Psychiatry #200311013

Dr. Dan O’Leary

Dr. Susan Schultz

Acute effects of marijuana on cerebral blood flow

Abstract:

This project is a continuing study, funded by NIDA, that explores the effects of marijuana on cognitive function and regional cerebral blood flow (rCBF) in occasional users of the drug, and the effects of regular, long-term (i.e., chronic) use on cognition and rCBF. Occasional users of the drug (less than 10 times a month) who find the drug pleasurable, are studied rath than individuals who have never used, because of concerns expressed by a previous IRB, that marijuana is a “gateway” drug, and because anxiety and other unpleasant experiences would be more common during the first use of the drug. Marijuana cigarettes of several potencies are obtained from NIDA as are placebo cigarettes (marijuana with THC removed), through federal and state licenses maintained by Robert Block Ph.D., and an IND held by Daniel O’Leary Ph.D.

We plan 4 studies, each comparing 20 occasional and 20 chronic users of the drug performing cognitive tasks before and after smoking marijuana and placebo cigarettes using a double-blind design. Each of the four studies involves two PET imaging sessions at least a week apart, to allow THC to clear from the body if it is smoked first. In the initial funding period we performed 4 studies that found that marijuana increases

perfusion in a large area of the ventral forebrain that have links to limbic regions, and in the cerebellum. The cerbellar increases in perfusion are associated with an increased rate of performance on tasks that require self-paced behavior. We hypothesized that smoking marijuana increases the speed of an “internal clock” located in the cerebellum (O’Leary et al, NeuroReport, 2003 Jun 11;14(8):1145-51). The four current studies will attempt to replicate this finding and to extend it, to assess the effects of smoking marijuana on other functions that may be mediated by the cerebellum.

The project described in the appended RO1 application was recently funded for 5 years by NIDA. This was the second submission of the grant and arterial line placement was added in line with the comments of reviewers’ of the first submission. The second review strongly suggested dropping the proposed study using hedonic stimuli (Study 4), and I have replaced it with a study of eye-blink conditioning that will be done in collaboration with John Freeman Ph.D. Dr. Freeman is faculty in the Psychology and is expert in eye-blink conditioning. We have performed a very similar study in collaboration with Nancy Andreasen M.D., Ph.D. in normal volunteers and in schizophrenic patients and found activation in the cerebellum. The reviewers’ suggested adding a placebo condition to Study 1 which I have done.