A 32-year-old woman presented for continuation of treatment in May 2021 with a chief complaint of “cognitive dysfunction and severe reduced functionality.” 8 months before her first appointment with one of the authors, the patient was in her usual state of health…She was employed as a senior associate at a high-level accounting firm and had graduated from a prestigious graduate school, both competitive environments in which she excelled. She enjoyed a rich and fulfilling social life with family and friends.
…In the fall of 2020, at the urging of friends, the patient decided to ingest psilocybin mushrooms. She was still consistently taking venlafaxine at the time of ingestion. She had a highly pleasurable experience after ingesting the mushrooms and decided to repeat the experience the following day with friends, all of whom consumed the same amount from the same supply and had uncomplicated drug experiences. The precise amount of psilocybin that she consumed over the 2 days is unclear. Within hours of her first ingestion, she began experiencing symptoms of mania. Hours after the second ingestion, she developed paranoid delusions, which persisted for months.
…As her mania and psychosis resolved, she settled into a severe depression. This next phase of her illness was primarily characterized by a total lack of feeling. She fulfilled diagnostic criteria for major depressive disorder on the basis of symptoms including severely depressed mood, anhedonia, insomnia, decreased concentration and appetite, fatigue, feelings of worthlessness, and suicidal ideation. Nothing in life carried any valence, positive or negative. All emotions—happiness, sadness, passion, disappointment—became foreign. Particularly notable was her total lack of connection with her previously beloved dog, whom she had raised as a puppy. She stopped socializing and was barely able to participate in work. She had no desire to be with friends or family, since she was not able to enjoy interpersonal interactions—another major change from her life prior to taking psilocybin. Routine tasks, like running errands and doing basic self-care, became nearly impossible. Her mood range was “zero”, with no variation in how she felt throughout the day. She also complained bitterly of cognitive dysfunction, including a profound inability to concentrate. She indicated that the only reason she had not been terminated from her position in the accounting firm was that these events had transpired during the COVID-19 pandemic.
…She was treated with multiple psychopharmacological agents, including lamotrigine, lurasidone, bupropion, venlafaxine, quetiapine, mixed amphetamine salts, lorazepam, zolpidem, eszopiclone, and trazodone, as well as melatonin, magnesium, and oxytocin. She completed several full courses of transcranial magnetic stimulation, using various configurations and multiple machines at a major academic medical center. She also went to holistic doctors and tried various dietary interventions, hypnotherapy, cannabidiol, nicotinamide adenine dinucleotide (NAD⁺) infusions, dialectical behavioral therapy, acceptance and commitment therapy, trauma-informed therapy, reiki healing, and spiritual guidance. Despite adequate trials of these interventions, none had any important beneficial effects.
During the depressive phase of her illness, the patient was referred for treatment with one of the authors. At her first evaluation, she indicated that she had spoken to several other professionals, who found her case “unique and intriguing, albeit too complex for them to resolve on their own.” On her second contact, she stated that she had almost lost hope after so many consultations, which had “wiped out [her] savings.” She reiterated the total failure of several interventions for which many clinicians had described her as “the perfect candidate.”
She declared that life would not be worth living if she remained unable to feel emotions or function at work. By this time, she had developed pervasive but passive suicidality related to the meaninglessness that her state of unfeeling induced.
…After 2 months, during which she titrated up to the relatively high dosage of 4.5 mg/day of pramipexole, she reported a substantial shift in her functioning. She started to feel emotions again, and began to perform basic errands and self-care. She was eventually able to change residences and participate in basic social functions. She developed motivation to see friends, and went on a date (although she still felt unable to emotionally connect with new people). Her suicidality diminished substantially, becoming only an infrequent disturbance, which she said was far less distressing.