Diminished gray matter in the hippocampus of cannabis users: possible protective effects of cannabidiol.

BACKGROUND: Chronic cannabis use has been associated with memory deficits and a volume reduction of the hippocampus, but none of the studies accounted for different effects of tetrahydrocannabinol (THC) and cannabidiol (CBD). METHODS: Using a voxel based morphometry approach optimized for small subcortical structures (DARTEL) gray matter (GM) concentration and volume of the hippocampus were measured in 11 chronic recreational cannabis users and 13 healthy controls, and correlated with THC and CBD from hair analyses. GM volume was calculated by modulating VBM using Jacobian determinants derived from the spatial normalization. RESULTS: Cannabis users showed lower GM volume located in a cluster of the right anterior hippocampus (P(uncorr)=0.002; effect size Cohen's d=1.34). In a regression analysis an inverse correlation of the ratio THC/CBD with the volume of the right hippocampus (P(uncorr) p<0.001, Cohen's d=3.43) was observed. Furthermore Cannabidiol correlated positively with GM concentration (unmodulated VBM data), but not with GM volume (modulated VBM) in the bilateral hippocampus (P=0.03 after correction for hippocampal volume; left hippocampus Cohen's d=4.37 and right hippocampus 4.65). CONCLUSIONS: Lower volume in the right hippocampus in chronic cannabis users was corroborated. Higher THC and lower CBD was associated with this volume reduction indicating neurotoxic effects of THC and neuroprotective effects of CBD. This confirms existing preclinical and clinical results. As a possible mechanism the influence of cannabinoids on hippocampal neurogenesis is suggested.

Impairment of cognitive abilities and decision making after chronic use of alcohol: the impact of multiple detoxifications.

AIMS: In the present study, the effect of previous detoxifications on prefrontal function and decision making was examined in alcohol-dependent patients. Further, we examined whether the length of abstinence affects cognitive function. METHODS: Forty-eight alcohol-dependent patients were recruited from an inpatient detoxification treatment facility and cognitive function was compared to a control group of 36 healthy controls. The patient population was then divided into a group of patients with less than two previous detoxifications (LO-detox group, n = 27) and a group of patients with two or more previous detoxifications (HI-detox group, n = 21) and cognitive function was compared. In addition, cognitive function of recently (i.e. less than 16 days; median split) and longer abstinent patients was compared. We assessed prefrontal function, memory function and intelligence. RESULTS: Alcoholics, when compared to healthy controls, performed worse with regard to the performance index Attention/Executive function. Cognitive impairment in these tasks was pronounced in recently abstinent patients. We found no significant differences between HI-detox and LO-detox patients with regard to the Attention/Executive function. However, in the IOWA gambling Task, the HI-detox group seemed to be less able to learn to choose cards from the more advantageous decks over time. CONCLUSIONS: Our results provide additional evidence for cognitive impairment of alcohol-dependent patients with regard to tasks sensitive to frontal lobe function and underline the importance of abstinence for these impairments to recover. We found only little evidence for the impairing effects of repeated withdrawal on prefrontal function and we suggest that executive function is affected earlier in dependence.

Decision making of heavy cannabis users on the Iowa Gambling Task: stronger association with THC of hair analysis than with personality traits of the Tridimensional Personality Questionnaire.

BACKGROUND: It is unclear whether impairment in decision making, measured by the Iowa Gambling Task (IGT), in addiction is substance-induced or the consequence of personality structure. METHODS: Analysis of the IGT, the Tridimensional Personality Questionnaire (TPQ) and cannabinoids in hair and urine were performed in 13 cannabis users and matched controls. RESULTS: Hair Delta(9)-tetrahydrocannabinol (THC) correlated negatively with the last subtrial (cards 80-100) of the IGT (R = -0.67). In all participants (n = 26) the TPQ dimension, harm avoidance, correlated negatively with the total IGT score (R = -0.46). The last IGT-subtrial correlated with adventure seeking (R = 0.43), harm avoidance (R = -0.39) and reward dependence (R = -0.44). The last subtrial gives information on whether a participant has learned the IGT strategy. Multiple regression confirmed the impact of THC on the last subtrial, whereas TPQ personality traits did not additionally explain variance. CONCLUSIONS: Former indications of the IGT performance depending on the amount of cannabis consumed were replicated with an objective measurement of chronic cannabis consumption (hair THC). Multiple regression analysis argues for a stronger impact of chronic THC consumption than personality traits, but does not provide a causal relationship. Other factors (e.g. genetic) may also play a role.

Dorsolateral prefrontal cortex N-acetylaspartate/total creatine (NAA/tCr) loss in male recreational cannabis users.

BACKGROUND: Cannabinoids present neurotoxic and neuroprotective properties in in vitro studies, inconsistent alterations in human neuroimaging studies, neuropsychological deficits, and an increased risk for psychotic episodes. METHODS: Proton magnetic resonance spectroscopy ((1)H-MRS), neuropsychological testing, and hair analysis for cannabinoids was performed in 13 male nontreatment-seeking recreational cannabis users and 13 male control subjects. RESULTS: A significantly diminished N-acetylaspartate/total creatine (NAA/tCr) ratio in the dorsolateral prefrontal cortex (DLPFC) was observed in cannabis users (p = .0003). The NAA/tCr in the putamen/globus pallidum region correlated significantly with cannabidiol (R(2) = .66, p = .004). Results of the Wisconsin Card Sorting test, Trail making Test, and D2 test for attention were influenced by cannabinoids. CONCLUSIONS: Chronic recreational cannabis use is associated with an indication of diminished neuronal and axonal integrity in the DLPFC in this study. As chronic cannabis use is a risk factor for psychosis, these results are interesting because diminished NAA/tCr ratios in the DLPFC and neuropsychological deficits were also reported in schizophrenia. The strong positive correlation of NAA/tCr and cannabidiol in the putamen/globus pallidum is in line with neuroprotective properties of cannabidiol, which were also observed in in vitro model studies of Parkinson's disease.

Alcohol consumption significantly influences the MR signal of frontal choline-containing compounds.

The aim of this work was to evaluate the relationship between the amount of alcohol consumption of a group of social drinkers and the magnetic resonance spectroscopy signal of choline-containing compounds (Cho) in the frontal lobe. Two independent long echo (TE = 135 ms) (1)H MRSI studies, the first comprising 24 subjects with very low alcohol consumption, the second 18 subjects with a more widespread alcohol consumption were conducted. Significant correlations of Cho measures from frontal white matter and from the anterior cingulate gyrus with alcohol consumption in the last 90 days prior to the MR examination were found. Age, gender, and smoking did not show significant effects on the metabolite measures. Partialling out the effect of the voxel white matter content did not change the correlation of choline measures with alcohol consumption. The main conclusion from the repeated finding of a positive correlation of alcohol consumption and frontal Cho signals is that monitoring for alcohol consumption is mandatory in MRS studies where pathology depended Cho changes are hypothesized.

Low efficacy of non-opioid drugs in opioid withdrawal symptoms.

Opioid withdrawal, stress or cues associated with opioid consumption can induce opioid craving. If opioids are not available, opioid-dependent patients usually search for alternative drugs. Because several non-opioid drugs stimulate the endogenous opioidergic system, this concept may explain their frequent use by opioid-dependent patients. We hypothesized that non-opioid drugs alleviate opioid withdrawal symptoms and are therefore consumed by opioid addicts. We asked 89 opioid-dependent patients participating in an out-patient opioid maintenance program to estimate the potential of several non-opioid drugs in being able to alleviate opioid withdrawal. We applied a five-point Lickert scale (1 = very good reduction of opioid withdrawal; 5 = no reduction of opioid withdrawal). Patients could also indicate a worsening of opioid withdrawal. Values (mean +/- SD) were: for benzodiazepines, 3.2 +/- 1.1; tricyclic antidepressants, 3.6 +/- 1.1; cannabis, 3.6 +/- 1.0; alcohol, 4.1 +/- 1.1; cocaine, 4.2 +/- 1.1; amphetamine, 4.4 +/- 0.9; nicotine, 4.7 +/- 0.7; and caffeine, 4.9 +/- 0.5. A worsening of opioid withdrawal was reported by 62% of the patients for cocaine, 62% for amphetamine, 50% for caffeine, 37.5% for cannabis, 27% for nicotine, 26% for alcohol, 8% for tricyclic antidepressants and 3% for benzodiazepines. Our study shows a low efficacy of non-opioid drugs in alleviating opioid withdrawal symptoms. The data basis of this study was good and the sample was suitable to be asked for estimations of drug-drug interactions. Of the patients, 26 - 62% even reported a worsening of opioid withdrawal for cannabis, alcohol, cocaine and amphetamine. Only benzodiazepines and tricyclic antidepressants were reported to have a moderate positive effect on opioid withdrawal.

Monitoring the effects of chronic alcohol consumption and abstinence on brain metabolism: a longitudinal proton magnetic resonance spectroscopy study.

BACKGROUND: This study focused on metabolic brain alterations in recently detoxified alcohol-dependent patients (S1) and their possible reversibility after 3 (S2) and 6 months (S3) of abstinence. METHODS: Thirty-three alcohol-dependent patients and 30 healthy control subjects were studied with multislice proton magnetic resonance spectroscopic imaging (echo time = 135 msec at 1.5 T at three time points). RESULTS: In the patient group, we found that choline-containing compounds (Ch) in three frontal and cerebellar subregions at S1 were significantly below normal, whereas N-acetyl aspartate (NAA) differences did not reach significance but showed a trend toward below-normal values in frontal white matter. Abstinent patients showed a significant increase of Ch in all subregions at S2. At S3, no further significant metabolite changes in abstinent patients compared with S2 could be detected. No significant increase of NAA could be detected at follow-up. CONCLUSIONS: The increase of the Ch signal in the follow-up measurement after 3 months in abstinent alcohol-dependent patients supports the hypotheses of an alcohol- or alcohol detoxification-induced altered cerebral metabolism of lipids in membranes or myelin, which seems to be reversible with duration of alcohol abstinence.