Cerebrum Winter 2021

y it was one of those most remarkable things they’ve eative insights and improvements in self-identity and mood.”

conjunction with talk therapy—in patients with major depressive disorder. Frederick Barrett , a researcher at the Center for Psychedelics and Consciousness Research, says the study showed an “impressive” positive effect in patients, with more than 70 percent showing a significant response within one month. “The psychedelic experience is very different than what people experience in waking consciousness,” he explains. “But when people have these experiences, especially when it’s supported by psychotherapy, they may see what is behind their depression and confront those things so they can move forward.” Johnson, who also worked on the trial, says he sees psilocybin-assisted therapy as a way to “bring psychology back into psychiatry.” “Everyone is depressed for different reasons,” Johnson says. “And the psychedelic experience can help you get to the heart of your own issues, which when you are guided by a mental health professional, seems to have really strong therapeutic effects.” psychiatry at Columbia University, says that he has concerns that there has not been enough research looking at psychedelics’ safety. There are risks of psychosis in some patients, as well as cardiovascular issues. “I don’t want to throw cold water on this reemergence because we could certainly use more treatments in depression,” he says. “But there are questions we need to answer: What is their comparative pharmacology (how these drugs compare to other psychedelics or antidepressant medications)? What is their duration of action? What happens when you do multiple dosing? What are the long-term effects to the brain? We don’t know yet.” Raison wholeheartedly agrees. With two to three percent of individuals in survey studies reporting worse outcomes after taking psychedelics, the answers to these questions matter, and matter greatly. “The research suggests that there will be a group of people who will not benefit from these agents,” he says. “It’s important we know who they are—who will benefit most and who may actually be harmed from their use—before we start giving it to people who are struggling with their mental health.” As researchers start to consider the potential of psychedelic treatment beyond depression (some suggest it will have beneficial effects for a host of conditions ranging from drug addiction to PTSD to Alzheimer’s disease), these safety issues will become even more important. And, to add to the mix, Joseph Barnby, a psychopharmacologist at King’s College London, also said he has concerns about the lack of active placebo in both current and future clinical trials. “In drug trials, you want to be blinded so neither you nor Despite such promise, many scientists urge caution. Jeffrey Lieberman , chairman of

the study participant knows whether they received the drug, so you are not subject to expectancy effects,” he says. “With psychedelics, you have such a profound shift in the way you experience sensory information, it’s hard to blind people to whether someone has received the drug or not. The effects we see could just be placebo—and, as different trials continue to move forward, that’s something we need to carefully consider.” Microdosing and the Future Psychedelics also have strong reputation as a performance enhancer. Many popular musicians, artists, and tech wunderkinds have stated that microdosing—using small doses to avoid large-scale effects—can promote well-being, creativity, and productivity. Certainly, several survey studies have shown that people who microdose report these kinds of positive effects. But while there may be potential there, Carhart-Harris says that full-scale clinical trials are necessary to see whether results hold up. “There is now a cultural phenomenon around microdosing, particularly in Silicon Valley, but the jury is still out on the evidence,” he says. “There’s been a lot of enthusiastic anecdotal reporting, but the evidence is lacking. Most of what we are seeing in our own lab suggests the effect is driven by positive expectations—it’s a placebo effect. But we need more thorough studies to know.” That work, as well as the work regarding safety, will hopefully come sooner rather than later. With some states considering legalizing or decriminalizing certain psychedelic substances— Oregon recently became the first state to legalize psilocybin— it’s expected that, as with marijuana, recreational use will likely grow. Barrett says while he is enthusiastic about the clinical potential of these drugs, it’s important for people to know they are not a mental health or performance panacea—and there are significant risks to their use. That’s one of the reasons why he is such a proponent of psychedelic-assisted therapy, as opposed to patients taking these sorts of mind-altering drugs on their own. “I don’t think anyone should be going to jail for using these drugs. But that doesn’t mean they don’t have powerful effects— and that people won’t get into trouble using them in unsafe conditions,” he says. “I believe the medicalization of these compounds will truly lead to a lot of people being healed if the larger studies replicate and confirm the clinical findings we have now. But people should proceed with caution.” Seth concurs: “Psychedelics aren’t a magic bullet—and with the boosterism surrounding these drugs at the moment, especially in Silicon Valley, I worry that people might go too far. But, that said, if psychedelics are treated with respect, there is a lot of potential for both basic science and clinical practice. So, there’s a moral, ethical, and scientific obligation to explore these opportunities as far as we can. Let’s follow the evidence and see where it takes us.” l



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