Multi-level neuroimaging of LSD

In 1966, Amanda met and began working with Bart Huges, a Dutch scientist of exceptional insight. He had recently developed a theory about the cascade of physiological events that follow the ingestion of a serotonergic psychedelic, such as LSD or psilocybin. For the next 30 years, she worked with him developing a hypothesis that proposes that a major factor underlying changes in the state of consciousness brought about by psychedelics, is a global and regional increase in the volume of blood in the brain capillaries, thereby providing extra energy (glucose and oxygen) to regions of the brain that do not normally have access to such a supply. This increase, and redistribution of resources, would result in an expanded field of simultaneous activity across the whole brain, and a global expansion of connectivity, which manifests as expanded consciousness. This hypothesis has never been investigated before in sufficient detail, and, if proven to be correct, will radically alter the way we interpret and understand the underlying physiology of expanded states of consciousness, and how best we can manage them in order to optimise their potential benefits.

​Our aim is to measure changes in capillary volume in the brain, at both a regional and global level, i.e. the overall changes in ratio between the two fluid volumes in the brain: blood and cerebrospinal fluid. Blood is heavier than cerebrospinal fluid, so gravity favours the CSF so that, in the upright position, Homo sapiens loses a small quantity of blood from the brain. To compensate for this, special mechanisms are developed, such as the Ego, a conditioned reflex of constriction to redirect the blood to the centres most essential for survival.

Until now, modern neuroscience has been almost exclusively focused on the impact of psychedelics on neural mechanisms, largely ignoring the fact that the serotonin system is deeply involved in many other important physiological mechanisms, in particular the regulation of the vascular tone, and therefore the distribution of blood in both the brain and body. Since the most widely used neuroimaging technique, fMRI, is based on fluctuations in the vascular signal, this lack of interest seems hard to believe.

Through this project, our aim is to address this ‘blind spot’ in current neuroscience, and investigate in much greater depth the hypothesis that Amanda has followed since 1966. With the advantages afforded by recent advances in brain imaging technology, we will perform, for the first time, multimodal recordings capable of relating changes in cerebral blood distribution with other well-known markers of the psychedelic state. Finally, we will investigate which imaging modality is best able to predict the subjective effects of psychedelics, by means of machine-learning models applied to the neuroimaging data. The same procedure will be repeated twice, with a high and low dose of LSD, thus comparing the effects of microdoses and full doses on brain function and conscious awareness.

​In this study, participants will receive varying doses of LSD in the experimental facilities, where we will perform multimodal recordings on the same subjects with fMRI (vascular activity measured with Arterial Spin Labelling [ASL], and neural activity measured with BOLD), PET (glucose metabolism), EEG (neural activity), MEG (magnetoencephalography) and Functional near-infrared spectroscopy (fNIRS) - a recently developed non-invasive optical-imaging technique that measures changes in haemoglobin concentrations within the brain, while the subject can move freely (unlike fMRI or MEG). These different imaging modalities are designed to measure either cerebral blood flow directly (PET, ASL, fNIRS), changes in metabolism linked to neuronal activity (BOLD fMRI, PET), or electrical activity (EEG).

Dr Enzo Tagliazucchi

Amanda is collaborating on this project with Dr Enzo Tagliazucchi and his lab at the University of Buenos Aires. Dr Tagliazucchi has been actively involved in the pioneering work of the Beckley/Imperial Psychedelic Research Programme, where he played an essential part in the analysis of the world’s first images of the human brain on LSD, revealing some of the key mechanisms behind its profound consciousness-altering effects. He is widely regarded as one of the most respected analysts in the field of psychedelic neuroimaging.