The acute effects of cannabidiol on emotional processing and anxiety: a neurocognitive imaging study.

RATIONALE: There is growing interest in the therapeutic potential of cannabidiol (CBD) across a range of psychiatric disorders. CBD has been found to reduce anxiety during experimentally induced stress in anxious individuals and healthy controls. However, the mechanisms underlying the putative anxiolytic effects of CBD are unknown. OBJECTIVES: We sought to investigate the behavioural and neural effects of a single dose of CBD vs. placebo on a range of emotion-related measures to test cognitive-mechanistic models of its effects on anxiety. METHODS: We conducted a randomised, double-blind, placebo-controlled, crossover, acute oral challenge of 600 mg of CBD in 24 healthy participants on emotional processing, with neuroimaging (viewing emotional faces during functional magnetic resonance imaging) and cognitive (emotional appraisal) measures as well as subjective response to experimentally induced anxiety. RESULTS: CBD did not produce effects on brain responses to emotional faces and cognitive measures of emotional processing, or modulate experimentally induced anxiety, relative to placebo. CONCLUSIONS: Given the rising popularity of CBD for its putative medical benefits, these findings question whether further research is warranted to investigate the clinical potential of CBD for the treatment of anxiety disorders.

The effects of licit and illicit recreational drugs on prospective memory: a meta-analytic review.

RATIONALE: There are no recent reports summarising the magnitude of prospective memory (PM) impairments in recreational drug users. OBJECTIVE: We performed a meta-analysis of studies (with a parallel group design) examining PM performance in users of common recreational drugs (including alcohol and tobacco) who were not intoxicated during testing. Studies were also evaluated for the presence of methodological bias. METHODS: Twenty-seven studies were included in the meta-analysis following literature searches of MEDLINE, EMBASE and PsycINFO. Effect sizes (standardised mean difference; SMD) were calculated separately for the effects of alcohol, cannabis, ecstasy, methamphetamine and tobacco use. The influences of drug use and study characteristics on effect sizes were explored using meta-regressions. Sources of study bias were also assessed. RESULTS: Heavy drinkers and regular drug users tended to perform worse than controls on event and time-based PM tasks. Effect sizes (standardised mean differences; SMDs) for event-based PM impairment across the different drug-using groups/heavy drinkers ranged between - 1.10 and - 0.49, with no 95% CI crossing 0.00. SMDs for time-based PM ranged between - 0.98 and - 0.70. Except for the CIs associated with the ES for smokers' time-based PM performance, no CIs crossed 0.00. CONCLUSIONS: Although all drug-using groups showed moderate-large impairments in event and time-based PM, effect sizes had low precision and moderate-high levels of heterogeneity. In addition, several methodological and reporting issues were identified in the majority of studies. As such, considerable uncertainty remains regarding the role of confounds and the magnitude of PM impairments in non-intoxicated recreational drug users.

Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study.

BACKGROUND: Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression. METHODS: In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797. FINDINGS: Psilocybin's acute psychedelic effects typically became detectable 30-60 min after dosing, peaked 2-3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0-1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1 week (mean QIDS difference -11·8, 95% CI -9·15 to -14·35, p=0·002, Hedges' g=3·1) and 3 months (-9·2, 95% CI -5·69 to -12·71, p=0·003, Hedges' g=2) after high-dose treatment. Marked and sustained improvements in anxiety and anhedonia were also noted. INTERPRETATION: This study provides preliminary support for the safety and efficacy of psilocybin for treatment-resistant depression and motivates further trials, with more rigorous designs, to better examine the therapeutic potential of this approach. FUNDING: Medical Research Council.

Identification of a narrow post-ovulatory window of vulnerability to distressing involuntary memories in healthy women.

Psychological disorders characterised by intrusive memories are more prevalent in women than men. The biological, social and cognitive processes underlying this gender-difference have yet to be fully elucidated. Some evidence suggests that (fluctuations in) ovarian hormone levels are responsible for altered sensitivity to emotional stimuli during certain phases in the menstrual-cycle and this may form the basis of a specific vulnerability to psychological disorders in women. The post-ovulatory (luteal) phase has been identified as a period of particular vulnerability to the development of post-traumatic stress disorder (PTSD). Using an experimental model of PTSD, we examine whether differences are detectable between discrete phases in the menstrual-cycle in the experience of intrusive memories. Women (18-35 years-old) in one of three tightly-defined periods within the menstrual cycle--mid-follicular (n=15), early-luteal (n=15) and late-luteal (n=11)--provided saliva samples for ovarian-hormone assay and watched a distressing film. Subsequent intrusive memories, assessed using a daily online-diary, occurred significantly more frequently in the early-luteal group compared to mid-follicular and late-luteal groups. Intrusion frequency was negatively correlated with the estradiol-to-progesterone ratio, but not estradiol or progesterone alone, suggesting that the interactive effect of low estradiol and high progesterone at encoding contributes to the observed effect. Our results support the need for further research in a clinical context with naturally-cycling women who experience a traumatic event, since assessment of days-since-last-menses and ovarian hormone levels may help to identify those at greatest risk of developing re-experiencing symptoms akin to those seen in psychological disorder such as depression and PTSD.

The effects of immediate-release morphine on cognitive functioning in patients receiving chronic opioid therapy in palliative care.

Morphine and other potent opioids are frequently used in palliative care and pain management. When sustained-release (SR) opioids do not provide adequate background analgesia, additional immediate-release (IR) opioid (e.g. short-acting morphine) may be required to alleviate breakthrough or episodic pain. Despite the frequent use of IR morphine on top of SR opioids, little is known about the effects of such treatment on patients' everyday cognitive functioning. This study therefore used a double-blind, placebo-controlled, cross-over design to assess cognitive functioning in 14 patients receiving palliative care. All patients were taking SR opioid preparations and required