Effects of smoking marijuana on brain perfusion and cognition.

The effects of smoking marijuana on regional cerebral blood flow (rCBF) and cognitive performance were assessed in 12 recreational users in a double-blinded, placebo-controlled study. PET with [(15)Oxygen]-labeled water ([(15)O]H(2)O) was used to measure rCBF before and after smoking of marijuana and placebo cigarettes, as subjects repeatedly performed an auditory attention task. Smoking marijuana resulted in intoxication, as assessed by a behavioral rating scale, but did not significantly alter mean behavioral performance on the attention task. Heart rate and blood pressure increased dramatically following smoking of marijuana but not placebo cigarettes. However, mean global CBF did not change significantly. Increased rCBF was observed in orbital and mesial frontal lobes, insula, temporal poles, anterior cingulate, as well as in the cerebellum. The increases in rCBF in anterior brain regions were predominantly in "paralimbic" regions and may be related to marijuana's mood-related effects. Reduced rCBF was observed in temporal lobe auditory regions, in visual cortex, and in brain regions that may be part of an attentional network (parietal lobe, frontal lobe and thalamus). These rCBF decreases may be the neural basis of perceptual and cognitive alterations that occur with acute marijuana intoxication. There was no significant rCBF change in the nucleus accumbens or other reward-related brain regions, nor in basal ganglia or hippocampus, which have a high density of cannabinoid receptors.

Marijuana alters the human cerebellar clock.

The effects of marijuana on brain perfusion and internal timing were assessed using [15O] water PET in occasional and chronic users. Twelve volunteers who smoked marijuana recreationally about once weekly, and 12 volunteers who smoked daily for a number of years performed a self-paced counting task during PET imaging, before and after smoking marijuana and placebo cigarettes. Smoking marijuana increased rCBF in the ventral forebrain and cerebellar cortex in both groups, but resulted in significantly less frontal lobe activation in chronic users. Counting rate increased after smoking marijuana in both groups, as did a behavioral measure of self-paced tapping, and both increases correlated with rCBF in the cerebellum. Smoking marijuana appears to accelerate a cerebellar clock altering self-paced behaviors.

Emotional blunting following left basal ganglia stroke: the role of depression and fronto-limbic functional alterations.

Disorders of the basal ganglia (BG) alter perception and experience of emotions. Left hemisphere BG (LBG) stroke is also associated with depression. The interplay between depression and alterations in emotional processing following LBG stroke was examined. Evoked affective responses to emotion-laden pictorial stimuli were compared among LBG stroke and healthy participants and participants with stroke damage in brain regions not including the LBG selected to equate depression severity (measured using the Hamilton Depression Scale) with LBG damage participants. Brain activity {[O(15)]water positron emission tomography, PET} was measured in LBG stroke relative to healthy participants to identify changes in regions associated with emotion processing and depression. LBG stroke subjects reported less intense emotions compared with healthy, but not stroke comparison participants. Depression negatively correlated with emotional experience for positive and negative emotions. In response to positive stimuli, LBG subjects exhibited higher activity in amygdala, anterior cingulate, dorsal prefrontal cortex, and insula compared to healthy volunteers. In response to negative stimuli, LBG subjects demonstrated lower activity in right frontal-polar region and fusiform gyrus. Higher baseline activity in amygdala and ventral and mesial prefrontal cortex and lower activity in left dorsal lateral prefrontal cortex were associated with higher depression scores. LBG stroke led to blunted emotions, and brain activity alterations accounting for reduced affective experience, awareness and depression. Depression and fronto-limbic activity changes may contribute to emotional blunting following LBG stroke.

Effects of smoking marijuana on focal attention and brain blood flow.

Using an attention task to control cognitive state, we previously found that smoking marijuana changes regional cerebral blood flow (rCBF). The present study measured rCBF during tasks requiring attention to left and right ears in different conditions. Twelve occasional marijuana users (mean age 23.5 years) were imaged with PET using [15O]water after smoking marijuana or placebo cigarettes as they performed a reaction time (RT) baseline task, and a dichotic listening task with attend-right- and attend-left-ear instructions. Smoking marijuana, but not placebo, resulted in increased normalized rCBF in orbital frontal cortex, anterior cingulate, temporal pole, insula, and cerebellum. RCBF was reduced in visual and auditory cortices. These changes occurred in all three tasks and replicated our earlier studies. They appear to reflect the direct effects of marijuana on the brain. Smoking marijuana lowered rCBF in auditory cortices compared to placebo but did not alter the normal pattern of attention-related rCBF asymmetry (i.e., greater rCBF in the temporal lobe contralateral to the direction of attention) that was also observed after placebo. These data indicate that marijuana has dramatic direct effects on rCBF, but causes relatively little change in the normal pattern of task-related rCBF on this auditory focused attention task.