Exercise or Fasting in Individuals With Type 2 Diabetes Receiving Once-Weekly Basal Insulin Icodec.

Psychedelic drugs induce profound altered states of consciousness including affective, sensory, and cognitive effects mediated by activation of downstream pathways initiated by agonism at the brain serotonin 2A receptor. In combination with psychological support, clinical studies up to phase 2b indicate promising clinical efficacy of psychedelics in the treatment of affective and behavioural neuropsychiatric disorders that may be associated with their acute effects. Similarly, psychedelics induce acute and lasting effects on behaviour and personality in healthy participants. In parallel to evaluating clinical treatment effects, human brain functional magnetic resonance imaging (fMRI) has begun to shed light on neural pathways affected by psychedelics. Several prominent theories of critically relevant psychedelic effects on brain function have been advanced. A prominent theory is the Entropic Brain Hypothesis (EBH), which posits that the ‘richness’ of the phenomenology of the acute psychedelic state reflects brain-wide increases in entropy of functional brain signals. The concept of entropy serves as a quantification of the degree of information or complexity contained in a system; it is typically expressed in bits, without physical dimensions. Entropy has been conceptualised as a metric of information content and is largely defined in terms of a probability distribution; the metric is commonly referred to by the eponymous name ‘Shannon entropy’ where H(X) refers to the Shannon entropy of probability mass function X containing bins (x) with probability (p). Other entropy metrics have been defined, e.g. Lempel-Ziv complexity and sample entropy, and adapted to characterise information contained in various data representations, e.g. complex networks or graph structures. To date, 13 studies have evaluated either acute or lasting psychedelic effects on the information-entropy of brain activity or connectivity using blood oxygen level dependent (BOLD) fMRI data (Fig. ), one of which evaluates two metrics, thus 14 entropy metrics have been previously evaluated in this field. Four papers analysed data from a study evaluating 2 mg intravenous psilocybin administration in up to 15 healthy participants. Three papers reported effects from a study evaluating 75 µg intravenous LSD administration in 15 healthy participants, one of which also evaluated the effect of 25 mg oral psilocybin in 6 healthy participants. Two papers evaluated data from both intravenous Datasets. Three papers reported effects from a study evaluating oral ayahuasca administration, containing 96–160 mg DMT and 25.2–42 mg harmine (a monoamine oxidase inhibitor that facilitated the oral bioavailability of DMT) in 9 healthy participants. Finally, one paper reported effects from a study evaluating lasting effects of 25 mg/70 kg bodyweight orally administered psilocybin in 11 healthy participants. Notably, and highlighted in a recent review, each of these reports quantified a distinctly different metric of brain entropy. Here we group these metrics into three categories: (1) static connectivity, (2) dynamic connectivity, i.e. the time-varying relation between two or more time-series, (3) dynamic activity, i.e. the entropy of regional time-series (Fig. ). Ten of these metrics are based on the Shannon entropy of distributions, three are Lempel-Ziv complexity metrics of a time-series, and one is the sample entropy of a time-series. Taken together, although there is a clear interest in evaluating psychedelic effects on brain entropy, prominent limitations include that none of these measures have been evaluated in an independent cohort, the set of effects have been evaluated in only a few Datasets, some with atypical modes of drug administration, and the inter-correlation between these metrics has not been considered. Previous studies compared pre-drug or placebo and a single post-drug scan. For the most part, these previous studies report increased brain entropy with only a few exceptions, e.g. two studies report non-significant psilocybin effects and one study reports no lasting changes. See Supplementary Data  for more details about the previous studies. Previous fMRI studies have reported reduced brain entropy in other states of reduced consciousness, including NREM sleep, minimal-consciousness and anaesthesia, whereas other studies have shown increased brain entropy following caffeine and Salvinorin A intake.