Oculomotor effects of delta-9-tetrahydrocannabinol in humans: implications for the functional neuroanatomy of the brain cannabinoid system.

The significance of cannabinoid signaling for human cognition and motor control is still poorly understood. Here, we have investigated acute behavioral effects of oral delta-9-tetrahydrocannabinol (THC) with oculomotor paradigms in 12 healthy human subjects. Compared to baseline testing: (i) THC increased latencies of reflexive visually guided saccades, while their accuracy was not affected; (ii) latencies of memory-guided saccades were unaffected, but THC modulated accuracy of these eye movements by increasing average gain and gain variability; (iii) frequency of anticipated memory-guided saccades and antisaccade errors was increased; (iv) the saccade amplitude/peak velocity relationships were not affected. These results show that THC acts on selected aspects of saccade control, namely spatial attention shifts, fine tuning of volitional saccades, spatial working memory and inhibition of inappropriate saccades. The pattern of effects suggests modulation of neuronal activity in substantia nigra pars reticulata and/or dorsolateral prefrontal cortex and sparing of the eye fields and the final motor pathway for saccades. Behaviorally, our findings reflect the distribution of CB-1 cannabinoid receptors in the human neocortex, basal ganglia and brainstem and provide evidence for participation of the cannabinoidergic system in high level control of saccades and associated cognitive functions. Saccadic eye movements may provide an objective measure of motor and cognitive effects of cannabinoids.