A Really Good Day

by Ayelet Waldman

  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 well-being.

  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.”

  Was he actually saying that microdosing was either as safe as or perhaps even safer than conventional antidepressants? I asked him, incredulous.

  “Oh, absolutely.”

  I am a rationalist who likes firm and clear explanations, and I was so excited to think I might have found one. Neuroplasticity! BDNF! Glutamate! Synapses and neurons and all sorts of things measurable by fMRI machines! But the brain does not give up its secrets so easily. For the time being, and perhaps forever, I’m going to have to accept not knowing exactly what is going on in my brain. As difficult as that is, I was comforted when Presti reiterated what I had learned, that psychedelics are not physically harmful to the body for most people, even at massive doses. He told me that he has absolute confidence in the safety of my project. It is, at least in the view of that one particular neurobiologist, perfectly safe. I tucked that thought away for the next time I felt like I was having a heart attack in the dead of night.

  * * *

  *1  Robin L. Carhart-Harris et al., “Psilocybin with Psychological Support for Treatment-resistant Depression: An Open-label Feasibility Study.”

  *2  See American College of Neuropsychopharmacology, “Active Ingredient in Magic Mushrooms Reduces Anxiety, Depression in Cancer Patients.”

  *3  See https://clusterbusters.org/.

  *4  R. A. Sewell, J. H. Halpern, and H. G. Pope, Jr., “Response of Cluster Headache to Psilocybin and LSD”; Matthew W. Johnson et al., “Pilot Study of the 5-HT2AR Agonist Psilocybin in the Treatment of Tobacco Addiction.”

  *5  R. L. Carhart-Harris et al., “The Paradoxical Psychological Effects of Lysergic Acid Diethylamide (LSD).”

  *6  Enzo Tagliazucchi et al., “Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution.”

  Day 6

  Normal Day

  Physical Sensations: None.

  Mood: Excellent.

  Conflict: None.

  Sleep: Woke up in the middle of t
he night, but fell back to sleep eventually.

  Work: The words took some time to flow.

  Pain: More or less the same as before I started the protocol.

  Feeling good will make a woman do strange things; today I called my father. The call with my mother a couple of days ago went so well I figured, hey, you’re already experimenting with illegal hallucinogens; why not do something really wild?

  When I talk to my father, it is less of a conversation than a monologue, or a series of mini-lectures. Kind of like attending a one-man TED conference at the Hebrew Home for the Aged. Today’s topics were, as ever, “Soviet History: The Stalin Era,” “Zionism and Trotskyist Theory,” and “Lincoln vs. McClellan: Whose Fault?” Or something like that. I admit I might have zoned out a few times during the call. What made today so unusual was that, instead of quickly losing patience and inventing an excuse to get off the phone, I hung in there. I stayed on the line. I heard the animation and even delight in my father’s voice as he gave me a detailed digest of his most recent haul from the Fort Lee Public Library. This is how he makes himself happy, I realized. Anyway, what did you expect? You call a telephone psychic, you get artful guesses and vague insights. Call Daddy and you get the Second Battle of Bull Run.

  My father and I have always had a difficult relationship, but now, when I look back, I realize that it is my own expectations—my ideas about the father I need, the father I wish I had—that have been the source of the longing, disappointment, frustration, and ultimately anger that have characterized my feelings about my father for so long.

  The futility of my expectations was made comically clear to me a couple of years ago, after my father somewhat mysteriously handed me a stack of microcassettes. They were recordings of his psychotherapy sessions, made during the early eighties with a New York City psychologist named Albert Ellis. I didn’t know what to make of this odd gift, what message they might contain, what he was trying to tell me by giving them to me. For a long time I didn’t listen to the tapes; I was too annoyed. You want to tell me something? I would imagine saying to him. Try talking! But sometimes I could not help wondering about what might be recorded on those microcassettes. All the feelings he had never expressed. His feelings about himself, his marriage. His feelings about managing his bipolar disorder. Most of all, his feelings about me. Maybe on those tapes I might hear the voice of a man who thought and wondered and cared about his daughter. The voice of the father I had always wished for, had always hoped, against hope, might be hiding in there, under there, somewhere.

  Finally, at the urging of a friend, I sat down and listened to the tapes—six hours, representing two months of sessions with one of the most prominent psychologists of the day. So what did they talk about, my dad and the great Dr. Ellis? His feelings, worries, and cares? The people he loved? The personal and professional ramifications of his mood disorder?

  Nope.

  What they talked about, in great detail, was the history of communism, class struggle, and the kibbutz movement. They never got around to Abraham Lincoln.

  When I was little, I used to wish my father could be more like Shimon.

  Shimon is an old friend of my parents. He lives in Israel—where I was born. He and his wife have two daughters, on whom he dotes. Even before my conscious memory of him begins, there are stories in my family of the particular affection Shimon showed for me, and of how eagerly I looked forward to seeing him. Shimon is expressive, warm, even effusive. I could always feel, from the time I was a little girl, how much he enjoyed my company. The last time I saw him, a couple of years ago, he remembered having visited our apartment in Jerusalem when I was a toddler. He said that I brought a little chair into the living room, sat down in front of him, and regaled him with my firm opinions on all manner of subjects. He no longer recalled what I had said, but he did remember how much he’d enjoyed listening to me. I have no memory of that particular moment, of course, but I have the clearest sense memory of Shimon’s dry kiss on my cheek, of the warmth of his big hand, missing the tip of one finger, enfolding my little one. We moved from Israel back to Montreal before my third birthday, and after that I saw Shimon only rarely, but whenever I did, I would feel a rush of excitement, as if something that had gone missing a long time ago was about to be returned to me.

  In my mind Shimon was always old, though he can’t have been more than forty-two or -three the first time I sat on his lap. On that last visit, in 2014, he was ancient, but his eyes still sparkled with pleasure when I walked in his front door. He cracked walnuts for me with his trembling yet still-strong hand, placing the nut meat in my palm just like he did when I was seven years old. I am a middle-aged woman, and I had not seen Shimon for more than twenty years. As I sat there eating the nuts he cracked for me, I felt beloved.

  How many other Shimons have there been over the years, older men whose company and attention I have eagerly sought, who listened when I set my (little) chair down in front of them? My high school English teacher Mr. Bennett. Derrick Bell, my constitutional law professor. John Cillag, a Hungarian gentleman with whom I struck up a conversation in a Budapest museum while researching my novel Love and Treasure; afterward, we corresponded by e-mail, met for coffee, and he was kind enough to read drafts of the book and offer helpful suggestions. A wise and gentle educator named Tom Little, head of Park Day School in Oakland for thirty-eight years before his untimely death in 2014.

  And Dr. James Fadiman.

  After he sent me the memo outlining his protocol, I asked Dr. Fadiman if he’d be willing to talk to me, not really expecting him to agree. I figured he was inundated with e-mails from people like me, people seeking a solution to some problem or a resolution of some pain. But he sent me his telephone number, and one evening, after I’d settled the kids for the night, I called him.

  Fadiman’s voice is deep and avuncular, and when he is smiling you can hear it. We ended up talking for a long time, and not just about the intricacies of microdosing. We talked about my moods and the troubles in my marriage. There was something in Fadiman’s voice and manner that made me feel I could confide in him, ask him for advice, seek and possibly earn his approval.

  A couple of weeks later, at Fadiman’s invitation, I drove down to Palo Alto to attend a lecture he gave on the topic of psychedelic research and mental health. After the talk, I went up to the stage to say hello. I was a little tentative, not wanting to intrude or impose. I didn’t know if he would be as eager to meet me as I was to meet him.

  Fadiman is a youthful seventy-six, hair still mostly brown, with sleepy eyes and a trim brown beard, only lightly threaded with silver. The moment I told him my name, his face lit up with the smile I had heard over the phone, and he gave me a warm, fatherly hug.

  During that long first phone call of ours, in the course of which I had confided more to Fadiman than I’ve confided to my father in my whole life, he asked me why I thought I was drawn to microdosing, what I thought I was looking for. My answer at the time was “the ability to manage my moods and enjoy my life,” but now it seems to me that maybe a more accurate answer might have been: “This.”

  If so, then it’s probably the sad truth that nothing, not even Dr. Hofmann’s magical “problem child,” can give me what I’m looking for. I’ll never have the father I’ve hoped for, wished for, needed all my life. But today, for whatever reason—thanks maybe to Albert Hofmann, or Jim Fadiman—when I called my father and settled in for the usual lecture, I didn’t get impatient. I didn’t get annoyed. I hung in there through the intricacies of the Molotov-Ribbentrop Pact (or maybe it was the Great Purge), thinking, Look, this is the father you got, and he’s the only father you have. Might as well let the man talk.

  Day 7

  Microdose Day

  Physical Sensations: Activated.

  Mood: Giddy.

  Conflict: None.

  Sleep: Slept well.

  Work: Amazing.

  Pain: Didn’t notice any.

  I’m feeling good today, per
haps a little too good. I am happy and cheerful, but my words are tumbling out faster than I can control. This feels a little like hypomania, that energetic state of mind that can be productive and pleasurable, but can also lead to risky, impulsive behavior. Though I’m not experiencing any delightful yet troubling euphoria, I am certainly disinhibited. This afternoon, I found myself telling the physical therapist who was working on my shoulder all about my experiment. I have, since I began taking the microdose, been so circumspect, confiding in only one or two very close friends. Yet here I was, gushing to a virtual stranger about microdosing and how it was making me so productive and happy. Ironically, one of the things about which I waxed poetic was how much less impulsive I’ve been. I have been feeling a certain unfamiliar control, I told her. I’m still getting triggered by the kids, the dog, the husband, the Internet, but for the last couple of days I have felt as though there is a little room around these triggers, space for me to decide how to react, instead of just reacting. But of course there I was, lying on a table, supposed to be breathing deeply and silently, and instead babbling on like a psychedelic twit.