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LSD findings could help understand how the brain generates behaviour

Researchers at Baylor College of Medicine have discovered changes in the brain triggered by LSD.



LSD findings could help understand how the brain generates behaviour

Researchers have discovered changes in the brain associated with LSD which they say could help gain insights into how the brain generates behaviour.

The team at Baylor College of Medicine have discovered changes in the brain triggered by LSD that may explain the altered behaviour associated with the compound. Published in the journal Cell Reports the findings demonstrated that rats that had been given LSD altered their running behaviour in a track they were familiar with compared to rats that had not been given the compound, and also increased their resting time. 

During this time the rats entered what the scientists describe as a state of being half-awake and half-asleep.

Corresponding author and professor of neuroscience at Baylor, Dr Daoyun Ji, commented: “Our lab is interested in improving the understanding of how the brain generates behaviour. 

“LSD triggers abnormal perceptions of the real world and altered behaviours. By studying how the drug works, we hope to gain insights into the neural mechanisms that mediate behaviour.”

During this half-awake and half-asleep state, the researchers observed a reduction of the normal communication between the hippocampus and the visual cortex in the brain. This reduction in communication may explain the changed behaviours according to the team.

Ji and his colleagues looked at the animals’ behaviour and their simultaneous brain activity with and without LSD, as the rats were running in a familiar C-shaped track, recording the number of laps the animals ran on the track and as well as how fast they ran. In order to measure brain activity, the researchers recorded the brain cells’ electrical spiking patterns in real-time in the hippocampus and the visual cortex. 

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The team found that the animals receiving the drug ran fewer laps and moved slower than those without LSD, and that the overall spiking activity of the hippocampus and visual cortex neurons was greatly reduced in the animals that received LSD. The rats receiving the LSD also had more periods of inactivity in the track.

“That means that when the animal was moving around in the track, the neurons generated fewer pulses, which probably affected the clarity of their guiding brain ‘map,’” Ji said.

Animal brains naturally develop a ‘map’ when moving around an environment in order to know where it is and how to go from point A to point B, allowing the animal to remember the place and guides future navigation in the same space. The hippocampus and the visual cortex work together to create this map. 

The team say that the LSD changed the spiking patterns that sustain this map, including what gives the animal direction, and the communication between the visual cortex and the hippocampus. 

The authors state: “When rats are immobile on the track, LSD enhances cortical firing synchrony in a state similar to the wakefulness-to-sleep transition, during which the hippocampal-cortical interaction remains dampened while hippocampal awake reactivation is maintained.

“Our results suggest that LSD suppresses hippocampal-cortical interactions during active behaviour and during immobility, leading to internal hippocampal representations that are degraded and isolated from external sensory input. These effects may contribute to LSD-produced abnormal perceptions.”

“We propose that LSD makes the map fuzzy,” Ji said. “These periods of inactivity triggered by LSD are like the normal transition from being awake to going to sleep. It suggests that maybe the drug induces a state similar to a half-conscious state in which a lot of dreaming-like activity is happening. More research is needed to enlighten this finding.”

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Study to investigate macro and microdoses of psychedelic compounds

The study will interrogate how these doses modulate expression levels of molecular biomarkers of brain plasticity in rats.



Study to investigate macro and microdoses of psychedelic compounds

Mindset Pharma and Canada’s top psychiatric research hospital, CAMH, have entered into a collaboration to build the molecular profile of MSP-1014 compared to psilocybin.

Under the collaboration, Mindset will sponsor a preclinical study at CAMH on its lead asset, MSP-1014. MSP-1014 is a novel and patented second-generation psilocybin-like compound that is being prepared for first-in-human studies alongside psilocybin.

Single psychedelic experiences can cause both short- and long-term behavioural changes in humans and the mechanisms of these are relatively under-explored. The study will interrogate how macro and microdoses of psychedelic compounds modulate expression levels of molecular biomarkers of brain plasticity in rats. 

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The team expects to uncover short- and long-term cFOS and BDNF expression changes that could underlie the long-term behavioural changes associated with a single psychedelic experience. 

It also expects to develop molecular insights into the magnitude of effects of its lead compound, MSP-1014, compared to psilocybin. 

CEO of Mindset, James Lanthier, commented: “Mindset’s drug discovery platform is built on a broad spectrum of high-quality scientific data generated in preclinical models. 

“This collaboration will profile and build our understanding of the observed superiority of our lead asset, MSP-1014, to psilocybin at the molecular level.”

Dr Anh Dzung Lê, senior scientist and Head of Neurobiology of Alcohol Lab in the Campbell Family Mental Health Research Institute at CAMH, will lead the study, supported by Dr Douglas Funk, a Project Scientist in the CAMH Neurobiology of Alcohol Lab. 

“We are excited to partner with Dr Lê and Dr Funk who are pioneers in mental health research to build this dataset and continue in our shared mission to advance groundbreaking new treatments to patients who are waiting,” said Lanthier.

“This study is the beginning of a strong partnership with CAMH, and we are excited for the research to come.”

“We are eager to work together with Mindset Pharma to contribute to the field of psychedelic knowledge. Given that by the time Canadians reach 40 years of age, 1 in 2 have – or have had – a mental illness, CAMH scientists and clinicians are dedicated to exploring treatment option that account for the unique needs of individual patients.

Dr Anh Dzung Lê commented: “We are pleased to partner with Mindset on this study as our missions are aligned in the prioritisation of mental health care.”

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FDA clears psilocybin for government-funded smoking cessation trial

Mydecine has announced its drug – MYCO-001 – has been cleared for clinical trials.



FDA clears psilocybin for government-funded smoking cessation trial

The US food and Drugs Administration (FDA) has given approval for MYCO-001 in a recent Investigational New Drug (IND) application, which will now be used in the first US Government-funded psychedelic study in 50 years.

MYCO-001 – a synthetic psilocybin – will now be supplied for a multi-site study investigating psilocybin therapy for smoking cessation. 

The randomised trial aims to determine if psilocybin increases smoking abstinence compared to a placebo, both paired with cognitive-behavioral therapy (CBT).

The trial is being carried out at Johns Hopkins University, New York University and the University of Alabama Birmingham, and will be led by Dr Matthew Johnson – a professor of psychiatry and behavioural sciences at Johns Hopkins University School of Medicine. 

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Johnson received an historical $4m grant from the National Institute on Drug Abuse (NIDA) to carry out the study – which was the first US Government grant in over 50 years for a study exploring the therapeutic benefits of a psychedelic compound.

Mydecine Innovations Group signed an open ended agreement with Johns Hopkins University Johns Hopkins University to study multiple molecules for multiple indications. The FDA approval for MYCO-001 for the smoking cessation study marks the first clearance of the company’s drug product.

Mydecine CEO Josh Bartch commented: “Mydecine looks forward to supplying the placebo and our MYCO-001 drug product for this study.

“The FDA clearance is encouraging as we prepare to submit the IND for our Industry Sponsored Phase 2b trial using the same drug products.”

Further Principal Investigators (PI) on the study include Michael P. Bogenschutz, M.D., Director of the New York University (NYU) Langone Center for Psychedelic Medicine and Professor, Department of Psychiatry at NYU Grossman School of Medicine, as well as Peter Hendricks, Ph.D., professor in the Department of Health Behavior at the University of Alabama School of Public Health and a site principal investigator.

The grant-funded research and Mydecine’s Phase 2b study expand on previous research led by Johnson and his team. A study conducted in 2014 assessed the efficacy of psilocybin, in combination with CBT, as a treatment for tobacco addiction. At six months, 80 per cent of individuals were biologically proven to be smoking abstinent.

Mydecine senior director of clinical and regulatory affairs, Jessica Riggleman, stated: “Supportive clinical trial results have generated interest in studying psychedelic-assisted therapy across multiple indications. 

“We look forward to supplying psilocybin to help advance the exploration of research in this field.”

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Ohio State launches new academic centre for psychedelic research

The centre is set to open at Ohio State University’s College of Social Work.



Ohio State launches new academic centre for psychedelic research

Ohio State University is launching The Center for Psychedelic Drug Research and Education (CPDRE).

The CPDRE is aiming to fill gaps in the field of psychedelic research and will formalise an expert of networks in different fields from across Ohio State University.

Specifically, research carried out at the centre is aiming to focus on populations and psychological disorders that are currently underrepresented in studies, and on preparing future scholars and clinicians through a variety of interdisciplinary educational initiatives.

The centre received $1.5m in financial support from the Fund for Psychedelic Drug Research and Education from two anonymous donors.

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Assistant Professor of Social Work, Alan Davis, director of the CPDRE, said in a statement: “Creating this infrastructure helps establish a system of values that shapes our goals and focuses our mission in strategic ways – all important steps given that the topic is so new.

“All of this allows us to demonstrate the ways we are capable as a group of investigators and instructors to best utilise resources for future work, which sets us up to be competitive for future funding.”

The centre will also be engaging centers focused on drug policy and substance misuse prevention and recovery and will be enables research and administrative staff, postdoctoral fellows and graduate students – all of which it says will help to propel the work.

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Associate professor of fungal evolutionary genomics in the Department of Plant Pathology, Jason Slot, who studies the evolution and ecology of psilocybin mushrooms, will act as director of educational initiatives for CPDRE.

College of Social Work Dean, Tom Gregoire, stated: “Although more mental health services are provided by social workers than all other disciplines combined, no other social work program in the country is engaged in this type of work that Dr. Davis and his colleagues are undertaking.

“This line of inquiry has great promise in helping individuals and families with what can be intractable challenges.

“Our purpose as scholars and educators is to advance innovation in practice and widely disseminate it so that it touches many lives. Our capacity to reach so many makes this commitment essential.”

“If psychedelics are made available at the national level for medical purposes, then there will be a rapid shift in our cultural perspective, one that will need to integrate psychedelics and psychedelic-assisted therapy into our communities, families and mental health system,” Davis said.

“Making sure we can educate people and help them understand what psychedelic experiences are, how people talk about these experiences, the history of psychedelics and their cultural context, how they act in the brain – are all critical endeavours which the CPDRE will undertake.”

The University has confirmed that a number of clinical studies are under development at the centre subject to regulatory approval at the federal, state and university levels. 

Additionally, it has confirmed it will be hosting the Psychedemia conference on Interdisciplinary Psychedelic Scholarship in August 2022 and will be developing a psychedelic studies curricula for an online continuing education certificate programme, as well as an interdisciplinary undergraduate minor. 

An existing course in the Department of Plant Pathology titled Psychedelic Studies: Neurochemistry, Plants, Fungi and Society will be a core component of the new programs.

Slot stated: “The interdisciplinary minor would be aimed at really bringing pieces together from drug discovery to historical and ethical aspects through the clinical realm.

“One big outcome will be that we can give a holistic education and perspective to our students both at the graduate and undergraduate level to be able to understand the history of what they’re working on, the pitfalls and the ethics.

“This being an explosive time in psychedelic science, it’s important to bring together different perspectives in an emerging field and create a place where people can focus together on psychedelics.”

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Psychedelic Health is a journalist-led news site. Any views expressed by interviewees or commentators do not reflect our own. We do not provide medical advice or promote the personal use of psychedelic compounds. Please seek professional medical advice if you are concerned about any of the issues raised.

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