Neurovascular effects 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 and psychological events that follow the ingestion of a serotonergic psychedelic, such as LSD or psilocybin. The hypothesis posits that a major factor in psychedelic-induced changes in consciousness is a regional and global increase in the volume of blood in the capillaries of the brain, thereby providing extra energy, in the form of glucose and oxygen, to regions of the brain that do not normally have access to such a supply. This increase, and redistribution of resources, results 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 with advanced brain imaging technology, 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 to both the individual and society as a whole.

​In February 2021, Amanda approached Prof Alex Kwan, a renowned neuroscientist then working at Yale University, who specialises in the study of microcircuits in the frontal cortex of the brain using optical imaging techniques. Interested in her long-held hypothesis, he introduced her to two of his colleagues at Cornell University, where he has since relocated: Prof. Chris Schaffer and Prof. Nozomi Nishimura. This trio of experts have agreed to collaborate in order to research Amanda's hypothesis, with a particular focus on LSD, a compound she considers as the ‘Queen of Psychedelics’, and on which the Beckley Foundation’s new ‘Double-Headed Programme’ is focused.

The first part of the project involves determining how psychedelics affect cerebral blood flow by directly measuring how the tone of the blood vessels is altered following administration of LSD. This will be done by studying live mice, using advanced optical imagining to record the diameter and flow rate of arterioles, capillaries, and venules in the frontal cortex, before and after LSD administration. Finally, regional changes (i.e. changes to the whole frontal cortex, as opposed to individual cells) will also be measured in order to give a more complete picture of how psychedelics alter cerebral blood flow, and thereby control which parts of the brain are being provided with sufficient blood to produce consciousness.

The second part of the project involves investigating how psychedelics influence neurovascular coupling, i.e. the way neuronal activity influences blood flow in surrounding vessels. This is an important new subject, which has not yet been properly addressed, as understanding precisely how psychedelics alter neurovascular coupling will allow for a more accurate interpretation of how they alter capillary volume, thus affecting brain activity and consciousness.

The revolutionary micro-imaging technique used in this project will open a window into the living brain of mice in order to observe, in real-time, the simultaneous effects of LSD on micro-vasculature and on the activity of specific groups of neurons. This will bring to light changes never yet explored at the microscopic level.

Only a few groups worldwide have the capability to study blood flow dynamics in the level of detail that my collaborators’ labs have mastered, and none to date have directly investigated the effects of psychedelics on the brain micro-vasculature. The unique combination of expertise brought together by this research team makes Cornell University the only place in the world in which this ground-breaking study could be carried out.

This two-part project will be complementary to other studies Amanda is currently developing with leading experts at King’s College London and UCL, and also at the University of Buenos Aires. These will be investigating the effects of a range of doses of LSD on brain function using the latest multimodal neuroimaging tools in humans, which has never been undertaken before.

Picture of brain micro-vasculature obtained with optical imaging

The team is ideally suited for the proposed work, bringing together complementary expertise in neuropharmacology from Alex Kwan, vascular imaging from Chris Schaffer and Nozomi Nishimura, and psychedelics from Amanda Feilding.

Professor Alex Kwan​

Alex Kwan is an associate professor in the Meinig School of Biomedical Engineering at Cornell University. The Kwan lab has a longstanding interest in understanding the impact of psychoactive drugs on cortical neural circuits. In prior studies, the lab studied psilocybin to show that a single dose leads to long-lasting modifications to the dendritic architecture. These results led to the proposal of an integrative framework for understanding the action of psychedelics.

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Alex recently published ground-breaking results in the prestigious journal Neuron, showing that a single dose of psilocybin enhanced the formation of dendritic spines, the branch-like appendages of neurons that receive communications from other cells, in the medial frontal cortex of the mouse. A month after administration, a third of new dendritic spines remained.

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These results, which complement our own, open up very promising therapeutic applications in psychiatry and neurology.

Professor Chris Schaffer

Chris Schaffer is an associate professor in the Meinig School of Biomedical Engineering at Cornell University. His lab develops and uses advanced laser microscopy to observe and manipulate cells in vivo (i.e. in live organisms) with the goal of constructing a microscopic scale understanding of physiological processes in the central nervous system. In exciting new work, the lab is beginning to elucidate the pathways by which changes in brain microvasculature interact with and exacerbate Alzheimer’s disease.

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Professor Nozomi Nishimura

Nozomi Nishimura is an associate professor in the Meinig School of Biomedical Engineering at Cornell University. She is interested in how the vasculature, immune and inflammatory systems, and cells native to tissue, interact in disease states.

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Her lab’s strategy is to develop novel tools to image the contribution of multiple physiological systems to disease with in vivo animal models.

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The Schaffer/Nishimura lab is a pioneer in the use of optical imaging methods to measure cerebral blood flow and neurovascular coupling. These methods have been applied successfully to reveal how vascular dynamics are altered by neurodegenerative diseases and show consequences of vascular occlusion after stroke

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Amanda Feilding

Amanda Feilding has been studying the mechanisms underlying non-ordinary states of consciousness brought about by psychedelics and other techniques for over 50 years, with a particular interest in changes to capillary volume in the brain, with the hypothesis that an increase provides the brain with an increased supply of energy, which in turn activates more brain cells simultaneously, thus increasing connectivity and expanding consciousness. Amanda set up the Beckley Foundation in 1998 to carry out pioneering scientific research using the latest brain imaging technologies and other techniques, and to reform global drug policy in order to facilitate research and access to these medicines.

By establishing key research collaborations with some of the world’s most prestigious academic institutions, she has propelled the field of psychedelic research forwards for over 20 years, conducting several landmark studies, such as the world’s first LSD brain imaging study, and the first study to show clinical benefits of psilocybin for treatment-resistant depression.