This placebo-controlled, cross-over, fMRI study (n=10) found that an injection of psilocybin (2mg) increased ratings of memory vividness and visual imagery. This may imply that autobiographical memories can be better accessed during psychedelic-assisted psychotherapy.

Abstract

“Background: Psilocybin is a classic psychedelic drug that has a history of use in psychotherapy. One of the rationales for its use was that it aids emotional insight by lowering psychological defences.

Aims: To test the hypothesis that psilocybin facilitates access to personal memories and emotions by comparing subjective and neural responses to positive autobiographical memories under psilocybin and placebo.

Method: Ten healthy participants received two functional magnetic resonance imaging scans (2mg intravenous psilocybin v. intravenous saline), separated by approximately 7 days, during which they viewed two different sets of 15 positive autobiographical memory cues. Participants viewed each cue for 6 s and then closed their eyes for 16 s and imagined re-experiencing the event. Activations during this recollection period were compared with an equivalent period of eyes-closed rest. We split the recollection period into an early phase (first 8 s) and a late phase (last 8 s) for analysis.

Results: Robust activations to the memories were seen in limbic and striatal regions in the early phase and the medial prefrontal cortex in the late phase in both conditions (P<0.001, whole brain cluster correction), but there were additional visual and other sensory cortical activations in the late phase under psilocybin that were absent under placebo. Ratings of memory vividness and visual imagery were significantly higher after psilocybin (P<0.05) and there was a significant positive correlation between vividness and subjective wellbeing at follow-up (P<0.01).

Conclusions: Evidence that psilocybin enhances autobiographical recollection implies that it may be useful in psychotherapy either as a tool to facilitate the recall of salient memories or to reverse negative cognitive biases.”

Authors: Robin L. Carhart-Harris, Robert Leech, Tim M. Williams, David Erritzoe, N. Abbasi, T. Bargiotas, P. Hobden, D. J. Sharp, John Evans, Amanda Feilding, Richard G. Wise & David J. Nutt

Summary

Psychedelic drugs were used extensively in psychotherapy in the 1950s to lower psychological defences and facilitate emotional insight. Some individuals reported spontaneous autobiographical recollections under psychedelics, and we observed large decreases in resting state activity in the medial prefrontal cortex after psilocybin.

The present study used psilocybin to test the hypothesis that psychedelic drugs facilitate autobiographical recollection. It found that psilocybin increased activations in the medial temporal and visual association regions.

This study was approved by a local research ethics committee and conducted in accordance with good clinical practice guidelines.

Participants

Fifteen healthy individuals were recruited via word of mouth. Nine were male, all were physically and mentally healthy, and had used psilocybin before, but not within 6 weeks of the use in psychotherapy.

Participants underwent fMRI scans with 2 mg of psilocybin intravenous vs. saline, and imagined re-experiencing 15 positive autobiographical memory cues. Psilocybin increased activation in the medial prefrontal cortex and the striatal regions in the early phase and late phase, respectively.

Participants were asked to remember specific life events, and were advised to encrypt especially personal memories so that they could only be understood by themselves. They were then randomly assigned to either the psilocybin or placebo condition, and were scan for magnetic resonance compatibility. We obtained a structural SPGR scan on a 3 T GE HD6MR system, and then obtained blood oxygen level-dependent fMRI data.

A gradient echo-planar imaging sequence was used to acquire 53 oblique-axial slices. Sixty-second manual infusions of either psilocybin or placebo began 6 min after the start of the resting-state scan, and the behavioural scan began 7.5 min after the start of the infusion.

Functional paradigm

Participants were presented with fifteen memory cues interleaved with rest and an auditory attention task. They were instructed to close their eyes and to open them when cued by a loud auditory tone played eyes-closed recollection. In the rest trials, individuals were first presented with a tone and visual instruction to relax, then a memory cue, then an attention task. The attention task consisted of a sequence of auditory tones of different pitch playing in either ear in a random order.

Participants were asked to rate their memories on a scale of 0-10 for vividness, emotional intensity, valence and visual imagery. They were followed up 2 weeks after their scans to assess any changes in their subjective well-being or life satisfaction.

Imaging analysis

All imaging analysis was carried out using FSL. A general linear model with four regressors was fitted to each participant, and two regressors were used for the 16 s memory recollection period – one for the first 8 s after the memory cue (early phase) and one for the remaining 8 – 16 s (late phase).

Brain activation under psilocybin was compared with activation under placebo. Regional BOLD changes were compared with subjective ratings, and anatomical regions of interest were created based on the Harvard – Oxford probabilistic atlas.

Under psilocybin, ratings of vivid and visual were significantly higher than under placebo.

During recollection, activations were seen in limbic/medial temporal lobe, striatal, mid-cingulate cortex, pre-sensorimotor area and precuneus regions, as well as the medial prefrontal cortex and frontal pole. There was a trend-level positive correlation between ’emotion’ scores and late phase bilateral parahippocampal activations.

There were significantly greater late phase activations under psilocybin than placebo, and these were found in three large clusters, including the left occipital pole and visual association region, mid-insula, primary and secondary auditory cortex, and superior parietal regions.

We looked at the first-level results for both conditions and calculated the mean percentage BOLD signal change to memories v. rest in the three above-mentioned clusters. We found that the left and right hemisphere clusters were deactivated under placebo, but true activations were found under psilocybin.

Follow-up ratings of well-being

When data from the complete sample were analysed, reports of well-being 2 weeks after each scan were significantly higher after psilocybin than placebo. Participants with the most pronounced subjective responses to positive memories had the largest increases in well-being after psilocybin.

This study used fMRI to test the hypothesis that psychedelics facilitate autobiographical memory by activating the neural processes underlying autobiographical recollection. Psilocybin caused greater late phase sensory activations and more intense subjective effects than placebo.

Previous studies have found that psilocybin augments the neural processes underlying autobiographical recollection, and the greater visual activations in the late recollection phase, when visual imagery becomes more pronounced, support this hypothesis.

Subjective experiences

Participants commented that they had a different kind of recollective experience after their second scan (placebo) than after their first scan (psilocybin). They said that they had used their imagination more this time, but the experience was still nice.

None of the participants reported dramatic relivings, and no medial temporal lobe activations were found, despite some compelling reasons to expect this. Wilder Penfield demonstrated that electrical stimulation of the temporal cortex could produce vivid recollections and reliving, and that stimulation of the medial temporal lobes could generate complex visual imagery. We failed to find an exaggerated medial temporal lobe response under psilocybin, which may explain the absence of relivings. However, we could explore this issue further with connectivity analyses, and we might find evidence for a decreased medial temporal lobe inhibition.

In order to minimise negative drug responses, we used only positive memory cues in this study. However, despite these limitations, the primary hypothesis that psilocybin augments subjective and neural responses to positive autobiographical memory cues was supported and the experience was well tolerated by all participants.

Psilocybin increases activity in the prefrontal cortex, which may contribute to the positive effects observed in participants. Psilocybin may also be used as a treatment for depression, as evidenced by decreased depression scores in patients with anxiety 6 months after a single high dose.

The self-selecting nature of the sample may have biased outcomes, but the increased brain activations to memories after psilocybin cannot be explained by prior assumptions about the positive value of these drugs.

Autobiographical memory cues were more vivid and visual under psilocybin, and a potential neurobiological mechanism is proposed: decreased medial prefrontal cortex activity leading to disinhibited limbic and sensory activity.

Sandison RA, Halgren E, Walter RD, Cherlow DG, Crandall PH, Hagenaars MA, van Minnen KA, Hoogduin KA, et al. found that the hippocampus formation and amygdala are involved in memory for fear extinction. Psilocybin, a hallucinogen, induces co-activation of the amygdala, hippocampus, and inferior frontal gyrus during autobiographical memory retrieval. A default mode of brain function, a world of the unconscious, is described, as well as enhanced imagery following ayahuasca ingestion, and belief and recollection of autobiographical memories in veterans with and without combat-related posttraumatic stress disorder.

A study of psilocybin treatment in advanced-stage cancer patients found that the hallucinogen led to increases in the personality domain of openness. The study also found that the subcallosal cingulate gyrus was involved in the experience of vivid memories.