By Mary Carpenter
PROMISES offered by mind-changing drugs—from relief of depression, anxiety and symptoms of OCD and PTSD, to a vastly improved sense of the self and the universe—have been burgeoning since the early 2000s. At that point, reputable scientists and research institutions restarted research on these drugs that had been on hold since the 1970s. This summer, the Netflix series How to Change Your Mind, based on Michael Pollan’s 2018 hugely bestselling book of the same name, highlighted the drugs’ immense potential.
In psychedelic therapy, psilocybin (known as magic mushrooms) and ketamine are “leading the way,” according to Field Trip Health, which runs ketamine-assisted therapy clinics. While the two compounds overlap in their effects and fall under the umbrella term psychedelics, psilocybin belongs in the category of hallucinogens while ketamine originated as a dissociative anesthesia drug.
The most recent Forbes weekly Innovation Rx email featured news items on both. First, to “advance its ketamine-based treatment for depression,” the biotech startup Freedom Biosciences received $10.5 million; and next, psilocybin combined with psychotherapy, “helps drastically curb alcohol addiction,” according to research at NYU. In the NYU trial that involved 93 participants who struggled with excessive drinking, by the end of eight months, half of those who received psilocybin had stopped drinking compared with about one-fourth of those who received a placebo.
“This is a watershed moment… a time for a lot of hope,” said Rachel Yehuda, mental health director at the Bronx Veterans Affairs Medical Center. Several trials of psychedelic substances now underway from the Department of Veterans Affairs became possible after the FDA’s recent designation of psilocybin and MDMA (Ecstasy) as “breakthrough therapies” for the treatment of PTSD and depression.
What convinced long-time psychedelics researcher Roland Griffiths, now at Johns Hopkins, was the data. In the Netflix series, Griffiths refers to the Mystical Experience Questionnaire —repeatedly validated by research—that assesses individual psychedelic experiences based on 30 questions addressing positive mood, sacredness and “experience of unity with ultimate reality.”
Johns Hopkins researchers have recently documented brain changes by comparing MRI scans from individuals after they had taken psilocybin to those after taking a placebo. With psilocybin, the scans showed decreased activity in the brain region called the claustrum, believed by some to be the “seat of consciousness.” According to the researchers, turning down activity in the claustrum “ties in with what people report…feelings of being connected to everything and reduced senses of self or ego.”
Despite increasing research showing the mental health benefits of psychedelic drugs, obstacles—both financial and legal — continue to impede their use. In addition, long-term therapy with ketamine can cause tolerance and urinary tract infections; and psilocybin “trip” experiences can be unpleasant.
Psilocybin is an illegal Schedule 1 drug, defined as having a high risk of abuse and no “currently accepted medical use.” As a result, taking psilocybin requires either locating and then qualifying for one of the rare research studies —or buying the drug illegally and, for some, seeking out sometimes-costly therapeutic trip support.
Although Oregon has legalized psilocybin and a few cities like Denver have reduced the legal consequences of possessing the drug, prospects for national legalization are dim: Drug companies have little motivation to support a chemical that can be found naturally in the wild and can require as little as one dose for successful treatment.
Ketamine, the only legally available psychedelic, has been in use since the 1960s for surgical anesthesia and has provided dramatic relief from both depression and anxiety in a matter of days—compared to weeks for traditional medications. “The most important breakthrough in antidepressant treatment in decades” is how Thomas Insel, past director of the National Institute of Mental Health, referred to ketamine.
But ketamine can be costly—with clinics around the country offering infusion sessions lasting about three hours for between $350 to $1,000 each, and most people return for additional doses several weeks or months apart. In addition, a STAT news investigation into hundreds of ketamine clinics found wide-ranging inconsistencies, with some having no mental-health professionals to check patients at each infusion.
Nasal spray delivery of the related esketamine, approved in 2019 by the FDA, makes the drug more accessible for some patients—although guidelines require use “under the supervision of a health care provider in a certified doctor’s office or clinic.” Despite some complaints about getting the dosage right, the spray can help prolong the period between infusions and offers the possibility of microdosing several times a day as needed.
The two drugs, psilocybin and ketamine, operate on different receptors in the brain— but both appear to enhance the ability of neurons to interact with each other by releasing neurotransmitters, while mood disorders can impair this ability. Psilocybin affects serotonin receptors, which alter mood and happiness; ketamine works on different brain receptors important for learning and memory. But both kinds of receptors are located in the brain’s prefrontal cortex which, UCDavis chemistry professor David Olson told the New York Times, “talks to a whole bunch of brain regions that regulate things like mood, emotion, fear, reward.”
Great variation exists in different people’s responses to both of these compounds— not unlike the way symptoms of mental health conditions may present differently, as well as the way individuals respond differently to drugs that treat anxiety and depression. In one study, psilocybin was similarly effective for treating depression as the antidepressant Lexapro—but some people didn’t respond to either drug. Of the estimated one-third of people with a mental health condition like depression who do not respond to psychedelic treatment, differences may be due to genetic variations in the serotonin receptors.
Responding in part to questions raised by the Netflix series, Michael Pollan and others at the Berkeley Center for the Science of Psychedelics have collected resources on a new website, which covers topics such as psychedelics and spirituality, risk and microdosing. The site also proposes questions, for example, how to choose a psychedelic therapist?
I am curious about these drugs—especially psilocybin, mostly because I have no disabling mental health problem that could justify paying for regular ketamine infusions. I have found organizations around the U.S. that offer “guided psychedelic trips”— Psychedelic Passage, for example, provides “trip sitters” for up to six individuals at a time. But I can’t imagine trusting an unfamiliar guide other than in a research institution study. For now, my curiosity is on hold although I anticipate changes in the world of psychedelics—possibly in the near future.
—Mary Carpenter regularly reports on need-to-know topics in health and medicine.