This morning, when I managed, despite feeling irritable, not to blow up at anyone, I began to believe that, though it’s obviously too early to tell, it’s at least possible that my hopes will be realized. The question, or at least one of them, is how.
I turned to a psychopharmacologist to find out what is going on in my brain when I consume the microdose. He told me that LSD is an agonist, a stimulator, of the 5-HT2A serotonin receptor. Antidepressants also act on 5-HT receptors, including 5-HT2A, but they work by inhibiting the reuptake of serotonin, causing it to remain in synapses longer. Because serotonin is one of the neurotransmitters thought to be most closely linked with feelings of wellbeing and happiness, the theory behind SSRIs is that having serotonin sit around longer, with your synapses marinating in it, makes you feel better. By contrast, when a psychedelic drug stimulates 5-HT2A receptors, that leads to the stimulation of brain-derived neurotrophic factor (BDNF), which my psychopharmacologist friend described as “like Miracle-Gro for your brain. It stimulates growth, connections, and activity.” A psychiatric researcher described the neurological effects of LSD to me this way: “By activating the 5-HT2A receptor, you increase the transmission of glutamate.” Glutamate is the neurotransmitter most responsible for brain functions like cognition, learning, and memory. Though they’re talking about two different substances in the brain, the two doctors are essentially saying the same thing. BDNF and glutamate are interrelated. Psychedelics enhance neuroplasticity, the ability of the brain to grow and change, by increasing the level of BDNF in the brain and by increasing glutamate activity.
Can this enhanced neuroplasticity, this stimulated growth and connectivity, be what’s causing me to be less impulsive? Rather than slowing me down, can it be making me more reflective and thus better able to control my anger? Can that be what’s making me feel better? Two Swiss researchers at the Neuropsychopharmacology and Brain Imaging Research Unit at the University Hospital of Psychiatry in Zürich published a paper in 2010 that suggests that this is possible. In “The Neurobiology of Psychedelic Drugs: Implications for the Treatment of Mood Disorders,” Franz X. Vollenweider and Michael Kometer reviewed forty years of LSD, psilocybin, and ketamine research in the context of “modern concepts of the neurobiology of psychiatric disorders.” They concluded that psychedelics may well be useful in treating mood disorders, depression, OCD, and anxiety. A British feasibility study published in the Lancet in the spring of 2016 found that psilocybin not only reduced depressive symptoms but also anxiety and anhedonia.*1
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.”