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. Psilocybin
distractors (Pylyshyn & Storm, 1988). Psilocybin
• 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. 1A&2A
(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). Introduction 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. THALAMUS
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
dissociation with psilocybin having greater effect on attentional
& cortical areas (preferentially into
Multiple object tracking = p < 0.05 HIPPOCAMPUS Multiple object tracking RAPHE NUCLEUS CEREBELLAR (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
• Pre-treatment with the selective 5-HT2A antagonist Ketanserin did not reduce this deficit.
• 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 receptor in attention/arousal. Psilocybin Is found in hallucinogenic psilocybe mushrooms.
Psilocin, the active metabolite of psilocybin, is an agonist at 5–
Spatial working memory Psilocybin
receptors & has a similar chemical structure to serotonin. Psilo + Ket Future Directions
HT1A/2A receptors & has a similar chemical structure to serotonin. Ketanserin
• 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
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
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
ip between attention, working memory and the
Serotonin1A&2A receptors. J Cog Neuroscience.
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