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Background3,4-Methylenedioxymethamphetamine (MDMA) is being actively researched as an adjunct to psychotherapy. It may be beneficial to trust, empathy and cooperative behaviour due to its acute prosocial effects.AimTo test (a) the acute effects of MDMA on measures of empathy, trust and cooperative behaviour, and (b) subacute changes in mood three days after MDMA administration.MethodsTwenty-five participants (n=7 female), participated in this double-blind, repeated-measures, placebo-controlled experiment. Participants attended two acute sessions, one week apart. Each acute session was followed by a subacute session three days later. Participants received placebo (100 mg ascorbic acid) during one acute session, and MDMA (100 mg MDMA-HCl) at the other, with order counterbalanced. Participants completed the following tasks assessing prosocial behaviour: a trust investment task, a trustworthy face rating task, an empathic stories task, a public project game, a dictator game and an ultimatum game. Participants reported subjective effects. Blood was taken pre-drug, 2 and 4 hours post-drug, and tested for plasma MDMA levels.ResultsMDMA acutely increased self-reported 'closeness to others' and 'euphoria' and increased plasma concentrations of MDMA. MDMA did not significantly change task-based empathy, trust or cooperative behaviour. Using Bayesian analyses, we found evidence that MDMA and placebo did not differ in their effects on empathy and cooperative behaviour. MDMA did not significantly change subacute mood and this was supported by our Bayesian analyses.ConclusionDespite augmentation in plasma MDMA levels and subjective drug effects, we found no increase in prosocial behaviour in a laboratory setting.

Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other 'psychedelics' yet were related to clinical outcomes. A 'reset' therapeutic mechanism is proposed.

Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen level-dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects. Increased visual cortex cerebral blood flow (CBF), decreased visual cortex alpha power, and a greatly expanded primary visual cortex (V1) functional connectivity profile correlated strongly with ratings of visual hallucinations, implying that intrinsic brain activity exerts greater influence on visual processing in the psychedelic state, thereby defining its hallucinatory quality. LSD's marked effects on the visual cortex did not significantly correlate with the drug's other characteristic effects on consciousness, however. Rather, decreased connectivity between the parahippocampus and retrosplenial cortex (RSC) correlated strongly with ratings of "ego-dissolution" and "altered meaning," implying the importance of this particular circuit for the maintenance of "self" or "ego" and its processing of "meaning." Strong relationships were also found between the different imaging metrics, enabling firmer inferences to be made about their functional significance. This uniquely comprehensive examination of the LSD state represents an important advance in scientific research with psychedelic drugs at a time of growing interest in their scientific and therapeutic value. The present results contribute important new insights into the characteristic hallucinatory and consciousness-altering properties of psychedelics that inform on how they can model certain pathological states and potentially treat others.

Aims: The aims of this study were to present an enhanced cannabis timeline followback (EC‐TLFB) enabling comprehensive assessment of cannabis use measures, including standard tetrahydrocannabinol (THC) units, and to validate these against objectively indexed urinary 11‐nor‐9‐carboxy‐tetrahydrocannabinol (THC‐COOH) concentrations. Design: We used cross‐sectional baseline data from the 'CannTeen' observational longitudinal study. Setting: The study was conducted in London, UK. Participants: A total of 147 participants who used cannabis regularly took part in the study (n = 71 female, n = 76 male; mean age = 21.90, standard deviation = 5.32). Measurements The EC‐TLFB was used to calculate frequency of cannabis use, method of administration, including co‐administration with tobacco, amount of cannabis used (measured with unaided self‐report and also using pictorial aided self‐report) and type of cannabis product (flower, hash) which was used to estimate THC concentration (both from published data on THC concentration of products and analysis of cannabis samples donated by participants in this study). We calculated total weekly standard THC units (i.e. 5 mg THC for all cannabis products and methods of administration) using the EC‐TLFB. The outcome variable for validation of past week EC‐TLFB assessments was creatinine‐normalized carboxy‐tetrahydrocannabinol (THC‐COOH) in urine. Findings All measures of cannabis exposure included in this analysis were positively correlated with levels of THC‐COOH in urine (r = 0.41–0.52). Standard THC units, calculated with average concentrations of THC in cannabis in the UK and unaided self‐report measures of amount of cannabis used in grams showed the strongest correlation with THC‐COOH in urine (r = 0.52, 95% bias‐corrected and accelerated = 0.26–0.70). Conclusions: The enhanced cannabis timeline followback (EC‐TLFB) can provide a valid assessment of a comprehensive set of cannabis use measures including standard tetrahydrocannabinol units as well as and traditional TLFB assessments (e.g. frequency of use and grams of cannabis use). [ABSTRACT FROM AUTHOR]