Research reportCerebellar activity and disturbed time sense after THC
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.
References (51)
- et al.
Neurobiology of marijuana abuse
Trends Neurosci.
(1992) - et al.
Accuracy and reproducibility of brain and tissue volumes using a magnetic resonance segmentation method
Psychiatry Res. Neuroimaging
(1996) - et al.
Cerebellar contributions to cognition
Behav. Brain Res.
(1995) - et al.
Acute changes in cerebral blood flow after smoking marijuana
Life Sci.
(1993) - et al.
Changes in middle cerebral artery velocity after marijuana smoking
Biol. Psychiatry
(1992) - et al.
Depersonalization after marijuana smoking
Biol. Psychiatry
(1993) - et al.
Cerebellar metabolic activation by delta-9-tetrahydrocannabinol in human brains: a study with positron emission tomography and -2-fluoro-2-deoxyglucose
Psychiatry Res. Neuroimaging
(1991) - et al.
Brain glucose metabolism in chronic marijuana users at baseline and during marijuana intoxication
Psychiatry Res. Neuroimaging
(1996) - American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 3rd edn., American Psychiatric...
- et al.
Screening depressed patients in family practice
Postgrad. Med.
(1972)
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 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 -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.
Cited by (98)
Task-independent acute effects of delta-9-tetrahydrocannabinol on human brain function and its relationship with cannabinoid receptor gene expression: A neuroimaging meta-regression analysis
2022, Neuroscience and Biobehavioral ReviewsCitation Excerpt :Thus, there is a pressing need to better understand the effects of THC on the human brain. A substantial number of studies have investigated the effects of THC-rich cannabis or THC isolate using single photon emission tomography (SPECT)/ positron emission tomography (PET) to measure cerebral blood flow (rCBF) (Volkow et al., 1996, 1991; Mathew et al., 1997, 1992, 1998, 1999, 2002, 1989; Mathew and Wilson, 1993) at rest, and functional MRI (fMRI) to measure the blood oxygen level dependent haemodynamic signal during cognitive activation (Bhattacharyya, Sep 24 et al., 2012; Gunasekera et al., 2021) to index brain function. However, conflicting results from these studies have not resulted in a clearer understanding as evident from two recent systematic reviews (Gunasekera et al., 2021; Bloomfield et al., 2019).
The Yin and Yang of Cannabis: A Systematic Review of Human Neuroimaging Evidence of the Differential Effects of Δ<sup>9</sup>-Tetrahydrocannabinol and Cannabidiol
2021, Biological Psychiatry: Cognitive Neuroscience and NeuroimagingAcute and chronic effects of Δ<sup>9</sup>-tetrahydrocannabinol (THC) on cerebral blood flow: A systematic review
2020, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :Seven studies used 15O-water PET to measure CBF in specific areas of the brain. All of the 7 studies, except one, demonstrated an increase in global CBF after THC administration (Mathew et al., 1997, 1998, 1999, 2002; O’Leary, 2000, 2007). ( O'Leary et al., 2002) did not show this significant increase but did show increased regional CBF (rCBF) in the frontal cortex, insula, cingulate gyrus, temporal poles and cerebellum.
The neuropsychopharmacology of cannabis: A review of human imaging studies
2019, Pharmacology and TherapeuticsPsychotomimetic and Cognitive Effects of Δ<sup>9</sup>-Tetrahydrocannabinol in Laboratory Settings
2018, The Complex Connection between Cannabis and Schizophrenia