Psychotic symptoms are uncommon and non-specific adverse effects of classic (serotonergic) psychedelics such as lysergic acid diethylamide (LSD), psilocybin, and mescaline. They can emerge during the acute phase of psychedelic drug effects, persist into the subacute ("afterglow") period, or, in rare cases, develop into long-term psychotic illness. Across all three scenarios, the symptoms can be deeply distressing due to their rapid changes, unpredictability, and significant adverse behavioral consequences.Psychedelics have a long history of use as research models for schizophrenia because of the phenomenological overlaps between their acute effects and the core symptoms of psychosis. This "model psychosis" paradigm, however, has been widely criticized: although certain acute symptoms may appear similar, the etiology and psychodynamic background of primary psychosis only partially apply to psychedelic-related psychosis. Moreover, it remains unclear whether psychotic symptoms following the use of classic psychedelics differ meaningfully from those associated with other substances, such as dopaminergic stimulants or cannabis.A transient porosity of ego boundaries is a core feature of acute psychedelic states, ranging from heightened feelings of connectedness with oneself and others to complete ego dissolution. These experiences are often perceived as positive and may be followed by a subacute phase characterized by sustained increases in openness to new experiences. In some cases, however, ego dissolution may become fear-inducing and progress from challenging but manageable experiences to paranoid psychotic reactions that require therapeutic guidance and intervention.In this chapter, we examine phenomenological similarities and differences between psychedelic-induced psychosis and primary psychosis. Consistent with current international diagnostic classification systems, we conclude that, with increasing temporal distance from the initial psychedelic "index" experience that predated the symptoms, persisting psychedelic-induced psychotic symptoms become indistinguishable from primary psychosis. Finally, we present a psychodynamic therapeutic approach for schizophrenia-spectrum psychosis that may, to some extent, be adapted to psychotic symptoms observed across all three phases of psychedelic drug effects.

Opioid use disorder (OUD) continues to be a global problem, with particularly high opioid usage rates in the United States. One major contributor to this crisis has been the high rate of opioid prescriptions, which has increased access to opioids and contributed to many vulnerable individuals becoming dependent or addicted. Many of these affected people are women of reproductive age, which in turn results in many women using or abusing opioids during pregnancy and thus many infants being exposed to illicit opioids. OUD is typically treated with either methadone or buprenorphine (BUP), two effective opioid-based medications for OUD (MOUD). BUP has recently gained more attention and replaced methadone as the "gold standard" of treatment since its unique pharmacodynamic properties seem to result in better compliance, less withdrawal symptoms, and improved infant outcomes compared to methadone. However, the effects of BUP exposure on the long-term outcome of the offspring and mother-infant dyad are not fully understood. This chapter will review the current state of the literature regarding effects of gestational opioid exposure on offspring outcomes, focusing on morphine as a commonly used illicit substance and BUP as a widely used MOUD. Collectively, the literature reviewed here highlights the need for future research into the impact of gestational opioid use on mothers, their care behavior, and their subsequent mother-infant bonds.

Alcohol use disorder (AUD) induces significant structural alterations in both gray and white matter, contributing to cognitive and functional impairments. This chapter presents a translational neuroimaging approach using diffusion-weighted MRI in humans and rodents to uncover novel pathophysiological mechanisms underlying AUD. Our studies demonstrate that increased mean diffusivity (MD) in gray matter reflects microglial reactivity and reduced extracellular space tortuosity, leading to enhanced volume neurotransmission. In white matter, fractional anisotropy (FA) reductions indicate progressive deterioration of key tracts, particularly the fimbria/fornix, linked to impaired cognitive flexibility. Importantly, longitudinal analyses reveal that white matter degeneration continues during early abstinence, suggesting that neuroinflammation and demyelination persist beyond alcohol cessation. Finally, we discuss how neuromodulatory interventions, such as transcranial magnetic stimulation (TMS), may promote recovery by enhancing myelin plasticity. These findings provide crucial insights into AUD's neurobiological underpinnings and highlight potential therapeutic targets for improving treatment outcomes.

Slow caressing of the skin activates C-tactile fibers in the periphery and the posterior insula cortex. Because of this, Bud Craig considered affective touch to be an interoceptive modality. Through the tactile sense, we perceive the border of our own body and the largest of our organs, the skin. Whether or not C-targeted touch is considered interoceptive, it contributes fundamentally to the development and maintenance of the bodily self. This is supported by experimental data from cases, where somatosensory processing is altered, and the other way around, i.e., when the bodily sense of self is changed either pharmacologically or in psychiatric conditions. Self-touch can be seen as a special case contributing to the bodily self-model by providing high fidelity signals within a closed feedback loop. Social touch, especially between parents and children and between romantic partners, plays a crucial role in social allostasis and the co-regulation of physiology and emotions. Touch, both self-touch and social touch, should therefore be considered foundational for the bodily self and essential for mental and physiological well-being. Through touch, we perceive the self in its most basic form, as a social body.

As psychedelics are being investigated for more medical indications, it has become important to characterize the adverse effects and pharmacological interactions with these medications. This chapter will summarize what is known about the toxicology and drug-drug interactions for classic psychedelics, such as LSD, psilocybin, DMT, 5-MeO-DMT, mescaline, 2C-B, Bromo-DragonFLY, and 25X-NBOMe.

The use of animal models continues to be essential for carrying out research into clinical phenomena, including addiction. However, the complexity of the clinical condition inevitably means that even the best animal models are inadequate, and this may go some way to account for the apparent failures of discoveries from animal models, including the identification of potential novel therapies, to translate to the clinic. We argue here that it is overambitious and misguided in the first place to attempt to model complex, multifacetted human disorders such as addiction in animals, and especially in rodents, and that all too frequently "validity" of such models is limited to superficial similarities, referred to as "face validity", that reflect quite different underlying phenomena and biological processes from the clinical situation. Instead, a more profitable approach is to identify (a) well-defined intermediate human behavioural phenotypes that reflect defined, limited aspects of, or contributors to, the human clinical disorder, and (b) to develop animal models that are homologous with those discrete human behavioural phenotypes in terms of psychological processes, and underlying neurobiological mechanisms. Examples of past and continuing weaknesses and suggestions for more limited approaches that may allow better homology between the test animal and human condition are made.

Complement is a critical component of innate immunity, evolved to defend against pathogens and clear toxic debris rangingfrom dead and dying cells to immune complexes. These roles make complement a key player in homeostasis; however, complement has a dark side. When the rigid control mechanisms fail, complement becomes dysregulated, acting as a driver of inflammation and resultant pathology in numerous diseases. Roles of complement in Alzheimer's disease (AD) and other dementias have emerged in recent years, supported by genetic, biomarker and pathological evidence and animal model studies. Numerous questions remain regarding the precise roles of complement in the brain in health and disease, including where and when complement is expressed, how it contributes to immune defence and garbage disposal in the healthy brain, and exactly how complement contributes to pathology in dementias. In this brief review, we will summarise current knowledge on complement roles in brain, present the evidence implicating complement in AD and explore whether complement represents an attractive therapeutic target for AD.

This chapter will review the basic pharmacology of the canonical cannabinoid receptors. The endocannabinoid system is a complex signalling network involved in a wide range of physiological processes, including pain modulation, appetite regulation, and synaptic plasticity. The canonical cannabinoid receptors, CB1 and CB2, are central in orchestrating this system. CB1 is highly enriched in the central nervous system (CNS), where it plays a crucial role in modulating neurotransmitter release and synaptic plasticity. In contrast, CB2 is predominantly expressed in peripheral tissues and immune cells, participating in anti-inflammatory processes. Here, we focus on cannabinoid receptor distribution, intracellular signalling, and receptor regulation. We describe the intracellular signalling pathways activated by CB1, including the modulation of ion channels, second messengers, and protein kinases. Overall, this chapter provides an overview of the canonical cannabinoid receptors and their role in the regulation of neuronal signalling and plasticity, highlighting the molecular and cellular mechanisms underlying their effects in the CNS.

Despite using the recommended anti-emetic treatments, control of nausea and vomiting is still an unmet need for cancer patients undergoing chemotherapy treatment. Few properly controlled clinical trials have evaluated the potential of exogenously administered cannabinoids or manipulations of the endogenous cannabinoid (eCB) system to treat nausea and vomiting. In this chapter, we explore the pre-clinicaland human clinical trial evidence for the potential ofexogenous cannabinoids and manipulations of the eCB system to reduce nausea and vomiting. Although there are limited high-quality human clinical trials, pre-clinical evidence suggests that cannabinoids and manipulations of the eCB system have anti-nausea/anti-emetic potential. The pre-clinical anti-nausea/anti-emetic evidence highlights the need for further evaluation of cannabinoids and manipulations of eCBs and other fatty acid amides in clinical trials.