Cannabis affects people differently: inter-subject variation in the psychotogenic effects of Δ9-tetrahydrocannabinol: a functional magnetic resonance imaging study with healthy volunteers.

BACKGROUND: Cannabis can induce transient psychotic symptoms, but not all users experience these adverse effects. We compared the neural response to Δ9-tetrahydrocannabinol (THC) in healthy volunteers in whom the drug did or did not induce acute psychotic symptoms. Method In a double-blind, placebo-controlled, pseudorandomized design, 21 healthy men with minimal experience of cannabis were given either 10 mg THC or placebo, orally. Behavioural and functional magnetic resonance imaging measures were then recorded whilst they performed a go/no-go task. RESULTS: The sample was subdivided on the basis of the Positive and Negative Syndrome Scale positive score following administration of THC into transiently psychotic (TP; n = 11) and non-psychotic (NP; n = 10) groups. During the THC condition, TP subjects made more frequent inhibition errors than the NP group and showed differential activation relative to the NP group in the left parahippocampal gyrus, the left and right middle temporal gyri and in the right cerebellum. In these regions, THC had opposite effects on activation relative to placebo in the two groups. The TP group also showed less activation than the NP group in the right middle temporal gyrus and cerebellum, independent of the effects of THC. CONCLUSIONS: In this first demonstration of inter-subject variability in sensitivity to the psychotogenic effects of THC, we found that the presence of acute psychotic symptoms was associated with a differential effect of THC on activation in the ventral and medial temporal cortex and cerebellum, suggesting that these regions mediate the effects of the drug on psychotic symptoms.

Five-year follow-up of a cohort of people with their first diabetic foot ulcer: the persistent effect of depression on mortality.

AIMS/HYPOTHESIS: Depressive disorders are associated with mortality within 18 months of presentation of diabetic foot ulcers (DFU). The main aim of this study was to determine whether depressive disorder is still associated with increased mortality in people with their first foot ulcer at 5 years. METHODS: This is a 5-year follow-up of a cohort of 253 patients presenting with their first DFU. At baseline, the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) 2.1 was used to define those who met DSM-IV (Diagnostic and Statistical Manual 4th edition) criteria for depressive disorder. Cox regression analysis controlled for potential covariates: age, sex, marital status, socioeconomic status, smoking, mean HbA(1c), diabetes complications and ulcer severity. The main outcome was mortality at 5 years. RESULTS: The prevalence of DSM-IV depressive disorder at baseline was 32.2% (n = 82). There were 92 (36.4%) deaths over the 5 years of follow-up. In the Cox regression (n = 246), after adjusting for covariates, baseline DSM-IV depressive disorder was significantly associated with a twofold increased risk of mortality for any depressive episode (HR 2.09, 95% CI 1.34, 3.25), minor (HR 1.93, 95% CI 1.00, 3.74) or major depressive disorders (HR 2.18, 95% CI 1.31, 3.65), compared with patients who were not depressed. CONCLUSIONS/INTERPRETATION: Depression is associated with a persistent twofold increased risk of mortality in people with their first DFU at 5 years.

Reasons for cannabis use in first-episode psychosis: does strength of endorsement change over 12 months?

BACKGROUND: Why patients with psychosis use cannabis remains debated. The self-medication hypothesis has received some support but other evidence points towards an alleviation of dysphoria model. This study investigated the reasons for cannabis use in first-episode psychosis (FEP) and whether strength in their endorsement changed over time. METHODS: FEP inpatients and outpatients at the South London and Maudsley, Oxleas and Sussex NHS Trusts UK, who used cannabis, rated their motives at baseline (n=69), 3 months (n=29) and 12 months (n=36). A random intercept model was used to test the change in strength of endorsement over the 12 months. Paired-sample t-tests assessed the differences in mean scores between the five subscales on the Reasons for Use Scale (enhancement, social motive, coping with unpleasant affect, conformity and acceptance and relief of positive symptoms and side effects), at each time-point. RESULTS: Time had a significant effect on scores when controlling for reason; average scores on each subscale were higher at baseline than at 3 months and 12 months. At each time-point, patients endorsed 'enhancement' followed by 'coping with unpleasant affect' and 'social motive' more highly for their cannabis use than any other reason. 'Conformity and acceptance' followed closely. 'Relief of positive symptoms and side effects' was the least endorsed motive. CONCLUSIONS: Patients endorsed their reasons for use at 3 months and 12 months less strongly than at baseline. Little support for the self-medication or alleviation of dysphoria models was found. Rather, patients rated 'enhancement' most highly for their cannabis use.