Imaging Study Reveals a Neurobiological Basis for the Potential Therapeutic Effect of Psilocybin
Authors and Disclosures
March 16, 2012 - Healthy adults recall memories much more vividly while under the influence of the hallucinogen psilocybin, and functional magnetic resonance imaging (fMRI) data reveal a neurobiological basis for this effect.
The study "may have implications for the use of psilocybin in psychotherapy," Robin Carhart-Harris, PhD, from the Neuropsychopharmacology Unit at Imperial College London in the United Kingdom, and colleagues say. "For example, psilocybin could be combined with positive memory cues as a treatment for depression - facilitating the recall of positive life events so to reverse pessimistic mind-sets," they suggest.
Psilocybin is a classic psychedelic drug pharmacologically related to lysergic acid diethylamide (LSD) and is the active ingredient in so-called "magic mushrooms." Psychedelic drugs were widely used in psychotherapy in the 1950s in the belief that they lower psychological defenses to facilitate access to salient emotions and memories.
The results of the current study, which is published in the March issue of the British Journal of Psychiatry, "provide initial support for this idea" and point to a potential neurobiological mechanism - decreased medial prefrontal cortex activity leading to disinhibited limbic and sensory activity.
More Vivid Memories
In a prior psilocybin fMRI study, reported by Medscape Medical News, the investigators observed decreased brain blood flow and venous oxygenation in the cingulate cortex and the medial prefrontal cortex after intravenous injections of psilocybin. One study participant reported a "striking reliving" under the drug, which motivated the investigators to test this phenomenon in a placebo-controlled crossover study.
The current study included 10 healthy adults (mean age, 31 years) who had used psilocybin before but not within 6 weeks before the study. Over at least 2 weeks, they provided the study team with at least 30 personal memories of specific life events that were especially positive and emotionally salient. The personal memories were divided into groups of 15.
Study participants underwent 2 fMRI scanning sessions separated by about 1 week. Participants were given either 2 mg intravenous psilocybin or saline. During the scans, they were given a visual memory cue for each of the memories and asked to close their eyes and imagine re-experiencing the event. Activations on fMRI during the memory task were compared with an initial scan taken when the participant was in a task-free resting state.
According to the investigators, the study participants rated their memories as significantly more vivid, visual, emotional, and positive under psilocybin than under placebo (P = .0003 when all 4 parameters were combined), and there was "a significant correlation" between vividness and subjective well-being at follow-up (P < .01).
On fMRI, "robust activations" to the memories were seen in limbic and striatal regions of the brain as well as the medial prefrontal cortex during both psilocybin and placebo conditions. However, there were additional visual and other sensory cortical activations under psilocybin that were absent under placebo, which may explain why recollections were rated as more vivid and visual under psilocybin, the investigators note.
They point out that a potential limitation of the study is that participants were required to have used psychedelics in the past, and many held prior assumptions about the positive effects of these drugs.
This may have contributed to the positive memory ratings and the reports of improved well-being on psilocybin. "Importantly, however, such biases cannot easily explain the increased brain activations to memories after psilocybin," Dr. Carhart-Harris and colleagues point out.
Commenting on the study for Medscape Medical News, Katherine MacLean, PhD, of the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine in Baltimore, Maryland, who has also studied psilocybin but was not involved in the current research, said the investigators took "a novel approach to characterizing the effects of psilocybin."
"There's quite a bit of anecdotal evidence...to support the idea that psilocybin helps people access vivid memories as well as vivid emotional experiences - both familiar and novel. But this is the first time that such effects have been quantified."
Dr. Carhart-Harris and colleagues propose that psilocybin "may be used in combination with cognitive strategies designed to reverse cognitive biases in depression." They further suggest that the hallucinogen "may be used in more classic dynamic therapy to assist the exploration and understanding of salient emotional themes."
Support for this line of thinking comes from a recent pilot study published in Archives of General Psychiatry in September 2010 and reported by Medscape Medical News at that time. In 12 patients with advanced-stage cancer, researchers found that a single experience with psilocybin was associated with a significant reduction in anxiety at 1 and 3 months after treatment and an improvement in mood that reached significance at 6 months.
In a study published last September in the Journal of Psychopharmacology, Dr. MacLean and colleagues noted improvements in well-being and the trait of openness persisting in healthy volunteers up to 2 years after a single high-dose of psilocybin (MacLean et al., J Psychopharmacol, 2011;25:1143-1161).
"One notable strength of the [current] finding is that it suggests direct, testable hypotheses for future studies in depression. In other words, you can characterize more than 'what happens to come up' during sessions and, instead, directly test whether specific memories are experienced more vividly," said Dr. MacLean.
She added it would also be interesting to test whether psilocybin changes the vividness or emotional tone of negative memories.
"In other words, is psilocybin turning up the gain on all memories and emotions or is it specifically enhancing positive memories? This kind of approach would help elucidate the effects of serotonin in the brain, as psilocybin is a fairly selective serotonin 5-HT2 [5-hydroxytryptamine-2] agonist," she said.
The study was supported by the Beckley Foundation, the Neuropsychoanalysis Foundation, the Multidisciplinary Association for Psychedelic Studies (MAPS), and the Hefter Research Institute. The authors and Dr. MacLean have disclosed no relevant financial relationships.
Br J Psychiatry. 2012;200:238-244. Abstract