know that one of the consequences of that deletion is to disrupt functional communication between these two brain regions, and we have evidence from the study that the disruption actually has an impact on a cognitive behavior that is disrupted in patients," said Joseph Gogos, the study's other senior author, in a prepared statement. "It is possible that similar abnormalities in functional connectivity may also account for other symptoms of the disease and can be used to better assess treatment response, and, most importantly, to develop new medications."

In addition to its role in the heightened risk for schizophrenia, "the gene deletion also increases the risk for other cognitive and psychiatric disorders," said Dolores Malaspina, a psychiatrist at New York University Langone Medical Center who was not involved in the study. The study is "an important step in illuminating how the deletion may be related to a brain dysfunction that is present in some people with mental illness," she added. "This is important information whether or not any of [the genes involved] turn out to be common causes of schizophrenia in the population."