A Really Good Day(16)

What we call hallucinogens or psychedelics are three different kinds of chemicals. Two are plant-derived: psilocybin and mescaline (which occurs in a number of cactus varieties, including peyote). The other is LSD and other derivatives of ergot. These three types of chemicals act on the brain in the same way, and thus can be grouped together. All three produce their hallucinogenic effects by stimulating 5-HT2A. This stimulation leads to “a robust, glutamate-dependent increase in the activity of pyramidal neurons, preferentially those in layer V of the prefrontal cortex.” The “stimulation of the postsynaptic 5-HT2A receptors on a subpopulation of pyramidal cells in the deep layers of the PFC leads to an increase in glutamatergic recurrent network activity.” For those of you for whom, like me, all that neurological stuff reads like a lecture by Charlie Brown’s teacher, Miss Othmar (“wah wah waaaah waah wah”), let’s just go with Miracle-Gro for the brain.

Hallucinogens increase the interaction between serotonin, BDNF, and glutamate, which can result in people’s developing a new perspective on things, including their own problems. Treatment with psychedelics reduces anxiety and improves the mood of patients facing death, as researchers at Johns Hopkins, UCLA, and NYU have recently shown. All three institutions have been or are currently engaged in psilocybin studies on volunteers with end-stage cancer, with astonishing results.*2 Patients dosed with psilocybin in a pleasant environment accompanied by two researchers providing comfort and support underwent spiritual experiences that didn’t just make them feel better, but transformed the way they thought about their illnesses, and allowed them to confront death without fear. It gave many of them the “good death” we all hope for. Other recent research with psilocybin has shown that it relieves cluster headaches,*3 and aids in the cessation of smoking.*4

Incidentally, when I asked a few people with firsthand knowledge why current researchers choose to use psilocybin rather than LSD in their studies, they told me that the sheer quantity of LSD research that was carried out in the middle of the last century would have actually made it a more logical substance to test—there was so much good data out there, it didn’t really make sense to start from scratch—but LSD simply has too much political baggage. Its reputation, though unearned, is terrible, and most researchers have made a calculation that federal approval would be less likely for studies that proposed dosing subjects with LSD. Psilocybin is relatively unknown; moreover, it’s a naturally occurring substance, which makes people more comfortable with it. Also, the effects of psilocybin last approximately six hours, not the ten or so of an LSD trip. Even psychiatric researchers want to make it home for dinner.

Among the only researchers currently using LSD in a therapeutic context is Peter Gasser, a Swiss psychiatrist who trained in the therapeutic use of psychedelics in the late 1980s and early ’90s, when such research was sanctioned in Switzerland. His work, ongoing, uses doses of two hundred micrograms of LSD as a tool of psychotherapy. He, like the psilocybin researchers, has seen notable results in increased wellbeing.

In a study at the Imperial College in London,*5 researchers discovered that a single dose of LSD “produced robust psychological effects; including heightened mood but also high scores on the PSI, an index of psychosis-like symptoms. Increased optimism and trait openness were observed 2 weeks after LSD and there were no changes in delusional thinking.” They concluded that, although psychedelics like LSD produce disturbing psychosis-like symptoms during the period of intoxication, in the long term they “leave a residue of ‘loosened cognition’…that is conducive to improved psychological wellbeing.”

Another recent study, using fMRI machines to track the brain’s response to LSD in healthy volunteers, found that the drug creates a kind of hyper-connectivity in the brain, allowing unrelated and usually discrete regions to communicate with one another.*6 It also appears to affect the default mode network (DMN), a network of regions in the brain active during wakeful rest or daydreaming. The DMN is involved in a variety of things, including self-reflection and remembering the past and imagining the future. LSD, at least in a dose large enough to make you trip, causes your DMN to become disorganized, which leads to ego dissolution, the sense that you are one with the world.

Basically, stimulating serotonin receptors loosens you up cognitively, which makes you happier.

Flush with my newfound understanding of neuroplasticity and neurobiology, I posed a simple question to Dr. David Presti, a professor of neurobiology in the department of molecular and cell biology at UC Berkeley and the author of the textbook Foundational Concepts in Neuroscience: A Brain-Mind Odyssey. “Is the small amount of LSD I’m taking making my brain more neuroplastic, and is that why I’m less irritable?”

Presti, an expert in the neurochemistry of drugs, said, “Sure, we can say these chemicals bind to serotonin 2A receptors and they activate glutamate circuits and they induce nerve growth factors, but we really just don’t have a clue how all that connects with what is happening in the psyche.”

Deflated, I sighed. But he reached out an encouraging hand. The important thing, he told me, is not necessarily what is going on inside my brain, but that I feel better. Presti believes in a more “globally integrated” theory of the brain than some of the other neuroscientists I consulted. He’s far more interested in experience and anecdote, in what I’m feeling, than in attaching a specific receptor to my mood. He was very encouraging about my experiment, far more than my friend the psychopharmacologist who, while curious, was clearly made anxious by the prospect of someone consuming without supervision a substance that has not been professionally tested. Presti said, “I really think there’s something going on with microdosing. I think when people do get around to researching it, it’s going to be relatively easy to demonstrate positive effects that are better than conventional antidepressants, which are awful.” About antidepressants Presti said, “They have all kinds of side effects, and we have no idea, really, what they’re doing. They cost a lot of money and they’re marketed with all kinds of flimflam.”