Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing.

Psychedelic microdosing describes the ingestion of near-threshold perceptible doses of classic psychedelic substances. Anecdotal reports and observational studies suggest that microdosing may promote positive mood and well-being, but recent placebo-controlled studies failed to find compelling evidence for this. The present study collected web-based mental health and related data using a prospective (before, during and after) design. Individuals planning a weekly microdosing regimen completed surveys at strategic timepoints, spanning a core four-week test period. Eighty-one participants completed the primary study endpoint. Results revealed increased self-reported psychological well-being, emotional stability and reductions in state anxiety and depressive symptoms at the four-week primary endpoint, plus increases in psychological resilience, social connectedness, agreeableness, nature relatedness and aspects of psychological flexibility. However, positive expectancy scores at baseline predicted subsequent improvements in well-being, suggestive of a significant placebo response. This study highlights a role for positive expectancy in predicting positive outcomes following psychedelic microdosing and cautions against zealous inferences on its putative therapeutic value.

Positive effects of psychedelics on depression and wellbeing scores in individuals reporting an eating disorder.

PURPOSE: Psychedelic therapy is showing promise for a broad range of mental health conditions, indicative of a transdiagnostic action. While the efficacy of symptom-focused treatments for eating disorders (EDs) is limited, improved mental health and psychological wellbeing are thought to contribute to greater treatment outcomes. This study provides the first quantitative exploration of the psychological effects of psychedelics in those reporting an ED diagnosis. METHODS: Prospective, online data were collected from individuals planning to take a psychedelic drug. Twenty-eight participants reporting a lifetime ED diagnosis completed measures of depressive symptomology (Quick Inventory of Depressive Symptomology; QIDS-SR16) and psychological wellbeing (Warwick-Edinburgh Mental Wellbeing Scale; WEMWBS) 1-2 weeks before, and 2 weeks after a psychedelic experience. Twenty-seven of these participants also completed a measure of emotional breakthrough [Emotional Breakthrough Inventory (EBI)] in relation to the acute psychedelic experience. RESULTS: Bayesian t tests demonstrated overwhelming evidence for improvements in depression and wellbeing scores following the psychedelic experience. Marginal evidence was also found for a correlation between emotional breakthrough and the relevant mental health improvements. CONCLUSION: These findings provide supportive evidence for positive psychological aftereffects of a psychedelic experience that are relevant to the treatment of EDs. It is hoped that this will encourage further research and will bolster initiatives to directly examine the safety and efficacy of psychedelic assisted therapy as a treatment of EDs in future clinical trials. LEVEL OF EVIDENCE: Level III, cohort study.

Neural plasticity is modified over the human menstrual cycle: Combined insight from sensory evoked potential LTP and repetition suppression.

In healthy women, fluctuations in hormones including progesterone and oestradiol lead to functional changes in the brain over the course of each menstrual cycle. Though considerable attention has been directed towards understanding changes in human cognition over the menstrual cycle, changes in underlying processes such as neural plasticity have largely only been studied in animals. In this study we explored predictive coding and repetition suppression via the roving mismatch negativity paradigm as a model of short-term plasticity (Garrido, Kilner, Kiebel, et al., 2009), and Hebbian learning via visual sensory long-term potentiation (LTP) as a model of long-term plasticity (Teyler et al., 2005). Electroencephalography (EEG) was recorded in 20 females during their early follicular and mid-luteal phases. Event-related potential (ERP) analyses were complemented with dynamic causal modelling (DCM) to characterise changes in the underlying neural architecture. More sustained variability in the ERP response to a change in tone during the luteal phase are interpreted as a delayed habituation of the P3a component in the luteal relative to the follicular phase. The additional increased forward connection strength over tone repetitions compared to the follicular phase suggests that, in this phase, females may be less efficient when processing deviations from predicted sensory input (error). In contrast, there appears to be no reliable change in sensory LTP. This suggests that predictive coding, but not Hebbian plasticity is modified in the mid-luteal compared to the follicular phase, at least at the days of the menstrual cycle tested. This finding implicates the human menstrual cycle in complex changes in neural plasticity and provides further evidence for the importance of considering the menstrual cycle when including females in electrophysiological research.

Indexing sensory plasticity: Evidence for distinct Predictive Coding and Hebbian learning mechanisms in the cerebral cortex.

The Roving Mismatch Negativity (MMN), and Visual LTP paradigms are widely used as independent measures of sensory plasticity. However, the paradigms are built upon fundamentally different (and seemingly opposing) models of perceptual learning; namely, Predictive Coding (MMN) and Hebbian plasticity (LTP). The aim of the current study was to compare the generative mechanisms of the MMN and visual LTP, therefore assessing whether Predictive Coding and Hebbian mechanisms co-occur in the brain. Forty participants were presented with both paradigms during EEG recording. Consistent with Predictive Coding and Hebbian predictions, Dynamic Causal Modelling revealed that the generation of the MMN modulates forward and backward connections in the underlying network, while visual LTP only modulates forward connections. These results suggest that both Predictive Coding and Hebbian mechanisms are utilized by the brain under different task demands. This therefore indicates that both tasks provide unique insight into plasticity mechanisms, which has important implications for future studies of aberrant plasticity in clinical populations.

Age-related alterations in human neocortical plasticity.

Age-related changes in neuroplasticity may be central to the cognitive decline associated with healthy ageing. Modulated Long-Term Potentiation (LTP) and Long-Term Depression (LTD) have been repeatedly demonstrated in aged rodents, however the translation to human research has been limited by a scarcity of non-invasive methods for doing so. We have previously demonstrated that, following a block of high frequency presentations of a visual stimulus (referred to as a "visual tetanus"), there is a LTP-like enhancement of the N1b component of the visually evoked potential (VEP) to subsequent low frequency presentations of the same stimulus. The aims of the current study were, firstly, to use this electroencephalography (EEG) paradigm to assess age group differences in neocortical plasticity in humans, and secondly, to expand on the visual LTP paradigm by examining plasticity in another component of the VEP; the P2a. While a young participant group (N=29, age range=19-35) demonstrated the expected LTP-like enhancement of the N1b immediately following the visual tetanus, an older participant group (N=19, age range=68-91) did not. However, both age groups demonstrated a positive shift of the P2a component after repeated presentations of low frequency baseline blocks, which is hypothesized to be an LTD-like shift in the VEP. These results support the rodent literature indicating an age-related shift in threshold for LTP, but a relative preservation of the threshold for LTD. This study not only provides valuable insight into healthy age-related alterations in neocortical plasticity, but is also the first to identify an LTD-like modulation of the VEP in humans.

Clinical, ethical and legal considerations in the treatment of newborns with non-ketotic hyperglycinaemia.

Non-ketotic hyperglycinaemia (NKH) is a devastating neurometabolic disorder leading, in its classical form, to early death or severe disability and poor quality of life in survivors. Affected neonates may need ventilatory support during a short period of respiratory depression. The transient dependence on ventilation dictates urgency in decision-making regarding withdrawal of therapy. The occurrence of patients with apparent transient forms of the disease, albeit rare, adds uncertainty to the prediction of clinical outcome and dictates that the current practice of withholding or withdrawing therapy in these neonates be reviewed. Both bioethics and law take the view that treatment decisions should be based on the best interests of the patient. The medical-ethics approach is based on the principles of non-maleficence, beneficence, autonomy and justice. The law relating to withholding or withdrawing life-sustaining treatment is complex and varies between jurisdictions. Physicians treating newborns with NKH need to provide families with accurate and complete information regarding the disease and the relative probability of possible outcomes of the neonatal presentation and to explore the extent to which family members are willing to take part in the decision making process. Cultural and religious attitudes, which may potentially clash with bioethical and juridical principles, need to be considered.

Is conceiving a child to benefit another against the interests of the new child?

Conceiving a child by way of embryo selection and tissue matching to benefit a sick sibling is generally justified on the grounds that as well as the potential to save the sick child, there is a benefit for the new baby. The new baby is selected so he or she will not have the disease suffered by the first child. It is not possible, however, to select against conditions for which there is no test and Jamie Whitaker's birth is a case where the process of in vitro fertilisation with tissue matching is viewed as being of benefit only to a third party-the sick child. Some people object to using the technology for this purpose. There are also good reasons to argue that the technology should be used to save a sick child, and that it would be morally remiss for Jamie's parents not to consent to the use of his cord blood.

Woman wants dead fiancé's baby: who owns a dead man's sperm.

The Brisbane Supreme Court has denied an Australian woman's request to harvest and freeze her dead fiancé's sperm for future impregnation. After she was denied access to the sperm, the woman learnt that her fiancé may have been a sperm donor and she began checking to find out if his sperm was still available. Given what we know, there is a good ethical argument that the woman should have access to the sperm and should be allowed to have her dead fiancé's child. Another aspect of this case is that it illustrates the way in which ethics, law, and personal opinion can differ.

Canaries in the mines: children, risk, non-therapeutic research, and justice.

The Kennedy Krieger lead paint study received a lot of attention after a US Court of Appeals ruled that a parent cannot consent to the participation of a child in non-therapeutic research. The ruling has raised fears that, if it goes unchallenged, valuable research might not proceed and ultimately all children would be harmed. The author discusses significant aspects of the study that have been neglected, and argues that the study was unethical because it involved injustice and its design meant that the study lacked importance and value. Issues of benefit, risk, and consent are vital, but it is sometimes a mistake to consider these issues before settling questions about justice and the importance and value of a research project. The author concludes by offering a strategy for researchers and reviewers of research to appreciate, in a vivid way, the implications of research participation.

Should HIV discordant couples have access to assisted reproductive technologies?

In this paper we identify and evaluate arguments for and against offering assisted reproductive technologies (ART), specifically IVF, to HIV discordant couples (male partner HIV positive, female partner HIV negative). The idea of offering ART to HIV discordant couples generates concerns about safety and public health and raises questions such as: what is an acceptable level of risk to offspring and should couples who want this assistance be subject to selection criteria; should they undergo scrutiny about their suitability as parents when those who are able to conceive naturally face no such scrutiny and people with other illnesses are given access to ART? We conclude that offering ART to HIV discordant couples is likely to produce more benefit than harm and violates no ethical principles. Nevertheless, a decision to deny treatment need not constitute unjustified discrimination.

Therapeutic cloning research and ethical oversight.

Cloning Trevor, a story about therapeutic cloning research, appeared in the June issue of The Atlantic Monthly. The story gives a human face to the people whom therapeutic cloning could benefit. It presents an argument for government funding and it puts the usual calls for a moratorium on embryonic stem cell research to allow for more debate, in a less favourable light. The story also highlights some problems with ethical oversight.

Lesbian couple create a child who is deaf like them.

A deaf lesbian couple who sought a sperm donor with a family history of deafness in order to have a child they hoped would be deaf have attracted a lot of criticism. They have been criticised for deliberately creating a deaf child, for denying their child a hearing aid, and for raising the child in a homosexual household.

"Saviour siblings".

The Victorian Infertility Treatment Authority has given permission to allow tissue typing in combination with preimplantation genetic diagnosis. This is a new application of IVF. Not only will it allow parents to select an embryo free from serious genetic disease it will allow them to simultaneously select for a match so that the umbilical cord blood of the resulting baby can provide stem cells to treat an existing sibling who has a disease.

Genetically selected baby free of inherited predisposition to early-onset Alzheimer's disease.

The application of preimplantation genetic diagnosis to select against early-onset Alzheimer's has been criticised on several grounds. Some critics think it is wrong to reject an embryo because it may develop a disease later on in middle age and some question whether a woman who will soon become incapacitated and unable to provide for her child should be a candidate for assisted reproductive technology.

The Perruche judgment and the "right not to be born".

The French government has given in to public pressure and overturned a controversial legal ruling which recognised the right of a disabled child to seek damages. Most notably, the ruling, widely described as establishing a child's right "not to be born", had provoked "outrage" amongst groups defending the rights of the disabled and led to a ban on prenatal scans by French gynaecologists. Once again, only parents will be able to seek damages but some people think the ruling has been misinterpreted.