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Psilocybin causes a functional dissociation between attention and working memory tasks
O. Carter1,3, D. Burr2, J. Pettigrew1, & F. Vollenweider3.
1 Vision touch and Hearing Research Centre, School of Biomedical Sciences, University of Queensland, Australia 2 Instotitp di Neuroscienze del CNR, Pisa, Italy
3 Heffter Research Centre, Department of Clinical Research, Psychiatric University Hospital Zurich, Switzerland
Attention & Working memory
Project Aims
Subjective effects
r 2 = 0.01
It is an advantage to be able to selectively direct & maintain r 2 = 0.93
To explore the role of serotonin (5-HT) in
attention while ignoring those events or objects deemed to be
5D-ASC self-rating scale (Dittrich 1998).
less relevant. Multiple object tracking is a task that measures
attention & working memory in normal and
less relevant. Multiple object tracking is a task that meas
sustained attention on a selected subset of targets amongst “psychosis-like” human states.
distractors (Pylyshyn & Storm, 1988).
To tease out the relative contribution of the
Working memory is a form of short-term memory enabling the
Psilo + Ket
storage & manipulation of information over short time periods Ketanserin
receptor in any observed effects.
(Baddeley, 1986). Attention & working memory are believed to be mutually dependent processes, subserved by similar regions of the frontal cortex (Courtney et al 1998; Culham et al 2001).
Psychosis - A number of clinical conditions (i.e. attention deficit
Serotonin (5-HT) - Serotonergic
disorder, autism, obsessive compulsive disorder & - Psilocybin produced subjective changes in conscious state.
schizophrenia) are associated with abnormalities in attention and - Ketanserin blocked most effects, except those relevant to Spatial working memory span
neurons originate in the Raphe nucleus in the brainstem. From here, working memory. Future drug development depends on a
- Individual data provides further evidence of a functional comprehensive understanding of the pharmacology underlying AMYGDALA
dissociation with psilocybin having greater effect on attentional & cortical areas (preferentially into Multiple object tracking
= p < 0.05
Multiple object tracking
(rostral & dorsal)
- 20 randomly moving dots - subjects track subset of 2-8 target dots • Hallucinogenic doses of the 5-H
psilocybin impair multiple object tracking but
involved in arousal (sleep/wake cycles), not spatial working memory.
cognition & is also implicated in clinical correct response
Pre-treatment with the selective 5-HT2A
antagonist Ketanserin did not reduce this
These findings suggest that it may be
Spatial working memory
Number of target dots
possible to tease apart the relationship
- Subjects have to reproduce a sequence of 2 - 9 spatial locations between attention and working memory.
- Psilocybin reduced attentional tracking performance.
- Ketanserin pretreatment did not block this effect.
Suggests involvement of the 5-HT
in attention/arousal.
Psilocybin Is found in hallucinogenic psilocybe mushrooms.
Psilocin, the active metabolite of psilocybin, is an agonist at 5– Spatial working memory
receptors & has a similar chemical structure to serotonin.
Psilo + Ket
Future Directions
HT1A/2A receptors & has a similar chemical structure to serotonin.
• Confirm the speculated involvement of the 5-HT ( Cortical activity)
Experimental design
• Investigate influence of impaired attention vs increased 8 Healthy human subjects - 4 conditions: placebo; psilocybin responses
g/kg); ketanserin 50mg/kg); psilocybin + ketanserin.
(215 µg/kg); ketanserin (50mg/kg); psilocybin + ketans References
Ketanserine/ Psilocybin/
Baddeley, A. (1986) Working memory. Oxford University Press. Oxford, UK.
Courtney, S., Petit, L., Maisog, J., Ungerleider, L. & Haxby, J frontal cortex. Science, 279, 1347-13 iser, N. (2001) Attention response functions: characterizing brain areas using ( 5-HT release)
during parametric variations of attentional load. Neuron, 32, 737-745.
Dittrich, A. (1998) The standardized psychometric assessment of altered states of consciousness (ASCs) in humans. Pharmacopsychiatry, 31 Suppl 2, 80-84.
- Psilocybin alone (& in combination with ketanserin) had no Attention &
Pylyshyn, Z. & Storm, R. (1988) Tracking multiple independent targets: evidence for a parallel tracking mechanism. Ketanserin - A selective antagonist at the 5-HT receptor.
Working Memory
effect on the total number of boxes remembered or the number ** Note: More detailed account of this work will be published at: Ca Psychometric
ip between attention, working memory and the Serotonin1A&2A receptors. J Cog Neuroscience.


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