Researchers at the University of Michigan have discovered that specific psychedelic substances enhance the brain’s capacity to adapt and learn new concepts flexibly over extended durations.
This type of cognitive adaptability is often compromised in various psychiatric and neurological disorders.
“Psychedelic substances are currently being evaluated in active clinical trials aimed at treating depression and PTSD,” stated Omar Ahmed, associate professor of psychology at U-M and principal author of the recently published research.
“These disorders, along with Alzheimer’s disease, frequently come with diminished cognitive adaptability. Our findings suggest that a single psychedelic dose can enhance flexible learning for several weeks in mice, emphasizing the potential of these substances to induce enduring and functionally significant alterations in the brain.”
The research team found that one administration of the psychedelic substance 25CN-NBOH enabled mice to think more flexibly and perform superiorly on behavioral assessments even weeks after receiving the drug.
This study, featured in the journal Psychedelics, illustrates the potential for clinical trials of psychedelic medications to assist individuals suffering from depression or PTSD.
“Current clinical trial designs for depression typically involve only one or two doses,” noted Elizabeth Brouns, a U-M psychology master’s candidate and the study’s lead author. “Our findings indicate, in mouse models, that even a single dose of a psychedelic can yield lasting benefits. We examined flexible learning up to three weeks following the sole dose and observed enhancements. The advantages might persist even longer.”
While this investigation used rodent subjects, the outcomes are likely to be relevant for humans.
“The nervous system of mice serves as an exceptional model to comprehend the workings of psychedelic drugs. Neurons in the prefrontal cortex of both mice and humans express serotonin 2a receptors, the primary target for psychedelic substances. These serotonin 2a receptors are believed to underlie the therapeutic effects of psychedelic treatments,” explained study co-author Tyler Ekins, a postdoctoral fellow in psychology at U-M.
The experiments involved administering mice with either the psychedelic substance or a control placebo injection. The mice engaged with an automated training tool known as the FED3, which rewarded them with food pellets for correctly poking their noses into designated holes in a specified order.
Once the mice mastered recalling this sequence over several days, the task’s rules were abruptly reversed, necessitating the mice to learn to visit the holes in the reverse order. Both male and female mice administered the psychedelic learned this new rule more rapidly than the control group, even three weeks following the initial psychedelic dose.
This automated task framework, created by the research team, represents a progression in how scientists investigate flexible learning over prolonged periods. It was designed to facilitate the assessment of cognitive adaptability and opens avenues for more effective and precise research into the impact of psychedelic substances on the brain, as noted by the researchers, requiring minimal human intervention.
Despite these findings, Ahmed cautions that numerous questions still exist. The field of psychedelic medicine remains nascent but advancing rapidly, he remarked.
“A considerable amount of foundational scientific and translational research is required to ensure that clinical trials implement the most effective versions and dosages of psychedelic drugs,” Ahmed stated.
For instance, the current study concentrated on the long-term impacts of a solitary psychedelic dose. An essential inquiry is what occurs with two, three, or even 20 doses taken over several months. Is each successive dosage increasingly advantageous for flexible learning, or is there a cap on effectiveness, or even adverse effects from excessive dosing? These pivotal questions must be addressed next in the effort to make psychedelic medicine more systematic and mechanistic, he said.