Roy J. Mathew

Brain morphological changes and early marijuana use: a magnetic resonance and positron emission tomography study.

Abstract Background: The focus of this report is on the possible role that the age of first use of marijuana may play on brain morphology and function. Methods: Magnetic resonance imaging (MRI) and positron emission tomography (PET) were utilized to study 57 subjects. Brain volume measures (whole brain, gray matter, white matter and lateral ventricle volumes), global cerebral blood flow (CBF) and body size were evaluated. Results: There are three primary findings related to age of first use of marijuana. Subjects who started using marijuana before age 17, compared to those who started later, had smaller whole brain and percent cortical gray matter and larger percent white matter volumes. Functionally, males who started using marijuana before 17 had significantly higher CBF than other males. Both males and females who started younger were physically smaller in height and weight, with the effects being greater in males. Conclusions: These findings suggest that the age at which exposure to marijuana begins is important. Early adolescence may be a critical period for effects that are not present when exposure begins later. These results are discussed in light of reported effects of marijuana on gonadal and pituitary hormones.

Sexual dysfunctions in depression

The incidence of sexual dysfunctions in a group of 51 drug-free depressed patients and in age- and sex-matched controls was studied. Three groups of sexual dysfunction were assessed: alterations of libido, genital symptoms, and menstrual irregularities. The Beck Rating Scale for Depression, the Eysenck Personality Inventory (EPI), and the State-Trait Anxiety Inventory were completed on each participant. Depressed patients obtained significantly higher scores on anxiety, depression, and alterations of libido than controls. Rating scale scores for anxiety and depression were strongly inter-correlated, making the separation of depression-related symptoms from anxiety difficult. In males, the genital symptoms correlated inversely with the L (lie) score of the Eysenck Personality Inventory. There were no inter-relationships between the three groups of sexual dysfunction.

Serotonin levels and platelet uptake during premenstrual tension.

Premenstrual tension was studied in 16 females, using both biochemical and psychological parameters during the pre- and postmenstrual phases. Uptake of serotonin (5-HT) and the levels of 5-HT in platelet-rich plasma and platelet-poor plasmas were determined. Degrees of distress experienced pre- and postmenstrually were quantified via the Moos menstrual distress questionnaire. The mean Vmax was significantly lower during the premenstrual (tension) phase (8.2 +/- 0.9 pmol/min) as compared to the postmenstrual (normal) phase (14.4 +/- 3.2 pmol/min). There was no significant difference in the Km values. A highly significant (p less than 0.001) reduction in the levels of 5-HT in platelet-rich plasma (-23.2%) and platelet-poor plasma (-19.1%) was found during the premenstrual phase. There were correlations between the kinetic parameters of 5-HT uptake and some of the Moos symptoms.

Marijuana intoxication and brain activation in marijuana smokers.

OBJECTIVE AND METHOD The acute effects of delta9 tetrahydrocannabinol (THC) on cerebral blood flow (CBF) were studied in human subjects. Regional CBF was measured with 15O-water and Positron Emission Tomography (PET) in 32 volunteers with a history of exposure to marijuana. Scans were performed before and after intravenous (I.V.) infusion of either of two doses of THC or a placebo, given under double blind conditions. RESULTS THC but not placebo increased CBF especially in the frontal regions bilaterally, insula and cingulate gyrus and sub-cortical regions with somewhat greater effects in the right hemisphere. While most regions showed significant change at 60 minutes for the lower dose group, the higher dose group had significant change at 30 and 60 minutes. There was a highly significant change in the anterior/posterior ratio for the two THC groups reflecting minimal change in occipital flow but significant increases in frontal flow. Self ratings of THC intoxication showed significant effects, and regression analysis indicated it correlated most markedly with the right frontal region. CONCLUSION Behavioral manifestations of marijuana intoxication may be associated with increased functional activity of the brain especially the frontal cortex, insula and cingulate gyrus.

Regional Cerebral Blood Flow after Marijuana Smoking

Regional CBF was measured with the 133Xe inhalation technique before and thrice after smoking marijuana of two strengths and placebo in 20 physically and mentally healthy male volunteers with a previous history of exposure to marijuana. They were drug-free at the time of the study. Blood pressure, pulse rate, end-tidal carbon dioxide, end-tidal carbon monoxide, and forehead skin perfusion were quantified during the CBF measurements. Blood samples were drawn for quantification of plasma levels of Δ9-tetrahydrocannabinol (THC) before and during the 2 h after smoking marijuana or placebo. Drug-induced intoxication and changes in mood were quantified with rating scales. Marijuana smoking was associated with bilateral CBF increase, which was maximal 30 min later. Greater CBF increases were seen in the frontal region and right hemisphere. No significant CBF changes were seen after placebo. Pulse rate and respiration increased significantly after marijuana but not placebo. Both marijuana and placebo smoking were associated with increased end-tidal carbon monoxide. CBF increase in both hemispheres correlated significantly with degree of intoxication, plasma levels of THC, and pulse rate.

Cerebellar activity and disturbed time sense after THC

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.

Acute changes in cerebral blood flow associated with marijuana smoking

ABSTRACT Cerebral blood flow (CBF) was measured in experienced (ES) and inexperienced (IS) marijuana smokers with the 133xenon inhalation technique before and after smoking both a high‐potency marijuana cigarette and a placebo marijuana cigarette. CBF was measured twice under resting conditions in a control group. Mood states before and after marijuana smoking were quantified with the Profile of Mood States (POMS). Analyses of POMS factors after smoking marijuana revealed IS had an increase in anxiety while ES had a decrease. IS also had a significant increase in depression and decrease in vigor, but neither variable changed in the ES. After marijuana, CBF decreased in IS, but in ES, it increased in comparison with the 2 control runs. In both IS and ES, CBF changes following placebo administration were similar to those associated with marijuana smoking. However, in IS, the marijuana‐induced CBF decrease was significantly higher than that associated with placebo. There were no statistically significant differences between the CBF increase seen after placebo and marijuana in ES. Anxiety, anger, fatigue, confusion and depression had significant negative correlations with CBF while vigor correlated positively, but the anxiety factor was the only one to account for a significant percentage of the change (partial correlation) in hemispheric CBF.

A study of the septum pellucidum and corpus callosum in schizophrenia with MR imaging

ABSTRACT– Surface areas of the septum pellucidum, corpus callosum and the brain were measured from mid‐saggital slices obtained with magnetic resonance imaging in 18 patients with schizophrenia and an equal number of normal volunteers. The patients showed larger septa and septo‐brain ratios. These indices correlated with age in both patients and controls. In the patients, septal area also correlated with duration of illness. Changes in the septum pellucidum were unrelated to the intensity of positive and negative symptoms of schizophrenia. The patients had significantly longer corpora callosa, but the two groups did not differ on its size or the ratio between the latter and the mid‐saggital slice area. Dimensions of the corpus callosum did not correlate with age, duration of the illness or positive and negative symptoms of schizophrenia. The anteroposterior elongation of the structure seemed to accompany enlargement of the septum pellucidum.

Regional cerebral blood flow and depersonalization after tetrahydrocannabinol administration

Mathew RJ, Wilson WH, Chiu NY, Turkington TG, Degrado TR, Coleman RE. Regional cerebral blood flow and depersonalization after tetrahydrocannabinol administration.

Time course of tetrahydrocannabinol-induced changes in regional cerebral blood flow measured with positron emission tomography

While several studies are available on the immediate effects of marijuana and its active ingredient tetrahydrocannabinol (THC) on regional cerebral blood flow (rCBF), we examined the effects of intravenous infusion of THC on rCBF and behavior over a 120-min. period using positron emission tomography. Indices of rCBF, intoxication and physiology were measured at baseline and 30, 60, 90 and 120 min. after a 20-min. intravenous infusion of 0.15 or 0.25 mg/min. of THC, or placebo given to 47 subjects. The rCBF remained increased up to 120 min. after the high-dose THC infusion. Significant increases were seen in global perfusion and in the frontal, insular and anterior cingulate regions. Changes were greater in the right hemisphere. After the high dose, cerebellar flow was increased at both 30 and 60 min. The anterioposterior ratio of cortical rCBF increased in both hemispheres, and remained significantly greater than in the placebo condition until 120 min. in the right hemisphere. Intoxication peaked at 30 min. and remained elevated at 120 min. THC had significant effects on global CBF and rCBF, and feeling intoxicated accounted for changes in rCBF better than plasma level of THC.