Cannabis modulation of the link between dopamine and creativity

An aspect of cannabis intoxication that is frequently mentioned by users is
enhanced creative thought. Self-reports indicate openness to contradictory
ideas and spontaneous insights during intoxication (Tart, 1971). However, the
impact of delta-9-tetrahydrocannabinol (THC) on creativity has not yet been
investigated, apart from one study that identified potential acute effects on
divergent and convergent thinking tasks (Weckowicz et al., 1975). Additionally,
no data can be found on the chronic impact of THC on performance on creativity
tasks. The issue of creativity has lately been linked to dopaminergic
functioning (Akbari Chermahini, & Hommel, 2010a). Given this finding, apart
from investigating the impact of THC on creativity itself, it is currently
possible to gain insight into how THC modulates the reciprocal relationship
between dopamine (DA) and creativity, both directly, as well as in the
long-term. Measures of creativity can be used to indirectly investigate the
effect of THC on dopaminergic functioning, which has been shown in a recent
study by Akbari Chermahini and Hommel (2010a).
The above-mentioned study established a direct link between individual DA level
and performance on divergent and convergent thinking creativity tasks.
Particularly, it has been shown that individual spontaneous eye blink rate
(EBR) predicted performance on these tasks. EBR is a clinical marker of
striatal DA production (Karson, 1983; Shukla, 1985; Taylor et al., 1999). The
relation between EBR and performance followed an inverted-U function for
divergent thinking, pointing to best performance with a medium DA level.
Convergent thinking followed a more linear relationship indicating best
performance with the lowest DA level. In the light of such evidence, it is
possible that a potential detrimental long-term effect of THC on striatal DA
level could also be observed in regard to performance on the two creativity
tasks.
It needs to be mentioned that EBR provides only a basic, subcortical measure of
dopaminergic functioning (Akbari Chermahini, & Hommel, 2010a). Although
performance on creativity tasks can also be treated as an indirect indicator of
DA level, better discrimination between the different dopaminergic pathways is
required. Measures of performance on various cognitive tasks can be considered
as indirect assessments of DA level in different regions of the brain. For
instance, an aspect that has been linked to deregulation of subcortical DA
level is inhibitory control. Particularly, too high or too low striatal DA has
been shown to impair the ability to inhibit a response in the Stop-signal task
(Colzato, van den Wildenberg, van der Does, & Hommel, 2010). Additionally,
task-switching performance has been shown to be a reliable indicator of
cognitive flexibility, which is also related to DA level in the striatum
(Colzato et al., 2010). Therefore, tasks which evaluate inhibitory control and
cognitive flexibility need to be applied in combination with EBR measures, in
order to give a better understanding of the impact of THC on dopaminergic
functioning.
Another cognitive function related to DA transmission is performance
monitoring. Performance monitoring describes the process of ensuring that the
results of an action are consistent with the goal. A neural indicator
associated with this process is the error-related negativity (ERN), a negative
event-related potential (ERP) generated in the anterior cingulate cortex. The
ERN can be observed when human participants commit errors in a variety of
psychological tasks (Holroyd, & Coles, 2002). Holroyd and Coles (2002)
suggested that the ERN signal is transmitted to the anterior cingulate cortex
by means of the mesencephalic DA system. It has also been shown that chronic
cannabis use impairs the process of performance monitoring (Hester, Nestor, &
Garavan, 2009). Therefore, it can be assumed that there is a long-term effect
of THC on the mesencephalic DA pathway. However, there is no data about the
acute effects of THC on performance monitoring. Due to the fact that cognitive
impairments of chronic users seem to diminish after administration of THC
(Kelleher, Stough, Sergejew, & Rolfe, 2004), it might be expected that
intoxicated users will demonstrate improved performance monitoring, as compared
to non-intoxicated ones. In any case, inclusion of performance monitoring to
the study might provide data on the direct effect of THC on the mesencephalic
DA pathway, as well as on the impact of the drug on this particular cognitive
function.

Primary objective
Does administration of THC produce an increase in subcortical dopamine level of
chronic cannabis users? Does this effect on dopamine modulate the link between
spontaneous eye blink rate, performance on divergent and convergent thinking
tasks and mood outlined by Chermahini and Hommel (2010a, 2010b)?

Secondary objectives
Does administration of THC to chronic cannabis users affect performance
monitoring during a flanker task, as indicated by the ERN component?
Does administration of THC to chronic cannabis users affect performance on the
Stop-signal and Global-local processing tasks?

We will employ a randomized, double-blind, between-subjects design. Each
participant will take part in one laboratory session during which they will
undergo two eye blink rate and four mood measurements. Each subject will also
be required to complete divergent and convergent thinking, Stop-signal and
Global-local processing tasks. An ERP recording during a flanker task will
additionally be applied. Two-third of participants will be administered THC,
one-third will be administered placebo. Three different dosages of THC will be
used: 2 and 8 mg. Neither the subjects nor the investigator conducting the
experiment will know which dosage is administered. The study will last 120
minutes.

Participants will inhale vapor obtained from medical grade Cannabis sativa
(Bedrocan) or placebo from a non-transparent polythene bag using a mouthpiece
with a valve, which prevents loss of THC between inhalations. Subjects will be
required to completely inhale the contents of the bag. Vapor will be produced
using the Volcano® vaporizer. Dosages of 2 and 8 mg of THC will be used.

There is a variety of potential effects of cannabis reported. These include
changed mood, insomnia, palpitations, relaxation, laughter, hunger, greater
sensitivity to sensations of color and music, a disturbed time-space experience
and lethargy. Also at higher doses a subjective *high* feeling can occur, which
is a state of mild euphoria gradually turning into a satisfied state of
calmness. It is difficult to predict exactly which effects may appear after
intoxication. All the effects disappear after a few hours.
Recent studies have indicated that chronic users of cannabis show some
tolerance to the subjective *high* effects (Ramaekers et al., 2009) and to the
cognitive impairing effects (Hart et al., 2010) of cannabis. Therefore, it can
be assumed that even a high (8 mg) single dose of THC administered to chronic
users will not likely result in adverse effects, such as psychotic symptoms. In
the case of the research by Ramaekers et al. (2009), a single high dose of THC
(500 µg/kg) did not produce any negative effects both in chronic, as well as
occasional users.