Does intravenous Δ9-tetrahydrocannabinol increase dopamine release? A SPET study

Intravenous (IV) Δ9-tetrahydrocannabinol (THC) induces transient psychotic symptoms in healthy subjects and in schizophrenic patients, but the psychotomimetic mechanism is unknown. One possibility is that THC stimulates dopamine (DA) release in the striatum. In this study we tested whether IV THC led to an increase in striatal DA release compared to placebo. We also investigated whether DA release and positive psychotic symptoms were related. Eleven healthy male volunteers completed two 123I-iodobenzamide ([123I]IBZM) single photon emission tomography (SPET) sessions and received IV THC (2.5 mg) or placebo in a randomized counterbalanced order, under double-blind conditions. Analysable data were obtained from nine participants. The Positive and Negative Syndrome Scale (PANSS) was used to rate psychotomimetic effects. Striatal binding index values were calculated using the occipital cortex as a reference region. Both the PANSS positive and general symptoms increased significantly at 30 min following IV THC. There were no significant differences in binding index in the caudate or putamen under THC compared to placebo conditions. Positive psychotic symptoms and DA release were unrelated. THC did not lead to a significant increase in DA release even though the dose was sufficient for participants to have psychotic symptoms. These findings do not support a central role for striatal DA in THC-elicited psychosis.

Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment

Community-based studies suggest that cannabis products that are high in Δ⁹-tetrahydrocannabinol (THC) but low in cannabidiol (CBD) are particularly hazardous for mental health. Laboratory-based studies are ideal for clarifying this issue because THC and CBD can be administered in pure form, under controlled conditions. In a between-subjects design, we tested the hypothesis that pre-treatment with CBD inhibited THC-elicited psychosis and cognitive impairment. Healthy participants were randomised to receive oral CBD 600 mg (n=22) or placebo (n=26), 210 min ahead of intravenous (IV) THC (1.5 mg). Post-THC, there were lower PANSS positive scores in the CBD group, but this did not reach statistical significance. However, clinically significant positive psychotic symptoms (defined a priori as increases ≥ 3 points) were less likely in the CBD group compared with the placebo group, odds ratio (OR)=0.22 (χ²=4.74, p<0.05). In agreement, post-THC paranoia, as rated with the State Social Paranoia Scale (SSPS), was less in the CBD group compared with the placebo group (t=2.28, p<0.05). Episodic memory, indexed by scores on the Hopkins Verbal Learning Task-revised (HVLT-R), was poorer, relative to baseline, in the placebo pre-treated group (-10.6 ± 18.9%) compared with the CBD group (-0.4% ± 9.7 %) (t=2.39, p<0.05). These findings support the idea that high-THC/low-CBD cannabis products are associated with increased risks for mental health.

T1(Gd) gives comparable information as Delta T1 relaxation rate in dGEMRIC evaluation of cartilage repair tissue

OBJECTIVES: To evaluate the relationship between T1 after intravenous contrast administration (T1Gd) and Delta relaxation rate (DeltaR1) = (1/T1(Gd) - 1/T1o) in the delayed Gadolinium-Enhanced MRI of cartilage (dGEMRIC) evaluation of cartilage repair tissue. MATERIALS AND METHODS: Thirty single MR examinations from 30 patients after matrix-associated autologous chondrocyte transplantations of the knee joint with different postoperative intervals were examined using an 8-channel knee-coil at 3T. T1 mapping using a 3D GRE sequence with a 35/10 degrees flip angle excitation pulse combination was performed before and after contrast administration (dGEMRIC technique). T1 postcontrast (T1(Gd)) and the DeltaR1 (relative index of pre- and postcontrast R1 value) were calculated for repair tissue and the weight-bearing normal appearing control cartilage. For evaluation of the different postoperative intervals, MR exams were subdivided into 3 groups (up to 12 months, 12-24 months, more than 24 months). For statistical analysis Spearman correlation coefficients were calculated. RESULTS: The mean value for T1 postcontrast was 427 +/- 159 ms, for DeltaR1 1.85 +/- 1.0; in reference cartilage 636 +/- 181 ms for T1 postcontrast and 0.83 +/- 0.5 for DeltaR1.The correlation coefficients were highly significant between T1 (Gd) and DeltaR1 for repair tissue (0.969) as well as normal reference cartilage (0.928) in total, and for the reparative cartilage in the early, middle postoperative, and late postoperative interval after surgery (R values: -0.986, -0.970, and -0.978, respectively). Using either T1(Gd) or DeltaR1, the 2 metrics resulted in similar conclusions regarding the time course of change of repair tissue and control tissue, namely that highly significant (P > 0.01) differences between cartilage repair tissue and reference cartilage were found for all follow-up groups. Additionally, for both metrics highly significant differences (P < 0.01) between early follow up and the 2 later postoperative groups for cartilage repair tissue were found. No statistical differences were found between the 2 later follow-up groups of reparative cartilage either for T1 (Gd) or DeltaR1. CONCLUSION: The high correlation between T1 (Gd) and DeltaR1 and the comparable conclusions reached utilizing metric implies that T1 mapping before intravenous administration of MR contrast agent is not necessary for the evaluation of repair tissue. This will help to reduce costs, inconvenience for the patients, simplifies the examination procedure, and makes dGEMRIC more attractive for follow-up of patients after cartilage repair surgeries.

Signatures of slope failures and river-delta collapses in a perialpine lake (Lake Lucerne, Switzerland)

Historical reports from the 17th Century document two destructive tsunamis with runups exceeding 5 m, affecting proximal basins of Lake Lucerne (Switzerland). One event in AD 1601 is coeval with a strong nearby earthquake (MW ca 5.9), which caused extensive slope failures in many parts of the lake. The second event in AD 1687 is associated with an apparently spontaneous partial collapse of the Muota river delta. This study combines high-resolution bathymetry, reflection seismic and lithological data in order to document the sedimentary and morphological signatures of the two subaqueous mass movements that probably generated the observed tsunamis. Such mass movements are significant as a common sedimentation process and as natural hazard in fjord-type lakes and similar environments. The deposits, covering large parts of the basins with thicknesses reaching >10 m, consist of two subunits: A lower ‘massflow deposit’ contains variably deformed sediments from the source areas. Its emplacement affected pre-existing sediments, incorporating thin sediment slices into the deposit and increasing its volume. Deep-reaching deformation near This is an Accepted Article that has been peer-reviewed and approved for publication in the Sedimentology, but has yet to undergo copy-editing and proof correction.

Absence of Hepatitis Delta Infection in a Large Rural HIV Cohort in Tanzania

OBJECTIVES The epidemiological and clinical determinants of hepatitis delta virus (HDV) infection in sub-Saharan Africa are ill-defined. We determined the prevalence of HDV infection in HIV/hepatitis B virus (HBV)-co-infected individuals in rural Tanzania. DESIGN AND METHODS We screened all hepatitis B virus (HBV)-infected adults under active follow-up in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) for anti-HDV antibodies. In positive samples, we performed a second serological test and nucleic acid amplification. Demographic and clinical characteristics at initiation of antiretroviral therapy (ART) were compared between anti-HDV-negative and positive patients. RESULTS Among 222 HIV/HBV-coinfected patients on ART, 219 (98.6%) had a stored serum sample available and were included. Median age was 37 years, 55% were female, 46% had WHO stage III/IV HIV disease and median CD4 count was 179 cells/μL. The prevalence of anti-HDV positivity was 5.0% (95% confidence interval 2.8%-8.9%). There was no significant predictor of anti-HDV positivity. HDV could not be amplified in any of the anti-HDV-positive patients and the second serological test was negative in all of them. CONCLUSIONS We found no confirmed case of HDV infection among over 200 HIV/HBV-co-infected patients in Tanzania. As false-positive serology results are common, screening results should be confirmed with a second test.