Cerebellar activity and disturbed time sense after THC

doi:10.1016/S0006-8993(98)00375-8

Brain Research

Volume 797, Issue 2, 29 June 1998, Pages 183-189

https://doi.org/10.1016/S0006-8993(98)00375-8 Get rights and content

Abstract

Because marijuana continues to be the most commonly used illicit drug, its effects on the brain function are of major interest. We utilized positron emission tomography (PET) and magnetic resonance imaging (MRI) to study the effects of delta-9-tetrahydrocannabinol (THC) infusion on brain blood flow and its behavioral correlates in 46 volunteers. Consistent with previous reports, there was a significant increase in cortical and cerebellar blood flow following THC, but not all subjects showed this effect. Those who showed a decrease in cerebellar CBF also had a significant alteration in time sense. The relationship between decreased cerebellar flow and impaired time sense is of interest because the cerebellum has been linked to an internal timing system.

Introduction

Marijuana continues to hold its status as the most commonly used illicit drug. According to the White House, in 1995, 77% of all current illicit drug users were marijuana smokers. Approximately 57% of current illicit drug users limited consumption exclusively to marijuana (The National Drug Control Strategy, February, 1977). Thus, the brain mechanisms associated with its behavioral effects are of considerable relevance. Marijuana intoxication is accompanied by a wide range of behavioral and physiological changes 1, 4, 15, 21. A number of reports are available on the acute effects of marijuana and its active ingredient tetrahydrocannabinol (THC) on brain function measured with cerebral blood flow (CBF) 23, 25, 27, 28, 29, 30and cerebral metabolism (CMR) 48, 49, 50. In short, smoking marijuana is followed by the characteristic intoxication, depersonalization, mood changes including anxiety and altered time sense. In the normal brain, CBF and CMR are tightly coupled to brain function and, therefore, they may be used as indices of brain activity 37, 41. After i.v. infusions of THC, CBF showed a global increase with more marked increases in frontal regions bilaterally and insula and cingulate gyrus in the right hemisphere. The changes peaked 30 to 60 min after the infusion [30].

Studies of CMR found increased cerebellar metabolism following THC administration in normal subjects [48]and subjects with a previous history of cannabis dependence [50]. In addition, marijuana users were found to have decreased cerebellar metabolism at baseline. Several investigators reported an association between time perception and cerebellum [22]. Marijuana intoxication is well known to cause impaired time perception 6, 26, 32, 33, 34, 35, 43, 44, 46. Although marijuana intoxication was found to correlate with CMR 47, 48, 50, no information is available on the relationship between marijuana induced alterations in time sense and cerebellar activity. We studied the effects of THC infusion on CBF and its behavioral correlates in 46 volunteers.

Section snippets

Subjects

Subjects were recruited through local advertising, and signed written informed consent. They were screened by a psychiatrist (RJM) who excluded significant physical or current vascular disorders including migraine and psychiatric disorders, abuse or addiction to any drug other than marijuana during the previous 6 months, current use of any prescribed or unprescribed medication and heavy alcohol use (more than two drinks per day for men and one drink per day for females). Substance abuse was

Results

Mean cerebellar and CBF are presented in Table 2. These values are changes from baseline at 30 min post-infusion. The MANOVA of cerebellar flow indicated a significant Group by Time interaction (Wilks lambda F=3.02; df=4,84; p<0.022). There was no difference between left and right lobes by group over time. Cortical CBF for six ROI (frontal, temporal, parietal, occipital, insula and anterior cingulate) in each hemisphere, were analyzed in a dose-group (placebo, low and high dose THC) by

Discussion

Cerebellar blood flow showed a bilateral significant increase after THC infusions in several but not all participants. Similarly some showed altered time sense but not others. When the participants who showed this increase in cerebellar flow were compared with the others on various behavioral indices, the two groups were different most strongly in temporal disintegration; those with post-THC cerebral and cerebellar CBF decrease showing a greater increase of disturbance of time sense.

Acknowledgements

The project was supported by a grant from NIDA, DA 04985. We wish to thank Sharon Hamblen, Thomas C. Hawk, Joe V. Lowe and Diane F. Wright for their considerable efforts in conducting this study.

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Research reportCerebellar activity and disturbed time sense after THC

Abstract

Introduction

Section snippets

Subjects

Results

Discussion

Acknowledgements

Trends Neurosci.

Psychiatry Res. Neuroimaging

Behav. Brain Res.

Life Sci.

Biol. Psychiatry

Biol. Psychiatry

Psychiatry Res. Neuroimaging

Psychiatry Res. Neuroimaging

Screening depressed patients in family practice

Postgrad. Med.

Behavioral effects of marijuana: experimental studies

Arch. Gen. Psychiatry

Method for quantification for brain, ventricular, and subarachnoid CSF volumes from MR images

J. Comput. Assisted Tomogr.

Depersonalization phenomena in a sample population of college students

Br. J. Psychiatry

Evidence of the limitations of water as a freely diffusible tracer in brain of monkey

Circ. Res.

Quantitative measurement of regional cerebral blood flow and oxygen metabolism in man using 15O and positron emission tomography: theory, procedure and normal values

J. Comput. Assisted Tomogr.

EMG analysis of patients with cerebellar deficits

J. Neurol. Neurosurg. Psychiatry

Cannabis—1988

Acta Psychiatr. Scand. Suppl.

Quantitative measurement of local cerebral blood flow in humans by positron computed tomography and 15O-water

J. Cereb. Blood Flow Metab.

Cerebellar involvement in the explicit representation of temporal information

Ann. New York Acad. Sci.

Timing functions of the cerebellum

J. Cogn. Neurosci.

Dissociation of the lateral and medium cerebellum in movement timing and movement execution

Exp. Brain Res.

Research report
Cerebellar activity and disturbed time sense after THC

Quantitative measurement of regional cerebral blood flow and oxygen metabolism in man using $^{15} O$ and positron emission tomography: theory, procedure and normal values

Quantitative measurement of local cerebral blood flow in humans by positron computed tomography and $^{15} O$ -water